WorldWideScience

Sample records for impact drug disposition

  1. Improving the prediction of the brain disposition for orally administered drugs using BDDCS

    DEFF Research Database (Denmark)

    Broccatelli, Fabio; Larregieu, Caroline A.; Cruciani, Gabriele

    2012-01-01

    outcome. Passive permeability and P-glycoprotein (Pgp, ABCB1) efflux have been successfully recognized to impact xenobiotic extrusion from the brain, as Pgp is known to play a role in limiting the BBB penetration of oral drugs in humans. However, these two properties alone fail to explain the BBB...... penetration for a significant number of marketed central nervous system (CNS) agents. The Biopharmaceutics Drug Disposition Classification System (BDDCS) has proved useful in predicting drug disposition in the human body, particularly in the liver and intestine. Here we discuss the value of using BDDCS...

  2. Impact of Social Studies Curriculum on Empathy Dispositions of ...

    African Journals Online (AJOL)

    This study investigated the impact of social studies curriculum on the affective dispositions of students of Colleges of Education in North-West Zone of Nigeria. The purpose of the study was to determine the level of NCE I and NCE III students' affective dispositions in the area of empathy. One research question and one ...

  3. Drug disposition in obesity and protein-energy malnutrition.

    Science.gov (United States)

    Boullata, Joseph I

    2010-11-01

    Clinical response to medication can differ between patients. Among the known sources of variability is an individual's nutrition status. This review defines some pharmacokinetic terms, provides relevant body size metrics and describes the physiologic influences of protein-energy malnutrition and obesity on drug disposition. Weight-based drug dosing, which presumes a healthy BMI, can be problematic in the protein-energy malnourished or obese patient. The use of total body weight, lean body weight, or an adjusted body weight depends on the drug and how it is differently handled in malnutrition or obesity. Most of the recognized influences are seen in drug distribution and drug elimination as a result of altered body composition and function. Distribution characteristics of each drug are determined by several drug-related factors (e.g. tissue affinity) in combination with body-related factors (e.g. composition). Drug elimination occurs through metabolic and excretory pathways that can also vary with body composition. The current data are limited to select drugs that have been reported in small studies or case reports. In the meantime, a rational approach to evaluate the potential influences of malnutrition and obesity can be used clinically based on available information. Antimicrobials are discussed as a useful example of this approach. Further advancement in this field would require collaboration between experts in body composition and those in drug disposition. Until more data are available, routine monitoring by the clinician of the protein-energy malnourished or obese patient receiving weight-based drug regimens is necessary.

  4. Surplus plutonium disposition draft environmental impact statement. Volume 2

    International Nuclear Information System (INIS)

    1998-07-01

    On May 22, 1997, DOE published a Notice of Intent (NOI) in the Federal Register (62 Federal Register 28009) announcing its decision to prepare an environmental impact statement (EIS) that would tier from the analysis and decisions reached in connection with the Storage and Disposition of Weapons-Usable Fissile Materials Final Programmatic EIS (Storage and Disposition PEIS). DOE's disposition strategy allows for both the immobilization of surplus plutonium and its use as mixed oxide (MOX) fuel in existing domestic, commercial reactors. The disposition of surplus plutonium would also involve disposal of the immobilized plutonium and MOX fuel (as spent nuclear fuel) in a geologic repository. The Surplus Plutonium Disposition Environmental Impact Statement analyzes alternatives that would use the immobilization approach (for some of the surplus plutonium) and the MOX fuel approach (for some of the surplus plutonium); alternatives that would immobilize all of the surplus plutonium; and the No Action Alternative. The alternatives include three disposition facilities that would be designed so that they could collectively accomplish disposition of up to 50 metric tons (55 tons) of surplus plutonium over their operating lives: (1) the pit disassembly and conversion facility would disassemble pits (a weapons component) and convert the recovered plutonium, as well as plutonium metal from other sources, into plutonium dioxide suitable for disposition; (2) the immobilization facility would include a collocated capability for converting nonpit plutonium materials into plutonium dioxide suitable for immobilization and would be located at either Hanford or SRS. DOE has identified SRS as the preferred site for an immobilization facility; (3) the MOX fuel fabrication facility would fabricate plutonium dioxide into MOX fuel. Volume 2 contains the appendices to the report and describe the following: Federal Register notices; contractor nondisclosure statement; adjunct melter

  5. Surplus plutonium disposition draft environmental impact statement. Summary

    International Nuclear Information System (INIS)

    1998-07-01

    On May 22, 1997, DOE published a Notice of Intent (NOI) in the Federal Register (62 Federal Register 28009) announcing its decision to prepare an environmental impact statement (EIS) that would tier from the analysis and decisions reached in connection with the Storage and Disposition of Weapons-Usable Fissile Materials Final Programmatic EIS (Storage and Disposition PEIS). DOE's disposition strategy allows for both the immobilization of surplus plutonium and its use as mixed oxide (MOX) fuel in existing domestic, commercial reactors. The disposition of surplus plutonium would also involve disposal of the immobilized plutonium and MOX fuel (as spent nuclear fuel) in a geologic repository. The Surplus Plutonium Disposition Environmental Impact Statement analyzes alternatives that would use the immobilization approach (for some of the surplus plutonium) and the MOX fuel approach (for some of the surplus plutonium); alternatives that would immobilize all of the surplus plutonium; and the No Action Alternative. The alternatives include three disposition facilities that would be designed so that they could collectively accomplish disposition of up to 50 metric tons (55 tons) of surplus plutonium over their operating lives: (1) the pit disassembly and conversion facility would disassemble pits (a weapons component) and convert the recovered plutonium, as well as plutonium metal from other sources, into plutonium dioxide suitable for disposition; (2) the immobilization facility would include a collocated capability for converting nonpit plutonium materials into plutonium dioxide suitable for immobilization and would be located at either Hanford or SRS. DOE has identified SRS as the preferred site for an immobilization facility; (3) the MOX fuel fabrication facility would fabricate plutonium dioxide into MOX fuel

  6. Target mediated drug disposition with drug-drug interaction, Part II: competitive and uncompetitive cases.

    Science.gov (United States)

    Koch, Gilbert; Jusko, William J; Schropp, Johannes

    2017-02-01

    We present competitive and uncompetitive drug-drug interaction (DDI) with target mediated drug disposition (TMDD) equations and investigate their pharmacokinetic DDI properties. For application of TMDD models, quasi-equilibrium (QE) or quasi-steady state (QSS) approximations are necessary to reduce the number of parameters. To realize those approximations of DDI TMDD models, we derive an ordinary differential equation (ODE) representation formulated in free concentration and free receptor variables. This ODE formulation can be straightforward implemented in typical PKPD software without solving any non-linear equation system arising from the QE or QSS approximation of the rapid binding assumptions. This manuscript is the second in a series to introduce and investigate DDI TMDD models and to apply the QE or QSS approximation.

  7. Variables Impacting Dispositional Empathy in Doctoral Psychology Students

    Science.gov (United States)

    Micheli, Amelia C.

    2014-01-01

    The purpose of this study was to explore variables impacting dispositional empathy in doctoral psychology students. While there is a great deal of research regarding empathy in practicing psychologists and mental health professionals, little is known about empathy in psychology trainees. This is especially surprising given the importance of…

  8. Preclinical experimental models of drug metabolism and disposition in drug discovery and development

    Directory of Open Access Journals (Sweden)

    Donglu Zhang

    2012-12-01

    Full Text Available Drug discovery and development involve the utilization of in vitro and in vivo experimental models. Different models, ranging from test tube experiments to cell cultures, animals, healthy human subjects, and even small numbers of patients that are involved in clinical trials, are used at different stages of drug discovery and development for determination of efficacy and safety. The proper selection and applications of correct models, as well as appropriate data interpretation, are critically important in decision making and successful advancement of drug candidates. In this review, we discuss strategies in the applications of both in vitro and in vivo experimental models of drug metabolism and disposition.

  9. Target-mediated drug disposition with drug-drug interaction, Part I: single drug case in alternative formulations.

    Science.gov (United States)

    Koch, Gilbert; Jusko, William J; Schropp, Johannes

    2017-02-01

    Target-mediated drug disposition (TMDD) describes drug binding with high affinity to a target such as a receptor. In application TMDD models are often over-parameterized and quasi-equilibrium (QE) or quasi-steady state (QSS) approximations are essential to reduce the number of parameters. However, implementation of such approximations becomes difficult for TMDD models with drug-drug interaction (DDI) mechanisms. Hence, alternative but equivalent formulations are necessary for QE or QSS approximations. To introduce and develop such formulations, the single drug case is reanalyzed. This work opens the route for straightforward implementation of QE or QSS approximations of DDI TMDD models. The manuscript is the first part to introduce DDI TMDD models with QE or QSS approximations.

  10. Drug disposition and drug-drug interaction data in 2013 FDA new drug applications: a systematic review.

    Science.gov (United States)

    Yu, Jingjing; Ritchie, Tasha K; Mulgaonkar, Aditi; Ragueneau-Majlessi, Isabelle

    2014-12-01

    The aim of the present work was to perform a systematic review of drug metabolism, transport, pharmacokinetics, and DDI data available in the NDAs approved by the FDA in 2013, using the University of Washington Drug Interaction Database, and to highlight significant findings. Among 27 NMEs approved, 22 (81%) were well characterized with regard to drug metabolism, transport, or organ impairment, in accordance with the FDA drug interaction guidance (2012) and were fully analyzed in this review. In vitro, a majority of the NMEs were found to be substrates or inhibitors/inducers of at least one drug metabolizing enzyme or transporter. However, in vivo, only half (n = 11) showed clinically relevant drug interactions, with most related to the NMEs as victim drugs and CYP3A being the most affected enzyme. As perpetrators, the overall effects for NMEs were much less pronounced, compared with when they served as victims. In addition, the pharmacokinetic evaluation in patients with hepatic or renal impairment provided useful information for further understanding of the drugs' disposition. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  11. Mathematical modeling analysis of intratumoral disposition of anticancer agents and drug delivery systems.

    Science.gov (United States)

    Popilski, Hen; Stepensky, David

    2015-05-01

    Solid tumors are characterized by complex morphology. Numerous factors relating to the composition of the cells and tumor stroma, vascularization and drainage of fluids affect the local microenvironment within a specific location inside the tumor. As a result, the intratumoral drug/drug delivery system (DDS) disposition following systemic or local administration is non-homogeneous and its complexity reflects the differences in the local microenvironment. Mathematical models can be used to analyze the intratumoral drug/DDS disposition and pharmacological effects and to assist in choice of optimal anticancer treatment strategies. The mathematical models that have been applied by different research groups to describe the intratumoral disposition of anticancer drugs/DDSs are summarized in this article. The properties of these models and of their suitability for prediction of the drug/DDS intratumoral disposition and pharmacological effects are reviewed. Currently available mathematical models appear to neglect some of the major factors that govern the drug/DDS intratumoral disposition, and apparently possess limited prediction capabilities. More sophisticated and detailed mathematical models and their extensive validation are needed for reliable prediction of different treatment scenarios and for optimization of drug treatment in the individual cancer patients.

  12. Supplement to the Surplus Plutonium Disposition Draft Environmental Impact Statement

    International Nuclear Information System (INIS)

    1999-01-01

    On May 22, 1997, DOE published a Notice of Intent in the Federal Register (62 Federal Register 28009) announcing its decision to prepare an environmental impact statement (EIS) that would tier from the analysis and decisions reached in connection with the ''Storage and Disposition of Weapons-Usable Fissile Materials Final Programmatic EIS (Storage and Disposition PEIS)''. ''The Surplus Plutonium Disposition Draft Environmental Impact Statement'' (SPD Draft EIS) (DOWEIS-0283-D) was prepared in accordance with NEPA and issued in July 1998. It identified the potential environmental impacts of reasonable alternatives for the proposed siting, construction, and operation of three facilities for plutonium disposition. These three facilities would accomplish pit disassembly and conversion, immobilization, and MOX fuel fabrication. For the alternatives that included MOX fuel fabrication, the draft also described the potential environmental impacts of using from three to eight commercial nuclear reactors to irradiate MOX fuel. The potential impacts were based on a generic reactor analysis that used actual reactor data and a range of potential site conditions. In May 1998, DCE initiated a procurement process to obtain MOX fuel fabrication and reactor irradiation services. The request for proposals defined limited activities that may be performed prior to issuance of the SPD EIS Record of Decision (ROD) including non-site-specific work associated with the development of the initial design for the MOX fuel fabrication facility, and plans (paper studies) for outreach, long lead-time procurements, regulatory management, facility quality assurance, safeguards, security, fuel qualification, and deactivation. No construction on the proposed MOX facility would begin before an SPD EIS ROD is issued. In March 1999, DOE awarded a contract to Duke Engineering and Services; COGEMA, Inc.; and Stone and Webster (known as DCS) to provide the requested services. The procurement process

  13. Supplement to the Surplus Plutonium Disposition Draft Environmental Impact Statement

    Energy Technology Data Exchange (ETDEWEB)

    N/A

    1999-05-14

    On May 22, 1997, DOE published a Notice of Intent in the Federal Register (62 Federal Register 28009) announcing its decision to prepare an environmental impact statement (EIS) that would tier from the analysis and decisions reached in connection with the ''Storage and Disposition of Weapons-Usable Fissile Materials Final Programmatic EIS (Storage and Disposition PEIS)''. ''The Surplus Plutonium Disposition Draft Environmental Impact Statement'' (SPD Draft EIS) (DOWEIS-0283-D) was prepared in accordance with NEPA and issued in July 1998. It identified the potential environmental impacts of reasonable alternatives for the proposed siting, construction, and operation of three facilities for plutonium disposition. These three facilities would accomplish pit disassembly and conversion, immobilization, and MOX fuel fabrication. For the alternatives that included MOX fuel fabrication, the draft also described the potential environmental impacts of using from three to eight commercial nuclear reactors to irradiate MOX fuel. The potential impacts were based on a generic reactor analysis that used actual reactor data and a range of potential site conditions. In May 1998, DCE initiated a procurement process to obtain MOX fuel fabrication and reactor irradiation services. The request for proposals defined limited activities that may be performed prior to issuance of the SPD EIS Record of Decision (ROD) including non-site-specific work associated with the development of the initial design for the MOX fuel fabrication facility, and plans (paper studies) for outreach, long lead-time procurements, regulatory management, facility quality assurance, safeguards, security, fuel qualification, and deactivation. No construction on the proposed MOX facility would begin before an SPD EIS ROD is issued. In March 1999, DOE awarded a contract to Duke Engineering & Services; COGEMA, Inc.; and Stone & Webster (known as DCS) to provide the requested

  14. Interplay of biopharmaceutics, biopharmaceutics drug disposition and salivary excretion classification systems

    Science.gov (United States)

    Idkaidek, Nasir M.

    2013-01-01

    The aim of this commentary is to investigate the interplay of Biopharmaceutics Classification System (BCS), Biopharmaceutics Drug Disposition Classification System (BDDCS) and Salivary Excretion Classification System (SECS). BCS first classified drugs based on permeability and solubility for the purpose of predicting oral drug absorption. Then BDDCS linked permeability with hepatic metabolism and classified drugs based on metabolism and solubility for the purpose of predicting oral drug disposition. On the other hand, SECS classified drugs based on permeability and protein binding for the purpose of predicting the salivary excretion of drugs. The role of metabolism, rather than permeability, on salivary excretion is investigated and the results are not in agreement with BDDCS. Conclusion The proposed Salivary Excretion Classification System (SECS) can be used as a guide for drug salivary excretion based on permeability (not metabolism) and protein binding. PMID:24493977

  15. Interplay of Drug-Metabolizing Enzymes and Transporters in Drug Absorption and Disposition.

    Science.gov (United States)

    Shi, Shaojun; Li, Yunqiao

    2014-01-01

    In recent years, the functional interplay between drug-metabolizing enzymes (DMEs) and drug transporters (DTs) in drug absorption and disposition, as well as the complex drug interactions (DIs), has become an intriguing contention, which has also been termed the "transport-metabolism interplay". The current mechanistic understanding for this interplay is first discussed. In the present article, studies investigating the interplay between cytochrome P450 enzymes (CYPs) and efflux transporters have been systematically reviewed in vitro, in situ, in silico, in animals and humans, followed by CYPs-uptake transporters, CYPs-uptake transporters-efflux transporters, and phase II metabolic enzymes-transporters interplay studies. Although several cellular, isolated organ and whole animal studies, in conjunction with simulation and modelling, have addressed the issue that DMEs and DTs can work cooperatively to affect the bioavailability of shared substrate drugs, convincing evidences in human studies are still lacking. Furthermore, the functional interplay between DMEs and DTs will be highly substrate- and dose- dependent. Additionally, we review recent studies to evaluate the influence of genetic variations in the interplay between DMEs and DTs, which might be helpful for the prediction of pharmacokinetics (PK) and possible DIs in human more correctly. There is strong evidence of coordinately regulated DEMs and DTs gene expression and protein activity (e.g. nuclear receptors). Taken together, further investigations and analysis are urgently needed to explore the functional interplay of DMEs and DTs and to delineate the underlying mechanisms.

  16. Target-mediated drug disposition model and its approximations for antibody-drug conjugates.

    Science.gov (United States)

    Gibiansky, Leonid; Gibiansky, Ekaterina

    2014-02-01

    Antibody-drug conjugate (ADC) is a complex structure composed of an antibody linked to several molecules of a biologically active cytotoxic drug. The number of ADC compounds in clinical development now exceeds 30, with two of them already on the market. However, there is no rigorous mechanistic model that describes pharmacokinetic (PK) properties of these compounds. PK modeling of ADCs is even more complicated than that of other biologics as the model should describe distribution, binding, and elimination of antibodies with different toxin load, and also the deconjugation process and PK of the released toxin. This work extends the target-mediated drug disposition (TMDD) model to describe ADCs, derives the rapid binding (quasi-equilibrium), quasi-steady-state, and Michaelis-Menten approximations of the TMDD model as applied to ADCs, derives the TMDD model and its approximations for ADCs with load-independent properties, and discusses further simplifications of the system under various assumptions. The developed models are shown to describe data simulated from the available clinical population PK models of trastuzumab emtansine (T-DM1), one of the two currently approved ADCs. Identifiability of model parameters is also discussed and illustrated on the simulated T-DM1 examples.

  17. Assessment of drug disposition in the perfused rat brain by statistical moment analysis

    International Nuclear Information System (INIS)

    Sakane, T.; Nakatsu, M.; Yamamoto, A.; Hashida, M.; Sezaki, H.; Yamashita, S.; Nadai, T.

    1991-01-01

    Drug disposition in the brain was investigated by statistical moment analysis using an improved in situ brain perfusion technique. The right cerebral hemisphere of the rat was perfused in situ. The drug and inulin were injected into the right internal carotid artery as a rapid bolus and the venous outflow curve at the posterior facial vein was obtained. The infusion rate was adjusted to minimize the flow of perfusion fluid into the left hemisphere. The obtained disposition parameters were characteristics and considered to reflect the physicochemical properties of each drug. Antipyrine showed a small degree of initial uptake. Therefore, its apparent distribution volume (Vi) and apparent intrinsic clearance (CLint,i) were small. Diazepam showed large degrees of both influx and efflux and, thus, a large Vi. Water showed parameters intermediate between those of antipyrine and those of diazepam. Imipramine, desipramine, and propranolol showed a large CLint,i compared with those of the other drugs. The extraction ratio of propranolol significantly decreased with increasing concentrations of unlabeled propranolol in the perfusion fluid. These findings may be explained partly by the tissue binding of these drugs. In conclusion, the present method is useful for studying drug disposition in the brain

  18. Disposition of surplus highly enriched uranium: Draft environmental impact statement

    International Nuclear Information System (INIS)

    1995-10-01

    This document assesses the environmental impacts at four potential sites that may result from alternatives for the disposition of United States-origin weapons-usable highly enriched uranium (HEU) that has been or may be declared surplus to national defense or defense-related program needs. In addition to the no action alternative, it assesses four alternatives that would eliminate the weapons-usability of HEU by blending it with depleted uranium, natural uranium, or low-enriched uranium (LEU) to create low-enriched uranium, either as commercial reactor fuel feedstock or as low-level radioactive waste. The potential blending sites are DOE's Y-12 Plant at Oak Ridge Reservation in Oak Ridge, Tennessee; DOE's Savannah River Site in Aiken, South Carolina; the Babcock ampersand Wilcox Naval Nuclear Fuel Division Facility in Lynchburg, Virginia; and the Nuclear Fuel Services Fuel Fabrication Plant in Erwin, Tennessee. Evaluations of impacts on site infrastructure, water resources, air quality and noise, socioeconomic resources, waste management, public and occupational health, and environmental justice for the potential blending sites are included in the assessment. The intersite transportation of nuclear and hazardous materials is also assessed. The preferred alternative is to blend down surplus HEU to LEU for maximum commercial use as reactor fuel feed which would likely be done at a combination of DOE and commercial sites

  19. Challenges and advances in the assessment of the disposition of antibody‐drug conjugates

    Science.gov (United States)

    Iyer, Suhasini

    2015-01-01

    Abstract Antibody‐drug conjugates (ADCs) are a rapidly growing therapeutic platform for the treatment of cancer. ADCs consist of a cytotoxic small molecule drug linked to an antibody to provide targeted delivery of the cytotoxic agent to the tumor. Understanding the pharmacokinetics (PK) and pharmacodynamics (PD) of ADCs is crucial in their design to optimize dose and regimen, to maximize efficacy and to minimize toxicity in patients. Significant progress has been made in recent years in this area, however, many fundamental questions still remain. This review discusses factors to consider while assessing the disposition of ADCs, and the unique challenges associated with these therapeutics. Current tools that are available and strategies to enable appropriate assessment are also discussed. © 2015 Genentech Inc. Biopharmaceutics & Drug Disposition Published by John Wiley & Sons Ltd. PMID:25904406

  20. Pathophysiological changes that affect drug disposition in protein-energy malnourished children

    Directory of Open Access Journals (Sweden)

    Oshikoya Kazeem A

    2009-12-01

    Full Text Available Abstract Protein-energy malnutrition (PEM is a major public health problem affecting a high proportion of infants and older children world-wide and accounts for a high childhood morbidity and mortality in the developing countries. The epidemiology of PEM has been extensively studied globally and management guidelines formulated by the World Health Organization (WHO. A wide spectrum of infections such as measles, malaria, acute respiratory tract infection, intestinal parasitosis, tuberculosis and HIV/AIDS may complicate PEM with two or more infections co-existing. Thus, numerous drugs may be required to treat the patients. In-spite of abundant literature on the epidemiology and management of PEM, focus on metabolism and therapeutic drug monitoring is lacking. A sound knowledge of pathophysiology of PEM and pharmacology of the drugs frequently used for their treatment is required for safe and rational treatment. In this review, we discuss the pathophysiological changes in children with PEM that may affect the disposition of drugs frequently used for their treatment. This review has established abnormal disposition of drugs in children with PEM that may require dosage modification. However, the relevance of these abnormalities to the clinical management of PEM remains inconclusive. At present, there are no good indications for drug dosage modification in PEM; but for drug safety purposes, further studies are required to accurately determine dosages of drugs frequently used for children with PEM.

  1. Diagnostic approach to constipation impacts pediatric emergency department disposition.

    Science.gov (United States)

    Chumpitazi, Corrie E; Rees, Chris A; Camp, Elizabeth A; Henkel, Erin B; Valdez, Karina L; Chumpitazi, Bruno P

    2017-10-01

    Constipation is a common cause of abdominal pain in children presenting to the emergency department (ED). The objectives of this study were to determine the diagnostic evaluation undertaken for constipation and to assess the association of the evaluation with final ED disposition. A retrospective chart review of children presenting to the pediatric ED of a quaternary care children's hospital with abdominal pain that received a soap suds enema therapy. A total of 512 children were included, 270 (52.7%) were female, and the median age was 8.0 (IQR: 4.0-11.0). One hundred and thirty eight patients (27%) had a digital rectal exam (DRE), 120 (22.8%) had bloodwork performed, 218 (43%) had urinalysis obtained, 397 (77.5%) had abdominal radiographs, 120 (23.4%) had abdominal ultrasounds, and 18 (3.5%) had computed tomography scans. Children who had a DRE had a younger median age (6.0, IQR: 3.0-9.25 vs. 8.0, IQR: 4.0-12.0; p<0.001) and were significantly less likely to have radiologic imaging (OR=0.50, 95% CI 0.32-0.78; p=0.002), but did not have an increased odds of being discharged home. After adjusting for gender, ethnicity, and significant past medical history those with an abdominal radiograph were less likely to be discharged to home (aOR=0.56, 95% CI 0.31-1.01; p=0.05). The diagnostic evaluation of children diagnosed with fecal impaction in the ED varied. Abdominal imaging may be avoided if children receive a DRE. When children presenting to the ED with abdominal pain had an abdominal radiograph, they were more likely to be admitted. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Drug Impact Index.

    Science.gov (United States)

    Western Center for Drug-Free Schools and Communities.

    The Drug Impact Index provides a set of indicators designed to determine the extent of the local drug problem in a community. Each indicator includes a technical note on the data sources, a graph showing comparative statistics on that indicator for the Portland area and for the State of Oregon, and brief remarks on the implications of the data.…

  3. Surplus plutonium disposition draft environmental impact statement. Volume 1, Part A

    International Nuclear Information System (INIS)

    1998-07-01

    On May 22, 1997, DOE published a Notice of Intent (NOI) in the Federal Register (62 Federal Register 28009) announcing its decision to prepare an environmental impact statement (EIS) that would tier from the analysis and decisions reached in connection with the Storage and Disposition of Weapons-Usable Fissile Materials Final Programmatic EIS (Storage and Disposition PEIS). DOE's disposition strategy allows for both the immobilization of surplus plutonium and its use as mixed oxide (MOX) fuel in existing domestic, commercial reactors. The disposition of surplus plutonium would also involve disposal of the immobilized plutonium and MOX fuel (as spent nuclear fuel) in a geologic repository. The Surplus Plutonium Disposition Environmental Impact Statement analyzes alternatives that would use the immobilization approach (for some of the surplus plutonium) and the MOX fuel approach (for some of the surplus plutonium); alternatives that would immobilize all of the surplus plutonium; and the No Action Alternative. The alternatives include three disposition facilities that would be designed so that they could collectively accomplish disposition of up to 50 metric tons (55 tons) of surplus plutonium over their operating lives: (1) the pit disassembly and conversion facility would disassemble pits (a weapons component) and convert the recovered plutonium, as well as plutonium metal from other sources, into plutonium dioxide suitable for disposition; (2) the immobilization facility would include a collocated capability for converting nonpit plutonium materials into plutonium dioxide suitable for immobilization and would be located at either Hanford or SRS. DOE has identified SRS as the preferred site for an immobilization facility; (3) the MOX fuel fabrication facility would fabricate plutonium dioxide into MOX fuel. This volume includes background information; purpose of and need for the proposed action; alternatives for disposition of surplus weapons useable plutonium; and

  4. Foucaults Dispositive

    DEFF Research Database (Denmark)

    Raffnsøe, Sverre; Gudmand-Høyer, Marius T.; Thaning, Morten Sørensen

    2016-01-01

    While Foucault’s work has had a crucial impact on organizational research, the analytical potential of the dispositive has not been sufficiently developed. The purpose of this article is to reconstruct the notion of the dispositive as a key conception in Foucault’s thought, particularly in his...

  5. Selective serotonin reuptake inhibitors and venlafaxine in pregnancy: Changes in drug disposition.

    Directory of Open Access Journals (Sweden)

    Andreas Austgulen Westin

    Full Text Available Pregnancy may cause changes in drug disposition. The clinical consequences may be profound and even counterintuitive; in some cases pregnant women may need more than twice their usual drug dose in order to maintain therapeutic drug levels. For antidepressants, evidence on drug disposition in pregnancy is scarce. The aim of this study was to determine the effects of pregnancy on serum levels of selective serotonin reuptake inhibitors (SSRIs and venlafaxine in a large and naturalistic patient material, in order to provide tentative dose recommendations for pregnant women.Using patient data from two routine therapeutic drug monitoring (TDM services in Norway with linkage to the national birth registry, dose-adjusted serum drug concentrations of SSRIs and venlafaxine during pregnancy were compared to the women's own baseline (non-pregnant values, using a linear mixed model.Overall, the TDM databases contained 196,726 serum concentration measurements from 54,393 women. After data linkage and drug selection (SSRIs or venlafaxine only, we identified 367 analyses obtained from a total of 290 pregnancies in 281 women, and 420 baseline observations from the same women. Serum concentrations in the third trimester were significantly lower than baseline for paroxetine (-51%; 95% confidence interval [CI], -66%, -30%; p<0.001, fluvoxamine (-56%; CI, -75%, -23%; p = 0.004 and citalopram (-24%; CI, -38%, -7%; p = 0,007, and higher than baseline for sertraline (+68%; CI, +37%, +106%; p<0.001. For escitalopram, fluoxetine and venlafaxine concentrations did not change significantly.For paroxetine and fluvoxamine the pronounced decline in maternal drug serum concentrations in pregnancy may necessitate a dose increase of about 100% during the third trimester in order to maintain stable concentrations. For fluoxetine, venlafaxine, citalopram, escitalopram and sertraline, the present study indicates that dose adjustments are generally not necessary during pregnancy.

  6. What practice can learn from theory: The potential impact of disposition decision factors on organisational performance

    Directory of Open Access Journals (Sweden)

    Amanda Badenhorst

    2018-02-01

    Full Text Available Background: Effective disposition decisions can lead to a number of value-adding benefits including economic, environmental and marketing benefits. Despite this, many organisations are not aware of the importance of disposition decisions and the impact they can have on organisational performance. Objectives: The aim of this study was to demonstrate the potential impact of disposition decision factors on organisational performance. Method: This study made use of a qualitative content analysis method on previously published scientific articles on reverse logistics. The sample included 67 published scientific articles between 2006 and 2016. ATLAS.ti software was used to assist with the data analysis process. Findings: The findings showed a number of factors for disposition decision-making resulting in a number of value-adding benefits, which can improve organisational performance. From the findings, a conceptual framework was developed linking the disposition decision factors with the value-adding benefits and areas of organisational performance improvements. Conclusion: The framework developed in this article contributes to new insights and can help organisations to identify different performance improvement areas associated with certain disposition decision factors.

  7. Surplus plutonium disposition draft environmental impact statement. Volume 1, Part B

    International Nuclear Information System (INIS)

    1998-07-01

    On May 22, 1997, DOE published a Notice of Intent (NOI) in the Federal Register (62 Federal Register 28009) announcing its decision to prepare an environmental impact statement (EIS) that would tier from the analysis and decisions reached in connection with the Storage and Disposition of Weapons-Usable Fissile Materials Final Programmatic EIS (Storage and Disposition PEIS). DOE's disposition strategy allows for both the immobilization of surplus plutonium and its use as mixed oxide (MOX) fuel in existing domestic, commercial reactors. The disposition of surplus plutonium would also involve disposal of the immobilized plutonium and MOX fuel (as spent nuclear fuel) in a geologic repository. The Surplus Plutonium Disposition Environmental Impact Statement analyzes alternatives that would use the immobilization approach (for some of the surplus plutonium) and the MOX fuel approach (for some of the surplus plutonium); alternatives that would immobilize all of the surplus plutonium; and the No Action Alternative. The alternatives include three disposition facilities that would be designed so that they could collectively accomplish disposition of up to 50 metric tons (55 tons) of surplus plutonium over their operating lives: (1) the pit disassembly and conversion facility would disassemble pits (a weapons component) and convert the recovered plutonium, as well as plutonium metal from other sources, into plutonium dioxide suitable for disposition; (2) the immobilization facility would include a collocated capability for converting nonpit plutonium materials into plutonium dioxide suitable for immobilization and would be located at either Hanford or SRS. DOE has identified SRS as the preferred site for an immobilization facility; (3) the MOX fuel fabrication facility would fabricate plutonium dioxide into MOX fuel. This volume has chapters on environmental consequences; environmental regulations, permits, and consultations; a glossary; list of preparers; distribution list

  8. Sandwich-Cultured Hepatocytes for Mechanistic Understanding of Hepatic Disposition of Parent Drugs and Metabolites by Transporter-Enzyme Interplay.

    Science.gov (United States)

    Matsunaga, Norikazu; Fukuchi, Yukina; Imawaka, Haruo; Tamai, Ikumi

    2018-05-01

    Functional interplay between transporters and drug-metabolizing enzymes is currently one of the hottest topics in the field of drug metabolism and pharmacokinetics. Uptake transporter-enzyme interplay is important to determine intrinsic hepatic clearance based on the extended clearance concept. Enzyme and efflux transporter interplay, which includes both sinusoidal (basolateral) and canalicular efflux transporters, determines the fate of metabolites formed in the liver. As sandwich-cultured hepatocytes (SCHs) maintain metabolic activities and form a canalicular network, the whole interplay between uptake and efflux transporters and drug-metabolizing enzymes can be investigated simultaneously. In this article, we review the utility and applicability of SCHs for mechanistic understanding of hepatic disposition of both parent drugs and metabolites. In addition, the utility of SCHs for mimicking species-specific disposition of parent drugs and metabolites in vivo is described. We also review application of SCHs for clinically relevant prediction of drug-drug interactions caused by drugs and metabolites. The usefulness of mathematical modeling of hepatic disposition of parent drugs and metabolites in SCHs is described to allow a quantitative understanding of an event in vitro and to develop a more advanced model to predict in vivo disposition. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  9. Atomoxetine: A Review of Its Pharmacokinetics and Pharmacogenomics Relative to Drug Disposition.

    Science.gov (United States)

    Yu, Guo; Li, Guo-Fu; Markowitz, John S

    2016-05-01

    Atomoxetine is a selective norepinephrine (NE) reuptake inhibitor approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children (≥6 years of age), adolescents, and adults. Its metabolism and disposition are fairly complex, and primarily governed by cytochrome P450 (CYP) 2D6 (CYP2D6), whose protein expression varies substantially from person to person, and by race and ethnicity because of genetic polymorphism. These differences can be substantial, resulting in 8-10-fold differences in atomoxetine exposure between CYP2D6 poor metabolizers and extensive metabolizers. In this review, we have attempted to revisit and analyze all published clinical pharmacokinetic data on atomoxetine inclusive of public access documents from the new drug application submitted to the United States Food and Drug Administration (FDA). The present review focuses on atomoxetine metabolism, disposition, and genetic polymorphisms of CYP2D6 as they specifically relate to atomoxetine, and provides an in-depth discussion of the fundamental pharmacokinetics of the drug including its absorption, distribution, metabolism, and excretion in pediatric and adult populations. Further, a summary of relationships between genetic variants of CYP2D6 and to some degree, CYP2C19, are provided with respect to atomoxetine plasma concentrations, central nervous system (CNS) pharmacokinetics, and associated clinical implications for pharmacotherapy. Lastly, dosage adjustments based on pharmacokinetic principles are discussed.

  10. Impact of aflatoxin B1 on the pharmacokinetic disposition of enrofloxacin in broiler chickens.

    Science.gov (United States)

    Kalpana, Starling; Srinivasa Rao, G; Malik, Jitendra K

    2015-09-01

    The potential impact of subchronic exposure of aflatoxin B1 was investigated on the pharmacokinetic disposition of enrofloxacin in broiler chickens. Broiler chickens given either normal or aflatoxin B1 (750μg/kg diet) supplemented diet for 6 weeks received a single oral dose of enrofloxacin (10mg/kg body wt). Blood samples were drawn from the brachial vein at predetermined time intervals after drug administration. Enrofloxacin plasma concentrations analyzed by RP-HPLC were significantly lower in aflatoxin B1-exposed broiler chickens at 0.167, 0.5 and 1.0h after drug administration. In aflatoxin B1-exposed broiler chickens, the absorption rate constant (ka) of enrofloxacin (0.20±0.05h(-1)) was significantly decreased as compared to the unexposed birds (0.98±0.31h(-1)). The values of [Formula: see text] , tmax and AUC0-∞ of enrofloxacin were nonsignificantly increased by 17%, 26% and 17% in aflatoxin-exposed broiler chickens, respectively. Subchronic aflatoxin B1 exposure markedly decreased the initial absorption of enrofloxacin without significantly influencing other pharmacokinetic parameters in broiler chickens. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. [Effects of sub-micro emulsion composition on cellular disposition of incorporated lipophilic drug].

    Science.gov (United States)

    Sun, Xiao-Yi; Xiang, Zhi-Qiang; Wu, Shuo; Lv, Yuan-Yuan; Liang, Wen-Quan

    2013-09-01

    To investigate the effects of sub-micro emulsion composition on cellular uptake and disposition of incorporated lipophilic drug. Sub-micro emulsions containing 10 % oil, 1.2 % lecithin and 2.25 % glycerol were prepared, and the fluorescent agent coumarin 6 was used as a model drug. The effects of oil types, co-surfactants and cationic lipid on uptake and elimination kinetics of 6-coumarin in HeLa cells were studied. The uptake mechanism of sub-micro emulsions was further investigated. Oil type and Tweens had no influence on the cellular uptake. Modifications of surfactants with Span series increased the cellular influx, among which Span 20 with hydrophilic-lipophilic balance (HLB) value of 8.6 was the best enhancer. The intracellular drug level reached up to (46.09 ± 1.98)ng/μg protein which had significant difference with control group [(38.54 ± 0.34)ng/μg protein]. The positively charged emulsions significantly increased the uptake rate constant and elimination rate constant which were 4 times and 1.5 times of those in anionic groups, respectively. The uptake enhancement was also observed in cationic emulsions, cellular concentrations at plateau were (42.73 ± 0.84)ng/μg protein, which was about 3 times of that in anionic emulsions [(15.71 ± 0.74)ng/μg protein], when extracellular drug concentration kept at 100 ng/ml. Cationic emulsions delivered the payload mainly by direct drug transfer to contacted cells, while the negative ones depended on both drug passive diffusion and clathrin-mediated endocytosis of drug containing oil droplets which accounted for 20% of the intracellular drug. Interfacial characteristic of sub-micro emulsions such as co-surfactants HLB as well as zeta potentials can influence lipophilic drug both in cellular uptake and elimination.

  12. Surplus plutonium disposition environmental impact statement. Public scoping meeting: Comment summary report

    International Nuclear Information System (INIS)

    1997-09-01

    The Department of Energy (DOE) issued a Record of Decision for the Storage and Disposition of Weapons-Usable Fissile Materials Programmatic Environmental Impact Statement (S ampersand D PEIS) (DOE/EIS-0229) on January 14, 1997. In that Record of Decision, DOE stated its decision to pursue a strategy for plutonium disposition that allows for immobilization of surplus weapons plutonium in glass or ceramic forms and irradiating the surplus plutonium as mixed oxide (MOX) fuel in existing reactors, while reserving the option to immobilize all the surplus weapons plutonium. The Department also decided that the extent to which either or both of these disposition approaches would ultimately be deployed would depend in part upon future National Environmental Policy Act (NEPA) review for surplus weapons plutonium disposition. On May 22, 1997, DOE published in the Federal Register (62 FR 28013) a Notice of Intent to prepare an environmental impact statement (tiered from the S ampersand D PEIS) on the disposition of United States' surplus weapons-usable plutonium. The purpose of the Notice of Intent was to describe DOE's proposed action, to solicit public input, and to announce the schedule for the public scoping meetings. During the public scoping period (May 22 - July 22, 1997), the public was invited to submit written comments by U.S. mail, fax, or through the Office of Fissile Materials Disposition's Website, as well as to provide oral comments by voicemail or by participating in public scoping meetings. Written and oral comments on the scope of the SPD EIS that were submitted during the formal comment period have been uniquely identified and have become part of the official record. This is the case whether the comments were submitted via U.S. mail, fax, website, toll-free telephone number, or through participation at a public scoping meeting

  13. Small-molecule compounds exhibiting target-mediated drug disposition - A case example of ABT-384.

    Science.gov (United States)

    An, Guohua; Liu, Wei; Dutta, Sandeep

    2015-10-01

    Nonlinearities are frequently encountered in pharmacokinetics, and they can occur when 1 or more processes of absorption, distribution, metabolism, and excretion are saturable. One special source of nonlinearity that has been noticed recently is the saturable binding of the drug to a high-affinity-low-capacity target, a phenomenon known as target-mediated drug disposition (TMDD). Although TMDD can occur in both small-molecule compounds and large-molecule compounds, the latter has received much more attention because of its high prevalence. With the development of more potent small-molecule drugs acting on highly specific targets and the availability of increasingly sensitive analytical techniques, small-molecule compounds exhibiting TMDD have been increasingly reported in the past several years. ABT-384 is a small-molecule drug candidate that exhibited significant nonlinear pharmacokinetics, potentially imparted by TMDD, in a first-in-human clinical trial conducted in healthy volunteers. Compared with published small-molecule compounds exhibiting TMDD, ABT-384 pharmacokinetic characteristics are more consistent with TMDD. To expand current knowledge of TMDD of small-molecule compounds and increase awareness of this interesting and clinically important phenomenon, in this review the general features of small-molecule compounds exhibiting TMDD are highlighted, with ABT-384 provided as an example. © 2015, The American College of Clinical Pharmacology.

  14. 78 FR 37527 - Draft Environmental Impact Statement for the Disposition of Hangars 2 and 3, Fort Wainwright, Alaska

    Science.gov (United States)

    2013-06-21

    ... Statement (EIS) for the disposition of two historic hangars at Fort Wainwright (FWA). The Draft EIS analyzes and evaluates the potential environmental impacts associated with proposed disposition options for two historic World War II-era hangars (Hangars 2 and 3) and supporting infrastructure located on the Main Post...

  15. Small-Molecule Compounds Exhibiting Target-Mediated Drug Disposition (TMDD): A Minireview.

    Science.gov (United States)

    An, Guohua

    2017-02-01

    Nonlinearities are commonplace in pharmacokinetics, and 1 special source is the saturable binding of the drug to a high-affinity, low-capacity target, a phenomenon known as target-mediated drug disposition (TMDD). Compared with large-molecule compounds undergoing TMDD, which has been well recognized due to its high prevalence, TMDD in small-molecule compounds is more counterintuitive and has not been well appreciated. With more and more potent small-molecule drugs acting on highly specific targets being developed as well as increasingly sensitive analytical techniques becoming available, many small-molecule compounds have recently been reported to have nonlinear pharmacokinetics imparted by TMDD. To expand our current knowledge of TMDD in small-molecule compounds and increase the awareness of this clinically important phenomenon, this minireview provides an overview of the small-molecule compounds that demonstrate nonlinear pharmacokinetics imparted by TMDD. The present review also summarizes the general features of TMDD in small-molecule compounds and highlights the differences between TMDD in small-molecule compounds and large-molecule compounds. © 2016, The American College of Clinical Pharmacology.

  16. Comparison of minipig, dog, monkey and human drug metabolism and disposition.

    Science.gov (United States)

    Dalgaard, Lars

    2015-01-01

    This article gives an overview of the drug metabolism and disposition (ADME) characteristics of the most common non-rodent species used in toxicity testing of drugs (minipigs, dogs, and monkeys) and compares these to human characteristics with regard to enzymes mediating the metabolism of drugs and the transport proteins which contribute to the absorption, distribution and excretion of drugs. Literature on ADME and regulatory guidelines of relevance in drug development of small molecules has been gathered. Non-human primates (monkeys) are the species that is closest to humans in terms of genetic homology. Dogs have an advantage due to the ready availability of comprehensive background data for toxicological safety assessment and dogs are easy to handle. Pigs have been used less than dogs and monkeys as a model in safety assessment of drug candidates. However, when a drug candidate is metabolised by aldehyde oxidase (AOX1), N-acetyltransferases (NAT1 and NAT2) or cytochrome (CYP2C9-like) enzymes which are not expressed in dogs, but are present in pigs, this species may be a better choice than dogs, provided that adequate exposure can be obtained in pigs. Conversely, pigs might not be the right choice if sulfation, involving 3-phospho-adenosyl-5-phosphosulphate sulphotransferase (PAPS) is an important pathway in the human metabolism of a drug candidate. In general, the species selection should be based on comparison between in vitro studies with human cell-based systems and animal-cell-based systems. Results from pharmacokinetic studies are also important for decision-making by establishing the obtainable exposure level in the species. Access to genetically humanized mouse models and highly sensitive analytical methods (accelerator mass spectrometry) makes it possible to improve the chance of finding all metabolites relevant for humans before clinical trials have been initiated and, if necessary, to include another animal species before long term toxicity studies are

  17. LLNL MOX fuel lead assemblies data report for the surplus plutonium disposition environmental impact statement

    International Nuclear Information System (INIS)

    O'Connor, D.G.; Fisher, S.E.; Holdaway, R.

    1998-08-01

    The purpose of this document is to support the US Department of Energy (DOE) Fissile Materials Disposition Program's preparation of the draft surplus plutonium disposition environmental impact statement. This is one of several responses to data call requests for background information on activities associated with the operation of the lead assembly (LA) mixed-oxide (MOX) fuel fabrication facility. The DOE Office of Fissile Materials Disposition (DOE-MD) has developed a dual-path strategy for disposition of surplus weapons-grade plutonium. One of the paths is to disposition surplus plutonium through irradiation of MOX fuel in commercial nuclear reactors. MOX fuel consists of plutonium and uranium oxides (PuO 2 and UO 2 ), typically containing 95% or more UO 2 . DOE-MD requested that the DOE Site Operations Offices nominate DOE sites that meet established minimum requirements that could produce MOX LAs. LLNL has proposed an LA MOX fuel fabrication approach that would be done entirely inside an S and S Category 1 area. This includes receipt and storage of PuO 2 powder, fabrication of MOX fuel pellets, assembly of fuel rods and bundles, and shipping of the packaged fuel to a commercial reactor site. Support activities will take place within a Category 1 area. Building 332 will be used to receive and store the bulk PuO 2 powder, fabricate MOX fuel pellets, and assemble fuel rods. Building 334 will be used to assemble, store, and ship fuel bundles. Only minor modifications would be required of Building 332. Uncontaminated glove boxes would need to be removed, petition walls would need to be removed, and minor modifications to the ventilation system would be required

  18. LLNL MOX fuel lead assemblies data report for the surplus plutonium disposition environmental impact statement

    Energy Technology Data Exchange (ETDEWEB)

    O`Connor, D.G.; Fisher, S.E.; Holdaway, R. [and others

    1998-08-01

    The purpose of this document is to support the US Department of Energy (DOE) Fissile Materials Disposition Program`s preparation of the draft surplus plutonium disposition environmental impact statement. This is one of several responses to data call requests for background information on activities associated with the operation of the lead assembly (LA) mixed-oxide (MOX) fuel fabrication facility. The DOE Office of Fissile Materials Disposition (DOE-MD) has developed a dual-path strategy for disposition of surplus weapons-grade plutonium. One of the paths is to disposition surplus plutonium through irradiation of MOX fuel in commercial nuclear reactors. MOX fuel consists of plutonium and uranium oxides (PuO{sub 2} and UO{sub 2}), typically containing 95% or more UO{sub 2}. DOE-MD requested that the DOE Site Operations Offices nominate DOE sites that meet established minimum requirements that could produce MOX LAs. LLNL has proposed an LA MOX fuel fabrication approach that would be done entirely inside an S and S Category 1 area. This includes receipt and storage of PuO{sub 2} powder, fabrication of MOX fuel pellets, assembly of fuel rods and bundles, and shipping of the packaged fuel to a commercial reactor site. Support activities will take place within a Category 1 area. Building 332 will be used to receive and store the bulk PuO{sub 2} powder, fabricate MOX fuel pellets, and assemble fuel rods. Building 334 will be used to assemble, store, and ship fuel bundles. Only minor modifications would be required of Building 332. Uncontaminated glove boxes would need to be removed, petition walls would need to be removed, and minor modifications to the ventilation system would be required.

  19. The dynamic gastric environment and its impact on drug and formulation behaviour.

    Science.gov (United States)

    Van Den Abeele, Jens; Rubbens, Jari; Brouwers, Joachim; Augustijns, Patrick

    2017-01-01

    Before being absorbed in the small intestine and/or colon, orally administered drugs inevitably need to pass through the stomach. Hence, it seems reasonable that the residence of a dosage form in the gastric environment, however brief it may be, may influence drug disposition further down the gastrointestinal tract and may potentially impact systemic exposure to a drug of interest. However, research efforts in the past mainly focused on drug disposition at the level of the intestine, i.e. the main site of absorption, hereby disregarding or oversimplifying the stomach's contribution to gastrointestinal drug disposition. In the first part of this review, the complexity of the stomach with regard to anatomy, physiology and gastric fluid composition is emphasized. Between-population differences in gastric functioning and physicochemical characteristics of gastric fluids are discussed. The second part of this review focuses on several of the processes to which a dosage form can be exposed during its passage through the stomach and the implications for gastrointestinal drug behaviour and systemic drug disposition. Finally, the influence of real-life dosing conditions on drug disposition is discussed in the context of the stomach. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. New Equilibrium Models of Drug-Receptor Interactions Derived from Target-Mediated Drug Disposition.

    Science.gov (United States)

    Peletier, Lambertus A; Gabrielsson, Johan

    2018-05-14

    In vivo analyses of pharmacological data are traditionally based on a closed system approach not incorporating turnover of target and ligand-target kinetics, but mainly focussing on ligand-target binding properties. This study incorporates information about target and ligand-target kinetics parallel to binding. In a previous paper, steady-state relationships between target- and ligand-target complex versus ligand exposure were derived and a new expression of in vivo potency was derived for a circulating target. This communication is extending the equilibrium relationships and in vivo potency expression for (i) two separate targets competing for one ligand, (ii) two different ligands competing for a single target and (iii) a single ligand-target interaction located in tissue. The derived expressions of the in vivo potencies will be useful both in drug-related discovery projects and mechanistic studies. The equilibrium states of two targets and one ligand may have implications in safety assessment, whilst the equilibrium states of two competing ligands for one target may cast light on when pharmacodynamic drug-drug interactions are important. The proposed equilibrium expressions for a peripherally located target may also be useful for small molecule interactions with extravascularly located targets. Including target turnover, ligand-target complex kinetics and binding properties in expressions of potency and efficacy will improve our understanding of within and between-individual (and across species) variability. The new expressions of potencies highlight the fact that the level of drug-induced target suppression is very much governed by target turnover properties rather than by the target expression level as such.

  1. Hydrocortisone-induced embryotoxicity and embryonic drug disposition in H-2 congenic mice

    International Nuclear Information System (INIS)

    Roberts, L.S.G.

    1986-01-01

    Congenic mouse strains C57BL/10Sn (B10) and B10.A/SgSn(B10A), genetically different only at the H-2 complex, were compared for sensitivity to glucocorticoid-induced embryotoxicity and embryonic drug disposition. B10A mice dosed intramuscularly with 0, 100, 150 and 200 mg hydrocortisone/kg body weight on gestational day twelve, and B10 mice injected with 0, 200, 400, 600, and 800 mg/kg, were evaluated at dissection on gestational day eighteen for signs of toxicity. In both strains, probit analysis of cleft palate production demonstrated a linear dose response. The ED50 for cleft palate production demonstrates a linear dose response. The ED50 for cleft palate production in B10A mice was 143.6 mg/kg and 512.0 mg/kg for the B10 strain. Embryonic exposure was evaluated by administration of 3 H-hydrocortisone (5 uCi/mouse) to pregnant mice on day twelve of gestation, at the ED50 for cleft palate production in B10A strain. The purposes of the experiment were to quantify the difference in susceptibility to steroid-induced cleft palate, determine if a milder manifestation of embryotoxicity, fetal growth retardation, occurred at sub-clefting dosages, and determine if the difference in sensitivity to hydrocortisone-induced embryotoxicity was the result of an underlying difference in embryonic exposure to the teratogen

  2. Further characterization of a furanocoumarin-free grapefruit juice on drug disposition: studies with cyclosporine.

    Science.gov (United States)

    Paine, Mary F; Widmer, Wilbur W; Pusek, Susan N; Beavers, Kimberly L; Criss, Anne B; Snyder, Jennifer; Watkins, Paul B

    2008-04-01

    We previously established furanocoumarins as mediators of the interaction between grapefruit juice (GFJ) and the model CYP3A4 substrate felodipine in healthy volunteers using a GFJ devoid of furanocoumarins. It remains unclear whether furanocoumarins mediate drug-GFJ interactions involving CYP3A4 substrates that are also P-glycoprotein substrates. The effects of furanocoumarin-free GFJ on drug disposition were further characterized by using the dual CYP3A4/P-glycoprotein substrate cyclosporine. By randomized crossover design, 18 healthy volunteers received cyclosporine (5 mg/kg) with 240 mL orange juice (control), GFJ, or furanocoumarin-free GFJ. Blood was collected over 24 h. Juice treatments were separated by > or = 1 wk. The effects of diluted extracts of each juice and of purified furanocoumarins on [3H]cyclosporine translocation in Caco-2 cells were then compared. The median (range) dose-corrected cyclosporine area under the curve and the maximum concentration with GFJ (P or = 0.50), were significantly higher than those with orange juice [15.6 (6.7-33.5) compared with 11.3 (4.8-22.0) x 10(-3) h/L and 3.0 (1.6-5.8) compared with 2.4 (1.1-3.1) mL(-1), respectively]. The median time to reach maximum concentration and terminal elimination half-life were not significantly different between the juices (2-3 and 7-8 h, respectively; P > or = 0.08). Relative to vehicle, the GFJ extract, orange juice extract, and purified furanocoumarins partially increased apical-to-basolateral and decreased basolateral-to-apical [3H]cyclosporine translocation in Caco-2 cells, whereas the furanocoumarin-free GFJ extract had negligible effects. Reanalysis of the clinical juices identified polymethoxyflavones as candidate P-glycoprotein inhibitors in orange juice but not in GFJ. Furanocoumarins mediate, at least partially, the cyclosporine-GFJ interaction in vivo. A plausible mechanism involves the combined inhibition of enteric CYP3A4 and P-glycoprotein.

  3. States, Traits, and Dispositions: The Impact of Emotion on Writing Development and Writing Transfer across College Courses and Beyond

    Science.gov (United States)

    Driscoll, Dana Lynn; Powell, Roger

    2016-01-01

    Drawing from a five-year longitudinal data set following thirteen college writers through undergraduate writing and beyond, we explore the impact of students' emotions and emotional dispositions on their ability to transfer writing knowledge and on their overall writing development. Participants experienced a range of emotions concerning their…

  4. THE IMPACT OF SELENIUM STATUS ON THE METABLISM AND DISPOSITION OF ARSENIC AND ITS IMPLICATIONS FOR EPIDEMIOLOGIC INVESTIGATIONS

    Science.gov (United States)

    The Impact of Selenium Status on the Metabolism and Disposition of Arsenic and Its Implications for Epidemiologic InvestigationsE. M. Kenyon1*, M.F. Hughes1, L.M. Del Razo2, and O.A. Levander31Office of Research and Development, Experimental Toxicology Division, N...

  5. ANL-W MOX fuel lead assemblies data report for the surplus plutonium disposition environmental impact statement

    International Nuclear Information System (INIS)

    O'Connor, D.G.; Fisher, S.E.; Holdaway, R.

    1997-08-01

    The purpose of this document is to support the US Department of Energy (DOE) Fissile Materials Disposition Program's preparation of the draft surplus plutonium disposition environmental impact statement (EIS). This is one of several responses to data call requests for background information on activities associated with the operation of the lead assembly (LA) mixed-oxide (MOX) fuel fabrication facility. The DOE Office of fissile Materials Disposition (DOE-MD) has developed a dual-path strategy for disposition of surplus weapons-grade plutonium. One of the paths is to disposition surplus plutonium through irradiation of MOX fuel in commercial nuclear reactors. MOX fuel consists of plutonium and uranium oxides (PuO 2 and UO 2 ), typically containing 95% or more UO 2 . DOE-MD requested that the DOE Site Operations Offices nominate DOE sites that meet established minimum requirements that could produce MOX LAs. The paper describes the following: Site map and the LA facility; process descriptions; resource needs; employment requirements; wastes, emissions, and exposures; accident analysis; transportation; qualitative decontamination and decommissioning; post-irradiation examination; LA fuel bundle fabrication; LA EIS data report assumptions; and LA EIS data report supplement

  6. ANL-W MOX fuel lead assemblies data report for the surplus plutonium disposition environmental impact statement

    Energy Technology Data Exchange (ETDEWEB)

    O`Connor, D.G.; Fisher, S.E.; Holdaway, R. [and others

    1997-08-01

    The purpose of this document is to support the US Department of Energy (DOE) Fissile Materials Disposition Program`s preparation of the draft surplus plutonium disposition environmental impact statement (EIS). This is one of several responses to data call requests for background information on activities associated with the operation of the lead assembly (LA) mixed-oxide (MOX) fuel fabrication facility. The DOE Office of fissile Materials Disposition (DOE-MD) has developed a dual-path strategy for disposition of surplus weapons-grade plutonium. One of the paths is to disposition surplus plutonium through irradiation of MOX fuel in commercial nuclear reactors. MOX fuel consists of plutonium and uranium oxides (PuO{sub 2} and UO{sub 2}), typically containing 95% or more UO{sub 2}. DOE-MD requested that the DOE Site Operations Offices nominate DOE sites that meet established minimum requirements that could produce MOX LAs. The paper describes the following: Site map and the LA facility; process descriptions; resource needs; employment requirements; wastes, emissions, and exposures; accident analysis; transportation; qualitative decontamination and decommissioning; post-irradiation examination; LA fuel bundle fabrication; LA EIS data report assumptions; and LA EIS data report supplement.

  7. The impact of inquiry-based learning on the critical thinking dispositions of pre-service science teachers

    Science.gov (United States)

    Arsal, Zeki

    2017-07-01

    In the study, the impact of inquiry-based learning on pre-service teachers' critical thinking dispositions was investigated. The sample of the study comprised of 56 pre-service teachers in the science education teacher education programme at the public university in the north of Turkey. In the study, quasi-experimental design with an experimental and a control group were applied to find out the impact of inquiry-based learning on the critical thinking dispositions of the pre-service teachers in the teacher education programme. The results showed that the pre-service teachers in the experimental group did not show statistically significant greater progress in terms of critical thinking dispositions than those in the control group. Teacher educators who are responsible for pedagogical courses in the teacher education programme should consider that the inquiry-based learning could not be effective method to improve pre-service teachers' critical thinking dispositions. The results are discussed in relation to potential impact on science teacher education and implications for future research.

  8. LANL MOX fuel lead assemblies data report for the surplus plutonium disposition environmental impact statement

    International Nuclear Information System (INIS)

    Fisher, S.E.; Holdaway, R.; Ludwig, S.B.

    1998-08-01

    The purpose of this document is to support the US Department of Energy (DOE) Fissile Materials Disposition Program's preparation of the draft surplus plutonium disposition environmental impact statement. This is one of several responses to data call requests for background information on activities associated with the operation of the lead assembly (LA) mixed-oxide (MOX) fuel fabrication facility. LANL has proposed an LA MOX fuel fabrication approach that would be done entirely inside an S and S Category 1 area. This includes receipt and storage of PuO 2 powder, fabrication of MOX fuel pellets, assembly of fuel rods and bundles, and shipping of the packaged fuel to a commercial reactor site. Support activities will take place within both Category 1 and 2 areas. Technical Area (TA) 55/Plutonium Facility 4 will be used to store the bulk PuO 2 powder, fabricate MOX fuel pellets, assemble rods, and store fuel bundles. Bundles will be assembled at a separate facility, several of which have been identified as suitable for that activity. The Chemistry and Metallurgy Research Building (at TA-3) will be used for analytical chemistry support. Waste operations will be conducted in TA-50 and TA-54. Only very minor modifications will be needed to accommodate the LA program. These modifications consist mostly of minor equipment upgrades. A commercial reactor operator has not been identified for the LA irradiation. Postirradiation examination (PIE) of the irradiated fuel will take place at either Oak Ridge National Laboratory or ANL-W. The only modifications required at either PIE site would be to accommodate full-length irradiated fuel rods. Results from this program are critical to the overall plutonium distribution schedule

  9. Hanford MOX fuel lead assemblies data report for the surplus plutonium disposition environmental impact statement

    International Nuclear Information System (INIS)

    O'Connor, D.G.; Fisher, S.E.; Holdaway, R.

    1998-08-01

    The purpose of this document is to support the US Department of Energy (DOE) Fissile Materials Disposition Program's preparation of the draft surplus plutonium disposition environmental impact statement. This is one of several responses to data call requests for background information on activities associated with the operation of the lead assembly (LA) mixed-oxide (MOX) fuel fabrication facility. DOE-MD requested that the DOE Site Operations Offices nominate DOE sites that meet established minimum requirements that could produce MOX LAs. Six initial site combinations were proposed: (1) Argonne National Laboratory-West (ANL-W) with support from Idaho National Engineering and Environmental Laboratory (INEEL), (2) Hanford, (3) Los Alamos National Laboratory (LANL) with support from Pantex, (4) Lawrence Livermore National Laboratory (LLNL), (5) Oak Ridge Reservation (ORR), and (6) Savannah River Site (SRS). After further analysis by the sites and DOE-MD, five site combinations were established as possible candidates for producing MOX LAs: (1) ANL-W with support from INEEL, (2) Hanford, (3) LANL, (4) LLNL, and (5) SRS. Hanford has proposed an LA MOX fuel fabrication approach that would be done entirely inside an S and S Category 1 area. An alternate approach would allow fabrication of fuel pellets and assembly of fuel rods in an S and S Category 1 facility. In all, a total of three LA MOX fuel fabrication options were identified by Hanford that could accommodate the program. In every case, only minor modification would be required to ready any of the facilities to accept the equipment necessary to accomplish the LA program

  10. Hanford MOX fuel lead assemblies data report for the surplus plutonium disposition environmental impact statement

    Energy Technology Data Exchange (ETDEWEB)

    O`Connor, D.G.; Fisher, S.E.; Holdaway, R. [and others

    1998-08-01

    The purpose of this document is to support the US Department of Energy (DOE) Fissile Materials Disposition Program`s preparation of the draft surplus plutonium disposition environmental impact statement. This is one of several responses to data call requests for background information on activities associated with the operation of the lead assembly (LA) mixed-oxide (MOX) fuel fabrication facility. DOE-MD requested that the DOE Site Operations Offices nominate DOE sites that meet established minimum requirements that could produce MOX LAs. Six initial site combinations were proposed: (1) Argonne National Laboratory-West (ANL-W) with support from Idaho National Engineering and Environmental Laboratory (INEEL), (2) Hanford, (3) Los Alamos National Laboratory (LANL) with support from Pantex, (4) Lawrence Livermore National Laboratory (LLNL), (5) Oak Ridge Reservation (ORR), and (6) Savannah River Site (SRS). After further analysis by the sites and DOE-MD, five site combinations were established as possible candidates for producing MOX LAs: (1) ANL-W with support from INEEL, (2) Hanford, (3) LANL, (4) LLNL, and (5) SRS. Hanford has proposed an LA MOX fuel fabrication approach that would be done entirely inside an S and S Category 1 area. An alternate approach would allow fabrication of fuel pellets and assembly of fuel rods in an S and S Category 1 facility. In all, a total of three LA MOX fuel fabrication options were identified by Hanford that could accommodate the program. In every case, only minor modification would be required to ready any of the facilities to accept the equipment necessary to accomplish the LA program.

  11. LANL MOX fuel lead assemblies data report for the surplus plutonium disposition environmental impact statement

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, S.E.; Holdaway, R.; Ludwig, S.B. [and others

    1998-08-01

    The purpose of this document is to support the US Department of Energy (DOE) Fissile Materials Disposition Program`s preparation of the draft surplus plutonium disposition environmental impact statement. This is one of several responses to data call requests for background information on activities associated with the operation of the lead assembly (LA) mixed-oxide (MOX) fuel fabrication facility. LANL has proposed an LA MOX fuel fabrication approach that would be done entirely inside an S and S Category 1 area. This includes receipt and storage of PuO{sub 2} powder, fabrication of MOX fuel pellets, assembly of fuel rods and bundles, and shipping of the packaged fuel to a commercial reactor site. Support activities will take place within both Category 1 and 2 areas. Technical Area (TA) 55/Plutonium Facility 4 will be used to store the bulk PuO{sub 2} powder, fabricate MOX fuel pellets, assemble rods, and store fuel bundles. Bundles will be assembled at a separate facility, several of which have been identified as suitable for that activity. The Chemistry and Metallurgy Research Building (at TA-3) will be used for analytical chemistry support. Waste operations will be conducted in TA-50 and TA-54. Only very minor modifications will be needed to accommodate the LA program. These modifications consist mostly of minor equipment upgrades. A commercial reactor operator has not been identified for the LA irradiation. Postirradiation examination (PIE) of the irradiated fuel will take place at either Oak Ridge National Laboratory or ANL-W. The only modifications required at either PIE site would be to accommodate full-length irradiated fuel rods. Results from this program are critical to the overall plutonium distribution schedule.

  12. The Impact of a Novel Curriculum on Secondary Biology Teachers' Dispositions toward Using Authentic Data and Media in Their Human Impact and Ecology Lessons

    Science.gov (United States)

    Wyner, Yael

    2013-01-01

    This study examines how the implementation of a novel curriculum, that emphasizes the use of published scientific data and media to learn about human impact and ecological function, influenced ninth-grade biology teacher (N - 36) dispositions toward using data and media in their ecology and human impact lesson plans. It explores how integration of…

  13. 76 FR 70978 - Environmental Impact Statement for Disposition of Hangars 2 and 3, Fort Wainwright, AK

    Science.gov (United States)

    2011-11-16

    ... Ladd Field World War II National Historic Landmark (NHL). The Department of the Army will use the... . SUPPLEMENTARY INFORMATION: The decision to be made by the Army is regarding the disposition of two historic...

  14. Dispositional logic

    Science.gov (United States)

    Le Balleur, J. C.

    1988-01-01

    The applicability of conventional mathematical analysis (based on the combination of two-valued logic and probability theory) to problems in which human judgment, perception, or emotions play significant roles is considered theoretically. It is shown that dispositional logic, a branch of fuzzy logic, has particular relevance to the common-sense reasoning typical of human decision-making. The concepts of dispositionality and usuality are defined analytically, and a dispositional conjunctive rule and dispositional modus ponens are derived.

  15. SRS MOX fuel lead assemblies data report for the surplus plutonium disposition environmental impact statement

    International Nuclear Information System (INIS)

    O'Connor, D.G.; Fisher, S.E.; Holdaway, R.

    1998-08-01

    The purpose of this document is to support the US Department of Energy (DOE) Fissile Materials Disposition Program's preparation of the draft surplus plutonium disposition environmental impact statement. This is one of several responses to data call requests for background information on activities associated with the operation of the lead assembly (LA) mixed-oxide (MOX) fuel fabrication facility. DOE-MD requested that the DOE Site Operations Offices nominate DOE sites that meet established minimum requirements that could produce MOX LAs. Six initial site combinations were proposed: (1) Argonne National Laboratory-West (ANL-W) with support from Idaho National Engineering and Environmental Laboratory (INEEL), (2) Hanford, (3) Los Alamos National Laboratory (LANL) with support from Pantex, (4) Lawrence Livermore National Laboratory (LLNL), (5) Oak Ridge Reservation (ORR), and (6) Savannah River Site(SRS). After further analysis by the sites and DOE-MD, five site combinations were established as possible candidates for producing MOX LAs: (1) ANL-W with support from INEEL, (2) Hanford, (3) LANL, (4) LLNL, and (5) SRS. SRS has proposed an LA MOX fuel fabrication approach that would be done entirely inside an S and S Category 1 area. An alternate approach would allow fabrication of fuel pellets and assembly of fuel rods in an S and S Category 2 or 3 facility with storage of bulk PuO 2 and assembly, storage, and shipping of fuel bundles in an S and S Category 1 facility. The total Category 1 approach, which is the recommended option, would be done in the 221-H Canyon Building. A facility that was never in service will be removed from one area, and a hardened wall will be constructed in another area to accommodate execution of the LA fuel fabrication. The non-Category 1 approach would require removal of process equipment in the FB-Line metal production and packaging glove boxes, which requires work in a contamination area. The Immobilization Hot Demonstration Program

  16. SRS MOX fuel lead assemblies data report for the surplus plutonium disposition environmental impact statement

    Energy Technology Data Exchange (ETDEWEB)

    O`Connor, D.G.; Fisher, S.E.; Holdaway, R. [and others

    1998-08-01

    The purpose of this document is to support the US Department of Energy (DOE) Fissile Materials Disposition Program`s preparation of the draft surplus plutonium disposition environmental impact statement. This is one of several responses to data call requests for background information on activities associated with the operation of the lead assembly (LA) mixed-oxide (MOX) fuel fabrication facility. DOE-MD requested that the DOE Site Operations Offices nominate DOE sites that meet established minimum requirements that could produce MOX LAs. Six initial site combinations were proposed: (1) Argonne National Laboratory-West (ANL-W) with support from Idaho National Engineering and Environmental Laboratory (INEEL), (2) Hanford, (3) Los Alamos National Laboratory (LANL) with support from Pantex, (4) Lawrence Livermore National Laboratory (LLNL), (5) Oak Ridge Reservation (ORR), and (6) Savannah River Site(SRS). After further analysis by the sites and DOE-MD, five site combinations were established as possible candidates for producing MOX LAs: (1) ANL-W with support from INEEL, (2) Hanford, (3) LANL, (4) LLNL, and (5) SRS. SRS has proposed an LA MOX fuel fabrication approach that would be done entirely inside an S and S Category 1 area. An alternate approach would allow fabrication of fuel pellets and assembly of fuel rods in an S and S Category 2 or 3 facility with storage of bulk PuO{sub 2} and assembly, storage, and shipping of fuel bundles in an S and S Category 1 facility. The total Category 1 approach, which is the recommended option, would be done in the 221-H Canyon Building. A facility that was never in service will be removed from one area, and a hardened wall will be constructed in another area to accommodate execution of the LA fuel fabrication. The non-Category 1 approach would require removal of process equipment in the FB-Line metal production and packaging glove boxes, which requires work in a contamination area. The Immobilization Hot Demonstration Program

  17. Impact of learning adaptability and time management disposition on study engagement among Chinese baccalaureate nursing students.

    Science.gov (United States)

    Liu, Jing-Ying; Liu, Yan-Hui; Yang, Ji-Peng

    2014-01-01

    The aim of this study was to explore the relationships among study engagement, learning adaptability, and time management disposition in a sample of Chinese baccalaureate nursing students. A convenient sample of 467 baccalaureate nursing students was surveyed in two universities in Tianjin, China. Students completed a questionnaire that included their demographic information, Chinese Utrecht Work Engagement Scale-Student Questionnaire, Learning Adaptability Scale, and Adolescence Time Management Disposition Scale. One-way analysis of variance tests were used to assess the relationship between certain characteristics of baccalaureate nursing students. Pearson correlation was performed to test the correlation among study engagement, learning adaptability, and time management disposition. Hierarchical linear regression analyses were performed to explore the mediating role of time management disposition. The results revealed that study engagement (F = 7.20, P < .01) and learning adaptability (F = 4.41, P < .01) differed across grade groups. Learning adaptability (r = 0.382, P < .01) and time management disposition (r = 0.741, P < .01) were positively related with study engagement. Time management disposition had a partially mediating effect on the relationship between study engagement and learning adaptability. The findings implicate that educators should not only promote interventions to increase engagement of baccalaureate nursing students but also focus on development, investment in adaptability, and time management. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Effect of oral coadministration of drugs on the disposition of (14C)-celiprolol HCl in rats

    International Nuclear Information System (INIS)

    Town, C.; Knipe, J.; Taft, C.; Tantillo, N.; Klunk, L.; Grebow, P.

    1986-01-01

    Celiprolol HCL (C) is a cardioselective β-blocker undergoing clinical trials as an antihypertensive agent. Studies with rats indicated that the oral coadministration of 2.5 mg/kg of chlorthalidone (CT) caused a 40% decrease in the urinary excretion of radioactivity from a 40 mg/kg dose of ( 14 C)-C(C). In order to further understand the nature of this interaction, groups of 6 rats were given 40 mg/kg of (C) alone and, one week later,/sub R.(C) pluse the drug to be tested. The vehicle was 0.5% Methocel. After each dosing, urine was collected for 96 hours from each rat and the amount of total radioactivity excreted was compared between treatments. The results showed that oral coadministration of 2.5 mg/kg hydrochlorothiazide, 2.5 mg/kg furosemide, 2.5 mg/kg indapamide, 5.0 mg/kg cimetidine, 10.0 mg/kg theophylline, and 1.0 mg/kg digoxin were without effect on the disposition of orally administered (C). Conversely, 2.5 mg/kg CT, 2.5 mg/kg acetazolamide (AZ) and 5.0 mg/kg hydralazine (H) caused a significant (p < 0.05) decrease in the urinary excretio of orally administered (C). CT and AZ are both potent inhibitors of carbonic anhydrase and their action on this enzyme may cause the effect on the disposition of (C). The action of H may be due to its pharmacologic action and warrants further study

  19. The effects of cyclodextrins on the disposition of intravenously injected drugs in the rat

    NARCIS (Netherlands)

    Frijlink, H W; Franssen, E J; Eissens, Anko; Oosting, Roelof; Lerk, C F; Meijer, D K

    Naproxen and flurbiprofen form complexes with hydroxypropyl-beta-cyclodextrin; with stability constants of 2207 and 12515 M-1, respectively. However, only small fractions of the drug remain complexed when the drug-cyclodextrin complex is added to plasma in vitro. This result can be explained by

  20. The Role of Anti-Drug Antibodies in the Pharmacokinetics, Disposition, Target Engagement, and Efficacy of a GITR Agonist Monoclonal Antibody in Mice.

    Science.gov (United States)

    Brunn, Nicholas D; Mauze, Smita; Gu, Danling; Wiswell, Derek; Ueda, Roanna; Hodges, Douglas; Beebe, Amy M; Zhang, Shuli; Escandón, Enrique

    2016-03-01

    Administration of biologics to enhance T-cell function is part of a rapidly growing field of cancer immunotherapy demonstrated by the unprecedented clinical success of several immunoregulatory receptor targeting antibodies. While these biologic agents confer significant anti-tumor activity through targeted immune response modulation, they can also elicit broad immune responses potentially including the production of anti-drug antibodies (ADAs). DTA-1, an agonist monoclonal antibody against GITR, is a highly effective anti-tumor treatment in preclinical models. We demonstrate that repeated dosing with murinized DTA-1 (mDTA-1) generates ADAs with corresponding reductions in drug exposure and engagement of GITR on circulating CD3(+) CD4(+) T cells, due to rapid hepatic drug uptake and catabolism. Mice implanted with tumors after induction of preexisting mDTA-1 ADA show no anti-tumor efficacy when given 3 mg/kg mDTA-1, an efficacious dose in naive mice. Nonetheless, increasing mDTA-1 treatment to 30 mg/kg in ADA-positive mice restores mDTA-1 exposure and GITR engagement on circulating CD3(+) CD4(+) T cells, thereby partially restoring anti-tumor efficacy. Formation of anti-mDTA-1 antibodies and changes in drug exposure and disposition does not occur in GITR(-/-) mice, consistent with a role for GITR agonism in humoral immunity. Finally, the administration of muDX400, a murinized monoclonal antibody against the checkpoint inhibitor PD-1, dosed alone or combined with mDTA-1 did not result in reduced muDX400 exposure, nor did it change the nature of the anti-mDTA-1 response. This indicates that anti-GITR immunogenicity may not necessarily impact the pharmacology of coadministered monoclonal antibodies, supporting combination immunomodulatory strategies. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  1. Drug safety and the impact of drug warnings

    DEFF Research Database (Denmark)

    Hostenkamp, G.; Fischer, K. E.; Borch-Johnsen, K.

    2016-01-01

    Objective To analyse the impact of drug safety warnings from the European Medicines Agency (EMA) on drug utilisation and their interaction with information released through national reimbursement bodies. Methods Insurance claims data on anti-diabetic drug prescriptions in primary care in Germany...

  2. ADAM, a hands-on patient simulator for teaching principles of drug disposition and compartmental pharmacokinetics.

    Science.gov (United States)

    Zuna, Ines; Holt, Andrew

    2017-11-01

    To design, construct and validate a pharmacokinetics simulator that offers students hands-on opportunities to participate in the design, administration and analysis of oral and intravenous dosing regimens. The Alberta Drug Administration Modeller (ADAM) is a mechanical patient in which peristaltic circulation of water through a network of silicone tubing and glass bottles creates a representation of the outcomes of drug absorption, distribution, metabolism and elimination. Changing peristaltic pump rates and volumes in bottles allows values for pharmacokinetic constants to be varied, thereby simulating differences in drug properties and in patient physiologies and pathologies. Following administration of methylene blue dye by oral or intravenous routes, plasma and/or urine samples are collected and drug concentrations are determined spectrophotometrically. The effectiveness of the simulator in enhancing student competence and confidence was assessed in two undergraduate laboratory classes. The simulator effectively models one- and two-compartment drug behaviour in a mathematically-robust and realistic manner. Data allow calculation of numerous pharmacokinetic constants, by traditional graphing methods or with curve-fitting software. Students' competence in solving pharmacokinetic problems involving calculations and graphing improved significantly, while an increase in confidence and understanding was reported. The ADAM is relatively inexpensive and straightforward to construct, and offers a realistic, hands-on pharmacokinetics learning opportunity for students that effectively complements didactic lectures. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

  3. Enterohepatic disposition of rosuvastatin in pigs and the impact of concomitant dosing with cyclosporine and gemfibrozil.

    Science.gov (United States)

    Bergman, Ebba; Lundahl, Anna; Fridblom, Patrik; Hedeland, Mikael; Bondesson, Ulf; Knutson, Lars; Lennernäs, Hans

    2009-12-01

    The hepatobiliary transport and local disposition of rosuvastatin in pig were investigated, along with the impact of concomitant dosing with two known multiple transport inhibitors; cyclosporine and gemfibrozil. Rosuvastatin (80 mg) was administered as an intrajejunal bolus dose in treatments I, II, and III (TI, TII, and TIII, respectively; n = 6 per treatment). Cyclosporine (300 mg) and gemfibrozil (600 mg) were administered in addition to the rosuvastatin dose in TII and TIII, respectively. Cyclosporine was administered as a 2-h intravenous infusion and gemfibrozil as an intrajejunal bolus dose. In treatment IV (TIV, n = 4) 5.9 mg of rosuvastatin was administered as an intravenous bolus dose. The study was conducted using a pig model, which enabled plasma sampling from the portal (VP), hepatic (VH), and femoral veins and bile from the common hepatic duct. The biliary recoveries of the administered rosuvastatin dose were 9.0 +/- 3.5 and 35.7 +/- 15.6% in TI and TIV, respectively. Rosuvastatin was highly transported into bile as shown by the median AUC(bile)/AUC(VH) ratio in TI of 1770 (1640-11,300). Gemfibrozil did not have an effect on the plasma pharmacokinetics of rosuvastatin, most likely because the unbound inhibitor concentrations did not exceed the reported IC(50) values. However, cyclosporine significantly reduced the hepatic extraction of rosuvastatin (TI, 0.89 +/- 0.06; TII, 0.46 +/- 0.13) and increased the AUC(VP) and AUC(VH) by 1.6- and 9.1-fold, respectively. In addition, the biliary exposure and f(e, bile) were reduced by approximately 50%. The strong effect of cyclosporine was in accordance with inhibition of sinusoidal uptake transporters, such as members of the organic anion-transporting polypeptide family, rather than canalicular transporters.

  4. Role of the Intestinal Bile Acid Transporters in Bile Acid and Drug Disposition

    Science.gov (United States)

    Dawson, Paul A.

    2011-01-01

    Membrane transporters expressed by the hepatocyte and enterocyte play critical roles in maintaining the enterohepatic circulation of bile acids, an effective recycling and conservation mechanism that largely restricts these potentially cytotoxic detergents to the intestinal and hepatobiliary compartments. In doing so, the hepatic and enterocyte transport systems ensure a continuous supply of bile acids to be used repeatedly during the digestion of multiple meals throughout the day. Absorption of bile acids from the intestinal lumen and export into the portal circulation is mediated by a series of transporters expressed on the enterocyte apical and basolateral membranes. The ileal apical sodium-dependent bile acid cotransporter (abbreviated ASBT; gene symbol, SLC10A2) is responsible for the initial uptake of bile acids across the enterocyte brush border membrane. The bile acids are then efficiently shuttled across the cell and exported across the basolateral membrane by the heteromeric Organic Solute Transporter, OSTα-OSTβ. This chapter briefly reviews the tissue expression, physiology, genetics, pathophysiology, and transport properties of the ASBT and OSTα-OSTα. In addition, the chapter discusses the relationship between the intestinal bile acid transporters and drug metabolism, including development of ASBT inhibitors as novel hypocholesterolemic or hepatoprotective agents, prodrug targeting of the ASBT to increase oral bioavailability, and involvement of the intestinal bile acid transporters in drug absorption and drug-drug interactions. PMID:21103970

  5. Application of Hill's equation for estimating area under the concentration-time curve (AUC) and use of time to AUC 90% for expressing kinetics of drug disposition.

    Science.gov (United States)

    Cheng, Hsien C

    2009-01-01

    Half life and its derived pharmacokinetic parameters are calculated on an assumption that the terminal phase of drug disposition follows a constant rate of disposition. In reality, this assumption may not necessarily be the case. A new method is needed for analyzing PK parameters if the disposition does not follow a first order PK kinetic. Cumulative area under the concentration-time curve (AUC) is plotted against time to yield a hyperbolic (or sigmoidal) AUC-time relationship curve which is then analyzed by Hill's equation to yield AUC(inf), time to achieving AUC50% (T(AUC50%)) or AUC90% (T(AUC90%)), and the Hill's slope. From these parameters, an AUC-time relationship curve can be reconstructed. Projected plasma concentration can be calculated for any time point. Time at which cumulative AUC reaches 90% (T(AUC90%)) can be used as an indicator for expressing how fast a drug is cleared. Clearance is calculated in a traditional manner (i.v. dose/AUC(inf)), and the volume of distribution is proposed to be calculated at T(AUC50%) (0.5 i.v. dose/plasma concentration at T(AUC50%)). This method of estimating AUC is applicable for both i.v. and oral data. It is concluded that the Hill's equation can be used as an alternative method for estimating AUC and analysis of PK parameters if the disposition does not follow a first order kinetic. T(AUC90%) is proposed to be used as an indicator for expressing how fast a drug is cleared from the system.

  6. Representing dispositions

    Directory of Open Access Journals (Sweden)

    Röhl Johannes

    2011-08-01

    Full Text Available Abstract Dispositions and tendencies feature significantly in the biomedical domain and therefore in representations of knowledge of that domain. They are not only important for specific applications like an infectious disease ontology, but also as part of a general strategy for modelling knowledge about molecular interactions. But the task of representing dispositions in some formal ontological systems is fraught with several problems, which are partly due to the fact that Description Logics can only deal well with binary relations. The paper will discuss some of the results of the philosophical debate about dispositions, in order to see whether the formal relations needed to represent dispositions can be broken down to binary relations. Finally, we will discuss problems arising from the possibility of the absence of realizations, of multi-track or multi-trigger dispositions and offer suggestions on how to deal with them.

  7. Impact of orphan drugs on Latvian budget.

    Science.gov (United States)

    Logviss, Konstantins; Krievins, Dainis; Purvina, Santa

    2016-05-11

    Number of orphan medicinal products on the market and number of rare disease patients, taking these usually expensive products, are increasing. As a result, budget impact of orphan drugs is growing. This factor, along with the cost-effectiveness of orphan drugs, is often considered in the reimbursement decisions, directly affecting accessibility of rare disease therapies. The current study aims to assess the budget impact of orphan drugs in Latvia. Our study covered a 5-year period, from 2010 to 2014. Impact of orphan drugs on Latvian budget was estimated from the National Health Service's perspective. It was calculated in absolute values and relative to total pharmaceutical market and total drug reimbursement budget. A literature review was performed for comparison with other European countries. Orphan drug annual expenditure ranged between EUR 2.065 and 3.065 million, with total 5-year expenditure EUR 12.467 million. It constituted, on average, 0.84 % of total pharmaceutical market and 2.14 % of total drug reimbursement budget, respectively. Average annual per patient expenditures varied widely, from EUR 1 534 to EUR 580 952. The most costly treatment was enzyme replacement therapy (Elaprase) for MPS II. Glivec had the highest share (34 %) of the total orphan drug expenditure. Oncological drugs represented more than a half of the total orphan drug expenditure, followed by drugs for metabolic and endocrine conditions and medicines for cardiopulmonary diseases. Three indications: Ph+ CML, MPS II, and PAH accounted for nearly 90 % of the total orphan drug expenditure. Budget impact of orphan drugs in Latvia is very small. It increased slightly over a period of five years, due to the slight increase in the number of patients and the number of orphan drugs reimbursed. Current Latvian drug reimbursement system is not sufficient for most orphan drugs.

  8. The Impact of Discharge Disposition on Episode-of-Care Reimbursement After Primary Total Hip Arthroplasty.

    Science.gov (United States)

    Sabeh, Karim G; Rosas, Samuel; Buller, Leonard T; Roche, Martin W; Hernandez, Victor H

    2017-10-01

    Total joint arthroplasty (TJA) accounts for more Medicare expenditure than any other inpatient procedure. The Comprehensive Care for Joint Replacement model was introduced to decrease cost and improve quality in TJA. The largest portion of episode-of-care costs occurs after discharge. This study sought to quantify the cost variation of primary total hip arthroplasty (THA) according to discharge disposition. The Medicare and Humana claims databases were used to extract charges and reimbursements to compare day-of-surgery and 91-day postoperative costs simulating episode-of-care reimbursements. Of the patients who underwent primary THA, 257,120 were identified (204,912 from Medicare and 52,208 from Humana). Patients were stratified by discharge disposition: home with home health, skilled nursing facility, or inpatient rehabilitation facility. There is a significant difference in the episode-of-care costs according to discharge disposition, with discharge to an inpatient rehabilitation facility the most costly and discharge to home the least costly. Postdischarge costs represent a sizeable portion of the overall expense in THA, and optimizing patients to allow safe discharge to home may help reduce the cost of THA. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Antinociceptive effects, metabolism and disposition of ketamine in ponies under target-controlled drug infusion

    International Nuclear Information System (INIS)

    Knobloch, M.; Portier, C.J.; Levionnois, O.L.; Theurillat, R.; Thormann, W.; Spadavecchia, C.; Mevissen, M.

    2006-01-01

    Ketamine is widely used as an anesthetic in a variety of drug combinations in human and veterinary medicine. Recently, it gained new interest for use in long-term pain therapy administered in sub-anesthetic doses in humans and animals. The purpose of this study was to develop a physiologically based pharmacokinetic (PBPk) model for ketamine in ponies and to investigate the effect of low-dose ketamine infusion on the amplitude and the duration of the nociceptive withdrawal reflex (NWR). A target-controlled infusion (TCI) of ketamine with a target plasma level of 1 μg/ml S-ketamine over 120 min under isoflurane anesthesia was performed in Shetland ponies. A quantitative electromyographic assessment of the NWR was done before, during and after the TCI. Plasma levels of R-/S-ketamine and R-/S-norketamine were determined by enantioselective capillary electrophoresis. These data and two additional data sets from bolus studies were used to build a PBPk model for ketamine in ponies. The peak-to-peak amplitude and the duration of the NWR decreased significantly during TCI and returned slowly toward baseline values after the end of TCI. The PBPk model provides reliable prediction of plasma and tissue levels of R- and S-ketamine and R- and S-norketamine. Furthermore, biotransformation of ketamine takes place in the liver and in the lung via first-pass metabolism. Plasma concentrations of S-norketamine were higher compared to R-norketamine during TCI at all time points. Analysis of the data suggested identical biotransformation rates from the parent compounds to the principle metabolites (R- and S-norketamine) but different downstream metabolism to further metabolites. The PBPk model can provide predictions of R- and S-ketamine and norketamine concentrations in other clinical settings (e.g. horses)

  10. Drug disposition model of radiolabeled etelcalcetide in patients with chronic kidney disease and secondary hyperparathyroidism on hemodialysis.

    Science.gov (United States)

    Wu, Liviawati; Melhem, Murad; Subramanian, Raju; Wu, Benjamin

    2017-02-01

    Etelcalcetide (AMG 416) is an allosteric activator of the calcium-sensing receptor for treatment of secondary hyperparathyroidism in patients with chronic kidney disease (CKD) on hemodialysis. To characterize the time course of etelcalcetide in different matrices (plasma, dialysate, urine, and feces), a drug disposition model was developed. Nonlinear mixed-effect modeling was used to describe data from six adults with CKD on hemodialysis who received a single intravenous dose of [ 14 C]etelcalcetide (10 mg; 710 nCi) after hemodialysis (study NCT02054572). A three-compartment model with the following attributes adequately described the observed concentration-time profiles of etelcalcetide in the different matrices: biotransformation in the central compartment; elimination in dialysate, urine, and feces; and a nonspecific elimination process. The terminal half-life of total C-14 in plasma was approximately 56 days. The ratio of conjugation-deconjugation rate constants between etelcalcetide and biotransformed products was 11.3. Simulations showed that three hemodialysis sessions per week for 52 weeks would contribute to 60.1% of the total clearance of etelcalcetide following single-dose intravenous etelcalcetide administration. Minimal amounts were eliminated in urine (2.5%) and feces (5.7%), whereas nonspecific elimination accounted for 31.2% of total elimination. In addition to removal of etelcalcetide, ~10% of small-molecular weight biotransformed products was estimated to have been removed through hemodialysis and in urine. This model provided a quantitative approach to describe biotransformation, distribution, and elimination of etelcalcetide, a unique synthetic D-amino acid peptide, in the relevant patient population.

  11. Savannah River Site's H-Canyon Facility: Impacts of Foreign Obligations on Special Nuclear Material Disposition

    International Nuclear Information System (INIS)

    Magoulas, Virginia

    2013-01-01

    The US has a non-proliferation policy to receive foreign and domestic research reactor returns of spent fuel materials of US origin. These spent fuel materials are returned to the Department of Energy (DOE) and placed in storage in the L-area spent fuel basin at the Savannah River Site (SRS). The foreign research reactor returns fall subject to the 123 agreements for peaceful cooperation. These ''123 agreements'' are named after section 123 of the Atomic Energy Act of 1954 and govern the conditions of nuclear cooperation with foreign partners. The SRS management of these foreign obligations while planning material disposition paths can be a challenge.

  12. Measuring Teacher Dispositions

    Science.gov (United States)

    Singh, Delar K.; Stoloff, David L.

    2007-01-01

    Teacher quality has become a top priority of our national agenda. There is empirical evidence that suggests that teacher inputs have impact on student outcomes. It is also believed that teacher dispositions are as crucial for student achievement as a teacher's pedagogical and content knowledge/skills. The National Council for Accreditation of…

  13. Population Impact of Drug Interactions with Warfarin

    DEFF Research Database (Denmark)

    Martín-Pérez, Mar; Gaist, David; de Abajo, Francisco J

    2018-01-01

    OBJECTIVE:  To investigate the population impact of previously reported interactions between warfarin and other drugs on international normalized ratio (INR) levels. METHODS:  Using The Health Improvement Network (THIN), a United Kingdom primary care database, a cohort of warfarin users between.......55) and in the proportion of patients with INR levels out of therapeutic range (population...

  14. Clinical impact of genetic variants of drug transporters in different ethnic groups within and across regions.

    Science.gov (United States)

    Ono, Chiho; Kikkawa, Hironori; Suzuki, Akiyuki; Suzuki, Misaki; Yamamoto, Yuichi; Ichikawa, Katsuomi; Fukae, Masato; Ieiri, Ichiro

    2013-11-01

    Drug transporters, together with drug metabolic enzymes, are major determinants of drug disposition and are known to alter the response to many commonly used drugs. Substantial frequency differences for known variants exist across geographic regions for certain drug transporters. To deliver efficacious medicine with the right dose for each patient, it is important to understand the contribution of genetic variants for drug transporters. Recently, mutual pharmacokinetic data usage among Asian regions, which are thought to be relatively similar in their own genetic background, is expected to accelerate new drug applications and reduce developmental costs. Polymorphisms of drug transporters could be key factors to be considered in implementing multiethnic global clinical trials. This review addresses the current knowledge on genetic variations of major drug transporters affecting drug disposition, efficacy and toxicity, focusing on the east Asian populations, and provides insights into future directions for precision medicine and drug development in east Asia.

  15. Drug development against tuberculosis: Impact of alkaloids.

    Science.gov (United States)

    Mishra, Shardendu K; Tripathi, Garima; Kishore, Navneet; Singh, Rakesh K; Singh, Archana; Tiwari, Vinod K

    2017-09-08

    Despite of the advances made in the treatment and management, tuberculosis (TB) still remains one of main public health problem. The contrary effects of first and second-line anti-tuberculosis drugs have generated extended research interest in natural products in the hope of devising new antitubercular leads. Interestingly, plethoras of natural products have been discovered to exhibit activity towards various resistant strains of M. tuberculosis. Extensive applications of alkaloids in the field of therapeutics is well-established and nowday's researches being pursued to develop new potent drugs from natural sources for tuberculosis. Alkaloids are categorized in quite a few groups according to their structures and isolation from both terrestrial and marine sources. These new drugs might be a watershed in the battle against tuberculosis. This review summarizes alkaloids, which were found active against Mycobacteria since last ten years with special attention on the study of structure-activity relationship (SAR) and mode of action with their impact in drug discovery and development against tuberculosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  16. [Impact of ECMO on drugs pharmacokinetics].

    Science.gov (United States)

    Hasni, Nesrine; Lemaitre, Florian; Fernandez, Christine; Combes, Alain; Farinotti, Robert

    2011-01-01

    Extracorporeal membrane oxygenation (ECMO) is a life support system used in the treatment of patients of all ages with severe respiratory or cardiorespiratory failure. Despite the intensive use of drugs in the treatment of patients on ECMO, few studies have been conducted to determine the impact of this device on the pharmacokinetics of drugs. Publications in this field have shown pharmacokinetics changes resulting in an increase in volume of distribution of drugs and/or decreased clearance with consequent increase of their half-life. Reduced plasma concentrations of some drugs due to their adsorption on the different components of the circuit further complicates the determination of pharmacokinetic parameters of patients treated by ECMO. The literature published up to now on the pharmacokinetic changes associated with ECMO provide preliminary support for dosage adjustment. However, more research is needed to identify dosage strategies for this patient population. © 2011 Société Française de Pharmacologie et de Thérapeutique.

  17. Impact of renal aging on drug therapy.

    Science.gov (United States)

    Musso, Carlos G; Belloso, Waldo H; Scibona, Paula; Bellizzi, Vincenzo; Macías Núñez, Juan F

    2015-08-01

    Elderly patients (age ≥ 65 years old) use up to 30% of all commonly prescribed medication, and they suffer more their adverse effects than the general population. In order to minimize this risk, physicians should avoid polypharmacy, dangerous pharmacological interactions and take into account pharmacodynamic and senile pharmacokinetic changes before prescribing any medication to the elderly. The present review article originally describes how renal physiology changes secondary to aging such as dysautonomia, glomerular filtration rate reduction, tubular back-filtration, sodium, calcium and magnesium loss, potassium retention, altered dilution-concentration capability, tubular frailty, genetics, internal milieu and body composition are senile changes that when combined predispose elderly people to suffer from pharmacological adverse effects. Knowledge of these physiological modifications associated with aging and their impact on the pharmacology of particular drugs may help to optimize drug use and to avoid complications in this age group.

  18. Current status of prediction of drug disposition and toxicity in humans using chimeric mice with humanized liver.

    Science.gov (United States)

    Kitamura, Shigeyuki; Sugihara, Kazumi

    2014-01-01

    1. Human-chimeric mice with humanized liver have been constructed by transplantation of human hepatocytes into several types of mice having genetic modifications that injure endogenous liver cells. Here, we focus on liver urokinase-type plasminogen activator-transgenic severe combined immunodeficiency (uPA/SCID) mice, which are the most widely used human-chimeric mice. Studies so far indicate that drug metabolism, drug transport, pharmacological effects and toxicological action in these mice are broadly similar to those in humans. 2. Expression of various drug-metabolizing enzymes is known to be different between humans and rodents. However, the expression pattern of cytochrome P450, aldehyde oxidase and phase II enzymes in the liver of human-chimeric mice resembles that in humans, not that in the host mice. 3. Metabolism of various drugs, including S-warfarin, zaleplon, ibuprofen, naproxen, coumarin, troglitazone and midazolam, in human-chimeric mice is mediated by human drug-metabolizing enzymes, not by host mouse enzymes, and thus resembles that in humans. 4. Pharmacological and toxicological effects of various drugs in human-chimeric mice are also similar to those in humans. 5. The current consensus is that chimeric mice with humanized liver are useful to predict drug metabolism catalyzed by cytochrome P450, aldehyde oxidase and phase II enzymes in humans in vivo and in vitro. Some remaining issues are discussed in this review.

  19. Comparative Proteomic Characterization of 4 Human Liver-Derived Single Cell Culture Models Reveals Significant Variation in the Capacity for Drug Disposition, Bioactivation, and Detoxication.

    Science.gov (United States)

    Sison-Young, Rowena L C; Mitsa, Dimitra; Jenkins, Rosalind E; Mottram, David; Alexandre, Eliane; Richert, Lysiane; Aerts, Hélène; Weaver, Richard J; Jones, Robert P; Johann, Esther; Hewitt, Philip G; Ingelman-Sundberg, Magnus; Goldring, Christopher E P; Kitteringham, Neil R; Park, B Kevin

    2015-10-01

    In vitro preclinical models for the assessment of drug-induced liver injury (DILI) are usually based on cryopreserved primary human hepatocytes (cPHH) or human hepatic tumor-derived cell lines; however, it is unclear how well such cell models reflect the normal function of liver cells. The physiological, pharmacological, and toxicological phenotyping of available cell-based systems is necessary in order to decide the testing purpose for which they are fit. We have therefore undertaken a global proteomic analysis of 3 human-derived hepatic cell lines (HepG2, Upcyte, and HepaRG) in comparison with cPHH with a focus on drug metabolizing enzymes and transport proteins (DMETs), as well as Nrf2-regulated proteins. In total, 4946 proteins were identified, of which 2722 proteins were common across all cell models, including 128 DMETs. Approximately 90% reduction in expression of cytochromes P450 was observed in HepG2 and Upcyte cells, and approximately 60% in HepaRG cells relative to cPHH. Drug transporter expression was also lower compared with cPHH with the exception of MRP3 and P-gp (MDR1) which appeared to be significantly expressed in HepaRG cells. In contrast, a high proportion of Nrf2-regulated proteins were more highly expressed in the cell lines compared with cPHH. The proteomic database derived here will provide a rational basis for the context-specific selection of the most appropriate 'hepatocyte-like' cell for the evaluation of particular cellular functions associated with DILI and, at the same time, assist in the construction of a testing paradigm which takes into account the in vivo disposition of a new drug. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology.

  20. Improving drug candidates by design: a focus on physicochemical properties as a means of improving compound disposition and safety.

    Science.gov (United States)

    Meanwell, Nicholas A

    2011-09-19

    The development of small molecule drug candidates from the discovery phase to a marketed product continues to be a challenging enterprise with very low success rates that have fostered the perception of poor productivity by the pharmaceutical industry. Although there have been significant advances in preclinical profiling that have improved compound triaging and altered the underlying reasons for compound attrition, the failure rates have not appreciably changed. As part of an effort to more deeply understand the reasons for candidate failure, there has been considerable interest in analyzing the physicochemical properties of marketed drugs for the purpose of comparing with drugs in discovery and development as a means capturing recent trends in drug design. The scenario that has emerged is one in which contemporary drug discovery is thought to be focused too heavily on advancing candidates with profiles that are most easily satisfied by molecules with increased molecular weight and higher overall lipophilicity. The preponderance of molecules expressing these properties is frequently a function of increased aromatic ring count when compared with that of the drugs launched in the latter half of the 20th century and may reflect a preoccupation with maximizing target affinity rather than taking a more holistic approach to drug design. These attributes not only present challenges for formulation and absorption but also may influence the manifestation of toxicity during development. By providing some definition around the optimal physicochemical properties associated with marketed drugs, guidelines for drug design have been developed that are based largely on calculated parameters and which may readily be applied by medicinal chemists as an aid to understanding candidate quality. The physicochemical properties of a molecule that are consistent with the potential for good oral absorption were initially defined by Lipinski, with additional insights allowing further

  1. Dispositional greed.

    Science.gov (United States)

    Seuntjens, Terri G; Zeelenberg, Marcel; van de Ven, Niels; Breugelmans, Seger M

    2015-06-01

    Greed is an important motive: it is seen as both productive (a source of ambition; the motor of the economy) and destructive (undermining social relationships; the cause of the late 2000s financial crisis). However, relatively little is known about what greed is and does. This article reports on 5 studies that develop and test the 7-item Dispositional Greed Scale (DGS). Study 1 (including 4 separate samples from 2 different countries, total N = 6092) provides evidence for the construct and discriminant validity of the DGS in terms of positive correlations with maximization, self-interest, envy, materialism, and impulsiveness, and negative correlations with self-control and life satisfaction. Study 2 (N = 290) presents further evidence for discriminant validity, finding that the DGS predicts greedy behavioral tendencies over and above materialism. Furthermore, the DGS predicts economic behavior: greedy people allocate more money to themselves in dictator games (Study 3, N = 300) and ultimatum games (Study 4, N = 603), and take more in a resource dilemma (Study 5, N = 305). These findings shed light on what greed is and does, how people differ in greed, and how greed can be measured. In addition, they show the importance of greed in economic behavior and provide directions for future studies. (c) 2015 APA, all rights reserved).

  2. The utilisation of short-lived radionuclides in the assessment of formulation and in vivo disposition of drugs

    International Nuclear Information System (INIS)

    Digenis, G.A.

    1982-01-01

    The utilisation of short-lived radionuclides in the assessment of drug formulations, and the in vivo distribution of drugs is discussed. Disintegration of tablets and capsules as a function of the formulation, and gastric emptying are important. The applicability of perturbed angular correlation to the study of the dissolution of water soluble substances from solid dosages in man is shown. Examples are given to illustrate how external scintigraphy can be applied to study the tissue distribution of 18 F-haloperidol, 82 Br-bromperidol, in rat and monkey. 11 C, L-andD-phenylalanine in rats, 11 C, D-leucine in mice with human colon tumours; 13 N-nitrosoureas and 13 N-nitroso-carbamates. (U.K.)

  3. Initial data report in response to the surplus plutonium disposition environmental impact statement data call for the UO2 supply. Revision 1

    International Nuclear Information System (INIS)

    White, V.S.; Cash, J.M.; Michelhaugh, R.D.

    1997-11-01

    The purpose of this document is to support the US Department of Energy (DOE) Fissile Materials Disposition Program's preparation of the draft Surplus Plutonium Disposition Environmental Impact Statement. This is one of several responses to data calls generated to provide background information on activities associated with the operation of the Mixed-Oxide (MOX) Fuel Fabrication Facility. Urania feed for the MOX Fuel Fabrication Facility may be either natural or depleted. Natural uranium typically contains 0.0057 wt% 234 U, 0.711 wt% 235 U, and the majority as 238 U. The fissile isotope is 235 U, and uranium is considered depleted if the total 235 U content is less than 0.711 wt% as found in nature. The average composition of 235 U in DOE's total depleted urania inventory is 0.20 wt%. The depleted uranium assay range proposed for use in this program is 0.2500--0.2509 wt%. Approximately 30% more natural uranium would be required than depleted uranium based on the importance of maintaining a specific fissile portion in the MOX fuel blend. If the uranium component constitutes a larger quantity of fissile material, less plutonium can be dispositioned on an annual basis. The percentage composition, referred to as assay, of low-enriched uranium necessary for controlled fission in commercial light-water nuclear power reactors is 1.8--5.0 wt% 235 U. This data report provides information on the schedule, acquisition, impacts, and conversion process for using uranium, derived from depleted uranium hexafluoride (UF 6 ), as the diluent for the weapons-grade plutonium declared as surplus. The case analyzed is use of depleted UF 6 in storage at the Portsmouth Gaseous Diffusion Plant in Piketon, Ohio, being transported to a representative UF 6 to uranium dioxide conversion facility (GE Nuclear Energy) for processing, and subsequently transported to the MOX Fuel Fabrication Facility

  4. The impact of the Orphan Drug Act on drug discovery.

    Science.gov (United States)

    Haffner, Marlene E; Maher, Paul D

    2006-11-01

    For nearly a quarter of a century the FDA Office of Orphan Products Development has administered the US Orphan Drug Act, which assists in bringing a wide variety of drug and biological (drug) products to treat rare diseases to market. Enthusiasm for rare disease product development has been sustained, seen throughout a wide spectrum of product types and disease conditions, and has resulted in clinically meaningful medical advances. Development of programmes for rare disease treatment worldwide, coupled with the development of drugs for diseases affecting developing countries, attests to the strength of this legislation. The marketing of almost 300 products in the US for rare diseases also testifies to the depth and intensity of scientific endeavour in this area.

  5. Happiness, Dispositions and the Self

    DEFF Research Database (Denmark)

    Klausen, Søren Harnow

    2016-01-01

    I argue that happiness is an exclusively categorical mental state. Daniel Haybron’s inclusion of dispositions into his emotional state theory rests of a confusion of constituents of happiness in the narrow psychological sense with objects of prudential concern, to which obviously belong “mood...... propensities” and other dispositional states. I further argue that while it is probably correct to require of a constituent of happiness that it must in some sense be “deep” and belong to, or directly impact on, a persons’ self, the importance of depth may be overrated by the emotional state theory, which also...

  6. The Dispositions Improvement Process

    Science.gov (United States)

    Brewer, Robin D.; Lindquist, Cynthia; Altemueller, Lisa

    2011-01-01

    Globally, teacher dispositions along with knowledge and skills continue to be the focal point of teacher education programs. Teachers influence children's development and therefore dispositions are a universal concern. For the past 20 years in the United States, teacher education programs have assessed dispositions. We, however, must now also use…

  7. The socioeconomic impact of drug-related crimes in Chile.

    Science.gov (United States)

    Fernández, Matías

    2012-11-01

    Illegal drug use and trafficking are closely connected to crime. This article estimates the socioeconomic impact of this connection in Chile. Goldstein's tripartite model was applied quantifying drug-crime connections and then using those estimates to measure the socioeconomic impact of drug-related crimes. This was estimated in terms of both the monetary cost of law enforcement, and lost productivity due to incarceration. This socioeconomic impact can be divided into: (a) the direct costs arising from infractions to Chile's Drug Law, and the indirect costs originated by crimes linked only partially to drug consumption and trafficking; (b) is measured in productivity losses, as well as in costs to the three branches of Chile's criminal justice system (police, judiciary, and prisons); and (c) is attributed to the three illicit drugs most prevalent in Chile: cannabis, cocaine hydrochloride (CH) and cocaine base paste (CBP). The socioeconomic impact of Chile's drug-crime relationship in 2006 is estimated to be USD 268 million. Out of this amount, 36% is spent on national Drug Law enforcement, and the remaining 64% comes from the connection of drug use and trafficking with non-Drug-Law-related crimes. The police bear the largest share of drug enforcement costs (32%), followed by penitentiaries (25%). Productivity losses due to incarceration for drug-related crimes represent 29% of the total impact. 53% of the costs are attributable to CBP, 29% to CH, and the remaining 18% to cannabis. The impact of CBP is greater when indirect costs are taken into account, although direct costs are primarily associated with CH. The majority of costs is attributed to the trafficking and consumption of CBP, a drug with a relatively low prevalence. Based on the results, this study suggests reviewing drug enforcement policies to differentiate them according to the social and individual harm caused by each drug. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Target-mediated drug disposition model for drugs with two binding sites that bind to a target with one binding site.

    Science.gov (United States)

    Gibiansky, Leonid; Gibiansky, Ekaterina

    2017-10-01

    The paper extended the TMDD model to drugs with two identical binding sites (2-1 TMDD). The quasi-steady-state (2-1 QSS), quasi-equilibrium (2-1 QE), irreversible binding (2-1 IB), and Michaelis-Menten (2-1 MM) approximations of the model were derived. Using simulations, the 2-1 QSS approximation was compared with the full 2-1 TMDD model. As expected and similarly to the standard TMDD for monoclonal antibodies (mAb), 2-1 QSS predictions were nearly identical to 2-1 TMDD predictions, except for times of fast changes following initiation of dosing, when equilibrium has not yet been reached. To illustrate properties of new equations and approximations, several variations of population PK data for mAbs with soluble (slow elimination of the complex) or membrane-bound (fast elimination of the complex) targets were simulated from a full 2-1 TMDD model and fitted to 2-1 TMDD models, to its approximations, and to the standard (1-1) QSS model. For a mAb with a soluble target, it was demonstrated that the 2-1 QSS model provided nearly identical description of the observed (simulated) free drug and total target concentrations, although there was some minor bias in predictions of unobserved free target concentrations. The standard QSS approximation also provided a good description of the observed data, but was not able to distinguish between free drug concentrations (with no target attached and both binding site free) and partially bound drug concentrations (with one of the binding sites occupied by the target). For a mAb with a membrane-bound target, the 2-1 MM approximation adequately described the data. The 2-1 QSS approximation converged 10 times faster than the full 2-1 TMDD, and its run time was comparable with the standard QSS model.

  9. Pharmacokinetics of dietary cancer chemopreventive compound dibenzoylmethane in rats and the impact of nanoemulsion and genetic knockout of Nrf2 on its disposition.

    Science.gov (United States)

    Lin, Wen; Hong, Jin-Liern; Shen, Guoxiang; Wu, Rachel T; Wang, Yuwen; Huang, Mou-Tuan; Newmark, Harold L; Huang, Qingrong; Khor, Tin Oo; Heimbach, Tycho; Kong, Ah-Ng

    2011-03-01

    The pharmacokinetic disposition of a dietary cancer chemopreventive compound dibenzoylmethane (DBM) was studied in male Sprague-Dawley rats after intravenous (i.v.) and oral (p.o.) administrations. Following a single i.v. bolus dose, the mean plasma clearance (CL) of DBM was low compared with the hepatic blood flow. DBM displayed a high volume of distribution (Vss). The elimination terminal t1/2 was long. The mean CL, Vss and AUC0-∞/dose were similar between the i.v. 10 and 10 mg/kg doses. After single oral doses (10, 50 and 250 mg/kg), the absolute oral bioavailability (F*) of DBM was 7.4%-13.6%. The increase in AUC was not proportional to the oral doses, suggesting non-linearity. In silico prediction of oral absorption also demonstrated low DBM absorption in vivo. An oil-in-water nanoemulsion containing DBM was formulated to potentially overcome the low F* due to poor water solubility of DBM, with enhanced oral absorption. Finally, to examine the role of Nrf2 on the pharmacokinetics of DBM, since DBM activates the Nrf2-dependent detoxification pathways, Nrf2 wild-type (+/+) mice and Nrf2 knockout (-/-) mice were utilized. There was an increased systemic plasma exposure of DBM in Nrf2 (-/-) mice, suggesting that the Nrf2 genotype could also play a role in the pharmacokinetic disposition of DBM. Taken together, the results show that DBM has low oral bioavailability which could be due in part to poor water solubility and this could be overcome by a nanotechnology-based drug delivery system and furthermore the Nrf2 genotype could also play a role in the pharmacokinetics of DBM. Copyright © 2010 John Wiley & Sons, Ltd.

  10. Impact of Tamsulosin, Tolterodine and drug-combination on the ...

    African Journals Online (AJOL)

    Impact of Tamsulosin, Tolterodine and drug-combination on the outcomes of lower urinary tract symptoms secondary to post-ureteroscopy ureteral stent: A prospective randomized controlled clinical study.

  11. The Impact of Drug Abuse upon Adolescent Suicide.

    Science.gov (United States)

    Downey, Ann M.

    1991-01-01

    Explored the hypothesis that the increased use, misuse, and abuse of drugs is one of the myriad explanations for the escalation in youth suicidal behavior during the past 25 years. Used clinical case histories and research results to exemplify the impact of heightened drug usage as an argument for the upsurge in youth suicide. (Author/LLL)

  12. Relationship between financial impact and coverage of drugs in Australia.

    Science.gov (United States)

    Mauskopf, Josephine; Chirila, Costel; Masaquel, Catherine; Boye, Kristina S; Bowman, Lee; Birt, Julie; Grainger, David

    2013-01-01

    The aim of this study was to estimate the relationship between the financial impact of a new drug and the recommendation for reimbursement by the Australian Pharmaceutical Benefits Advisory Committee (PBAC). Data in the PBAC summary database were abstracted for decisions made between July 2005 and November 2009. Financial impact-the upper bound of the values presented in the PBAC summary database-was categorized as ≤A$0, >A$0 up to A$10 million, A$10 million up to A$30 million, and >A$30 million per year. Descriptive, logistic, survival, and recursive partitioning decision analyses were used to estimate the relationship between the financial impact of a new drug indication and the recommendation for reimbursement. Multivariable analyses controlled for other clinical and economic variables, including cost per quality-adjusted life-year gained. Financial impact was a significant predictor of the recommendation for reimbursement. In the logistic analysis, the odds ratios of reimbursement for drug submissions with financial impacts ≥A$10 million to ≥A$30 million or >A$0 to impact compared with those with a zero or negative financial impact. In Australia, financial impact on the drug budget is an important determinant of whether a new drug is recommended for reimbursement when cost-effectiveness estimates and other clinical and economic variables are controlled.

  13. Impact of pharmaceutical cocrystals: the effects on drug pharmacokinetics.

    Science.gov (United States)

    Shan, Ning; Perry, Miranda L; Weyna, David R; Zaworotko, Michael J

    2014-09-01

    Pharmaceutical cocrystallization has emerged in the past decade as a new strategy to enhance the clinical performance of orally administered drugs. A pharmaceutical cocrystal is a multi-component crystalline material in which the active pharmaceutical ingredient is in a stoichiometric ratio with a second compound that is generally a solid under ambient conditions. The resulting cocrystal exhibits different solid-state thermodynamics, leading to changes in physicochemical properties that offer the potential to significantly modify drug pharmacokinetics. The impact of cocrystallization upon drug pharmacokinetics has not yet been well delineated. Herein, we compile previously published data to address two salient questions: what effect does cocrystallization impart upon physicochemical properties of a drug substance and to what degree can those effects impact its pharmacokinetics. Cocrystals can impact various aspects of drug pharmacokinetics, including, but not limited to, drug absorption. The diversity of solid forms offered through cocrystallization can facilitate drastic changes in solubility and pharmacokinetics. Therefore, it is unsurprising that cocrystal screening is now a routine step in early-stage drug development. With the increasing recognition of pharmaceutical cocrystals from clinical, regulatory and legal perspectives, the systematic commercialization of cocrystal containing drug products is just a matter of time.

  14. Impact of nanotechnology on drug delivery.

    Science.gov (United States)

    Farokhzad, Omid C; Langer, Robert

    2009-01-27

    Nanotechnology is the engineering and manufacturing of materials at the atomic and molecular scale. In its strictest definition from the National Nanotechnology Initiative, nanotechnology refers to structures roughly in the 1-100 nm size regime in at least one dimension. Despite this size restriction, nanotechnology commonly refers to structures that are up to several hundred nanometers in size and that are developed by top-down or bottom-up engineering of individual components. Herein, we focus on the application of nanotechnology to drug delivery and highlight several areas of opportunity where current and emerging nanotechnologies could enable entirely novel classes of therapeutics.

  15. Effects on enantiomeric drug disposition and open-field behavior after chronic treatment with venlafaxine in the P-glycoprotein knockout mice model.

    Science.gov (United States)

    Karlsson, Louise; Hiemke, Christoph; Carlsson, Björn; Josefsson, Martin; Ahlner, Johan; Bengtsson, Finn; Schmitt, Ulrich; Kugelberg, Fredrik C

    2011-05-01

    P-glycoprotein (P-gp) plays an important role in the efflux of drugs from the brain back into the bloodstream and can influence the pharmacokinetics and pharmacodynamics of drug molecules. To our knowledge, no studies have reported pharmacodynamic effects of any antidepressant drug in the P-gp knockout mice model. The aim of this study was to investigate the enantiomeric venlafaxine and metabolite concentrations in serum and brain of abcb1ab⁻/⁻ mice compared to wild-type mice upon chronic dosing, and to assess the effect of venlafaxine treatment on open-field behavior. P-gp knockout and wild-type mice received two daily intraperitoneal injections of venlafaxine (10 mg/kg) over ten consecutive days. Locomotor and rearing activities were assessed on days 7 and 9. After 10 days, drug and metabolite concentrations in brain and serum were determined using an enantioselective LC/MS/MS method. The brain concentrations of venlafaxine and its three demethylated metabolites were two to four times higher in abcb1ab⁻/⁻ mice compared to abcb1ab+/+ mice. The behavioral results indicated an impact on exploration-related behaviors in the open-field as center activity was increased, and rears were decreased by venlafaxine treatment. Our results show that P-gp at the blood-brain barrier plays an important role in limiting brain entry of the enantiomers of venlafaxine and its metabolites after chronic dosing. Taken together, the present pharmacokinetic and pharmacodynamic findings offer the possibility that the expression of P-gp in patients may be a contributing factor for limited treatment response.

  16. The impact of drugs on male fertility: a review.

    Science.gov (United States)

    Semet, M; Paci, M; Saïas-Magnan, J; Metzler-Guillemain, C; Boissier, R; Lejeune, H; Perrin, J

    2017-07-01

    Beside cytotoxic drugs, other drugs can impact men's fertility through various mechanisms. Via the modification of the hypothalamic-pituitary-gonadal axis hormones or by non-hormonal mechanisms, drugs may directly and indirectly induce sexual dysfunction and spermatogenesis impairment and alteration of epididymal maturation. This systematic literature review summarizes existing data about the negative impact and associations of pharmacological treatments on male fertility (excluding cytotoxic drugs), with a view to making these data more readily available for medical staff. In most cases, these effects on spermatogenesis/sperm maturation/sexual function are reversible after the discontinuation of the drug. When a reprotoxic treatment cannot be stopped and/or when the impact on semen parameters/sperm DNA is potentially irreversible (Sulfasalazine Azathioprine, Mycophenolate mofetil and Methotrexate), the cryopreservation of spermatozoa before treatment must be proposed. Deleterious impacts on fertility of drugs with very good or good level of evidence (Testosterone, Sulfasalazine, Anabolic steroids, Cyproterone acetate, Opioids, Tramadol, GhRH analogues and Sartan) are developed. © 2017 American Society of Andrology and European Academy of Andrology.

  17. 77 FR 3259 - Notice of Intent To Prepare an Environmental Impact Statement for the Disposition of the...

    Science.gov (United States)

    2012-01-23

    ... analyze potential impacts on environmental, social, cultural, and economic resources. DOE has options...: land use, aesthetics, climate and air quality, geology and soils, water resources, biological resources...

  18. The impact of population ageing on future Danish drug expenditure

    DEFF Research Database (Denmark)

    Kildemoes, Helle Wallach

    expenditure among the elderly partly is due the high "costs of dying". Aims The aim of this study was to estimate the impact of the ageing Danish population on future total expenditures on out-of-hospital prescription drugs and to describe the association between age and drug expenditure among survivors......Background Population ageing is likely to place an increasing burden on future health care budgets. Several studies have demonstrated that the impact of ageing on future hospital expenditures will be overestimated when not accounting for proximity to death. This is because greater health care...... compared to that of decedents. Methods Taking expenditure during the last year of life and the changes in mortality rates into account, future drug expenditure was projected by multiplying estimated mean annual drug expenditure according to age, gender and survival status by the predicted future number...

  19. What is a Dispositive?

    DEFF Research Database (Denmark)

    Raffnsøe, Sverre; Gudmand-Høyer, Marius T.; Thaning, Morten Sørensen

    perspective – indeed it forms a lesser known intermediary between these. Foucault’s dispositional analysis articulates a history of connected social technologies that we have constructed to relate to each other. Expounding these points, the article distinguishes various dispositional prototypes and develops...... key ‘socio-ontological’ implications of the analy-sis. Reinstating the proper analytical status of the dispositive contributes to the reception of the important notion; the interpretation of Foucault’s entire oeuvre; and a resourceful approach to the study of contemporary societal problems....

  20. Impact of HIV prevention programs on drug users in Malaysia.

    Science.gov (United States)

    Kamarulzaman, Adeeba

    2009-11-01

    Faced with a rising HIV epidemic among injecting drug users, harm reduction policies and programs were introduced in Malaysia in 2005. The positive impact seen since the introduction of these programs comprise the inclusion of the health aspects of illicit drug use in the country's drug policies; better access to antiretroviral therapy for injecting drug users who are HIV infected; reduction in HIV-risk behavior; and greater social benefits, including increased employment. Despite these achievements, tension between law enforcement and public health persists, as harm reduction exists alongside an overall drug policy that is based on abstinence and zero tolerance. Unless there is harmonization of this policy, sustainability and scale-up of harm reduction programs will remain a challenge.

  1. The impact of cancer drug wastage on economic evaluations.

    Science.gov (United States)

    Truong, Judy; Cheung, Matthew C; Mai, Helen; Letargo, Jessa; Chambers, Alexandra; Sabharwal, Mona; Trudeau, Maureen E; Chan, Kelvin K W

    2017-09-15

    The objective of this study was to determine the impact of modeling cancer drug wastage in economic evaluations because wastage can result from single-dose vials on account of body surface area- or weight-based dosing. Intravenous chemotherapy drugs were identified from the pan-Canadian Oncology Drug Review (pCODR) program as of January 2015. Economic evaluations performed by drug manufacturers and pCODR were reviewed. Cost-effectiveness analyses and budget impact analyses were conducted for no-wastage and maximum-wastage scenarios (ie, the entire unused portion of the vial was discarded at each infusion). Sensitivity analyses were performed for a range of body surface areas and weights. Twelve drugs used for 17 indications were analyzed. Wastage was reported (ie, assumptions were explicit) in 71% of the models and was incorporated into 53% by manufacturers; this resulted in a mean incremental cost-effectiveness ratio increase of 6.1% (range, 1.3%-14.6%). pCODR reported and incorporated wastage for 59% of the models, and this resulted in a mean incremental cost-effectiveness ratio increase of 15.0% (range, 2.6%-48.2%). In the maximum-wastage scenario, there was a mean increase in the incremental cost-effectiveness ratio of 24.0% (range, 0.0%-97.2%), a mean increase in the 3-year total incremental budget costs of 26.0% (range, 0.0%-83.1%), and an increase in the 3-year total incremental drug budget cost of approximately CaD $102 million nationally. Changing the mean body surface area or body weight caused 45% of the drugs to have a change in the vial size and/or quantity, and this resulted in increased drug costs. Cancer drug wastage can increase drug costs but is not uniformly modeled in economic evaluations. Cancer 2017;123:3583-90. © 2017 American Cancer Society. © 2017 American Cancer Society.

  2. Impact of FDA-Approved Drugs on the Prostaglandin Transporter OATP2A1/SLCO2A1.

    Science.gov (United States)

    Kamo, Shunsuke; Nakanishi, Takeo; Aotani, Rika; Nakamura, Yoshinobu; Gose, Tomoka; Tamai, Ikumi

    2017-09-01

    To understand interaction of drugs with the prostaglandin transporter OATP2A1/SLCO2A1 that regulates disposition of prostaglandins, we explored the impact of 636 drugs in an FDA-approved drug library on 6-carboxyfluorescein (6-CF) uptake by OATP2A1-expressing HEK293 cells (HEK/2A1). Fifty-one and 10 drugs were found to inhibit and enhance 6-CF uptake by more than 50%, respectively. Effect of the 51 drugs on 6-CF uptake was positively correlated with that on PGE 2 uptake (r = 0.64, p < 0.001). Among those, 5 drugs not structurally related to prostaglandins, suramin, pranlukast, zafirlukast, olmesartan medoxomil, and losartan potassium, exhibited more than 90% PGE 2 uptake inhibition. Inhibitory affinity of suramin to OATP2A1 was the highest (IC 50,2A1 of 0.17 μM), and its IC 50 values to MRP4-mediated PGE 2 transport (IC 50,MRP4 ) and PGE 2 synthesis in human U-937 cells treated with phorbol 12-myristate 13-acetate (IC 50,Syn ) were 73.6 and 336.7 times higher than IC 50,2A1 , respectively. Moreover, structure-activity relationship study in 29 nonsteroidal anti-inflammatory drugs contained in the library displayed inhibitory activities of anthranilic acid derivatives, but enhancing effects of propionic acid derivatives. These results demonstrate that suramin is a potent selective inhibitor of OATP2A1, providing a comprehensive information about drugs in clinical use that interact with OATP2A1. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  3. Cell culture media impact on drug product solution stability.

    Science.gov (United States)

    Purdie, Jennifer L; Kowle, Ronald L; Langland, Amie L; Patel, Chetan N; Ouyang, Anli; Olson, Donald J

    2016-07-08

    To enable subcutaneous administration of monoclonal antibodies, drug product solutions are often needed at high concentrations. A significant risk associated with high drug product concentrations is an increase in aggregate level over the shelf-life dating period. While much work has been done to understand the impact of drug product formulation on aggregation, there is limited understanding of the link between cell culture process conditions and soluble aggregate growth in drug product. During cell culture process development, soluble aggregates are often measured at harvest using cell-free material purified by Protein A chromatography. In the work reported here, cell culture media components were evaluated with respect to their impact on aggregate levels in high concentration solution drug product during accelerated stability studies. Two components, cysteine and ferric ammonium citrate, were found to impact aggregate growth rates in our current media (version 1) leading to the development of new chemically defined media and concentrated feed formulations. The new version of media and associated concentrated feeds (version 2) were evaluated across four cell lines producing recombinant IgG4 monoclonal antibodies and a bispecific antibody. In all four cell lines, the version 2 media reduced aggregate growth over the course of a 12 week accelerated stability study compared with the version 1 media, although the degree to which aggregate growth decreased was cell line dependent. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:998-1008, 2016. © 2016 American Institute of Chemical Engineers.

  4. Employment Trajectories: Exploring Gender Differences and Impacts of Drug Use

    Science.gov (United States)

    Huang, David Y. C.; Evans, Elizabeth; Hara, Motoaki; Weiss, Robert E.; Hser, Yih-Ing

    2011-01-01

    This study investigated the impact of drug use on employment over 20 years among men and women, utilizing data on 7661 participants in the National Longitudinal Survey of Youth. Growth mixture modeling was applied, and five distinct employment trajectory groups were identified for both men and women. The identified patterns were largely similar…

  5. Nano-formulations of drugs: Recent developments, impact and challenges.

    Science.gov (United States)

    Jeevanandam, Jaison; Chan, Yen San; Danquah, Michael K

    2016-01-01

    Nano-formulations of medicinal drugs have attracted the interest of many researchers for drug delivery applications. These nano-formulations enhance the properties of conventional drugs and are specific to the targeted delivery site. Dendrimers, polymeric nanoparticles, liposomes, nano-emulsions and micelles are some of the nano-formulations that are gaining prominence in pharmaceutical industry for enhanced drug formulation. Wide varieties of synthesis methods are available for the preparation of nano-formulations to deliver drugs in biological system. The choice of synthesis methods depend on the size and shape of particulate formulation, biochemical properties of drug, and the targeted site. This article discusses recent developments in nano-formulation and the progressive impact on pharmaceutical research and industries. Additionally, process challenges relating to consistent generation of nano-formulations for drug delivery are discussed. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  6. Drugs and development: the global impact of drug use and trafficking on social and economic development.

    Science.gov (United States)

    Singer, Merrill

    2008-12-01

    Locating development efforts within the context of globalism and global drug capitalism, this article examines the significant health and social impact both legal and illegal drugs have on international development efforts. The paper takes on an issue that is generally overlooked in the development debate and is not much addressed in the current international development standard, the Millennium Development Goals, and yet is one that places serious constraints on the ability of underdeveloped nations to achieve improvement. The relationship between psychotropic or "mind/mood altering" drugs and sustainable development is rooted in the contribution that the legal and illegal drug trade makes to a set of barriers to development, including: (1) interpersonal crime and community violence; (2) the corruption of public servants and the disintegration of social institutions; (3) the emergence of new or enhanced health problems; (4) the lowering of worker productivity; (5) the ensnarement of youth in drug distribution and away from productive education or employment; (6) the skewing of economies to drug production and money laundering. The paper emphasizes the need for new approaches for diminishing the burden placed by drugs on development.

  7. Advertisements impact the physiological efficacy of a branded drug

    Science.gov (United States)

    Kamenica, Emir; Naclerio, Robert; Malani, Anup

    2013-01-01

    We conducted randomized clinical trials to examine the impact of direct-to-consumer advertisements on the efficacy of a branded drug. We compared the objectively measured, physiological effect of Claritin (Merck & Co.), a leading antihistamine medication, across subjects randomized to watch a movie spliced with advertisements for Claritin or advertisements for Zyrtec (McNeil), a competitor antihistamine. Among subjects who test negative for common allergies, exposure to Claritin advertisements rather than Zyrtec advertisements increases the efficacy of Claritin. We conclude that branded drugs can interact with exposure to television advertisements. PMID:23878212

  8. History of the US weapons-usable plutonium disposition program leading to DOE's record of decision

    International Nuclear Information System (INIS)

    Spellman, D.J.; Thomas, J.F.; Bugos, R.G.

    1997-04-01

    This report highlights important events and studies concerning surplus weapons-usable plutonium disposition in the United States. Included are major events that led to the creation of the U.S. Department of Energy (DOE) Office of Fissile Materials Disposition in 1994 and to that DOE office issuing the January 1997 Record of Decision for the Storage and Disposition of Weapons-Useable Fissile Materials Final Programmatic Environmental Impact Statement. Emphasis has been given to reactor-based plutonium disposition alternatives

  9. The Impact of Information on Doctors’ Attitudes Toward Generic Drugs

    Directory of Open Access Journals (Sweden)

    Aggeliki V. Tsaprantzi MD

    2016-03-01

    Full Text Available The objective of this study is to assess the impact of information on doctors’ attitudes and perceptions toward generics. A cross-sectional survey based on a specially designed 21-item questionnaire was conducted. The survey involved doctors of different specialties working in a public hospital in Greece. The analysis includes descriptive and inferential statistics, reliability and validity tests, as well as structural equation modeling to evaluate the causal model. Statistical analysis was accomplished by using SPSS 20 and Amos 20. A total of 134 questionnaires out of 162 were received, providing a response rate of 82.71%. A number of significant associations were found between information and perceptions about generic medicines with demographic characteristics. It seems that the provision of quality information on generic drugs influences doctors’ attitudes and prescription practices toward generic drugs. This is not a static process but a rather dynamic issue involving information provision policies for strengthening the proper doctors’ attitudes toward generic drugs.

  10. Comparison of provincial prescription drug plans and the impact on patients' annual drug expenditures.

    Science.gov (United States)

    Demers, Virginie; Melo, Magda; Jackevicius, Cynthia; Cox, Jafna; Kalavrouziotis, Dimitri; Rinfret, Stéphane; Humphries, Karin H; Johansen, Helen; Tu, Jack V; Pilote, Louise

    2008-02-12

    Reimbursement for outpatient prescription drugs is not mandated by the Canada Health Act or any other federal legislation. Provincial governments independently establish reimbursement plans. We sought to describe variations in publicly funded provincial drug plans across Canada and to examine the impact of this variation on patients' annual expenditures. We collected information, accurate to December 2006, about publicly funded prescription drug plans from all 10 Canadian provinces. Using clinical scenarios, we calculated the impact of provincial cost-sharing strategies on individual annual drug expenditures for 3 categories of patients with different levels of income and 2 levels of annual prescription burden ($260 and $1000). We found that eligibility criteria and cost-sharing details of the publicly funded prescription drug plans differed markedly across Canada, as did the personal financial burden due to prescription drug costs. Seniors pay 35% or less of their prescription costs in 2 provinces, but elsewhere they may pay as much as 100%. With few exceptions, nonseniors pay more than 35% of their prescription costs in every province. Most social assistance recipients pay 35% or less of their prescription costs in 5 provinces and pay no costs in the other 5. In an example of a patient with congestive heart failure, his out-of-pocket costs for a prescription burden of $1283 varied between $74 and $1332 across the provinces. Considerable interprovincial variation in publicly funded prescription drug plans results in substantial variation in annual expenditures by Canadians with identical prescription burdens. A revised pharmaceutical strategy might reduce these major inequities.

  11. Impact of Drug Metabolism/Pharmacokinetics and Their Relevance upon Taxus-based Drug Development.

    Science.gov (United States)

    Hao, Da-Cheng; Ge, Guang-Bo; Wang, Ping; Yang, Ling

    2018-05-22

    Drug metabolism and pharmacokinetic (DMPK) studies of Taxus natural products, their semi-synthetic derivatives and analogs are indispensable in the optimization of lead compounds and clinical therapy. These studies can lead to development of new drug entities with improved absorption, distribution, metabolism, excretion and toxicity (ADME/T) profiles. To date, there have been no comprehensive reviews of the DMPK features of Taxus derived medicinal compounds.Natural and semi-synthetic taxanes may cause and could be affected by drug-drug interaction (DDI). Hence ADME/T studies of various taxane-containing formulations are important; to date these studies indicate that the role of cytochrome p450s and drug transporters is more prominent than phase II drug metabolizing enzymes. Mechanisms of taxane DMPK mediated by nuclear receptors, microRNAs, and single nucleotide polymorphisms are being revealed. Herein we review the latest knowledge on these topics, as well as the gaps in knowledge of the DMPK issues of Taxus compounds. DDIs significantly impact the PK/pharmacodynamics performance of taxanes and co-administered chemicals, which may inspire researchers to develop novel formula. While the ADME/T profiles of some taxanes are well defined, DMPK studies should be extended to more Taxus compounds, species, and Taxus -involved formulations, which would be streamlined by versatile omics platforms and computational analyses. Further biopharmaceutical investigations will be beneficial tothe translation of bench findings to the clinical applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Excess plutonium disposition: The deep borehole option

    International Nuclear Information System (INIS)

    Ferguson, K.L.

    1994-01-01

    This report reviews the current status of technologies required for the disposition of plutonium in Very Deep Holes (VDH). It is in response to a recent National Academy of Sciences (NAS) report which addressed the management of excess weapons plutonium and recommended three approaches to the ultimate disposition of excess plutonium: (1) fabrication and use as a fuel in existing or modified reactors in a once-through cycle, (2) vitrification with high-level radioactive waste for repository disposition, (3) burial in deep boreholes. As indicated in the NAS report, substantial effort would be required to address the broad range of issues related to deep bore-hole emplacement. Subjects reviewed in this report include geology and hydrology, design and engineering, safety and licensing, policy decisions that can impact the viability of the concept, and applicable international programs. Key technical areas that would require attention should decisions be made to further develop the borehole emplacement option are identified

  13. The impact of genetics on future drug discovery in schizophrenia.

    Science.gov (United States)

    Matsumoto, Mitsuyuki; Walton, Noah M; Yamada, Hiroshi; Kondo, Yuji; Marek, Gerard J; Tajinda, Katsunori

    2017-07-01

    Failures of investigational new drugs (INDs) for schizophrenia have left huge unmet medical needs for patients. Given the recent lackluster results, it is imperative that new drug discovery approaches (and resultant drug candidates) target pathophysiological alterations that are shared in specific, stratified patient populations that are selected based on pre-identified biological signatures. One path to implementing this paradigm is achievable by leveraging recent advances in genetic information and technologies. Genome-wide exome sequencing and meta-analysis of single nucleotide polymorphism (SNP)-based association studies have already revealed rare deleterious variants and SNPs in patient populations. Areas covered: Herein, the authors review the impact that genetics have on the future of schizophrenia drug discovery. The high polygenicity of schizophrenia strongly indicates that this disease is biologically heterogeneous so the identification of unique subgroups (by patient stratification) is becoming increasingly necessary for future investigational new drugs. Expert opinion: The authors propose a pathophysiology-based stratification of genetically-defined subgroups that share deficits in particular biological pathways. Existing tools, including lower-cost genomic sequencing and advanced gene-editing technology render this strategy ever more feasible. Genetically complex psychiatric disorders such as schizophrenia may also benefit from synergistic research with simpler monogenic disorders that share perturbations in similar biological pathways.

  14. Preferred drug lists: Potential impact on healthcare economics

    Directory of Open Access Journals (Sweden)

    Kimberly Ovsag

    2008-04-01

    Full Text Available Kimberly Ovsag, Sabrina Hydery, Shaker A MousaPharmaceutical Research Institute at Albany College of Pharmacy, Albany, New York, USAObjectives: To analyze the implementation of Medicaid preferred drug lists (PDLs in a number of states and determine its impact on quality of care and cost relative to other segments of healthcare.Methods: We reviewed research and case studies found by searching library databases, primarily MEDLINE and EBSCOHost, and searching pertinent journals. Keywords initially included “drug lists,” “prior authorization,” “prior approval,” and “Medicaid.” We added terms such as “influence use of other healthcare services,” “quality of care,” and “overall economic impact.” We mainly used primary sources.Results: Based on our literature review, we determined that there are a number of issues regarding Medicaid PDLs that need to be addressed. Some issues include: (a the potential for PDLs to influence the utilization of other healthcare services, (b criteria used by Medicaid for determining acceptance of drugs onto a PDL, (c the effect of PDL implementation on compliance to new regimens, (d the potential effects of restricting medication availability on quality of care, (e administrative costs associated with PDLs, and (f satisfaction rates among patients and medical providers. This review highlighted expected short-term cost savings with limited degree of compromised quality of PDL implementation, but raised the concern about the potential long-term decline in quality of care and overall economic impact.Conclusions: The number of concerns raised indicates that further studies are warranted regarding both short-term cost benefits as well as potential long-term effects of Medicaid PDL implementation. Objective analysis of these effects is necessary to ensure cost-effectiveness and quality of care.Keywords: preferred drug lists, medicaid, healthcare costs, managed care

  15. The impact of ageing and changing utilization patterns on future cardiovascular drug expenditure: a pharmacoepidemiological projection approach

    DEFF Research Database (Denmark)

    Kildemoes, Helle Wallach; Andersen, Morten; Støvring, Henrik

    2010-01-01

    To develop a method for projecting the impact of ageing and changing drug utilization patterns on future drug expenditure.......To develop a method for projecting the impact of ageing and changing drug utilization patterns on future drug expenditure....

  16. Character, attitude and disposition

    OpenAIRE

    Webber, Jonathan

    2015-01-01

    Recent debate over the empirical psychological presuppositions of virtue ethics has focused on reactive behavioural dispositions. But there are many character traits that cannot be understood properly in this way. Such traits are well described by attitude psychology. Moreover, the findings of attitude psychology support virtue ethics in three ways. First, they confirm the role of habituation in the development of character. Further, they show virtue ethics to be compatible with the situation...

  17. The Alterations in the Expression and Function of P-Glycoprotein in Vitamin A-Deficient Rats as well as the Effect of Drug Disposition in Vivo

    Directory of Open Access Journals (Sweden)

    Yubang Wang

    2015-12-01

    Full Text Available This study was aimed to investigate whether vitamin A deficiency could alter P-GP expression and function in tissues of rats and whether such effects affected the drug distribution in vivo of vitamin A-deficient rats. We induced vitamin A-deficient rats by giving them a vitamin A-free diet for 12 weeks. Then, Abcb1/P-GP expression was evaluated by qRT-PCR and Western blot. qRT-PCR analysis revealed that Abcb1a mRNA levels were increased in hippocampus and liver. In kidney, it only showed an upward trend. Abcb1b mRNA levels were increased in hippocampus, but decreased in cerebral cortex, liver and kidney. Western blot results were in good accordance with the alterations of Abcb1b mRNA levels. P-GP function was investigated through tissue distribution and body fluid excretion of rhodamine 123 (Rho123, and the results proclaimed that P-GP activities were also in good accordance with P-GP expression in cerebral cortex, liver and kidney. The change of drug distribution was also investigated through the tissue distribution of vincristine, and the results showed a significantly upward trend in all indicated tissues of vitamin A-deficient rats. In conclusion, vitamin A deficiency may alter Abcb1/P-GP expression and function in rat tissues, and the alterations may increase drug activity/toxicity through the increase of tissue accumulation.

  18. Drug Brand Response and Its Impact on Compliance and Efficacy in Depression Patients

    OpenAIRE

    Li, Mingming; Cai, Jian; Zhang, Ping; Fei, Chunhua; Xu, Feng

    2017-01-01

    Introduction: Patient's response to drug brand is a comprehensive physiological and psychological effect which might impact the compliance and efficacy of drugs. Whether the therapeutic outcome altered on patients with brand response after they experience drug switch is not clear. Methods: 459 outpatients with mild-to-moderate depression were divided into the imported (joint venture) drug group and the domestic drug group according to their current drug application. Two groups of patients ...

  19. In vitro disposition profiling of heterocyclic compounds.

    Science.gov (United States)

    Keemink, Janneke; Wuyts, Benjamin; Nicolaï, Johan; Jonghe, Steven De; Stella, Alessandro; Herdewijn, Piet; Augustijns, Patrick; Annaert, Pieter

    2015-08-01

    Compound libraries that are screened for biological activity commonly contain heterocycles. Besides potency, drug-like properties need to be evaluated to ensure in vivo efficacy of test compounds. In this context, we determined hepatic and intestinal disposition profiles for 17 heterocyclic compounds. All studied compounds showed rapid uptake in suspended rat hepatocytes, whereas metabolism was poor and the rate-limiting step in hepatic elimination. In vitro assays demonstrated a relatively low solubility and high intestinal permeability. Based on these in vitro data, heterocycles were categorized in the biopharmaceutics classification system (BCS) and the biopharmaceutics drug disposition classification system (BDDCS) to predict disposition characteristics before clinical data are available. Our findings emphasized the importance to use hepatocytes in addition to microsomes to study metabolism, since the latter lack non-microsomal enzymes and cellular context. Moreover, intracellular exposure should be considered to gain insight in the relevant fraction of the compound available at the enzymatic site. Finally, the study reveals discrepancies associated with the classification of heterocycles in BCS versus BDDCS. These probably originate from the binary character of both systems. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. The impact of drug policy liberalisation on willingness to seek help for problem drug use: A comparison of 20 countries.

    Science.gov (United States)

    Benfer, Isabella; Zahnow, Renee; Barratt, Monica J; Maier, Larissa; Winstock, Adam; Ferris, Jason

    2018-06-01

    While the impact of changing drug policies on rates of drug use has been investigated, research into how help-seeking behaviour changes as drug policies become more public-health focused is limited. This paper investigates reported changes in confidence to utilise drug services following hypothetical changes in national drug policy among a sample of individuals who report recent illicit drug use. We predict that liberalising national drug policy will increase the propensity for people who take illegal drugs to utilise health services. The data were drawn from a sample of self-reported responses to the 2014 Global Drug Survey. Respondents were asked if they would be more confident seeking help if each of the following policy changes were made in their country; a) drugs were legalised; b) penalties for possession of small amounts of drugs were reduced to a fine only; c) drugs were legally available through governments outlets. Multiple correspondence analysis and multinomial logistic regression with post-estimation linear hypothesis testing were conducted. Individuals residing in countries with relatively liberal drug policy regimes report their help-seeking behaviour is unlikely to change given the hypothetical policy amendments. Individuals from countries with prohibition-based drug policies reported a far greater propensity for changing their help-seeking behaviour in the event of hypothetical policy amendments, citing reduced fear of criminal sanctions as the major reason. Age and sex differences were also found. The current study demonstrates the capacity for national drug policy reform to influence drug use risk by facilitating or impeding health service engagement among individuals who use illicit substances. We suggest national drug policy requires careful consideration of both prevention goals and the needs of individuals already engaged in illicit substance use; more liberal drug policies may actually encourage the adoption of harm reduction strategies such

  1. Pharmacokinetics of Dietary Cancer Chemopreventive Compound Dibenzoylmethane in the Rats and Impacts of Nanoemulsion and Genetic knockout of Nrf2 on its Disposition

    OpenAIRE

    Lin, Wen; Hong, Jin-Liern; Shen, Guoxiang; Wu, Rachel T.; Wu, Yuwen; Huang, Mou-Tuan; Newmark, Harold L.; Huang, Qingrong; Khor, Tin Oo; Heimbach, Tycho; Kong, Ah-Ng

    2010-01-01

    The pharmacokinetic disposition of a dietary cancer chemopreventive compound dibenzoylmethane (DBM) was studied in male Sprague-Dawley rats after intravenous (i.v.) and oral (p.o.) administrations. Following a single i.v. bolus dose, the mean plasma clearance (CL) of DBM was low as compared to the hepatic blood flow. DBM displayed a high volume of distribution (Vss). The elimination terminal t1/2 was long. The mean CL, Vss and AUC0-∞/dose were similar between the i.v. 10 and 10 mg/kg doses. A...

  2. Critical thinking dispositions among newly graduated nurses

    Science.gov (United States)

    Wangensteen, Sigrid; Johansson, Inger S; Björkström, Monica E; Nordström, Gun

    2010-01-01

    wangensteen s., johansson i.s., björkström m.e. & nordström g. (2010) Critical thinking dispositions among newly graduated nurses. Journal of Advanced Nursing66(10), 2170–2181. Aim The aim of the study was to describe critical thinking dispositions among newly graduated nurses in Norway, and to study whether background data had any impact on critical thinking dispositions. Background Competence in critical thinking is one of the expectations of nursing education. Critical thinkers are described as well-informed, inquisitive, open-minded and orderly in complex matters. Critical thinking competence has thus been designated as an outcome for judging the quality of nursing education programmes and for the development of clinical judgement. The ability to think critically is also described as reducing the research–practice gap and fostering evidence-based nursing. Methods A cross-sectional descriptive study was performed. The data were collected between October 2006 and April 2007 using the California Critical Thinking Disposition Inventory. The response rate was 33% (n= 618). Pearson’s chi-square tests were used to analyse the data. Results Nearly 80% of the respondents reported a positive disposition towards critical thinking. The highest mean score was on the Inquisitiveness subscale and the lowest on the Truth-seeking subscale. A statistically significant higher proportion of nurses with high critical thinking scores were found among those older than 30 years, those with university education prior to nursing education, and those working in community health care. Conclusion Nurse leaders and nurse teachers should encourage and nurture critical thinking among newly graduated nurses and nursing students. The low Truth-seeking scores found may be a result of traditional teaching strategies in nursing education and might indicate a need for more student-active learning models. PMID:20384637

  3. Impact of Active Drug Use on Antiretroviral Therapy Adherence and Viral Suppression in HIV-infected Drug Users

    OpenAIRE

    Arnsten, Julia H; Demas, Penelope A; Grant, Richard W; Gourevitch, Marc N; Farzadegan, Homayoon; Howard, Andrea A; Schoenbaum, Ellie E

    2002-01-01

    Despite a burgeoning literature on adherence to HIV therapies, few studies have examined the impact of ongoing drug use on adherence and viral suppression, and none of these have utilized electronic monitors to quantify adherence among drug users. We used 262 electronic monitors to measure adherence with all antiretrovirals in 85 HIV-infected current and former drug users, and found that active cocaine use, female gender, not receiving Social Security benefits, not being married, screening po...

  4. Impact of drug resistance on the tuberculosis treatment outcome

    Directory of Open Access Journals (Sweden)

    E. Lesnic

    2017-03-01

    Full Text Available Background. The standard treatment of a new case of multidrug-resistant tuberculosis (MDR-TB according to WHO recommendations in the Republic of Moldova is performed since 2005 showing a low treatment succes. Actually the treatment success rate increased due to excluding of MDR-TB patients from the general cohort. The major rate of patients with low outcome is represented by the failed and lost to follow-up cases. The purpose of the study was to assess the impact of multidrug-resiatnce and MDR-TB on the tuberculosis treatment outcome. Materials and methods. A retrospective selective, descriptive study targeting social, demographic, economic and epidemiological peculiarities, case-management, diagnostic radiological aspects and microbiological characteristics of 187 patients with pulmonary tuberculosis registered during 2013–2015 distributed in two groups: 1st group (61 patients with established multidrug-resistant strains using conventional cultural methods and the 2nd group (126 patients with MDR-TB. Results. Multidrug-resistance was established more frequently in new cases and MDR-TB in two thirds of retreated patients. No difference was identified in gender and age distribution, social, economical, educational characteristics; case-management assessment identified a similar proportion of patients revealed by general practitioners and specialists, with low rate of screened high risk groups. All patients from the multidrug-resistant group began the standard treatment for drug-responsiveness tuberculosis before drug susceptibility testing and one third of MDR-TB group was treated from the onset with the DOTS-Plus regimen. Highest success rate was identified in the new-case subgroups of both groups and higher rate of died patients was determined in the retreated subgroups. Such a low rate of patients aggrevates the resistance. Conclusions. Early diagnosis, drug responsiveness testing and raising awareness among about treatment compliance will

  5. The Impact of Residential and Nonresidential Drug Treatment on Recidivism among Drug-Involved Probationers: A Survival Analysis

    Science.gov (United States)

    Krebs, Christopher P.; Strom, Kevin J.; Koetse, Willem H.; Lattimore, Pamela K.

    2009-01-01

    A variety of approaches for addressing drug use and drug-related crime among the nearly 5 million offenders on community supervision in the United States has been tried and evaluated, but questions remain about which policies or programs are most effective. The authors use a large data set to assess the impact of residential and nonresidential…

  6. The law on the streets: Evaluating the impact of Mexico's drug decriminalization reform on drug possession arrests in Tijuana, Mexico.

    Science.gov (United States)

    Arredondo, J; Gaines, T; Manian, S; Vilalta, C; Bañuelos, A; Strathdee, S A; Beletsky, L

    2018-04-01

    In 2009, Mexican Federal Government enacted "narcomenudeo" reforms decriminalizing possession of small amounts of drugs, delegating prosecution of retail drug sales to the state courts, and mandating treatment diversion for habitual drug users. There has been insufficient effort to formally assess the decriminalization policy's population-level impact, despite mounting interest in analagous reforms across the globe. Using a dataset of municipal police incident reports, we examined patterns of drug possession, and violent and non-violent crime arrests between January 2009 and December 2014. A hierarchical panel data analysis with random effects was conducted to assess the impact of narcomenudeo's drug decriminalization provision. The reforms had no significant impact on the number of drug possession or violent crime arrests, after controlling for other variables (e.g. time trends, electoral cycles, and precinct-level socioeconomic factors). Time periods directly preceding local elections were observed to be statistically associated with elevated arrest volume. Analysis of police statistics parallel prior findings that Mexico's reform decriminalizing small amounts of drugs does not appear to have significantly shifted drug law enforcement in Tijuana. More research is required to fully understand the policy transformation process for drug decriminalization and other structural interventions in Mexico and similar regional and international efforts. Observed relationship between policing and political cycles echo associations in other settings whereby law-and-order activities increase during mayoral electoral campaigns. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Entecavir Interacts with Influx Transporters hOAT1, hCNT2, hCNT3, but Not with hOCT2: The Potential for Renal Transporter-Mediated Cytotoxicity and Drug-Drug Interactions

    Czech Academy of Sciences Publication Activity Database

    Mandíková, J.; Volková, M.; Pávek, P.; Navrátilová, L.; Hyršová, L.; Janeba, Zlatko; Pavlík, J.; Bárta, P.; Trejtnar, F.

    2016-01-01

    Roč. 6, Jan 5 (2016), č. článku 304. ISSN 1663-9812 Institutional support: RVO:61388963 Keywords : antivirals * nephrotoxicity * renal disposition * drug-drug interactions Subject RIV: CC - Organic Chemistry Impact factor: 4.400, year: 2016 http://journal.frontiersin.org/article/10.3389/fphar.2015.00304/full

  8. DISPOSITION PATHS FOR ROCKY FLATS GLOVEBOXES: EVALUATING OPTIONS

    International Nuclear Information System (INIS)

    Lobdell, D.; Geimer, R.; Larsen, P.; Loveland, K.

    2003-01-01

    The Kaiser-Hill Company, LLC has the responsibility for closure activities at the Rocky Flats Environmental Technology Site (RFETS). One of the challenges faced for closure is the disposition of radiologically contaminated gloveboxes. Evaluation of the disposition options for gloveboxes included a detailed analysis of available treatment capabilities, disposal facilities, and lifecycle costs. The Kaiser-Hill Company, LLC followed several processes in determining how the gloveboxes would be managed for disposition. Currently, multiple disposition paths have been chosen to accommodate the needs of the varying styles and conditions of the gloveboxes, meet the needs of the decommissioning team, and to best manage lifecycle costs. Several challenges associated with developing a disposition path that addresses both the radiological and RCRA concerns as well as offering the most cost-effective solution were encountered. These challenges included meeting the radiological waste acceptance criteria of available disposal facilities, making a RCRA determination, evaluating treatment options and costs, addressing void requirements associated with disposal, and identifying packaging and transportation options. The varying disposal facility requirements affected disposition choices. Facility conditions that impacted decisions included radiological and chemical waste acceptance criteria, physical requirements, and measurement for payment options. The facility requirements also impacted onsite activities including management strategies, decontamination activities, and life-cycle cost

  9. Update to the Fissile Materials Disposition program SST/SGT transportation estimation

    International Nuclear Information System (INIS)

    John Didlake

    1999-01-01

    This report is an update to ''Fissile Materials Disposition Program SST/SGT Transportation Estimation,'' SAND98-8244, June 1998. The Department of Energy Office of Fissile Materials Disposition requested this update as a basis for providing the public with an updated estimation of the number of transportation loads, load miles, and costs associated with the preferred alternative in the Surplus Plutonium Disposition Final Environmental Impact Statement (EIS)

  10. The Development Impact of the Illegality of Drug Trade

    OpenAIRE

    Keefer, Philip; Loayza, Norman V.; Soares, Rodrigo R.

    2008-01-01

    This paper reviews the unintended consequences of the war on drugs, particularly for developing countries, and weighs them against the evidence regarding the efficacy of prohibition to curb drug use and trade. It reviews the available evidence and presents new results that indicate that prohibition has limited effects on drug prevalence and prices, most likely indicating a combination of i...

  11. Excluding Orphan Drugs from the 340B Drug Discount Program: the Impact on 18 Critical Access Hospitals

    Directory of Open Access Journals (Sweden)

    Madeline Carpinelli Wallack

    2012-01-01

    Full Text Available Purpose: The 340B Drug Pricing Program is a federal program designed to reduce the amount that safety net providers spend on outpatient drugs. The Patient Protection and Affordable Health Care Act of 2010 extended eligibility for 340B to critical access hospitals (CAHs for all drugs except those designated as “orphan.” Because this policy is unprecedented, this study quantifies the gross financial impact that this exemption has on a group of CAHs. Methods: Drug spending for 2010 from 18 CAHs in Minnesota and Wisconsin are reviewed to identify the prevalence of orphan drug purchases and to calculate the price differentials between the 340B price and the hospitals’ current cost. Results: The 18 CAHs’ purchases of orphan drugs comprise an average of 44% of the total annual drug budgets, but only 5% of units purchased, thus representing a very high proportion of their expenditures. In the aggregate, the 18 hospitals would have saved $3.1 million ($171,000 average per hospital had purchases of drugs with orphan designations been made at the 340B price. Because CAH claims for Medicare are reimbursed on a cost-basis, the Federal government is losing an opportunity for savings. Conclusion: The high prevalence of orphan drug use and considerable potential for cost reduction through the 340B program demonstrate the loss of benefit to the hospitals, Federal government and the states.

  12. The Impact of College Drug Policy on Students' Drug Usage

    Science.gov (United States)

    Sawyer, Holly N.

    2012-01-01

    Illicit drug usage at Historically Black Colleges and Universities (HBCU) is a topic of limited research. The research questions that guided this study were (a) What is the relationship between college policy on illicit drugs and students' frequency of drug usage after controlling for college location (urban or rural) and students' age,…

  13. Impact of Dendrimers on Solubility of Hydrophobic Drug Molecules

    Directory of Open Access Journals (Sweden)

    Sonam Choudhary

    2017-05-01

    Full Text Available Adequate aqueous solubility has been one of the desired properties while selecting drug molecules and other bio-actives for product development. Often solubility of a drug determines its pharmaceutical and therapeutic performance. Majority of newly synthesized drug molecules fail or are rejected during the early phases of drug discovery and development due to their limited solubility. Sufficient permeability, aqueous solubility and physicochemical stability of the drug are important for achieving adequate bioavailability and therapeutic outcome. A number of different approaches including co-solvency, micellar solubilization, micronization, pH adjustment, chemical modification, and solid dispersion have been explored toward improving the solubility of various poorly aqueous-soluble drugs. Dendrimers, a new class of polymers, possess great potential for drug solubility improvement, by virtue of their unique properties. These hyper-branched, mono-dispersed molecules have the distinct ability to bind the drug molecules on periphery as well as to encapsulate these molecules within the dendritic structure. There are numerous reported studies which have successfully used dendrimers to enhance the solubilization of poorly soluble drugs. These promising outcomes have encouraged the researchers to design, synthesize, and evaluate various dendritic polymers for their use in drug delivery and product development. This review will discuss the aspects and role of dendrimers in the solubility enhancement of poorly soluble drugs. The review will also highlight the important and relevant properties of dendrimers which contribute toward drug solubilization. Finally, hydrophobic drugs which have been explored for dendrimer assisted solubilization, and the current marketing status of dendrimers will be discussed.

  14. Critical thinking dispositions among newly graduated nurses.

    Science.gov (United States)

    Wangensteen, Sigrid; Johansson, Inger S; Björkström, Monica E; Nordström, Gun

    2010-10-01

    The aim of the study was to describe critical thinking dispositions among newly graduated nurses in Norway, and to study whether background data had any impact on critical thinking dispositions. Competence in critical thinking is one of the expectations of nursing education. Critical thinkers are described as well-informed, inquisitive, open-minded and orderly in complex matters. Critical thinking competence has thus been designated as an outcome for judging the quality of nursing education programmes and for the development of clinical judgement. The ability to think critically is also described as reducing the research-practice gap and fostering evidence-based nursing. A cross-sectional descriptive study was performed. The data were collected between October 2006 and April 2007 using the California Critical Thinking Disposition Inventory. The response rate was 33% (n = 618). Pearson's chi-square tests were used to analyse the data. Nearly 80% of the respondents reported a positive disposition towards critical thinking. The highest mean score was on the Inquisitiveness subscale and the lowest on the Truth-seeking subscale. A statistically significant higher proportion of nurses with high critical thinking scores were found among those older than 30 years, those with university education prior to nursing education, and those working in community health care. Nurse leaders and nurse teachers should encourage and nurture critical thinking among newly graduated nurses and nursing students. The low Truth-seeking scores found may be a result of traditional teaching strategies in nursing education and might indicate a need for more student-active learning models. © 2010 The Authors. Journal of Advanced Nursing © 2010 Blackwell Publishing Ltd.

  15. The impact of the written request process on drug development in childhood cancer.

    Science.gov (United States)

    Snyder, Kristen M; Reaman, Gregory; Avant, Debbie; Pazdur, Richard

    2013-04-01

    The Food and Drug Administration (FDA) Modernization Act, enacted in 1997, created a pediatric exclusivity incentive allowing sponsors to qualify for an additional 6 months of marketing exclusivity after satisfying the requirements outlined in the Written Request (WR). This review evaluates the impact of the WR mechanism on the development of oncology drugs in children. A search of the FDA document archiving, reporting, and regulatory tracking system was performed for January 1, 2000 to December 31, 2010. Drugs were identified and pediatric-specific labeling information was obtained from Drugs@fda.gov and FDA Pediatric Labeling Changes Table. Fifty WRs have been issued for oncology drugs. Pediatric studies have been submitted for 14 drugs. Thirteen received pediatric exclusivity. As of December 31, 2010, labeling changes have been made for 11 drugs. Three drugs were approved for pediatric use. WRs have provided a mechanism to promote the study of drugs in pediatric malignancies. Information from studies resulting from the WRs regarding safety, pharmacokinetics, and tolerability of oncology drugs has been incorporated into pediatric labeling for 11/14 of the drugs. Earlier communication and collaboration between the FDA, National Cancer Institute, clinical investigators, and commercial sponsors are envisioned to facilitate the identification and prioritization of emerging new drugs of interest for WR consideration. Since this is the only regulatory mechanism, resulting from specific legislative initiatives relevant to cancer drug development for children, efforts to enhance its impact on increasing drug approval for pediatric cancer indications are warranted. Copyright © 2013 Wiley Periodicals, Inc.

  16. FS65 Disposition Option Report

    Energy Technology Data Exchange (ETDEWEB)

    Wenz, Tracy R. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-09-25

    This report outlines the options for dispositioning the MOX fuel stored in FS65 containers at LANL. Additional discussion regarding the support equipment for loading and unloading the FS65 transport containers is included at the end of the report.

  17. Focused use of drug screening in overdose patients increases impact on management.

    OpenAIRE

    Erdmann, A.; Werner, D.; Hugli, O.; Yersin, B.

    2015-01-01

    UNLABELLED: Drug poisoning is a common cause for attendance in the emergency department. Several toxicology centres suggest performing urinary drug screens, even though they rarely influence patient management. STUDY OBJECTIVES: Measuring the impact on patient management, in a University Emergency Department with approximately 40 000 admissions annually, of a rapid urinary drug screening test using specifically focused indications. Drug screening was restricted to patients having a first p...

  18. Indian aspects of drug information resources and impact of drug information centre on community.

    Science.gov (United States)

    Chauhan, Nitesh; Moin, Sabeeya; Pandey, Anushree; Mittal, Ashu; Bajaj, Umakant

    2013-04-01

    Drug information centre refer to facility specially set aside for, and specializing in the provision of drug information and related issues. The purpose of drug information center is to provide authentic individualized, accurate, relevant and unbiased drug information to the consumers and healthcare professionals regarding medication related inquiries to the nation for health care and drug safety aspects by answering their call regarding the all critical problems on drug information, their uses and their side effects. Apart from that the center also provides in-depth, impartial source of crucial drug information to meet the needs of the practicing physicians, pharmacists and other health care professionals to safeguard the health, financial and legal interests of the patient and to broaden the pharmacist role visible in the society and community. The service should include collecting, reviewing, evaluating, indexing and distributing information on drugs to health workers. Drug and poisons information centers are best established within major teaching hospitals. This allows access to clinical experience, libraries, research facilities and educational activities. Information present in the current paper will not only enlighten the role of drug information center but also focused on the rational use of drug.

  19. Indian aspects of drug information resources and impact of drug information centre on community

    Directory of Open Access Journals (Sweden)

    Nitesh Chauhan

    2013-01-01

    Full Text Available Drug information centre refer to facility specially set aside for, and specializing in the provision of drug information and related issues. The purpose of drug information center is to provide authentic individualized, accurate, relevant and unbiased drug information to the consumers and healthcare professionals regarding medication related inquiries to the nation for health care and drug safety aspects by answering their call regarding the all critical problems on drug information, their uses and their side effects. Apart from that the center also provides in-depth, impartial source of crucial drug information to meet the needs of the practicing physicians, pharmacists and other health care professionals to safeguard the health, financial and legal interests of the patient and to broaden the pharmacist role visible in the society and community. The service should include collecting, reviewing, evaluating, indexing and distributing information on drugs to health workers. Drug and poisons information centers are best established within major teaching hospitals. This allows access to clinical experience, libraries, research facilities and educational activities. Information present in the current paper will not only enlighten the role of drug information center but also focused on the rational use of drug.

  20. Drug Brand Response and Its Impact on Compliance and Efficacy in Depression Patients.

    Science.gov (United States)

    Li, Mingming; Cai, Jian; Zhang, Ping; Fei, Chunhua; Xu, Feng

    2016-01-01

    Introduction: Patient's response to drug brand is a comprehensive physiological and psychological effect which might impact the compliance and efficacy of drugs. Whether the therapeutic outcome altered on patients with brand response after they experience drug switch is not clear. Methods: 459 outpatients with mild-to-moderate depression were divided into the imported (joint venture) drug group and the domestic drug group according to their current drug application. Two groups of patients were assessed by drug brand preference questionnaire and medication compliance questionnaire. Patients with brand preference in imported (joint venture) drugs group received rational use of limited medical resource and pharmacoeconomics education, and then switched with domestic drug for 8 weeks. Safety and efficacy were evaluated both before and after the drug switch. Results: Overall, there were 27% of patients in imported drug group and 35% of patients in domestic drug group have brand response, respectively. About 2/3 patients in both groups showed low or no brand response. The compliance was similar in both groups with no significant difference (6.04 ± 2.08 vs. 4.74 ± 2.13, respectively, P > 0.05). The efficacy of imported drug group was significantly better than of the domestic drug group. Correlation analysis showed that in imported (joint venture) drugs group, medication compliance was closely related with brand response, but negatively correlated with age and duration. In domestic drugs group, medication compliance was independent of brand response, but closely related with education, age, and duration. After drug switch with domestic drug on patients with brand response, patients continued to maintain good antidepressant effect, and no severe adverse reaction occurred. Conclusion: The results suggested that domestic drugs switch might be feasible for patients using imported drugs with brand response, while providing patients with rational use of drug education and

  1. Plutonium Disposition by Immobilization

    International Nuclear Information System (INIS)

    Gould, T.; DiSabatino, A.; Mitchell, M.

    2000-01-01

    The ultimate goal of the Department of Energy (DOE) Immobilization Project is to develop, construct, and operate facilities that will immobilize between 17 to 50 tonnes (MT) of U.S. surplus weapons-usable plutonium materials in waste forms that meet the ''spent fuel'' standard and are acceptable for disposal in a geologic repository. Using the ceramic can-in-canister technology selected for immobilization, surplus plutonium materials will be chemically combined into ceramic forms which will be encapsulated within large canisters of high level waste (HLW) glass. Deployment of the immobilization capability should occur by 2008 and be completed within 10 years. In support of this goal, the DOE Office of Fissile Materials Disposition (MD) is conducting development and testing (D and T) activities at four DOE laboratories under the technical leadership of Lawrence Livermore National Laboratory (LLNL). The Savannah River Site has been selected as the site for the planned Plutonium Immobilization Plant (PIP). The D and T effort, now in its third year, will establish the technical bases for the design, construction, and operation of the U. S. capability to immobilize surplus plutonium in a suitable and cost-effective manner. Based on the D and T effort and on the development of a conceptual design of the PIP, automation is expected to play a key role in the design and operation of the Immobilization Plant. Automation and remote handling are needed to achieve required dose reduction and to enhance operational efficiency

  2. Plutonium dispositioning in CANDU

    International Nuclear Information System (INIS)

    Boczar, P.G.; Feinroth, H.; Luxat, J.C.

    1995-07-01

    Recently, the U.S. Department of Energy (DOE) sponsored Atomic Energy of Canada Limited (AECL) to evaluate salient technical, strategic, schedule, and cost-related parameters of using CANDU reactors for dispositioning of weapons-grade plutonium in the form of Mixed OXide (MOX) fuel. A study team, consisting of key staff from the CANDU reactor designers and researchers (AECL), operators (Ontario Hydro) and fuel suppliers, analyzed all significant factors involved in such application, with the objective of identifying an arrangement that would permit the burning of MOX in CANDU at the earliest date. One of Ontario Hydro's multi-unit stations, Bruce A nuclear generating station (4x769 MW(e)), was chosen as the reference for the study. The assessment showed that no significant modifications of reactor or process systems are necessary to operate with a full MOX core. Plant modifications would be limited to fuel handling and modifications necessary to accommodate enhanced security and safeguards requirements. No safety limitations were identified

  3. Pharmacogenomics and its potential impact on drug and formulation development.

    Science.gov (United States)

    Regnstrom, Karin; Burgess, Diane J

    2005-01-01

    Recent advances in genomic research have provided the basis for new insights into the importance of genetic and genomic markers during the different stages of drug development. A new field of research, pharmacogenomics, which studies the relationship between drug effects and the genome, has emerged. Structural pharmacogenomics maps the complete DNA sequences of whole genomes (genotypes) including individual variations, and functional pharmacogenomics assesses the expression levels of thousands of genes in one single experiment. Together, these two areas of pharmacogenomics have generated massive databases, which have become a challenge for the research field of informatics and have fostered a new branch of research, bioinformatics. If skillfully used, the databases generated by pharmacogenomics together with data mining on the Web promise to improve the drug development process in a variety of areas: identification of drug targets, evaluation of toxicity, classification of diseases, evaluation of formulations, assessment of drug response and treatment, post-marketing applications, and development of personalized medicines.

  4. The Impact of Breakthrough Therapy Designation on Development Strategies and Timelines for Nononcology Drugs and Vaccines.

    Science.gov (United States)

    Poirier, A F; Murphy, W R

    2016-12-01

    The US Food and Drug Administration (FDA) Safety and Innovation Act (FDASIA, 2012) introduced the Breakthrough Therapy Designation (BTD), a new tool to expedite development of medicines to treat serious or life-threatening diseases. The majority of BTDs have gone to oncology drugs, and a recent publication by Shea et al. 1 reviewed the impact of BTD on oncology drug development. This article reviews the impact of BTD on development strategies and timelines for nononcology drugs. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  5. The impact of South Korea's new drug-pricing policy on market competition among off-patent drugs.

    Science.gov (United States)

    Kwon, Hye-Young; Kim, Hyungmin; Godman, Brian; Reich, Michael R

    2015-01-01

    A new pricing policy was introduced in Korea in April 2012 with the aim of strengthening competition among off-patent drugs by eliminating price gaps between originators and generics. Examine the effect of newly implemented pricing policy. Retrospectively examining the effects through extracting from the National Health Insurance claims data a 30-month panel dataset (January 2011-June 2013) containing consumption data in four major therapeutic classes (antihypertensives, lipid-lowering drugs, antiulcerants and antidepressants). Proxies for market competition were examined before and after the policy. The new pricing policy did not enhance competition among off-patent drugs. In fact, price dispersion significantly decreased as opposed to the expected change. Originator-to-generic utilization increased 6.12 times (p = 0.000) after the new policy. The new pricing policy made no impact on competition among off-patent drugs. Competition in the off-patent market cannot be enhanced unless both supply and demand side measures are coordinated.

  6. 1 Impact of praziquantel mass drug administration campaign on ...

    African Journals Online (AJOL)

    used to collect information on MDA uptake, knowledge of schistosomiasis, sources .... transmission and in which Praziquantel mass drug administration has been ..... MoHSW (2012) Tanzania Mainland Strategic Master Plan for the Neglected ...

  7. NRC comprehensive records disposition schedule

    International Nuclear Information System (INIS)

    1992-03-01

    Title 44 United States Code, ''Public Printing and Documents,'' regulations cited in the General Services Administration's (GSA) ''Federal Information Resources Management Regulations'' (FIRMR), Part 201-9, ''Creation, Maintenance, and Use of Records,'' and regulation issued by the National Archives and Records Administration (NARA) in 36 CFR Chapter XII, Subchapter B, ''Records Management,'' require each agency to prepare and issue a comprehensive records disposition schedule that contains the NARA approved records disposition schedules for records unique to the agency and contains the NARA's General Records Schedules for records common to several or all agencies. The approved records disposition schedules specify the appropriate duration of retention and the final disposition for records created or maintained by the NRC. NUREG-0910, Rev. 2, contains ''NRC's Comprehensive Records Disposition Schedule,'' and the original authorized approved citation numbers issued by NARA. Rev. 2 totally reorganizes the records schedules from a functional arrangement to an arrangement by the host office. A subject index and a conversion table have also been developed for the NRC schedules to allow staff to identify the new schedule numbers easily and to improve their ability to locate applicable schedules

  8. Visual, Critical, and Scientific Thinking Dispositions in a 3rd Grade Science Classroom

    Science.gov (United States)

    Foss, Stacy

    Many American students leave school without the required 21st century critical thinking skills. This qualitative case study, based on the theoretical concepts of Facione, Arheim, and Vygotsky, explored the development of thinking dispositions through the arts in science on the development of scientific thinking skills when used as a conceptual thinking routine in a rural 3rd grade classroom. Research questions examined the disposition to think critically through the arts in science and focused on the perceptions and experiences of 25 students with the Visual Thinking Strategy (VTS) process. Data were collected from classroom observations (n = 10), student interviews (n = 25), teacher interviews ( n = 1), a focus group discussion (n = 3), and artifacts of student work (n = 25); these data included perceptions of VTS, school culture, and classroom characteristics. An inductive analysis of qualitative data resulted in several emergent themes regarding disposition development and students generating questions while increasing affective motivation. The most prevalent dispositions were open-mindedness, the truth-seeking disposition, the analytical disposition, and the systematicity disposition. The findings about the teachers indicated that VTS questions in science supported "gradual release of responsibility", the internalization of process skills and vocabulary, and argumentation. This case study offers descriptive research that links visual arts inquiry and the development of critical thinking dispositions in science at the elementary level. A science curriculum could be developed, that emphasizes the development of thinking dispositions through the arts in science, which in turn, could impact the professional development of teachers and learning outcomes for students.

  9. The Impact of Disease and Drugs on Hip Fracture Risk.

    Science.gov (United States)

    Leavy, Breiffni; Michaëlsson, Karl; Åberg, Anna Cristina; Melhus, Håkan; Byberg, Liisa

    2017-01-01

    We report the risks of a comprehensive range of disease and drug categories on hip fracture occurrence using a strict population-based cohort design. Participants included the source population of a Swedish county, aged ≥50 years (n = 117,494) including all incident hip fractures during 1 year (n = 477). The outcome was hospitalization for hip fracture (ICD-10 codes S72.0-S72.2) during 1 year (2009-2010). Exposures included: prevalence of (1) inpatient diseases [International Classification of Diseases (ICD) codes A00-T98 in the National Patient Register 1987-2010] and (2) prescribed drugs dispensed in 2010 or the year prior to fracture. We present age- and sex-standardized risk ratios (RRs), risk differences (RDs) and population attributable risks (PARs) of disease and drug categories in relation to hip fracture risk. All disease categories were associated with increased risk of hip fracture. Largest risk ratios and differences were for mental and behavioral disorders, diseases of the blood and previous fracture (RRs between 2.44 and 3.00; RDs (per 1000 person-years) between 5.0 and 6.9). For specific drugs, strongest associations were seen for antiparkinson (RR 2.32 [95 % CI 1.48-1.65]; RD 5.2 [1.1-9.4]) and antidepressive drugs (RR 1.90 [1.55-2.32]; RD 3.1 [2.0-4.3]). Being prescribed ≥10 drugs during 1 year incurred an increased risk of hip fracture, whereas prescription of cardiovascular drugs or ≤5 drugs did not appear to increase risk. Diseases inferring the greatest PARs included: cardiovascular diseases PAR 22 % (95 % CI 14-29) and previous injuries (PAR 21 % [95 % CI 16-25]; for specific drugs, antidepressants posed the greatest risk (PAR 16 % [95 % CI 12.0-19.3]).

  10. Impact of biomarker development on drug safety assessment

    International Nuclear Information System (INIS)

    Marrer, Estelle; Dieterle, Frank

    2010-01-01

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

  11. FAILED FUEL DISPOSITION STUDY

    Energy Technology Data Exchange (ETDEWEB)

    THIELGES, J.R.

    2004-12-20

    In May 2004 alpha contamination was found on the lid of the pre-filter housing in the Sodium Removal Ion Exchange System during routine filter change. Subsequent investigation determined that the alpha contamination likely came from a fuel pin(s) contained in an Ident-69 (ID-69) type pin storage container serial number 9 (ID-69-9) that was washed in the Sodium Removal System (SRS) in January 2004. Because all evidence indicated that the wash water interacted with the fuel, this ID49 is designated as containing a failed fuel pin with gross cladding defect and was set aside in the Interim Examination and Maintenance (IEM) Cell until it could be determined how to proceed for long term dry storage of the fuel pin container. This ID49 contained fuel pins from the driver fuel assembly (DFA) 16392, which was identified as a Delayed Neutron Monitor (DNM) leaker assembly. However, this DFA was disassembled and the fuel pin that was thought to be the failed pin was encapsulated and was not located in this ID49 container. This failed fuel disposition study discusses two alternatives that could be used to address long term storage for the contents of ID-69-9. The first alternative evaluated utilizes the current method of identifying and storing DNM leaker fuel pin(s) in tubes and thus, verifying that the alpha contamination found in the SRS came from a failed pin in this pin container. This approach will require unloading selected fuel pins from the ID-69, visually examining and possibly weighing suspect fuel pins to identify the failed pin(s), inserting the failed pin(s) in storage tubes, and reloading the fuel pins into ID49 containers. Safety analysis must be performed to revise the 200 Area Interim Storage Area (ISA) Final Safety Analysis Report (FSAR) (Reference 1) for this fuel configuration. The second alternative considered is to store the failed fuel as-is in the ID-69. This was evaluated to determine if this approach would comply with storage requirements. This

  12. FAILED FUEL DISPOSITION STUDY

    International Nuclear Information System (INIS)

    THIELGES, J.R.

    2004-01-01

    In May 2004 alpha contamination was found on the lid of the pre-filter housing in the Sodium Removal Ion Exchange System during routine filter change. Subsequent investigation determined that the alpha contamination likely came from a fuel pin(s) contained in an Ident-69 (ID-69) type pin storage container serial number 9 (ID-69-9) that was washed in the Sodium Removal System (SRS) in January 2004. Because all evidence indicated that the wash water interacted with the fuel, this ID49 is designated as containing a failed fuel pin with gross cladding defect and was set aside in the Interim Examination and Maintenance (IEM) Cell until it could be determined how to proceed for long term dry storage of the fuel pin container. This ID49 contained fuel pins from the driver fuel assembly (DFA) 16392, which was identified as a Delayed Neutron Monitor (DNM) leaker assembly. However, this DFA was disassembled and the fuel pin that was thought to be the failed pin was encapsulated and was not located in this ID49 container. This failed fuel disposition study discusses two alternatives that could be used to address long term storage for the contents of ID-69-9. The first alternative evaluated utilizes the current method of identifying and storing DNM leaker fuel pin(s) in tubes and thus, verifying that the alpha contamination found in the SRS came from a failed pin in this pin container. This approach will require unloading selected fuel pins from the ID-69, visually examining and possibly weighing suspect fuel pins to identify the failed pin(s), inserting the failed pin(s) in storage tubes, and reloading the fuel pins into ID49 containers. Safety analysis must be performed to revise the 200 Area Interim Storage Area (ISA) Final Safety Analysis Report (FSAR) (Reference 1) for this fuel configuration. The second alternative considered is to store the failed fuel as-is in the ID-69. This was evaluated to determine if this approach would comply with storage requirements. This

  13. Twenty years on: the impact of fragments on drug discovery.

    Science.gov (United States)

    Erlanson, Daniel A; Fesik, Stephen W; Hubbard, Roderick E; Jahnke, Wolfgang; Jhoti, Harren

    2016-09-01

    After 20 years of sometimes quiet growth, fragment-based drug discovery (FBDD) has become mainstream. More than 30 drug candidates derived from fragments have entered the clinic, with two approved and several more in advanced trials. FBDD has been widely applied in both academia and industry, as evidenced by the large number of papers from universities, non-profit research institutions, biotechnology companies and pharmaceutical companies. Moreover, FBDD draws on a diverse range of disciplines, from biochemistry and biophysics to computational and medicinal chemistry. As the promise of FBDD strategies becomes increasingly realized, now is an opportune time to draw lessons and point the way to the future. This Review briefly discusses how to design fragment libraries, how to select screening techniques and how to make the most of information gleaned from them. It also shows how concepts from FBDD have permeated and enhanced drug discovery efforts.

  14. Disposition Options for Uranium-233

    International Nuclear Information System (INIS)

    Beahm, E.C.; Dole, L.R.; Forsberg, C.W.; Icenhour, A.S.; Storch, S.N.

    1999-01-01

    The U.S. Department of Energy (DOE) Fissile Materials Disposition Program (MD), in support of the U.S. arms-control and nonproliferation policies, has initiated a program to disposition surplus weapons-usable fissile material by making it inaccessible and unattractive for use in nuclear weapons. Weapons-usable fissile materials include plutonium, high-enriched uranium (HEU), and uranium-233 (sup 233)U. In support of this program, Oak Ridge National Laboratory led DOE's contractor efforts to identify and characterize options for the long-term storage and disposal of excess (sup 233)U. Five storage and 17 disposal options were identified and are described herein

  15. NRC comprehensive records disposition schedule

    International Nuclear Information System (INIS)

    1982-07-01

    Effective January 1, 1982, NRC will institute records retention and disposal practices in accordance with the approved Comprehensive Records Disposition Schedule (CRDS). CRDS is comprised of NRC Schedules (NRCS) 1 to 4 which apply to the agency's program or substantive records and General Records Schedules (GRS) 1 to 22 which apply to housekeeping or facilitative records. The schedules are assembled functionally/organizationally to facilitate their use. Preceding the records descriptions and disposition instructions for both NRCS and GRS, there are brief statements on the organizational units which accumulate the records in each functional area, and other information regarding the schedules' applicability

  16. Waste forms for plutonium disposition

    International Nuclear Information System (INIS)

    Johnson, S.G.; O'Holleran, T.P.; Frank, S.M.; Meyer, M.K.; Hanson, M.; Staples, B.A.; Knecht, D.A.; Kong, P.C.

    1997-01-01

    The field of plutonium disposition is varied and of much importance, since the Department of Energy has decided on the hybrid option for disposing of the weapons materials. This consists of either placing the Pu into mixed oxide fuel for reactors or placing the material into a stable waste form such as glass. The waste form used for Pu disposition should exhibit certain qualities: (1) provide for a suitable deterrent to guard against proliferation; (2) be of minimal volume, i.e., maximize the loading; and (3) be reasonably durable under repository-like conditions. This paper will discuss several Pu waste forms that display promising characteristics

  17. Prudent Use of Veterinary Drugs: Impact on Safe Animal Products ...

    African Journals Online (AJOL)

    Like any other therapeutic compounds, veterinary drugs are used to alleviate diseases in animals as either therapeutic or prophylactic compounds for specific disease entities. They can also be used as production aids in food producing animals to increase market sale of these animals whereby the producers save on the ...

  18. Impact of Tamsulosin, Tolterodine and drug-combination on the ...

    African Journals Online (AJOL)

    Objectives: To compare the role of alpha-blocker (Tamsulosin) monotherapy, anticholinergic (Tolterodine) monotherapy or combination of both drugs versus analgesics in improving post-ureteroscopy (URS) lower urinary tract symptoms related to double-J ureteral stent. Patients and methods: Between January 2009 and ...

  19. Impact of adult atopic dermatitis on topical drug penetration

    DEFF Research Database (Denmark)

    Garcia Ortiz, Patricia; Hansen, Steen H; Shah, Vinod P

    2009-01-01

    Appropriate methodologies for the determination of drug penetration in diseased skin have not yet been established. The aim of this study was to determine the cutaneous penetration of a metronidazole cream formulation in atopic dermatitis, employing dermal microdialysis and tape strip sampling...

  20. An Impact Evaluation of a Rural Youth Drug Education Program.

    Science.gov (United States)

    Sarvela, Paul D.; McClendon, E. J.

    1987-01-01

    Examined effects of mixed affective-cognitive drug education program on rural northern Michigan and northeastern Wisconsin sixth and seventh graders' (N=265) substance use health beliefs and behaviors. Alcohol use in this population was determined to be much higher than national average for similar age groups while marijuana, cigarette, and…

  1. Pricing of prescription drugs and its impact on physicians' choice behavior.

    Science.gov (United States)

    Miao-Sheng, Chen; Yu-Ti, Shih

    2008-09-01

    This research presents an analysis of Taiwan's health care market with the focus on the pricing of prescription drugs and its impact on physicians' choice behavior. Since the advent of Taiwan's national health insurance, with the competent authority being Bureau of National Health Insurance (BNHI), hospitals are allowed to sell prescription drugs to patients at prices above the purchasing prices, so each prescription drug has two prices: one at which drugs are sold to hospitals; the other which BNHI reimbursement to hospitals. The margin between the different prices is the sales discount that pharmaceutical companies offer to the hospitals. We find that sales discount has a great impact on physicians' choice behavior: i.e., physicians are price-sensitive to prescription drugs. In addition, it is found that too high a sales discount of a prescription drug would result in a too low weighted average price of that drug sold; thus BNHI would be more likely to adjust downward the rate it reimbursement to the hospital. This presents a sales strategy problem to pharmaceutical companies. To solve this, we use the distribution of physicians' evaluations of prescription drugs to establish a profit maximization model in hopes of helping companies to price drugs and find the optimal promotion expending. Ten popular prescription drugs are used in this research as examples.

  2. Financial Impact of Cancer Drug Wastage and Potential Cost Savings From Mitigation Strategies.

    Science.gov (United States)

    Leung, Caitlyn Y W; Cheung, Matthew C; Charbonneau, Lauren F; Prica, Anca; Ng, Pamela; Chan, Kelvin K W

    2017-07-01

    Cancer drug wastage occurs when a parenteral drug within a fixed vial is not administered fully to a patient. This study investigated the extent of drug wastage, the financial impact on the hospital budget, and the cost savings associated with current mitigation strategies. We conducted a cross-sectional study in three University of Toronto-affiliated hospitals of various sizes. We recorded the actual amount of drug wasted over a 2-week period while using current mitigation strategies. Single-dose vial cancer drugs with the highest wastage potentials were identified (14 drugs). To calculate the hypothetical drug wastage with no mitigation strategies, we determined how many vials of drugs would be needed to fill a single prescription. The total drug costs over the 2 weeks ranged from $50,257 to $716,983 in the three institutions. With existing mitigation strategies, the actual drug wastage over the 2 weeks ranged from $928 to $5,472, which was approximately 1% to 2% of the total drug costs. In the hypothetical model with no mitigation strategies implemented, the projected drug cost wastage would have been $11,232 to $149,131, which accounted for 16% to 18% of the total drug costs. As a result, the potential annual savings while using current mitigation strategies range from 15% to 17%. The financial impact of drug wastage is substantial. Mitigation strategies lead to substantial cost savings, with the opportunity to reinvest those savings. More research is needed to determine the appropriate methods to minimize risk to patients while using the cost-saving mitigation strategies.

  3. Impact of online counseling on drug use: a pilot study.

    Science.gov (United States)

    Alemi, Farrokh; Haack, Mary; Nemes, Susie; Harge, Angela; Baghi, Heibatollah

    2010-01-01

    To examine the effect of online counseling abuse counseling on drug use among underserved patients. Subjects were recruited from an Indian Reservation in Eagle Butte, South Dakota; a family court in Newark, New Jersey; a probation office in Alexandria, Virginia; and a co-occurring disorders treatment clinic in Washington, District of Columbia. Subjects were predominantly poor, undereducated, unemployed, court involved, or diagnosed with co-occurring psychiatric disorders. A total of 79 subjects volunteered to participate in the project. Subjects were randomly assigned to either a control group or an experimental group. The control and experimental groups were both issued an Internet-ready computer and 1 year of Internet service. Only the experimental group had access to online counseling intervention. Drug use was measured using a combination of self-usage reporting and supervised urine tests. Urine tests were available for 37% of subjects. Exit surveys containing self-reported usage were obtained from 54% of the subjects. Self-usage reports or urine test results were available from 70% of subjects. The difference of the rates of drug use in the control and experimental groups (as calculated from urine tests or through self-report) was not significantly different from zero, suggesting that online counseling had not led to a reduction in substance use. It is possible that the study lacked sufficient power to detect small differences in the rate of drug use in the experimental and control groups. Additional research is needed to establish the efficacy of online counseling in hard-to-reach populations.

  4. The impact of worker values on client outcomes within a drug treatment service.

    Science.gov (United States)

    Phillips, Rosie; Bourne, Humphrey

    2008-02-01

    Little attention has been paid to understanding the impact of values, attributes and characteristics of drugs workers on therapeutic relationships and treatment outcomes. Interaction of values with other variables is considered to be of importance since values play a role in determining attitudes and behaviours. This exploratory study investigates the impact of drug workers' personal values on client outcomes within a drug treatment service. Eight drug workers and 58 clients were recruited at a UK charity working with problematic drug users who are also socially excluded. Drug workers completed a validated questionnaire to elicit their personal values. Client outcomes were assessed using the Christo Inventory for Substance Misuse Services. The relationship between client outcomes and worker values were analysed using Spearman's rank test of association. Drug workers prioritising stimulation, self-direction and hedonism value types experienced more positive client outcomes compared with those prioritising security, conformity, benevolence, tradition and universalism types. The value types associated with positive outcomes fall within Schwartz's 'openness to change' superordinate dimension, whereas those related to more negative outcomes fall within the 'conservation' dimension. The study suggests that drug workers' personal values may have a significant impact upon client outcomes in the treatment of substance misuse. Reasons for this finding are explored, as are limitations of this study and suggestions for future research.

  5. Budget impact analysis of drugs for ultra-orphan non-oncological diseases in Europe.

    Science.gov (United States)

    Schlander, Michael; Adarkwah, Charles Christian; Gandjour, Afschin

    2015-02-01

    Ultra-orphan diseases (UODs) have been defined by a prevalence of less than 1 per 50,000 persons. However, little is known about budget impact of ultra-orphan drugs. For analysis, the budget impact analysis (BIA) had a time horizon of 10 years (2012-2021) and a pan-European payer's perspective, based on prevalence data for UODs for which patented drugs are available and/or for which drugs are in clinical development. A total of 18 drugs under patent protection or orphan drug designation for non-oncological UODs were identified. Furthermore, 29 ultra-orphan drugs for non-oncological diseases under development that have the potential of reaching the market by 2021 were found. Total budget impact over 10 years was estimated to be €15,660 and €4965 million for approved and pipeline ultra-orphan drugs, respectively (total: €20,625 million). The analysis does not support concerns regarding an uncontrolled growth in expenditures for drugs for UODs.

  6. Metabolic drug interactions - the impact of prescribed drug regimens on the medication safety.

    NARCIS (Netherlands)

    Fialova, D.; Vrbensky, K.; Topinkova, E.; Vlcek, J.; Soerbye, L.W.; Wagner, C.; Bernabei, R.

    2005-01-01

    Background and objective: Risk/benefit profile of prescribed drug regimens is unkown. Over 60% of commonly used medications interact on metabolic pathways (cytochrom P450 (CYP450), uridyl-glucuronyl tranferasis (UGT I, II) and P-glycoprotein (PGP) transport). Using an up-to-date knowledge on

  7. A disposition of interpolation techniques

    NARCIS (Netherlands)

    Knotters, M.; Heuvelink, G.B.M.

    2010-01-01

    A large collection of interpolation techniques is available for application in environmental research. To help environmental scientists in choosing an appropriate technique a disposition is made, based on 1) applicability in space, time and space-time, 2) quantification of accuracy of interpolated

  8. Dispositional optimism and stock investments

    NARCIS (Netherlands)

    Angelini, Viola; Cavapozzi, D.

    This paper analyzes the relationship between dispositional optimism and stock investments, controlling for cognitive skills and personality traits such as trust, social interactions and risk aversion. We use data from the Survey of Health, Ageing and Retirement in Europe (SHARE) on investors aged

  9. Sexual addiction in drug addicts: The impact of drug of choice and poly-addiction.

    Science.gov (United States)

    Antonio, Nelson; Diehl, Alessandra; Niel, Marcelo; Pillon, Sandra; Ratto, Lilian; Pinheiro, Maria Carolina; Silveira, Dartiu; Otani, Thais Zelia; Otani, Victor; Cordeiro, Quirino; Ushida, Ricardo

    2017-05-01

    To compare the risk of comorbid sexual addiction in a sample of individuals with a diagnosis of substance dependence, stratifying the sample by drug of choice as well as by mono versus polysubstance addiction. All data were collected at Santa Casa de São Paulo, Brazil. The study sample comprised all alcohol or drug dependents admitted to the Addiction Treatment Unit between November 2013 and August 2014. A generalized linear model with a binomial distribution was performed to compare the odds of having a Sexual Addiction Screening Test (SAST) score greater than 6 points in the subgroups analyzed. A total of 133 participants were included in our analysis, all reporting cocaine/crack and/or alcohol as drug of choice. Polysubstance addicts had a significant higher risk of a positive screening for sexual addiction compared to monosubstance addicts, age-sex adjusted odds ratios of sexual addiction being respectively 2.72 (95CI 1.1-6.71) and 0.37 (95CI 0.15-0.91). The odds of a SAST score greater than 6 was not statistically different between the cocaine/crack and alcohol groups, respectively 0.38 (95CI 0.14-1.02) and 2.67 (95CI 0.98-7.25). We found a significant relation between stronger drug addiction and greater levels of sexual addiction in the cocaine/crack group (p=0.0012), but not in the alcohol group. Our study reinforces the importance of assessing sexual behavior of drug addicts in clinical practice, especially considering users of multiple substances or with severe dependence.

  10. Signs, dispositions, and semiotic scaffolding.

    Science.gov (United States)

    Fernández, Eliseo

    2015-12-01

    In theoretical work we distinguish living beings from inanimate objects on the basis of some paramount attributes, such as agency and autonomy. These abstract features are not directly accessible to our scrutiny, but we surmise their nature through observation of the purpose-oriented behavior of organisms. I intend to show that organismal purposefulness springs from the intrinsic, constitutive kind of finality that is the hallmark of all semiotic transactions. To this aim I develop a dispositionalist account of organismal causation based on a distinction between two kinds of causal dispositions: fixed (efficient) dispositions and traveling dispositions. Fixed dispositions are rigidly attached to physical structures and processes; these are the dispositions regularly invoked in current discussions of causal explanation. Traveling dispositions are able to move freely from one location to another by becoming embodied into suitable supporting media. I introduce these notions to articulate a view of semiosis I deem best suited to the life sciences, and contend that sign tokens are vehicles of traveling dispositions. This account places the origin of purposive behavior at the interaction of physical and semiotic causation. To properly motivate the discussion I briefly review some recent developments in the philosophy of science concerning various forms of causation invoked by scientists across disciplines to frame explanations and make predictions. The ensuing discussion gives particular prominence to mechanistic (as distinct from mechanicist) explanatory accounts of biological phenomena. This review is followed by a brief characterization of a "nomological machine," a comprehensive schema introduced and developed by Nancy Cartwright with the goal of explaining causal mechanisms in a general setting. By capitalizing on this model's heuristic virtues I seek to formulate a compelling view of the interactions between physical and semiotic causation at play in semiotic

  11. The Impact of Herbal Drug Use on Adverse Drug Reaction Profiles of Patients on Antiretroviral Therapy in Zimbabwe

    Directory of Open Access Journals (Sweden)

    Tinashe Mudzviti

    2012-01-01

    Full Text Available Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART. Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2% of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%, Bidens pilosa (66.0%, Eucalyptus globulus (52.3%, Moringa oleifera (44.1%, Lippia javanica (36.3%, and Peltoforum africanum (34.3%. Two indigenous herbs, Musakavakadzi (OR=0.25; 95% CI 0.076–0.828 and Peltoforum africanum (OR=0.495; 95% CI 0.292–0.839 reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles.

  12. An Overview of Clinical and Commercial Impact of Drug Delivery Systems

    Science.gov (United States)

    Anselmo, Aaron C.; Mitragotri, Samir

    2014-01-01

    Drug delivery systems are widely researched and developed to improve the delivery of pharmaceutical compounds and molecules. The last few decades have seen a marked growth of the field fueled by increased number of researchers, research funding, venture capital and the number of start-ups. Collectively, the growth has led to novel systems that make use of micro/nano-particles, transdermal patches, inhalers, drug reservoir implants and antibody-drug conjugates. While the increased research activity is clearly an indication of proliferation of the field, clinical and commercial translation of early-stage research ideas is critically important for future growth and interest in the field. Here, we will highlight some of the examples of novel drug delivery systems that have undergone such translation. Specifically, we will discuss the developments, advantages, limitations and lessons learned from: (i) microparticle-based depot formulations, (ii) nanoparticle-based cancer drugs, (iii) transdermal systems, (iv) oral drug delivery systems, (v) pulmonary drug delivery, (vi) implants and (vii) antibody-drug conjugates. These systems have impacted treatment of many prevalent diseases including diabetes, cancer and cardiovascular diseases, among others. At the same time, these systems are integral and enabling components of products that collectively generate annual revenues exceeding US $100 billion. These examples provide strong evidence of the clinical and commercial impact of drug delivery systems. PMID:24747160

  13. Improving critical thinking : Effects of dispositions and instructions oneconomics students' reasoning skills

    NARCIS (Netherlands)

    Heijltjes, Anita; van Gog, Tamara; Leppink, Jimmie; Paas, Fred

    2014-01-01

    This experiment investigated the impact of critical thinking dispositions and instructions on economics students' performance on reasoning skills. Participants (. N=. 183) were exposed to one of four conditions: critical thinking instruction, critical thinking instruction with self-explanation

  14. The Impact of Disease and Drugs on Hip Fracture Risk

    OpenAIRE

    Leavy, Breiffni; Michaëlsson, Karl; Åberg, Anna Cristina; Melhus, Håkan; Byberg, Liisa

    2017-01-01

    We report the risks of a comprehensive range of disease and drug categories on hip fracture occurrence using a strict population-based cohort design. Participants included the source population of a Swedish county, aged ?50?years (n?=?117,494) including all incident hip fractures during 1?year (n?=?477). The outcome was hospitalization for hip fracture (ICD-10 codes S72.0?S72.2) during 1?year (2009?2010). Exposures included: prevalence of (1) inpatient diseases [International Classification o...

  15. HIV protease drug resistance and its impact on inhibitor design.

    Science.gov (United States)

    Ala, P J; Rodgers, J D; Chang, C H

    1999-07-01

    The primary cause of resistance to the currently available HIV protease inhibitors is the accumulation of multiple mutations in the viral protease. So far more than 20 substitutions have been observed in the active site, dimer interface, surface loops and flaps of the homodimer. While many mutations reduce the protease's affinity for inhibitors, others appear to enhance its catalytic efficiency. This high degree of genetic flexibility has made the protease an elusive drug target. The design of the next generation of HIV protease inhibitors will be discussed in light of the current structural information.

  16. Age related differences in the disposition of acetanilide.

    Science.gov (United States)

    Playfer, J R; Baty, J D; Lamb, J; Powell, C; Price-Evans, D A

    1978-01-01

    1 The metabolism of fifteen elderly hospital in-patients and fifteen young people was studied, using a gas chromatography mass spectrometer method. 2 The results suggest that there is no significant change in hepatic oxidation of acetanilide with age. 3 The concentrations of metabolites were however, significantly elevated in the older group. 4 These results illustrate the importance of the decline in renal function with age in the disposition of drugs. PMID:728323

  17. In silico ADME in drug design – enhancing the impact

    Directory of Open Access Journals (Sweden)

    Susanne Winiwarter

    2018-03-01

    Full Text Available Each year the pharmaceutical industry makes thousands of compounds, many of which do not meet the desired efficacy or pharmacokinetic properties, describing the absorption, distribution, metabolism and excretion (ADME behavior. Parameters such as lipophilicity, solubility and metabolic stability can be measured in high throughput in vitro assays. However, a compound needs to be synthesized in order to be tested. In silico models for these endpoints exist, although with varying quality. Such models can be used before synthesis and, together with a potency estimation, influence the decision to make a compound. In practice, it appears that often only one or two predicted properties are considered prior to synthesis, usually including a prediction of lipophilicity. While it is important to use all information when deciding which compound to make, it is somewhat challenging to combine multiple predictions unambiguously. This work investigates the possibility of combining in silico ADME predictions to define the minimum required potency for a specified human dose with sufficient confidence. Using a set of drug discovery compounds,in silico predictions were utilized to compare the relative ranking based on minimum potency calculation with the outcomes from the selection of lead compounds. The approach was also tested on a set of marketed drugs and the influence of the input parameters investigated.

  18. Other drug use does not impact cognitive impairments in chronic ketamine users.

    Science.gov (United States)

    Zhang, Chenxi; Tang, Wai Kwong; Liang, Hua Jun; Ungvari, Gabor Sandor; Lin, Shih-Ku

    2018-05-01

    Ketamine abuse causes cognitive impairments, which negatively impact on users' abstinence, prognosis, and quality of life. of cognitive impairments in chronic ketamine users have been inconsistent across studies, possibly due to the small sample sizes and the confounding effects of concomitant use of other illicit drugs. This study investigated the cognitive impairment and its related factors in chronic ketamine users with a large sample size and explored the impact of another drug use on cognitive functions. Cognitive functions, including working, verbal and visual memory and executive functions were assessed in ketamine users: 286 non-heavy other drug users and 279 heavy other drug users, and 261 healthy controls. Correlations between cognitive impairment and patterns of ketamine use were analysed. Verbal and visual memory were impaired, but working memory and executive functions were intact for all ketamine users. No significant cognitive differences were found between the two ketamine groups. Greater number of days of ketamine use in the past month was associated with worse visual memory performance in non-heavy other drug users. Higher dose of ketamine use was associated with worse short-term verbal memory in heavy other drug users. Verbal and visual memory are impaired in chronic ketamine users. Other drug use appears to have no impact on ketamine users' cognitive performance. Copyright © 2018. Published by Elsevier B.V.

  19. 77 FR 75177 - Impact of Approved Drug Labeling on Chronic Opioid Therapy; Public Hearing; Request for Comments

    Science.gov (United States)

    2012-12-19

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-1172] Impact of Approved Drug Labeling on Chronic Opioid Therapy; Public Hearing; Request for Comments AGENCY... impact the entire class of opioid drugs or a large subcategory thereof (e.g., ER/LA opioids), such as the...

  20. Impact of the CYP2C8 *3 polymorphism on the drug-drug interaction between gemfibrozil and pioglitazone.

    Science.gov (United States)

    Aquilante, Christina L; Kosmiski, Lisa A; Bourne, David W A; Bushman, Lane R; Daily, Elizabeth B; Hammond, Kyle P; Hopley, Charles W; Kadam, Rajendra S; Kanack, Alexander T; Kompella, Uday B; Le, Merry; Predhomme, Julie A; Rower, Joseph E; Sidhom, Maha S

    2013-01-01

    The objective of this study was to determine the extent to which the CYP2C8*3 allele influences pharmacokinetic variability in the drug-drug interaction between gemfibrozil (CYP2C8 inhibitor) and pioglitazone (CYP2C8 substrate). In this randomized, two phase crossover study, 30 healthy Caucasian subjects were enrolled based on CYP2C8*3 genotype (n = 15, CYP2C8*1/*1; n = 15, CYP2C8*3 carriers). Subjects received a single 15 mg dose of pioglitazone or gemfibrozil 600 mg every 12 h for 4 days with a single 15 mg dose of pioglitazone administered on the morning of day 3. A 48 h pharmacokinetic study followed each pioglitazone dose and the study phases were separated by a 14 day washout period. Gemfibrozil significantly increased mean pioglitazone AUC(0,∞) by 4.3-fold (P gemfibrozil administration was significantly influenced by CYP2C8 genotype. Specifically, CYP2C8*3 carriers had a 5.2-fold mean increase in pioglitazone AUC(0,∞) compared with a 3.3-fold mean increase in CYP2C8*1 homozygotes (P = 0.02). CYP2C8*3 is associated with decreased pioglitazone plasma exposure in vivo and significantly influences the pharmacokinetic magnitude of the gemfibrozil-pioglitazone drug-drug interaction. Additional studies are needed to evaluate the impact of CYP2C8 genetics on the pharmacokinetics of other CYP2C8-mediated drug-drug interactions. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  1. The impact of pharmacophore modeling in drug design.

    Science.gov (United States)

    Guner, Osman F

    2005-07-01

    With the reliable use of computer simulations in scientific research, it is possible to achieve significant increases in productivity as well as a reduction in research costs compared with experimental approaches. For example, computer-simulation can substantially enchance productivity by focusing the scientist to better, more informed choices, while also driving the 'fail-early' concept to result in a significant reduction in cost. Pharmacophore modeling is a reliable computer-aided design tool used in the discovery of new classes of compounds for a given therapeutic category. This commentary will briefly review the benefits and applications of this technology in drug discovery and design, and will also highlight its historical evolution. The two most commonly used approaches for pharmacophore model development will be discussed, and several examples of how this technology was successfully applied to identify new potent leads will be provided. The article concludes with a brief outline of the controversial issue of patentability of pharmacophore models.

  2. Effect of perceived stress on depression of Chinese "Ant Tribe" and the moderating role of dispositional optimism.

    Science.gov (United States)

    Liu, Bo; Pu, Jun; Hou, Hanpo

    2015-05-08

    This study examines the moderating role of dispositional optimism on the relationship between perceived stress and depression of the Chinese "Ant Tribe." A total of 427 participants from an Ant Tribe community completed the measures of perceived stress, optimism, and depression. The structural equation modeling (SEM) analysis showed that dispositional optimism moderated the association between perceived stress and depression. The Ant Tribe with high perceived stress reported higher scores in depression than those with low perceived stress at low dispositional optimism level. However, the impact of perceived stress on depression was insignificant in the high dispositional optimism group. © The Author(s) 2015.

  3. Fissile material disposition and proliferation risk

    Energy Technology Data Exchange (ETDEWEB)

    Dreicer, J.S.; Rutherford, D.A. [Los Alamos National Lab., NM (United States). NIS Div.

    1996-05-01

    The proliferation risk of a facility is dependent on the material attractiveness, level of safeguards, and physical protection applied to the material in conjunction with an assessment of the impact of the socioeconomic circumstances and threat environment. Proliferation risk is a complementary extension of proliferation resistance. The authors believe a better determination of nuclear material proliferation can be achieved by establishing the proliferation risk for facilities that contain nuclear material. Developing a method that incorporates the socioeconomic circumstances and threat environment inherent to each country enables a global proliferation assessment. In order to effectively reduce the nuclear danger, a broadly based set of criteria is needed that provides the capability to relatively assess a wide range of disposition options/facilities in different countries and still ensure a global decrease in proliferation risk for plutonium.

  4. Fissile material disposition and proliferation risk

    International Nuclear Information System (INIS)

    Dreicer, J.S.; Rutherford, D.A.

    1996-01-01

    The proliferation risk of a facility is dependent on the material attractiveness, level of safeguards, and physical protection applied to the material in conjunction with an assessment of the impact of the socioeconomic circumstances and threat environment. Proliferation risk is a complementary extension of proliferation resistance. The authors believe a better determination of nuclear material proliferation can be achieved by establishing the proliferation risk for facilities that contain nuclear material. Developing a method that incorporates the socioeconomic circumstances and threat environment inherent to each country enables a global proliferation assessment. In order to effectively reduce the nuclear danger, a broadly based set of criteria is needed that provides the capability to relatively assess a wide range of disposition options/facilities in different countries and still ensure a global decrease in proliferation risk for plutonium

  5. Analysis of abused drugs by selected ion monitoring: quantitative comparison of electron impact and chemical ionization

    International Nuclear Information System (INIS)

    Foltz, R.L.; Knowlton, D.A.; Lin, D.C.K.; Fentiman, A.F. Jr.

    1975-01-01

    A comparison was made of the relative sensitivities of electron impact and chemical ionization when used for selected ion monitoring analysis of commonly abused drugs. For most of the drugs examined chemical ionization using ammonia as the reactant gas gave the largest single m/e ion current response per unit weight of sample. However, if maximum sensitivity is desired it is important to evaluate electron impact and chemical ionization with respect to both maximum response and degree of interference from background and endogenous materials

  6. Drug-drug interactions involving lysosomes: mechanisms and potential clinical implications.

    Science.gov (United States)

    Logan, Randall; Funk, Ryan S; Axcell, Erick; Krise, Jeffrey P

    2012-08-01

    Many commercially available, weakly basic drugs have been shown to be lysosomotropic, meaning they are subject to extensive sequestration in lysosomes through an ion trapping-type mechanism. The extent of lysosomal trapping of a drug is an important therapeutic consideration because it can influence both activity and pharmacokinetic disposition. The administration of certain drugs can alter lysosomes such that their accumulation capacity for co-administered and/or secondarily administered drugs is altered. In this review the authors explore what is known regarding the mechanistic basis for drug-drug interactions involving lysosomes. Specifically, the authors address the influence of drugs on lysosomal pH, volume and lipid processing. Many drugs are known to extensively accumulate in lysosomes and significantly alter their structure and function; however, the therapeutic and toxicological implications of this remain controversial. The authors propose that drug-drug interactions involving lysosomes represent an important potential source of variability in drug activity and pharmacokinetics. Most evaluations of drug-drug interactions involving lysosomes have been performed in cultured cells and isolated tissues. More comprehensive in vivo evaluations are needed to fully explore the impact of this drug-drug interaction pathway on therapeutic outcomes.

  7. Budgetary impact analysis on funding smoking-cessation drugs in patients with COPD in Spain.

    Science.gov (United States)

    Jiménez-Ruiz, Carlos A; Solano-Reina, Segismundo; Signes-Costa, Jaime; de Higes-Martinez, Eva; Granda-Orive, José I; Lorza-Blasco, José J; Riesco-Miranda, Juan A; Altet-Gomez, Neus; Barrueco, Miguel; Oyagüez, Itziar; Rejas, Javier

    2015-01-01

    The aim of the study was to assess the budgetary impact of funding smoking-cessation drugs in COPD patients in Spain. A hybrid model (cohort and Markov) was developed for a 5-year time horizon. Only approved cessation drugs (varenicline, bupropion, and nicotine replacement therapy) were considered. Irrespective of the drug, the model allowed for an initial cessation attempt, and up to three additional attempts in case of failure or smoking relapse during a 5-year period. Drug effectiveness was based on controlled clinical trials. National Health System perspective was applied; therefore, only medical resources were included. The pharmaceutical costs for smoking-cessation drugs, extra medical follow-up as a consequence of public reimbursement, and annual savings for health costs avoided due to stopping smoking were considered. The model estimated that 17,756 COPD patients would stop smoking if public funding was available, compared with 1,303 without reimbursement. In the reimbursement scenario, the savings accounted for a total of €48.0 million, compensating for expenditures on drugs and medical visits (€40.4 million). Accumulated total additional savings in 5 years (€4.3 million) compared with the scenario without reimbursement was shown. Sensitivity analyses supported the results robustness. Funding smoking-cessation drugs in COPD patients seems to be an efficient option and a National Health System drug reimbursement scheme would represent a cost-saving policy in Spain.

  8. Impact of Maine's Medicaid drug formulary change on non-Medicaid markets: spillover effects of a restrictive drug formulary.

    Science.gov (United States)

    Wang, Y Richard; Pauly, Mark V; Lin, Y Aileen

    2003-10-01

    Market penetration of HMOs affect physician practice styles for non-HMO patients. To study the impact of a restrictive Medicaid drug formulary on prescribing patterns for other patients, ie, so-called spillover effects. A before-and-after, 3-state comparison study. On January 1, 2001, Maine's Medicaid program implemented a restrictive drug formulary for the proton pump inhibitor class, with pantoprazole as the only preferred drug. The Medicaid and non-Medicaid market shares of pantoprazole in Maine (vs New Hampshire and Vermont and among Maine physicians with different Medicaid share of practice. After 3 months, the market share of pantoprazole in Maine (vs 2 control states) increased 79% among Medicaid prescriptions (vs 1%-2%), 10% among cash prescriptions (vs 3%), and 7% among other third-party payer prescriptions (vs 1%). The market shares increased more among Maine physicians with a higher Medicaid share of practice (high vs middle vs low [market]: 16% vs 8% vs 5% [cash]; 11% vs 5% vs 4% [other third-party payers]). Linear regression results indicate that practicing medicine in Maine leads to a 72% increase in pantoprazole share among Medicaid prescriptions (P markets, with somewhat stronger effects in the cash market.

  9. Derivation of plutonium-239 materials disposition categories

    International Nuclear Information System (INIS)

    Brough, W.G.

    1995-01-01

    At this time, the Office of Fissile Materials Disposition within the DOE, is assessing alternatives for the disposition of excess fissile materials. To facilitate the assessment, the Plutonium-Bearing Materials Feed Report for the DOE Fissile Materials Disposition Program Alternatives report was written. The development of the material categories and the derivation of the inventory quantities associated with those categories is documented in this report

  10. Assessing the potential impact of artemisinin and partner drug resistance in sub-Saharan Africa.

    Science.gov (United States)

    Slater, Hannah C; Griffin, Jamie T; Ghani, Azra C; Okell, Lucy C

    2016-01-06

    Artemisinin and partner drug resistant malaria parasites have emerged in Southeast Asia. If resistance were to emerge in Africa it could have a devastating impact on malaria-related morbidity and mortality. This study estimates the potential impact of artemisinin and partner drug resistance on disease burden in Africa if it were to emerge. Using data from Asia and Africa, five possible artemisinin and partner drug resistance scenarios are characterized. An individual-based malaria transmission model is used to estimate the impact of each resistance scenario on clinical incidence and parasite prevalence across Africa. Artemisinin resistance is characterized by slow parasite clearance and partner drug resistance is associated with late clinical failure or late parasitological failure. Scenarios with high levels of recrudescent infections resulted in far greater increases in clinical incidence compared to scenarios with high levels of slow parasite clearance. Across Africa, it is estimated that artemisinin and partner drug resistance at levels similar to those observed in Oddar Meanchey province in Cambodia could result in an additional 78 million cases over a 5 year period, a 7% increase in cases compared to a scenario with no resistance. A scenario with high levels of slow clearance but no recrudescence resulted in an additional 10 million additional cases over the same period. Artemisinin resistance is potentially a more pressing concern than partner drug resistance due to the lack of viable alternatives. However, it is predicted that a failing partner drug will result in greater increases in malaria cases and morbidity than would be observed from artemisinin resistance only.

  11. A Methodological Review of US Budget-Impact Models for New Drugs.

    Science.gov (United States)

    Mauskopf, Josephine; Earnshaw, Stephanie

    2016-11-01

    A budget-impact analysis is required by many jurisdictions when adding a new drug to the formulary. However, previous reviews have indicated that adherence to methodological guidelines is variable. In this methodological review, we assess the extent to which US budget-impact analyses for new drugs use recommended practices. We describe recommended practice for seven key elements in the design of a budget-impact analysis. Targeted literature searches for US studies reporting estimates of the budget impact of a new drug were performed and we prepared a summary of how each study addressed the seven key elements. The primary finding from this review is that recommended practice is not followed in many budget-impact analyses. For example, we found that growth in the treated population size and/or changes in disease-related costs expected during the model time horizon for more effective treatments was not included in several analyses for chronic conditions. In addition, all drug-related costs were not captured in the majority of the models. Finally, for most studies, one-way sensitivity and scenario analyses were very limited, and the ranges used in one-way sensitivity analyses were frequently arbitrary percentages rather than being data driven. The conclusions from our review are that changes in population size, disease severity mix, and/or disease-related costs should be properly accounted for to avoid over- or underestimating the budget impact. Since each budget holder might have different perspectives and different values for many of the input parameters, it is also critical for published budget-impact analyses to include extensive sensitivity and scenario analyses based on realistic input values.

  12. Quasi-Banach spaces of almost universal disposition

    Czech Academy of Sciences Publication Activity Database

    Sánchez, C. F.; Garbulińska, J.; Kubiś, Wieslaw

    2014-01-01

    Roč. 267, č. 3 (2014), s. 744-771 ISSN 0022-1236 R&D Projects: GA ČR(CZ) GAP201/12/0290 Institutional support: RVO:67985840 Keywords : p-Gurarii space * space of universal disposition * isometry Subject RIV: BA - General Mathematics Impact factor: 1.322, year: 2014 http://www.sciencedirect.com/science/article/pii/S0022123614002043

  13. The Potential Impact of Up-Front Drug Sensitivity Testing on India's Epidemic of Multi-Drug Resistant Tuberculosis.

    Directory of Open Access Journals (Sweden)

    Kuldeep Singh Sachdeva

    Full Text Available In India as elsewhere, multi-drug resistance (MDR poses a serious challenge in the control of tuberculosis (TB. The End TB strategy, recently approved by the world health assembly, aims to reduce TB deaths by 95% and new cases by 90% between 2015 and 2035. A key pillar of this approach is early diagnosis of tuberculosis, including use of higher-sensitivity diagnostic testing and universal rapid drug susceptibility testing (DST. Despite limitations of current laboratory assays, universal access to rapid DST could become more feasible with the advent of new and emerging technologies. Here we use a mathematical model of TB transmission, calibrated to the TB epidemic in India, to explore the potential impact of a major national scale-up of rapid DST. To inform key parameters in a clinical setting, we take GeneXpert as an example of a technology that could enable such scale-up. We draw from a recent multi-centric demonstration study conducted in India that involved upfront Xpert MTB/RIF testing of all TB suspects.We find that widespread, public-sector deployment of high-sensitivity diagnostic testing and universal DST appropriately linked with treatment could substantially impact MDR-TB in India. Achieving 75% access over 3 years amongst all cases being diagnosed for TB in the public sector alone could avert over 180,000 cases of MDR-TB (95% CI 44187 - 317077 cases between 2015 and 2025. Sufficiently wide deployment of Xpert could, moreover, turn an increasing MDR epidemic into a diminishing one. Synergistic effects were observed with assumptions of simultaneously improving MDR-TB treatment outcomes. Our results illustrate the potential impact of new and emerging technologies that enable widespread, timely DST, and the important effect that universal rapid DST in the public sector can have on the MDR-TB epidemic in India.

  14. Focused use of drug screening in overdose patients increases impact on management.

    Science.gov (United States)

    Erdmann, Andreas; Werner, Dominique; Hugli, Olivier; Yersin, Bertrand

    2015-01-01

    Drug poisoning is a common cause for attendance in the emergency department. Several toxicology centres suggest performing urinary drug screens, even though they rarely influence patient management. Measuring the impact on patient management, in a University Emergency Department with approximately 40 000 admissions annually, of a rapid urinary drug screening test using specifically focused indications. Drug screening was restricted to patients having a first psychotic episode or cases demonstrating respiratory failure, coma, seizures, a sympathomimetic toxidrome, severe opiate overdose necessitating naloxone, hypotension, ventricular arrhythmia, acquired long QT or QRS >100 ms, and high-degree heart block. Retrospective analysis of Triage® TOX drug screen tests performed between September 2009 and November 2011, and between January 2013 and March 2014. A total of 262 patients were included, mean age 35 ± 14.6 (standard deviation) years, 63% men; 29% poisoning with alcohol, and 2.3% deaths. Indications for testing were as follows: 34% were first psychotic episodes; 20% had acute respiratory failure; 16% coma; 8% seizures; 8% sympathomimetic toxidromes; 7% severe opioid toxidromes; 4% hypotension; 3% ventricular arrhythmias or acquired long QT intervals on electrocardiogram. A total of 78% of the tests were positive (median two substances, maximum five). The test resulted in drug-specific therapy in 6.1%, drug specific diagnostic tests in 13.3 %, prolonged monitoring in 10.7% of methadone-positive tests, and psychiatric admission in 4.2%. Overall, 34.3% tests influenced patient management. In contrast to previous studies showing modest effects of toxicological testing, restricted use of rapid urinary drug testing increases the impact on management of suspected overdose patients in the ED.

  15. 75 FR 53971 - Guidance for Industry and Food and Drug Administration Staff; Impact-Resistant Lenses: Questions...

    Science.gov (United States)

    2010-09-02

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0367] Guidance for Industry and Food and Drug Administration Staff; Impact-Resistant Lenses: Questions and Answers; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

  16. Economic Impacts of the Generic Drug User Fee Act Fee Structure.

    Science.gov (United States)

    Dong, Ke; Boehm, Garth; Zheng, Qiang

    2017-06-01

    A Food and Drug Administration (FDA) Generic Drug User system, Generic Drug User Fee Amendment of 2012 (GDUFA), started October 1, 2012, and has been in place for over 3 years. There is controversy about the GDUFA fee structure but no analysis of GDUFA data that we could find. To look at the economic impact of the GDUFA fee structure. We compared the structure of GDUFA with that of other FDA Human Drug User fees. We then, using FDA-published information, analyzed where GDUFA facility and Drug Master File fees are coming from. We used the Orange Book to identify the sponsors of all approved Abbreviated New Drug Applications (ANDAs) and the S&P Capital IQ database to find the ultimate parent companies of sponsors of approved ANDAs. The key differences between the previous structure for Human Drug User fees and the GDUFA are as follows: GDUFA has no approved product fee and no first-time or small business fee exemptions and GDUFA charges facility fees from the time of filing and charges a foreign facility levy. Most GDUFA fees are paid by or on behalf of foreign entities. The top 10 companies hold nearly 50% of all approved ANDAs but pay about 14% of GDUFA facility fees. We conclude that the regressive nature of the GDUFA fee structure penalizes small, new, and foreign firms while benefiting the large established firms. A progressive fee structure in line with other human drug user fees is needed to ensure a healthy generic drug industry. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  17. Social Dominance Orientation, Dispositional Empathy, and Need for Cognitive Closure Moderate the Impact of Empathy-Skills Training, but Not Patient Contact, on Medical Students' Negative Attitudes toward Higher-Weight Patients.

    Science.gov (United States)

    Meadows, Angela; Higgs, Suzanne; Burke, Sara E; Dovidio, John F; van Ryn, Michelle; Phelan, Sean M

    2017-01-01

    Anti-fat bias in healthcare providers and medical students has serious implications for quality of care of higher-weight patients. Studies of interventions aimed at reducing anti-fat attitudes in medical students have generally been disappointing, with little enduring effect. It is possible that some students may be more receptive to prejudice-reducing influences than others, due to underlying differences in their personal characteristics. It is also possible that attitudes toward patients, specifically, may differ from anti-fat attitudes in general, and prejudice-reduction effectiveness on patient-specific attitudes has not yet been evaluated. The present study explored the effect on general and patient-specific anti-fat attitudes of (1) contact with higher-weight individuals prior to and during medical school; and (2) training designed to increase medical students' empathy toward patients by encouraging them to take the patient's perspective during clinical encounters. The moderating role of individual difference factors on effectiveness of contact and student-reported hours of empathy training on patient-specific attitudes was assessed. A total of 3,576 students enrolled across 49 US medical schools completed an online survey at the start of their first year of medical school and at the end of their fourth year. Favorable contact experience with higher-weight patients predicted improved attitudes toward heavier patients after 4 years of medical school, and appeared sufficient to partially offset the effects of dislike of higher-weight individuals at baseline. The impact of favorable contact on general anti-fat attitudes was less strong, highlighting the importance of using target-specific outcome measures. The positive effects of favorable contact on attitudes toward higher-weight patients did not differ based on students' baseline levels of social dominance orientation, dispositional empathy, or need for cognitive closure. In contrast, the effectiveness of

  18. 75 FR 24967 - Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication

    Science.gov (United States)

    2010-05-06

    ... Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication. DATES: June 24, 2010... INTERNATIONAL TRADE COMMISSION [Investigation No. 332-352] Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication AGENCY: United States International Trade...

  19. 77 FR 31039 - Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication

    Science.gov (United States)

    2012-05-24

    .... 332-352, Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication... INTERNATIONAL TRADE COMMISSION [Investigation No. 332-352] Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication AGENCY: United States International Trade...

  20. Plutonium Disposition Now exclamation point

    International Nuclear Information System (INIS)

    Buckner, M.R.

    1995-01-01

    A means for use of existing processing facilities and reactors for plutonium disposition is described which requires a minimum capital investment and allows rapid implementation. The scenario includes interim storage and processing under IAEA control, and fabrication into MOX fuel in existing or planned facilities in Europe for use in operating reactors in the two home countries. Conceptual studies indicate that existing Westinghouse four-loop designs can safety dispose of 0.94 MT of plutonium per calendar year. Thus, it would be possible to consume the expected US excess stockpile of about 50 MT in two to three units of this type, and it is highly likely that a comparable amount of the FSU excess plutonium could be deposed of in a few VVER-1000's. The only major capital project for this mode of plutonium disposition would be the weapons-grade plutonium processing which could be done in a dedicated international facility or using existing facilities in the US and FSU under IAEA control. This option offers the potential for quick implementation at a very low cost to the governments of the two countries

  1. NRC comprehensive records disposition schedule

    International Nuclear Information System (INIS)

    1983-05-01

    Effective January 1, 1982, NRC will institute records retention and disposal practives in accordance with the approved Comprehensive Records Disposition Schedule (CRDS). CRDS is comprised of NRC Schedules (NRCS) 1 to 4 which apply to the agency's program or substantive records and General Records Schedules (GRS) 1 to 24 which apply to housekeeping or facilitative records. NRCS-I applies to records common to all or most NRC offices; NRCS-II applies to program records as found in the various offices of the Commission, Atomic Safety and Licensing Board Panel, and the Atomic Safety and Licensing Appeal Panel; NRCS-III applies to records accumulated by the Advisory Committee on Reactor Safeguards; and NRCS-IV applies to records accumulated in the various NRC offices under the Executive Director for Operations. The schedules are assembled functionally/organizationally to facilitate their use. Preceding the records descriptions and disposition instructions for both NRCS and GRS, there are brief statements on the organizational units which accumulate the records in each functional area, and other information regarding the schedules' applicability

  2. Measuring the Multicultural Dispositions of Preservice Teachers

    Science.gov (United States)

    Jensen, Bryant; Whiting, Erin Feinauer; Chapman, Sara

    2018-01-01

    Claims abound in the research literature regarding multicultural teacher dispositions, including how to foster them in teacher preparation programs. However, measures of multicultural dispositions of teachers that (a) capture the range of conceptually rich constructs and (b) demonstrate strong psychometric properties are not represented in the…

  3. Linguistic variables, approximate reasoning and dispositions

    Energy Technology Data Exchange (ETDEWEB)

    Zadeh, L.A.

    1983-07-01

    Test-score semantics is applied to the representation of meaning of dispositions, that is, propositions with suppressed fuzzy quantifiers, e.g. overeating causes obesity, icy roads are slippery, young men like young women, etc. The concept of a disposition plays an especially important role in the representation of commonsense knowledge. 45 references.

  4. Evaluation of Calcine Disposition Path Forward

    International Nuclear Information System (INIS)

    Birrer, S.A.; Heiser, M.B.

    2003-01-01

    This document describes an evaluation of the baseline and two alternative disposition paths for the final disposition of the calcine wastes stored at the Idaho Nuclear Technology and Engineering Center at the Idaho National Engineering and Environmental Laboratory. The pathways are evaluated against a prescribed set of criteria and a recommendation is made for the path forward

  5. Overview of surplus weapons plutonium disposition

    Energy Technology Data Exchange (ETDEWEB)

    Rudy, G.

    1996-05-01

    The safe disposition of surplus weapons useable plutonium is a very important and urgent task. While the functions of long term storage and disposition directly relate to the Department`s weapons program and the environmental management program, the focus of this effort is particularly national security and nonproliferation.

  6. Dispositions, Emotions, Episodes and the Autonomous Learner.

    Science.gov (United States)

    Wesson, Anthony J.

    1986-01-01

    Explores the relationship between dispositions (i.e., continuities of inclinations and habits), episodic behavior, emotions, and desires; and the development of moral autonomy. Argues that autonomy requires a settled disposition toward the good. Contrasts theories of autonomy based on wants/desires and on ideals. (AYC)

  7. Dispositions in Education: Nonentities Worth Talking about

    Science.gov (United States)

    Splitter, Laurance J.

    2010-01-01

    The concept of dispositions has commanded considerable attention in both philosophy and education. In this essay, Laurance Splitter draws on philosophy to take a fresh look at dispositions in education, specifically teacher education. Bypassing the pitfalls of both subjectivity and crude behaviorism, he proposes a conceptual framework in which…

  8. Population Impact of Drug Interactions with Warfarin: A Real-World Data Approach.

    Science.gov (United States)

    Martín-Pérez, Mar; Gaist, David; de Abajo, Francisco J; Rodríguez, Luis A García

    2018-03-01

     To investigate the population impact of previously reported interactions between warfarin and other drugs on international normalized ratio (INR) levels.  Using The Health Improvement Network (THIN), a United Kingdom primary care database, a cohort of warfarin users between 2005 and 2013 ( N  = 121,962) was followed until the first qualifying prescription for the potential interacting drugs was evaluated. Sixteen sub-cohorts, one for each study drug, and a control sub-cohort of warfarin were ascertained. Short-term changes in INR levels were assessed by comparing INR values measured before and after initiation of the interacting drug with paired Student's t -test. We also evaluated the proportion of patients with INR values outside the therapeutic range (INR: 2-3).  Miconazole use was associated with the highest mean increase in INR (+3.35), followed by amiodarone (+1.28), fluconazole (+0.79), metronidazole (+0.75) and nystatin (+0.65). After subtracting the natural INR variation observed in the control sub-cohort, supra-therapeutic levels (INR > 3) were found in 53.2% (miconazole), 45.5% (amiodarone), 23.3% (metronidazole), 23.2% (fluconazole) and 17.6% (nystatin) of patients initiating treatment with these drugs. Carbamazepine use was associated with a mean INR decrease of -0.63 and infra-therapeutic levels (INR < 2) were observed in 46.2% of patients initiating carbamazepine. For all other drugs, the change was small to moderate, in absolute INR units (+0.23 to +0.55) and in the proportion of patients with INR levels out of therapeutic range (<16%).  Clinically potentially important interactions were observed in several study drugs. The majority of them, although confirmed, had little impact after adjusting for standard INR variability in the general population of warfarin users. Schattauer GmbH Stuttgart.

  9. Impact of celebrity pitch in direct-to-consumer advertising of prescription drugs.

    Science.gov (United States)

    Bhutada, Nilesh S; Menon, Ajit M; Deshpande, Aparna D; Perri, Matthew

    2012-01-01

    Online surveys were conducted to determine the impact of endorser credibility, endorser effectiveness, and consumers' involvement in direct-to-consumer advertising. In a randomized posttest only study, using the elaboration likelihood model, survey participants (U.S. adults) were either exposed to a fictitious prescription drug ad with a celebrity or a noncelebrity endorser. There was no significant difference in credibility and effectiveness between the celebrity and the noncelebrity endorser. High involvement consumers viewed the ad more favorably and exhibited significantly stronger drug inquiry intentions during their next doctor visit. Further, consumers' involvement did not moderate the effect of celebrity endorser.

  10. The impact of treatment density and molecular weight for fractional laser-assisted drug delivery

    DEFF Research Database (Denmark)

    Haak, Christina S; Bhayana, Brijesh; Farinelli, William A

    2012-01-01

    Ablative fractional lasers (AFXL) facilitate uptake of topically applied drugs by creating narrow open micro-channels into the skin, but there is limited information on optimal laser settings for delivery of specific molecules. The objective of this study was to investigate the impact of laser...... treatment density (% of skin occupied by channels) and molecular weight (MW) for fractional CO(2) laser-assisted drug delivery. AFXL substantially increased intra- and transcutaneous delivery of polyethylene glycols (PEGs) in a MW range from 240 to 4300 Da (Nuclear Magnetic Resonance, p...

  11. Public and private sector contributions to the discovery and development of "impact" drugs.

    Science.gov (United States)

    Reichert, Janice M; Milne, Christopher-Paul

    2002-01-01

    Recently, well-publicized reports by Public Citizen and the Joint Economic Committee (JEC) of the US Congress questioned the role of the drug industry in the discovery and development of therapeutically important drugs. To gain a better understanding of the relative roles of the public and private sectors in pharmaceutic innovation, the Tufts Center for the Study of Drug Development evaluated the underlying National Institutes of Health (NIH) and academic research cited in the Public Citizen and JEC reports and performed its own assessment of the relationship between the private and public sectors in drug discovery and development of 21 "impact" drugs. We found that, ultimately, any attempt to measure the relative contribution of the public and private sectors to the research and development (R&D) of therapeutically important drugs by output alone, such as counting publications or even product approvals, is flawed. Several key factors (eg, degree of uncertainty, expected market value, potential social benefit) affect investment decisions and determine whether public or private sector funds, or both, are most appropriate. Because of the competitiveness and complexity of today's R&D environment, both sectors are increasingly challenged to show returns on their investment and the traditional boundaries separating the roles of the private and public research spheres have become increasingly blurred. What remains clear, however, is that the process still starts with good science and ends with good medicine.

  12. Safeguard and security issues for the U.S. Fissile Materials Disposition Program

    International Nuclear Information System (INIS)

    Jaeger, C.D.; Moya, R.W.; Duggan, R.A.

    1995-01-01

    The Department of Energy's Office of Materials Disposition (MD) is analyzing long-term storage and disposition options for fissile materials, preparing a Programmatic Environmental Impact Statement (PEIS), preparing for a Record of Decision (ROD) regarding this material, and conducting other related activities. A primary objective of this program is to support U.S. nonproliferation policy by reducing major security risks. Particular areas of concern are the acquisition of this material by unauthorized persons and preventing the reintroduction of the material for use in weapons. This paper presents some of the issues, definitions, and assumptions addressed by the Safeguards and Security Project Team in support of the Fissile Materials Disposition Program (FMDP). The discussion also includes some preliminary ideas regarding safeguards and security criteria that are applicable to the screening of disposition options

  13. Safeguards and security issues for the U.S. Fissile Materials Disposition Program

    International Nuclear Information System (INIS)

    Jaeger, C.D.; Moya, R.W.; Duggan, R.A.

    1995-01-01

    The Department of Energy's Office of Materials Disposition (MD) is analyzing long-term storage and disposition options for fissile materials, preparing a Programmatic Environmental Impact Statement (PEIS), preparing for a Record of Decision (ROD) regarding this material, and conducting other related activities. A primary objective of this program is to support US nonproliferation policy by reducing major security risks. Particular areas of concern are the acquisition of this material by unauthorized persons and preventing the reintroduction of the material for use in weapons. This paper presents some of the issues, definitions, and assumptions addressed by the Safeguards and Security Project Team in support of the Fissile Materials Disposition Program (FMDP). The discussion also includes some preliminary ideas regarding safeguards and security criteria that are applicable to the screening of disposition options

  14. Assessing the Impact of Antidrug Advertising on Adolescent Drug Consumption: Results From a Behavioral Economic Model

    Science.gov (United States)

    Block, Lauren G.; Morwitz, Vicki G.; Putsis, William P.; Sen, Subrata K.

    2002-01-01

    Objectives. This study examined whether adolescents’ recall of antidrug advertising is associated with a decreased probability of using illicit drugs and, given drug use, a reduced volume of use. Methods. A behavioral economic model of influences on drug consumption was developed with survey data from a nationally representative sample of adolescents to determine the incremental impact of antidrug advertising. Results. The findings provided evidence that recall of antidrug advertising was associated with a lower probability of marijuana and cocaine/crack use. Recall of such advertising was not associated with the decision of how much marijuana or cocaine/crack to use. Results suggest that individuals predisposed to try marijuana are also predisposed to try cocaine/crack. Conclusions. The present results provide support for the effectiveness of antidrug advertising programs. (Am J Public Health. 2002;92:1346–1351) PMID:12144995

  15. Impact of Spacing of Practice on Learning Brand Name and Generic Drugs.

    Science.gov (United States)

    Terenyi, James; Anksorus, Heidi; Persky, Adam M

    2018-02-01

    Objective. To test the impact of schedules of retrieval practice on learning brand and generic name drug information in a self-paced course. Methods. Students completed weekly quizzes on brand and generic name conversions for 100 commonly prescribed drugs. Each student completed part of the drug list on a schedule of equal, expanding, or contracting spacing, one practice (massed) or study only in a partial block design. Results. On measures of long-term retention, the contracting spacing schedule led to superior retention (67%) compared to the massed practice (50%) and study-only condition (46%); contracting practice also was significantly higher than expanding practice (58%,) or equal practice (59%). Overall performance decreased by almost 50% (final exam 95%, long-term retention 55%) over a 6-week period. Conclusion. A contracting spacing schedule was the most effective schedule of practice, and all spacing schedules were superior to massed practice or study-only conditions.

  16. The impact of race, income, drug abuse and dependence on health insurance coverage among US adults.

    Science.gov (United States)

    Wang, Nianyang; Xie, Xin

    2017-06-01

    Little is known about the impact of drug abuse/dependence on health insurance coverage, especially by race groups and income levels. In this study, we examine the disparities in health insurance predictors and investigate the impact of drug use (alcohol abuse/dependence, nicotine dependence, and illicit drug abuse/dependence) on lack of insurance across different race and income groups. To perform the analysis, we used insurance data (8057 uninsured and 28,590 insured individual adults) from the National Surveys on Drug Use and Health (NSDUH 2011). To analyze the likelihood of being uninsured we performed weighted binomial logistic regression analyses. The results show that the overall prevalence of lacking insurance was 19.6 %. However, race differences in lack of insurance exist, especially for Hispanics who observe the highest probability of being uninsured (38.5 %). Furthermore, we observe that the lowest income level bracket (annual income <$20,000) is associated with the highest likelihood of being uninsured (37.3 %). As the result of this investigation, we observed the following relationship between drug use and lack of insurance: alcohol abuse/dependence and nicotine dependence tend to increase the risk of lack of insurance for African Americans and whites, respectively; illicit drug use increases such risk for whites; alcohol abuse/dependence increases the likelihood of lack of insurance for the group with incomes $20,000-$49,999, whereas nicotine dependence is associated with higher probability of lack of insurance for most income groups. These findings provide some useful insights for policy makers in making decisions regarding unmet health insurance coverage.

  17. Impacts of Weather Shocks on Murder and Drug Cartel Violence in Mexico

    Science.gov (United States)

    Miguel, E.; Hsiang, S. M.; Burke, M.; Gonzalez, F.; Baysan, C.

    2014-12-01

    We estimate impacts of weather shocks on several dimensions of violence in Mexico during 1990-2010, using disaggregated data at the state-by-month level. Controlling for location and time fixed effects, we show that higher than normal temperatures lead to: (i) higher total murder rates, (ii) higher rates of drug cartel related murders, and (iii) higher suicide rates. The effects of high temperatures on inter-personal violence (murders) and on inter-group violence (drug cartel related murders) are large, statistically significant and similar to those found in other recent settings. The use of panel data econometric methods to examine the effect of weather on suicide incidence is novel. We assess the role of economic channels (i.e., agricultural production affected by weather) and conclude that they cannot account for most of the estimated impacts, suggesting that other mechanisms, including psychological explanations, are likely to be important in this setting.

  18. Fernald waste management and disposition

    International Nuclear Information System (INIS)

    West, M.L.; Fisher, L.A.; Frost, M.L.; Rast, D.M.

    1995-01-01

    Historically waste management within the Department of Energy complex has evolved around the operating principle of packaging waste generated and storing until a later date. In many cases wastes were delivered to onsite waste management organizations with little or no traceability to origin of generation. Sites then stored their waste for later disposition offsite or onsite burial. While the wastes were stored, sites incurred additional labor costs for maintaining, inspecting and repackaging containers and capital costs for storage warehouses. Increased costs, combined with the inherent safety hazards associated with storage of hazardous material make these practices less attractive. This paper will describe the methods used at the Department of Energy's Fernald site by the Waste Programs Management Division to integrate with other site divisions to plan in situ waste characterization prior to removal. This information was utilized to evaluate and select disposal options and then to package and ship removed wastes without storage

  19. In silico analysis of the anti-hypertensive drugs impact on myocardial oxygen balance.

    Science.gov (United States)

    Guala, A; Leone, D; Milan, A; Ridolfi, L

    2017-06-01

    Hypertension is a very common pathology, and its clinical treatment largely relies on different drugs. Some of these drugs exhibit specific protective functions in addition to those resulting from blood pressure reduction. In this work, we study the impact of commonly used anti-hypertensive drugs (RAAS, [Formula: see text] and calcium channel blockers) on myocardial oxygen supply-consumption balance, which plays a crucial role in type 2 myocardial infarction. To this aim, 42 wash-out hypertensive patients were selected, a number of measured data were used to set a validated multi-scale cardiovascular model to subject-specific conditions, and the administration of different drugs was suitably simulated. Our results ascribe the well-known major cardioprotective efficiency of [Formula: see text] blockers compared to other drugs to a positive change of myocardial oxygen balance due to the concomitant: (1) reduction in aortic systolic, diastolic and pulse pressures, (2) decrease in left ventricular work, diastolic cavity pressure and oxygen consumption, (3) increase in coronary flow and (4) ejection efficiency improvement. RAAS blockers share several positive outcomes with [Formula: see text] blockers, although to a reduced extent. In contrast, calcium channel blockers seem to induce some potentially negative effects on the myocardial oxygen balance.

  20. Impact of common cytostatic drugs on pollen fertility in higher plants.

    Science.gov (United States)

    Mišík, Miroslav; Kundi, Michael; Pichler, Clemens; Filipic, Metka; Rainer, Bernhard; Mišíková, Katarina; Nersesyan, Armen; Knasmueller, Siegfried

    2016-08-01

    Cytostatic drugs are among the most toxic chemicals which are produced. Many of them cause damage of the genetic material which may affect the fertility of higher organisms. To study the impact of the widely used anticancer drugs [cisplatin (CisPt), etoposide (Et), and 5-fluorouracil (5-FU)] on the reproduction of higher plants, pollen abortion experiments were conducted with species which belong to major plant families, namely with Tradescantia paludosa (Commelinaceae), Arabidopsis thaliana (Brassicaceae), Chelidonium majus (Papaveraceae), and Alisma plantago-aquatica (Alismataceae). All compounds increased the frequencies of abortive grains. The lowest effective doses were in general in a narrow range (i.e., 1 and 10 mg/kg of dry soil). The effects of the individual drugs were similar in T. paludosa, A. plantago-aquatica, and Ch. majus, while A. thaliana was consistently less sensitive. The highest abortion rate was obtained in most experiments with CisPt, followed by 5-FU and Et. Comparisons of the doses which caused effects in the present experiments in the different species with the predicted environment concentrations and with the levels of the cytostatics which were detected in hospital wastewaters show that the realistic environmental concentrations of the drugs are 4-6 orders of magnitude lower. Therefore, it is unlikely that these drugs affect the fertility of higher plants in aquatic and terrestrial ecosystems.

  1. Residual Complexity Does Impact Organic Chemistry and Drug Discovery: The Case of Rufomyazine and Rufomycin.

    Science.gov (United States)

    Choules, Mary P; Klein, Larry L; Lankin, David C; McAlpine, James B; Cho, Sang-Hyun; Cheng, Jinhua; Lee, Hanki; Suh, Joo-Won; Jaki, Birgit U; Franzblau, Scott G; Pauli, Guido F

    2018-05-24

    Residual complexity (RC) involves the impact of subtle but critical structural and biological features on drug lead validation, including unexplained effects related to unidentified impurities. RC commonly plagues drug discovery efforts due to the inherent imperfections of chromatographic separation methods. The new diketopiperazine, rufomyazine (6), and the previously known antibiotic, rufomycin (7), represent a prototypical case of RC that (almost) resulted in the misassignment of biological activity. The case exemplifies that impurities well below the natural abundance of 13 C (1.1%) can be highly relevant and calls for advanced analytical characterization of drug leads with extended molar dynamic ranges of >1:1,000 using qNMR and LC-MS. Isolated from an actinomycete strain, 6 was originally found to be active against Mycobacterium tuberculosis with a minimum inhibitory concentration (MIC) of 2 μg/mL and high selectivity. As a part of lead validation, the dipeptide was synthesized and surprisingly found to be inactive. The initially observed activity was eventually attributed to a very minor contamination (0.24% [m/m]) with a highly active cyclic peptide (MIC ∼ 0.02 μM), subsequently identified as an analogue of 7. This study illustrates the serious implications RC can exert on organic chemistry and drug discovery, and what efforts are vital to improve lead validation and efficiency, especially in NP-related drug discovery programs.

  2. Impact of repeated intravenous cocaine administration on incentive motivation depends on mode of drug delivery.

    Science.gov (United States)

    LeBlanc, Kimberly H; Maidment, Nigel T; Ostlund, Sean B

    2014-11-01

    The incentive sensitization theory of addiction posits that repeated exposure to drugs of abuse, like cocaine, can lead to long-term adaptations in the neural circuits that support motivated behavior, providing an account of pathological drug-seeking behavior. Although pre-clinical findings provide strong support for this theory, much remains unknown about the conditions that support incentive sensitization. The current study examined whether the mode of cocaine administration is an important factor governing that drug's long-term impact on behavior. Separate groups of rats were allowed either to self-administer intravenous cocaine or were given an equivalent number and distribution of unsignaled cocaine or saline infusions. During the subsequent test of incentive motivation (Pavlovian-to-instrumental transfer), we found that rats with a history of cocaine self-administration showed strong cue-evoked food seeking, in contrast to rats given unsignaled cocaine or saline. This finding indicates that the manner in which cocaine is administered can determine its lasting behavioral effects, suggesting that subjective experiences during drug use play a critical role in the addiction process. Our findings may therefore have important implications for the study and treatment of compulsive drug seeking. © 2013 Society for the Study of Addiction.

  3. SC lipid model membranes designed for studying impact of ceramide species on drug diffusion and permeation--part II: diffusion and permeation of model drugs.

    Science.gov (United States)

    Ochalek, M; Podhaisky, H; Ruettinger, H-H; Wohlrab, J; Neubert, R H H

    2012-10-01

    The barrier function of two quaternary stratum corneum (SC) lipid model membranes, which were previously characterized with regard to the lipid organization, was investigated based on diffusion studies of model drugs with varying lipophilicities. Diffusion experiments of a hydrophilic drug, urea, and more lipophilic drugs than urea (i.e. caffeine, diclofenac sodium) were conducted using Franz-type diffusion cells. The amount of permeated drug was analyzed using either HPLC or CE technique. The subjects of interest in the present study were the investigation of the influence of physicochemical properties of model drugs on their diffusion and permeation through SC lipid model membranes, as well as the study of the impact of the constituents of these artificial systems (particularly ceramide species) on their barrier properties. The diffusion through both SC lipid model membranes and the human SC of the most hydrophilic model drug, urea, was faster than the permeation of the more lipophilic drugs. The slowest rate of permeation through SC lipid systems occurred in the case of caffeine. The composition of SC lipid model membranes has a significant impact on their barrier function. Model drugs diffused and permeated faster through Membrane II (presence of Cer [EOS]). In terms of the barrier properties, Membrane II is much more similar to the human SC than Membrane I. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Impact of pharmacist’s interventions on cost of drug therapy in intensive care unit. Pharmacy

    Directory of Open Access Journals (Sweden)

    Saokaew S

    2009-06-01

    Full Text Available Pharmacist participation in patient care team has been shown to reduce incidence of adverse drug events, and overall drug costs. However, impact of pharmacist participation in the multidisciplinary intensive care team on cost saving and cost avoidance has little been studied in Thailand.Objective: To describe the characteristics of the interventions and to determine pharmacist’s interventions led to change in cost saving and cost avoidance in intensive care unit (ICU. Methods: A Prospective, standard care-controlled study design was used to compare cost saving and cost avoidance of patients receiving care from patient care team (including a clinical pharmacist versus standard care (no pharmacist on team. All patients admitted to the medical intensive care unit 1 and 2 during the same period were included in the study. The outcome measures were overall drug cost and length of ICU stay. Interventions made by the pharmacist in the study group were documented. The analyses of acceptance and cost saving and/or cost avoidance were also performed. Results: A total of 65 patients were admitted to either ICU 1 or 2 during the 5 week- study period. The pharmacist participated in patient care and made total of 127 interventions for the ICU-1 team. Ninety-eight percent of the interventions were accepted and implemented by physicians. The difference of overall drug cost per patient between two groups was 182.01 USD (1,076.37 USD in study group and 1,258.38 USD in control group, p=0.138. The average length of ICU stay for the intervention group and the control group was not significantly different (7.16 days vs. 6.18 days, p=0.995. The 125 accepted interventions were evaluated for cost saving and cost avoidance. Pharmacist’s interventions yielded a total of 1,971.43 USD from drug cost saving and 294.62 USD from adverse drug event cost avoidance. The net cost saved and avoided from pharmacist interventions was 2,266.05 USD. Interventions involving

  5. Proliferation resistance criteria for fissile material disposition

    International Nuclear Information System (INIS)

    Close, D.A.; Fearey, B.L.; Markin, J.T.; Rutherford, D.A.; Duggan, R.A.; Jaeger, C.D.; Mangan, D.L.; Moya, R.W.; Moore, L.R.; Strait, R.S.

    1995-04-01

    The 1994 National Academy of Sciences study open-quotes Management and Disposition of Excess Weapons Plutoniumclose quotes defined options for reducing the national and international proliferation risks of materials declared excess to the nuclear weapons program. This report proposes criteria for assessing the proliferation resistance of these options. The criteria are general, encompassing all stages of the disposition process from storage through intermediate processing to final disposition including the facilities, processing technologies and materials, the level of safeguards for these materials, and the national/subnational threat to the materials

  6. Promoting Value, Affordability, and Innovation in Cancer Drug Treatment - The Rising Cost of Cancer Drugs: Impact on Patients and Society

    Science.gov (United States)

    Innovative new drugs have improved outcomes for many cancer patients. But spending on cancer drugs has increased dramatically in recent years, placing a burden on cancer patients and a strain on health system and societal resources.

  7. Safeguards and security issues for the disposition of fissile materials

    International Nuclear Information System (INIS)

    Jaeger, C.D.; Moya, R.W.; Duggan, R.A.; Mangan, D.L.; Tolk, K.M.; Rutherford, D.; Fearey, B.; Moore, L.

    1995-01-01

    The Department of Energy's Office of Fissile Material Disposition (FMD) is analyzing long-term storage and disposition options for surplus weapons-usable fissile materials, preparing a programmatic environmental impact statement (PEIS), preparing for a record of decision (ROD) regarding this material and conducting other activities. The primary security objectives of this program are to reduce major security risks and strengthen arms reduction and nonproliferation (NP). To help achieve these objectives, a safeguards and security (S ampersand S) team consisting of participants from Sandia, Los Alamos, and Lawrence Livermore National Laboratories was established. The S ampersand S activity for this program is a cross-cutting task which addresses all of the FMD program options. It includes both domestic and international safeguards and includes areas such as physical protection, nuclear materials accountability and material containment and surveillance. This paper will discuss the activities of the Fissile Materials Disposition Program (FMDP) S ampersand S team as well as some specific S ampersand S issues associated with various FMDP options/facilities. Some of the items to be discussed include the threat, S ampersand S requirements, S ampersand S criteria for assessing risk, S ampersand S issues concerning fissile material processing/facilities, and international and domestic safeguards

  8. Guidelines for conducting pharmaceutical budget impact analyses for submission to public drug plans in Canada.

    Science.gov (United States)

    Marshall, Deborah A; Douglas, Patrick R; Drummond, Michael F; Torrance, George W; Macleod, Stuart; Manti, Orlando; Cheruvu, Lokanadha; Corvari, Ron

    2008-01-01

    Until now, there has been no standardized method of performing and presenting budget impact analyses (BIAs) in Canada. Nevertheless, most drug plan managers have been requiring this economic data to inform drug reimbursement decisions. This paper describes the process used to develop the Canadian BIA Guidelines; describes the Guidelines themselves, including the model template; and compares this guidance with other guidance on BIAs. The intended audience includes those who develop, submit or use BIA models, and drug plan managers who evaluate BIA submissions. The Patented Medicine Prices Review Board (PMPRB) initiated the development of the Canadian BIA Guidelines on behalf of the National Prescription Drug Utilisation Information System (NPDUIS). The findings and recommendations from a needs assessment with respect to BIA submissions were reviewed to inform guideline development. In addition, a literature review was performed to identify existing BIA guidance. The detailed guidance was developed on this basis, and with the input of the NPDUIS Advisory Committee, including drug plan managers from multiple provinces in Canada and a representative from the Canadian Agency for Drugs and Technologies in Health. A Microsoft Excel-based interactive model template was designed to support BIA model development. Input regarding the guidelines and model template was sought from each NPDUIS Advisory Committee member to ensure compatibility with existing drug plan needs. Decisions were made by consensus through multiple rounds of review and discussion. Finally, BIA guidance in Canadian provinces and other countries were compared on the basis of multiple criteria. The BIA guidelines consist of three major sections: Analytic Framework, Inputs and Data Sources, and Reporting Format. The Analytic Framework section contains a discussion of nine general issues surrounding BIAs (model design, analytic perspective, time horizon, target population, costing, scenarios to be compared

  9. Impact of Fusarium mycotoxins on hepatic and intestinal mRNA expression of cytochrome P450 enzymes and drug transporters, and on the pharmacokinetics of oral enrofloxacin in broiler chickens.

    Science.gov (United States)

    Antonissen, Gunther; Devreese, Mathias; De Baere, Siegrid; Martel, An; Van Immerseel, Filip; Croubels, Siska

    2017-03-01

    Cytochrome P450 (CYP450) drug biotransformation enzymes and multidrug resistance (MDR) proteins may influence drug disposition processes. The first part of the study aimed to evaluate the effect of mycotoxins deoxynivalenol (DON) and/or fumonisins (FBs), at contamination levels approaching European Union guidance levels, on intestinal and hepatic CYP450 enzymes and MDR proteins gene expression in broiler chickens. mRNA expression of genes encoding CYP450 enzymes (CYP3A37, CYP1A4 and CYP1A5) and drug transporters (MDR1/ABCB1 and MRP2/ABCC2) was determined using qRT-PCR. A significant up-regulation of CYP1A4 (P = 0.037) and MDR1 (P = 0.036) was observed in the jejunum of chickens fed a diet contaminated with FBs. The second part of this study aimed to investigate the impact of feeding a FBs contaminated diet on the oral absorption of enrofloxacin (10 mg/kg BW), a MDR1 substrate. A significant (P = 0.045), however small, decreased area under the plasma concentration-time curve (AUC 0-48  h, mean ± SD) was observed for enrofloxacin in chickens fed the FBs contaminated diet compared to the control group, 16.28 ± 1.82 h μg/mL versus 18.27 ± 1.79 h μg/mL. These findings suggest that concurrent administration of drugs with FBs contaminated feed might alter the pharmacokinetic characteristics of CYP1A4 substrate drugs and MDR1 substrates, such as enrofloxacin. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Trends in oral drug bioavailability following bariatric surgery: examining the variable extent of impact on exposure of different drug classes.

    Science.gov (United States)

    Darwich, Adam S; Henderson, Kathryn; Burgin, Angela; Ward, Nicola; Whittam, Janet; Ammori, Basil J; Ashcroft, Darren M; Rostami-Hodjegan, Amin

    2012-11-01

    Changes to oral drug bioavailability have been observed post bariatric surgery. However, the magnitude and the direction of changes have not been assessed systematically to provide insights into the parameters governing the observed trends. Understanding these can help with dose adjustments. Analysis of drug characteristics based on a biopharmaceutical classification system is not adequate to explain observed trends in altered oral drug bioavailability following bariatric surgery, although the findings suggest solubility to play an important role. To identify the most commonly prescribed drugs in a bariatric surgery population and to assess existing evidence regarding trends in oral drug bioavailability post bariatric surgery. A retrospective audit was undertaken to document commonly prescribed drugs amongst patients undergoing bariatric surgery in an NHS hospital in the UK and to assess practice for drug administration following bariatric surgery. The available literature was examined for trends relating to drug permeability and solubility with regards to the Biopharmaceutics Classification System (BCS) and main route of elimination. No significant difference in the 'post/pre surgery oral drug exposure ratio' (ppR) was apparent between BCS class I to IV drugs, with regards to dose number (Do) or main route of elimination. Drugs classified as 'solubility limited' displayed an overall reduction as compared with 'freely soluble' compounds, as well as an unaltered and increased ppR. Clinical studies establishing guidelines for commonly prescribed drugs, and the monitoring of drugs exhibiting a narrow therapeutic window or without a readily assessed clinical endpoint, are warranted. Using mechanistically based pharmacokinetic modelling for simulating the multivariate nature of changes in drug exposure may serve as a useful tool in the further understanding of postoperative trends in oral drug exposure and in developing practical clinical guidance. © 2012 The Authors

  11. The impact of cardiovascular drugs on the efficacy of local anesthesia in dentistry.

    Science.gov (United States)

    Milosavljevic, Мarko J; Jankovic, Slobodan M

    2016-12-01

    Drugs used chronically by patients with diseases of the cardiovascular system (group C of the ATC classification) may act on adrenergic receptors and/or certain ion channels, which gives them the potential to interact with the action of local dental anesthetics. The aim of the study was to investigate the effect of systemically administered chronic cardiovascular medication (oral route) on the efficacy of intraoral local anesthesia in patients with diseases of the cardiovascular system. This was a prospective cohort study which analyzed the efficacy of local terminal anesthesia (onset of anesthesia, duration anesthetized area) in the upper jaw of 70 patients: 40 patients on medication for cardiovascular system disorders and 30 patients who were not using these drugs (the control group). The following cardiovascular drugs were used: beta blockers, angiotensin converting enzyme inhibitors, calcium channel blockers, vasodilatators, diuretics, angiotensin receptor blockers, antiarrhythmics, statins and alfa blockers. The onset of anesthesia on the vestibular side was faster in those taking cardiovascular drugs (40.50±19.87 s) than the control patients (58.93±31.07 s; P = 0.004) and duration of anesthesia on this side was shorter. Although the difference was not significant, it was evident that on vestibular and palatal side the anesthetized area was more rapidly reduced in the patients taking cardiovascular drugs. The duration of cardiovascular therapy also had a significant impact on the anesthetized area. Drugs acting on cardiovascular system may influence the effect of local anesthetics used in dentistry, possibly through interaction with autonomic receptors and ion channels.

  12. [Evolution of reimbursement of high-cost anticancer drugs: Financial impact within a university hospital].

    Science.gov (United States)

    Baudouin, Amandine; Fargier, Emilie; Cerruti, Ariane; Dubromel, Amélie; Vantard, Nicolas; Ranchon, Florence; Schwiertz, Vérane; Salles, Gilles; Souquet, Pierre-Jean; Thomas, Luc; Bérard, Frédéric; Nancey, Stéphane; Freyer, Gilles; Trillet-Lenoir, Véronique; Rioufol, Catherine

    2017-06-01

    In the context of health expenses control, reimbursement of high-cost medicines with a 'minor' or 'nonexistent' improvement in actual health benefit evaluated by the Haute Autorité de santé is revised by the decree of March 24, 2016 related to the procedure and terms of registration of high-cost pharmaceutical drugs. This study aims to set up the economic impact of this measure. A six months retrospective study was conducted within a French university hospital from July 1, 2015 to December 31, 2015. For each injectable high-cost anticancer drug prescribed to a patient with cancer, the therapeutic indication, its status in relation to the marketing authorization and the associated improvement in actual health benefit were examined. The total costs of these treatments, the cost per type of indication and, in the case of marketing authorization indications, the cost per improvement in actual health benefit were evaluated considering that all drugs affected by the decree would be struck off. Over six months, 4416 high-cost injectable anticancer drugs were prescribed for a total cost of 4.2 million euros. The costs of drugs with a minor or nonexistent improvement in actual benefit and which comparator is not onerous amount 557,564 euros. The reform of modalities of inscription on the list of onerous drugs represents a significant additional cost for health institutions (1.1 million euros for our hospital) and raises the question of the accessibility to these treatments for cancer patients. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  13. Social Media Impact of the Food and Drug Administration's Drug Safety Communication Messaging About Zolpidem: Mixed-Methods Analysis.

    Science.gov (United States)

    Sinha, Michael S; Freifeld, Clark C; Brownstein, John S; Donneyong, Macarius M; Rausch, Paula; Lappin, Brian M; Zhou, Esther H; Dal Pan, Gerald J; Pawar, Ajinkya M; Hwang, Thomas J; Avorn, Jerry; Kesselheim, Aaron S

    2018-01-05

    The Food and Drug Administration (FDA) issues drug safety communications (DSCs) to health care professionals, patients, and the public when safety issues emerge related to FDA-approved drug products. These safety messages are disseminated through social media to ensure broad uptake. The objective of this study was to assess the social media dissemination of 2 DSCs released in 2013 for the sleep aid zolpidem. We used the MedWatcher Social program and the DataSift historic query tool to aggregate Twitter and Facebook posts from October 1, 2012 through August 31, 2013, a period beginning approximately 3 months before the first DSC and ending 3 months after the second. Posts were categorized as (1) junk, (2) mention, and (3) adverse event (AE) based on a score between -0.2 (completely unrelated) to 1 (perfectly related). We also looked at Google Trends data and Wikipedia edits for the same time period. Google Trends search volume is scaled on a range of 0 to 100 and includes "Related queries" during the relevant time periods. An interrupted time series (ITS) analysis assessed the impact of DSCs on the counts of posts with specific mention of zolpidem-containing products. Chow tests for known structural breaks were conducted on data from Twitter, Facebook, and Google Trends. Finally, Wikipedia edits were pulled from the website's editorial history, which lists all revisions to a given page and the editor's identity. In total, 174,286 Twitter posts and 59,641 Facebook posts met entry criteria. Of those, 16.63% (28,989/174,286) of Twitter posts and 25.91% (15,453/59,641) of Facebook posts were labeled as junk and excluded. AEs and mentions represented 9.21% (16,051/174,286) and 74.16% (129,246/174,286) of Twitter posts and 5.11% (3,050/59,641) and 68.98% (41,138/59,641) of Facebook posts, respectively. Total daily counts of posts about zolpidem-containing products increased on Twitter and Facebook on the day of the first DSC; Google searches increased on the week of the

  14. Disposition pathways and pharmacokinetics of herbal medicines in humans.

    Science.gov (United States)

    He, S-M; Li, C G; Liu, J-P; Chan, E; Duan, W; Zhou, S-F

    2010-01-01

    Pharmacokinetic studies have become an integral part of modern drug development, but these studies are not regulatory needs for herbal remedies. This paper updates our current knowledge on the disposition pathways and pharmacokinetic properties of commonly used herbal medicines in humans. To retrieve relevant data, the authors have searched through computer-based literatures by full text search in Medline (via Pubmed), ScienceDirect, Current Contents Connect (ISI), Cochrance Library, CINAHL (EBSCO), CrossRef Search and Embase (all from inception to May 2010). Many herbal compounds undergo Phase I and/or Phase II metabolism in vivo, with cytochrome P450s (CYPs) and uridine diphosphate glucuronosyltransferases (UGTs) playing a major role. Some herbal ingredients are substrates of P-glycoprotein (P-gp) which is highly expressed in the intestine, liver, brain and kidney. As such, the activities of these drug metabolizing enzymes and drug transporters are determining factors for the in vivo bioavailability, disposition and distribution of herbal remedies. There are increasing pharmacokinetic studies of herbal remedies, but these studies are mainly focused on a small number of herbal remedies including St John's wort, milk thistle, sculcap, curcumin, echinacea, ginseng, ginkgo, and ginger. The pharmacokinetic data of a small number of purified herbal ingredients, including anthocyanins, berberine, catechins, curcumin, lutein and quercetin, are available. For the majority of herbal remedies used in folk medicines, data on their disposition and biological fate in humans are lacking or in paucity. For a herbal medicine, the pharmacological effect is achieved when the bioactive agents or the metabolites reach and sustain proper levels at their sites of action. Both the dose levels and fates of active components in the body govern their target-site concentrations after administration of an herbal remedy. In this regard, a safe and optimal use of herbal medicines requires a

  15. Tissue disposition of bifenthrin in the rat

    Data.gov (United States)

    U.S. Environmental Protection Agency — Tissue disposition of bifenthrin in the rat and oral and intravenous administration. This dataset is associated with the following publication: Hughes , M., D. Ross...

  16. The personal dispositions of violent extremism

    Directory of Open Access Journals (Sweden)

    Davydov D.G.

    2017-04-01

    Full Text Available The paper presents the differences in the nature of extremism and radicalism, and the necessity of introducing the concept of "violent extremism." It is shown that the ideology is the explanation of extremist behavior, rather than its cause. The ideology of extremism often eclectic, contradictory and can easily be transformed by changing the object of hostility, depending on the situation. For the description of the psychological causes of extremism it is proposed to use the concept of personal disposition. Disposition is the preferred way to subjective interpretation of reality and reflects both the specific needs of a person as well the typical social situations where it realized and personal experience. Considered the following dispositions of violent extremism: the Cult of force and aggression, Intolerance, Out-group hostility Conventional coercion, Social pessimism and destructiveness, Mystical, Fighting and overcoming, Nihilism to law, Anti-subjectivism. It is proposed to use these dispositions as diagnostic criteria and for preventing and correcting.

  17. 49 CFR 244.19 - Disposition.

    Science.gov (United States)

    2010-10-01

    ... Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS ON SAFETY INTEGRATION PLANS GOVERNING RAILROAD CONSOLIDATIONS, MERGERS, AND ACQUISITIONS OF CONTROL Safety Integration Plans § 244.19 Disposition. (a) Standard of review. FRA reviews an...

  18. KE Basin water dispositioning engineering study

    International Nuclear Information System (INIS)

    Hunacek, G.S.; Gahir, S.S.

    1994-01-01

    This engineering study is a feasibility study of KE Basin water treatment to an acceptable level and dispositioning the treated water to Columbia River, ground through ETF or to air through evaporation

  19. Excess plutonium disposition using ALWR technology

    International Nuclear Information System (INIS)

    Phillips, A.; Buckner, M.R.; Radder, J.A.; Angelos, J.G.; Inhaber, H.

    1993-02-01

    The Office of Nuclear Energy of the Department of Energy chartered the Plutonium Disposition Task Force in August 1992. The Task Force was created to assess the range of practicable means of disposition of excess weapons-grade plutonium. Within the Task Force, working groups were formed to consider: (1) storage, (2) disposal,and(3) fission options for this disposition,and a separate group to evaluate nonproliferation concerns of each of the alternatives. As a member of the Fission Working Group, the Savannah River Technology Center acted as a sponsor for light water reactor (LWR) technology. The information contained in this report details the submittal that was made to the Fission Working Group of the technical assessment of LWR technology for plutonium disposition. The following aspects were considered: (1) proliferation issues, (2) technical feasibility, (3) technical availability, (4) economics, (5) regulatory issues, and (6) political acceptance

  20. Drug repurposing in pharmaceutical industry and its impact on market access: market access implications

    Science.gov (United States)

    Murteira, Susana; Millier, Aurélie; Toumi, Mondher

    2014-01-01

    Background Drug repurposing is a group of development strategies employed in order to overcome some of the hurdles innate to drug research and development. Drug repurposing includes drug repositioning, reformulation and combination. Objective This study aimed to identify the determinants of successful market access outcome for drug repurposing in the United States of America (USA) and in Europe. Methods The case studies of repurposing strategies were identified through a systematic review of the literature. Price information and reimbursement conditions for all the case studies were collected mainly through access of public datasources. A list of attributes that could be associated with market access outcome (price level and reimbursement conditions) was developed, discussed, and validated by an external expert group. Detailed information for all attributes was researched and collected for each case study. Bivariate regression models were conducted to identify factors associated with price change for all repurposing cases. A similar analysis was performed for reformulation and repositioning cases, in the USA and in Europe, separately. A significance level of 5% was used for all analyses. Results A total of 144 repurposing case studies were included in the statistical analysis for evaluation of mean price change. Combination cases (the combination of two or more individual drug components) were excluded from the statistical analysis due to the low number of cases retrieved. The main attributes associated with a significant price increase for overall repurposing cases were ‘change in administration setting to hospital’ (374%, ptarget product had a different administration route than the source product, and having a similar brand name for repurposed and original products, were variables that impacted a positive price change for repurposed drugs overall. Our research results also suggested that orphan designation could have a positive impact for repositioning in

  1. Drug repurposing in pharmaceutical industry and its impact on market access: market access implications.

    Science.gov (United States)

    Murteira, Susana; Millier, Aurélie; Toumi, Mondher

    2014-01-01

    Drug repurposing is a group of development strategies employed in order to overcome some of the hurdles innate to drug research and development. Drug repurposing includes drug repositioning, reformulation and combination. This study aimed to identify the determinants of successful market access outcome for drug repurposing in the United States of America (USA) and in Europe. The case studies of repurposing strategies were identified through a systematic review of the literature. Price information and reimbursement conditions for all the case studies were collected mainly through access of public datasources. A list of attributes that could be associated with market access outcome (price level and reimbursement conditions) was developed, discussed, and validated by an external expert group. Detailed information for all attributes was researched and collected for each case study. Bivariate regression models were conducted to identify factors associated with price change for all repurposing cases. A similar analysis was performed for reformulation and repositioning cases, in the USA and in Europe, separately. A significance level of 5% was used for all analyses. A total of 144 repurposing case studies were included in the statistical analysis for evaluation of mean price change. Combination cases (the combination of two or more individual drug components) were excluded from the statistical analysis due to the low number of cases retrieved. The main attributes associated with a significant price increase for overall repurposing cases were 'change in administration setting to hospital' (374%, ptarget product had a different administration route than the source product, and having a similar brand name for repurposed and original products, were variables that impacted a positive price change for repurposed drugs overall. Our research results also suggested that orphan designation could have a positive impact for repositioning in the USA, in particular. Although a change

  2. How drug life-cycle management patent strategies may impact formulary management.

    Science.gov (United States)

    Berger, Jan; Dunn, Jeffrey D; Johnson, Margaret M; Karst, Kurt R; Shear, W Chad

    2016-10-01

    Drug manufacturers may employ various life-cycle management patent strategies, which may impact managed care decision making regarding formulary planning and management strategies when single-source, branded oral pharmaceutical products move to generic status. Passage of the Hatch-Waxman Act enabled more rapid access to generic medications through the abbreviated new drug application process. Patent expirations of small-molecule medications and approvals of generic versions have led to substantial cost savings for health plans, government programs, insurers, pharmacy benefits managers, and their customers. However, considering that the cost of developing a single medication is estimated at $2.6 billion (2013 dollars), pharmaceutical patent protection enables companies to recoup investments, creating an incentive for innovation. Under current law, patent protection holds for 20 years from time of patent filing, although much of this time is spent in product development and regulatory review, leaving an effective remaining patent life of 7 to 10 years at the time of approval. To extend the product life cycle, drug manufacturers may develop variations of originator products and file for patents on isomers, metabolites, prodrugs, new drug formulations (eg, extended-release versions), and fixed-dose combinations. These additional patents and the complexities surrounding the timing of generic availability create challenges for managed care stakeholders attempting to gauge when generics may enter the market. An understanding of pharmaceutical patents and how intellectual property protection may be extended would benefit managed care stakeholders and help inform decisions regarding benefit management.

  3. Impact of the counterion on the solubility and physicochemical properties of salts of carboxylic acid drugs.

    Science.gov (United States)

    David, S E; Timmins, P; Conway, B R

    2012-01-01

    Salt formation is a widely used approach to improve the physicochemical and solid state properties of an active pharmaceutical ingredient. In order to better understand the relationships between the active drug, the selected counterion and the resultant salt form, crystalline salts were formed using four different carboxylic acid drugs and a closely related series of amine counterions. Thirty-six related crystalline salts were prepared, characterized and the relationship between solubility and dissolution behaviour and other properties of the salt and the counterion studied. Salts of four model acid drugs, gemfibrozil, flurbiprofen, ibuprofen and etodolac were prepared using the counterions butylamine, hexylamine, octylamine, benzylamine, cyclohexylamine, tert-butylamine, 2-amino-2-methylpropan-1-ol, 2-amino-2-methylpropan-1,3-diol and tris(hydroxymethyl)aminomethane. Salt formation was confirmed, the salts were characterized and their corresponding solubilities determined and rationalized with respect to the counterions' properties. The properties of the salt highly dependent on the nature of the counterion and, although there is considerable variation, some general conclusion can be drawn. For the alkyl amines series, increasing chain length leads to a reduction in solubility across all the acidic drugs studied and a reduction in melting point, thus contradicting simplistic relationships between solubility and melting point. Small, compact counterions consistently produce crystalline salts with high melting point accompanied with a modest improvement in solubility and the nature of hydrogen bonding between the ions has a major impact on the solubility.

  4. Impact of speciation on the electron charge transfer properties of nanodiamond drug carriers.

    Science.gov (United States)

    Sun, Baichuan; Barnard, Amanda S

    2016-08-07

    Unpassivated diamond nanoparticles (bucky-diamonds) exhibit a unique surface reconstruction involving graphitization of certain crystal facets, giving rise to hybrid core-shell particles containing both aromatic and aliphatic carbon. Considerable effort is directed toward eliminating the aromatic shell, but persistent graphitization of subsequent subsurface-layers makes perdurable purification a challenge. In this study we use some simple statistical methods, in combination with electronic structure simulations, to predict the impact of different fractions of aromatic and aliphatic carbon on the charge transfer properties of the ensembles of bucky-diamonds. By predicting quality factors for a variety of cases, we find that perfect purification is not necessary to preserve selectivity, and there is a clear motivation for purifying samples to improve the sensitivity of charge transfer reactions. This may prove useful in designing drug delivery systems where the release of (selected) drugs needs to be sensitive to specific conditions at the point of delivery.

  5. Impact of pharmacist recommendations on the cost of drug therapy in ICU patients at a Malaysian hospital

    NARCIS (Netherlands)

    Zaidi, S.T.R.; Hassan, Y.; Postma, Maarten; Hain Ng, S.

    2003-01-01

    Objectives: To analyse clinical pharmacists interventions in the ICU of the Penang General Hospital (Penang, Malaysia) and to assess the pharmaco-economic impact of these interventions. Methods: A clinical pharmacist reviewed drug prescriptions during one month. Drug-related problems were documented

  6. Thermodynamics of Highly Supersaturated Aqueous Solutions of Poorly Water-Soluble Drugs-Impact of a Second Drug on the Solution Phase Behavior and Implications for Combination Products.

    Science.gov (United States)

    Trasi, Niraj S; Taylor, Lynne S

    2015-08-01

    There is increasing interest in formulating combination products that contain two or more drugs. Furthermore, it is also common for different drug products to be taken simultaneously. This raises the possibility of interactions between different drugs that may impact formulation performance. For poorly water-soluble compounds, the supersaturation behavior may be a critical factor in determining the extent of oral absorption. The goal of the current study was to evaluate the maximum achievable supersaturation for several poorly water-soluble compounds alone, and in combination. Model compounds included ritonavir, lopinavir, paclitaxel, felodipine, and diclofenac. The "amorphous solubility" for the pure drugs was determined using different techniques and the change in this solubility was then measured in the presence of differing amounts of a second drug. The results showed that "amorphous solubility" of each component in aqueous solution is substantially decreased by the second component, as long as the two drugs are miscible in the amorphous state. A simple thermodynamic model could be used to predict the changes in solubility as a function of composition. This information is of great value when developing co-amorphous or other supersaturating formulations and should contribute to a broader understanding of drug-drug physicochemical interactions in in vitro assays as well as in the gastrointestinal tract. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  7. Final disposition of MTR fuel

    International Nuclear Information System (INIS)

    Jonnson, Erik B.

    1996-01-01

    The final disposition of power reactor fuel has been investigated for a long time and some promising solutions to the problem have been shown. The research reactor fuels are normally not compatible with the zirkonium clad power reactor fuel and can thus not rely on the same disposal methods. The MTR fuels are typically Al-clad UAl x or U 3 Si 2 , HEU resp. LEU with essentially higher remaining enrichment than the corresponding power reactor fuel after full utilization of the uranium. The problems arising when evaluating the conditions at the final repository are the high corrosion rate of aluminum and uranium metal and the risk for secondary criticality due to the high content on fissionable material in the fully burnt MTR fuel. The newly adopted US policy to take back Foreign Research Reactor Spent Fuel of US origin for a period of ten years have given the research reactor society a reasonable time to evaluate different possibilities to solve the back end of the fuel cycle. The problem is, however, complicated and requires a solid engagement from the research reactor community. The task would be a suitable continuation of the RERTR program as it involves both the development of new fuel types and collecting data for the safe long-term disposal of the spent MTR fuel. (author)

  8. Total hepatocellular disposition profiling of rosuvastatin and pitavastatin in sandwich-cultured human hepatocytes.

    Science.gov (United States)

    Kanda, Katsuhiro; Takahashi, Ryosuke; Yoshikado, Takashi; Sugiyama, Yuichi

    2018-04-09

    This study describes the total disposition profiling of rosuvastatin (RSV) and pitavastatin (PTV) using a single systematic procedure called D-PREX (Disposition Profile Exploration) in sandwich-cultured human hepatocytes (SCHH). The biliary excretion fractions of both statins were clearly observed, which were significantly decreased dependent on the concentration of Ko143, an inhibitor for breast cancer resistance protein (BCRP). Ko143 also decreased the basolateral efflux fraction of RSV, whereas that of PTV was not significantly affected. To understand these phenomena, effects of Ko143 on biliary excretion (BCRP and multidrug resistance-associated protein (MRP) 2) and basolateral efflux (MRP3 and MRP4) transporters were examined using transporter-expressing membrane vesicles. BCRP, MRP3 and MRP4-mediated transport of RSV was observed, and Ko143 inhibited these transporters except MRP3. BCRP and MRP4 also mediated the transport of PTV, but the Ko143-mediated inhibition was only clear for BCRP. These results might explain the Ko143-mediated complete and partial inhibition of the biliary excretion and the basolateral efflux of RSV, respectively, in SCHH. In conclusion, D-PREX with sequential sampling of supernatants prior to cell lysis enables the evaluation of total drug disposition profiles resulting from complex interplays of intracellular pathways, which would provide high-throughput evaluation of drug disposition during drug discovery. Copyright © 2018 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  9. Impact of a transient instability of the ecstasy market on health concerns and drug use patterns in The Netherlands.

    Science.gov (United States)

    Brunt, Tibor M; Niesink, Raymond J M; van den Brink, Wim

    2012-03-01

    A recent decline in MDMA-like substances in ecstasy tablets has been reported by a number of countries in the European Union. This study describes the instability of the ecstasy market in The Netherlands during 2008 and 2009, and investigates whether this had any impact on drug testing or patterns of drug use. The health concerns of drug users handing in drug samples at drug testing facilities was measured using intervention time-series analysis. In addition, these ecstasy users were asked about changes in their drug use. Nationally, the unstable market situation for ecstasy has increased the number of users handing in ecstasy tablets for testing because of health concern. There was no change in the number of users handing in cocaine or gamma hydroxybutyrate (GHB). Respondents reported no major changes in their drug use resulting from the shortage of MDMA-like substances. These findings provide further insight in drug policy based on both harm reduction and use reduction. In the event of reduced ecstasy quality, ecstasy users in The Netherlands have increasingly used drug testing as a potential harm reduction tool, rather than changing their patterns of drug use. This might indicate that a transient reduction of drug quality does not serve as a good drug use reduction strategy for ecstasy users. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Drug pricing reform in China: analysis of piloted approaches and potential impact of the reform

    Science.gov (United States)

    Chen, Yixi; Hu, Shanlian; Dong, Peng; Kornfeld, Åsa; Jaros, Patrycja; Yan, Jing; Ma, Fangfang; Toumi, Mondher

    2016-01-01

    Objectives In 2009, the Chinese government launched a national healthcare reform programme aiming to control healthcare expenditure and increase the quality of care. As part of this programme, a new drug pricing reform was initiated on 1 June 2015. The objective of this study was to describe the changing landscape of drug pricing policy in China and analyse the potential impact of the reform. Methods The authors conducted thorough research on the drug pricing reform using three Chinese databases (CNKI, Wanfang, and Weipu), Chinese health authority websites, relevant press releases, and pharmaceutical blogs and discussion forums. This research was complemented with qualitative research based on targeted interviews with key Chinese opinion leaders representing the authorities’ and prescribers’ perspectives. Results With the current reform, the government has attempted to replace its direct control over the prices of reimbursable drugs with indirect, incentive-driven influence. Although the exact implementation of the reform remains unclear at the moment, the changes introduced so far and the pilot project designs indicate that China is considering adaptation of some form of internal and external reference pricing policies, commonly used in the Organisation for Economic Co-operation and Development countries. Several challenges related to the potential new mechanism were identified: 1) the risk of hospital underfunding, if hospital funding reform is not prioritised; 2) the risk of promoting the use of cheap, low-quality drugs, if a reliable quality control system is not in place and discrepancy between the available drugs is present; 3) the risk of increasing disparity in access to care between poor and rich regions, in case of country-wide price convergence; and 4) the risk of industry underinvestment, resulting in reduced competition, issues with quality and sustainability of supply, and potentially negative social impact. Conclusions Foreign pricing policies

  11. Theoretical and experimental investigation of drug-polymer interaction and miscibility and its impact on drug supersaturation in aqueous medium.

    Science.gov (United States)

    Baghel, Shrawan; Cathcart, Helen; O'Reilly, Niall J

    2016-10-01

    Amorphous solid dispersions (ASDs) have the potential to offer higher apparent solubility and bioavailability of BCS class II drugs. Knowledge of the solid state drug-polymer solubility/miscibility and their mutual interaction are fundamental requirements for the effective design and development of such systems. To this end, we have carried out a comprehensive investigation of various ASD systems of dipyridamole and cinnarizine in polyvinylpyrrolidone (PVP) and polyacrylic acid (PAA) at different drug loadings. Theoretical and experimental examinations (by implementing binary and ternary Flory-Huggins (F-H) theory) related to drug-polymer interaction/miscibility including solubility parameter approach, melting point depression method, phase diagram, drug-polymer interaction in the presence of moisture and the effect of drug loading on interaction parameter were performed. The information obtained from this study was used to predict the stability of ASDs at different drug loadings and under different thermal and moisture conditions. Thermal and moisture sorption analysis not only provided the composition-dependent interaction parameter but also predicted the composition dependent miscibility. DPM-PVP, DPM-PAA and CNZ-PAA systems have shown molecular level mixing over the complete range of drug loading. For CNZ-PVP, the presence of a single Tg at lower drug loadings (10, 20 and 35%w/w) indicates the formation of solid solution. However, drug recrystallization was observed for samples with higher drug weight fractions (50 and 65%w/w). Finally, the role of polymer in maintaining drug supersaturation has also been explored. It has been found that drug-polymer combinations capable of hydrogen-bonding in the solution state (DPM-PVP, DPM-PAA and CNZ-PAA) are more effective in preventing drug crystallization compared to the drug-polymer systems without such interaction (CNZ-PVP). The DPM-PAA system outperformed all other ASDs in various stability conditions (dry-state, in

  12. The impact of compulsory drug detention exposure on the avoidance of healthcare among injection drug users in Thailand.

    Science.gov (United States)

    Kerr, Thomas; Hayashi, Kanna; Ti, Lianping; Kaplan, Karyn; Suwannawong, Paisan; Wood, Evan

    2014-01-01

    Although Thailand has relied on the use of compulsory drug detention centres as a strategy to try to address problematic drug use, little is known about the effects of exposure to these centres on people who inject drugs (IDU). Therefore, we undertook this study to explore whether exposure to compulsory drug detention was associated with avoiding healthcare among Thai IDU. Using Poisson regression analyses, we examined the relationship between compulsory drug detention exposure and avoiding healthcare among participants in the Mitsampan Community Research Project based in Bangkok. 435 IDU participated in this study, including 111 (25.5%) participants who reported avoiding healthcare. In multivariate analyses, avoiding healthcare was positively associated with exposure to compulsory drug detention (adjusted prevalence ratio [APR]=1.60; 95% confidence interval [CI]: 1.16-2.21), having been refused healthcare (APR=3.46; 95% CI: 2.61-4.60), and experiencing shame associated with one's drug use (APR=1.93; 95% CI: 1.21-3.09). Exposure to compulsory drug detention was associated with avoiding healthcare among Thai IDU, suggesting that this system of detention may be contributing to the burden of preventable morbidity among IDU in this setting. Although further research is needed to confirm these findings, the results of this study reinforce previous calls to replace the system of compulsory drug detention with evidence-based public health interventions for IDU. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Non-proliferation, safeguards, and security for the fissile materials disposition program immobilization alternatives

    Energy Technology Data Exchange (ETDEWEB)

    Duggan, R.A.; Jaeger, C.D.; Tolk, K.M. [Sandia National Labs., Albuquerque, NM (United States); Moore, L.R. [Lawrence Livermore National Lab., CA (United States)

    1996-05-01

    The Department of Energy is analyzing long-term storage and disposition alternatives for surplus weapons-usable fissile materials. A number of different disposition alternatives are being considered. These include facilities for storage, conversion and stabilization of fissile materials, immobilization in glass or ceramic material, fabrication of fissile material into mixed oxide (MOX) fuel for reactors, use of reactor based technologies to convert material into spent fuel, and disposal of fissile material using geologic alternatives. This paper will focus on how the objectives of reducing security and proliferation risks are being considered, and the possible facility impacts. Some of the areas discussed in this paper include: (1) domestic and international safeguards requirements, (2) non-proliferation criteria and measures, (3) the threats, and (4) potential proliferation, safeguards, and security issues and impacts on the facilities. Issues applicable to all of the possible disposition alternatives will be discussed in this paper. However, particular attention is given to the plutonium immobilization alternatives.

  14. Strategic characterization of anti-drug antibody responses for the assessment of clinical relevance and impact.

    Science.gov (United States)

    Tatarewicz, Suzanna M; Mytych, Daniel T; Manning, Marta Starcevic; Swanson, Steven J; Moxness, Michael S; Chirmule, Narendra

    2014-06-01

    All therapeutic proteins have the potential to induce anti-drug antibodies (ADA). Clinically relevant ADA can impact efficacy and/or safety of a biological therapeutic. Immunogenicity assessment strategy evaluates binding and neutralizing ADA, and the need for additional characterization (e.g., epitope, titer and so on) is determined using a risk-based approach. The choice of characterization assays depends on the type, application and immunogenicity of the therapeutic. ADA characterization can impact the interpretation of the risk profile of a given therapeutic, and offers insight into opportunities for risk mitigation and management. This article describes common ADA characterization methods. Strategic assessment and characterization of clinically relevant ADA are discussed, in order to support clinical options for safe and effective patient care and disease management.

  15. The impact of a multiple intelligences teaching approach drug education programme on drug refusal skills of Nigerian pupils.

    Science.gov (United States)

    Nwagu, Evelyn N; Ezedum, Chuks E; Nwagu, Eric K N

    2015-09-01

    The rising incidence of drug abuse among youths in Nigeria is a source of concern for health educators. This study was carried out on primary six pupils to determine the effect of a Multiple Intelligences Teaching Approach Drug Education Programme (MITA-DEP) on pupils' acquisition of drug refusal skills. A programme of drug education based on the Multiple Intelligences Teaching Approach (MITA) was developed. An experimental group was taught using this programme while a control group was taught using the same programme but developed based on the Traditional Teaching Approach. Pupils taught with the MITA acquired more drug refusal skills than those taught with the Traditional Teaching Approach. Urban pupils taught with the MITA acquired more skills than rural pupils. There was no statistically significant difference in the mean refusal skills of male and female pupils taught with the MITA. © The Author(s) 2014.

  16. Impact of sodium dodecyl sulphate on the dissolution of poorly soluble drug into biorelevant medium from drug-surfactant discs

    DEFF Research Database (Denmark)

    Madelung, Peter; Ostergaard, Jesper; Bertelsen, Poul

    2014-01-01

    The purpose was to elucidate the mechanism of action of sodium dodecyl sulphate (SDS) on drug dissolution from discs under physiologically relevant conditions. The effect of incorporating SDS (4-30%, w/w) and drug into discs on the dissolution constant and solubility were evaluated for the poorly...... soluble drugs griseofulvin and felodipine in a biorelevant dissolution medium (BDM). Dissolution constants from dissolution profiles of drug discs with and without SDS were measured using miniaturized rotating disc dissolution. Solid state changes were investigated by X-ray diffraction. Solubility...... showed that the addition of SDS made the BS:PC micelles grow up to 2.5 times in volume. As a function of SDS addition, the dissolution constant showed an apparent exponential increase, while drug solubility showed a weak linear dependence. The pronounced effect on dissolution constant with SDS...

  17. Treatment as Part of Drug Court: The Impact on Graduation Rates

    Science.gov (United States)

    Taxman, Faye S.; Bouffard, Jeffrey A.

    2005-01-01

    Drug treatment is one of the critical components of drug court programming, yet it has not been thoroughly studied in the drug court literature. Very little is understood about the nature of drug treatment services provided in the drug court setting. The purpose of this study was to examine the effects of selected treatment variables on drug court…

  18. Acquired resistance of malarial parasites against artemisinin-based drugs: social and economic impacts

    Directory of Open Access Journals (Sweden)

    Johanna M Porter-Kelley

    2010-08-01

    Full Text Available Johanna M Porter-Kelley1, Joann Cofie2, Sophonie Jean2, Mark E Brooks1, Mia Lassiter1, DC Ghislaine Mayer21Life Sciences Department, ­Winston-Salem State University, Winston Salem, NC, USA; 2Department of Biology, Virginia Commonwealth University, Richmond, VA, USAAbstract: Malaria, a disease of poverty and high morbidity and mortality in the tropical world, has led to a worldwide search for control measures. To that end, good antimalarial chemotherapies have been difficult to find in the global market and those that seem to be most effective are rapidly becoming ineffective due to the emergence and spread of drug resistance. Artemisinin, a very effective yet expensive antimalarial, has quickly become the recommended drug of choice when all other possibilities fail. However, for all its promise as the next great antimalarial, the outlook is bleak. Resistance is developing to artemisinin while another effective antimalarial is not in sight. Malaria endemic areas which are mostly in developing countries must deal with the multifaceted process of changing and implementing new national malaria treatment guidelines. This requires complex interactions between several sectors of the affected society which in some cases take place within the context of political instability. Moreover, the cost associated with preventing and containing the spread of antimalarial resistance is detrimental to economic progress. This review addresses the impact of artemisinin resistance on the socioeconomic structure of malaria endemic countries.Keywords: artemisinin-based drugs, social, economic, malarial parasite resistance

  19. Impact of Conflict and Displacement on Risk Behaviours Amongst People Who Inject Drugs in Kabul, Afghanistan

    Science.gov (United States)

    Todd, Catherine S.; Nasir, Abdul; Stanekzai, Mohammad Raza; Fiekert, Katja; Sipsma, Heather L.; Strathdee, Steffanie A.; Vlahov, David

    2015-01-01

    Background Theoretical work posits that drug-related risk behaviour increases during armed conflict; however, few studies have been conducted in conflict settings. The objective of this analysis is to determine whether conflict or local displacement impact risk behaviours among people who inject drugs (PWID) in Kabul, Afghanistan. Methods Consenting PWIDs aged ≥18 years completed interviews at 3, 6, 9, 12, 18, and 24 months of follow-up. Quarters with peak conflict or local displacement exposure were defined and associations with injecting drug use and sexual risk behaviours analysed with generalized estimating equations. Results Of 483 PWID enrolled, 385 completed ≥1 follow-up visit (483.8 person-years) between 2007 and 2009. All participants were male, with 35% initiating injecting as a refugee. Sharing syringes (Odds Ratio (OR))=8.53, 95% Confidence Interval (CI): 2.58 – 28.2) and sexually transmitted infection (STI) symptoms (OR=1.72, 95% CI: 1.00 – 2.96) increased significantly during peak conflict quarters, while odds of STI symptoms (OR=0.06, 95% CI: 0.02 – 0.20) and arrest (OR=0.61, 95% CI: 0.40 – 0.93) were significantly lower during periods of displacement. Conclusion Syringe sharing significantly increased during peak conflict periods amongst PWID in Kabul. Programming should include instruction for coping with conflict and prepare clients for harm reduction needs during conflict. PMID:26303577

  20. Impact insertion of transfer-molded microneedle for localized and minimally invasive ocular drug delivery.

    Science.gov (United States)

    Song, Hyun Beom; Lee, Kang Ju; Seo, Il Ho; Lee, Ji Yong; Lee, Sang-Mok; Kim, Jin Hyoung; Kim, Jeong Hun; Ryu, WonHyoung

    2015-07-10

    It has been challenging for microneedles to deliver drugs effectively to thin tissues with little background support such as the cornea. Herein, we designed a microneedle pen system, a single microneedle with a spring-loaded microneedle applicator to provide impact insertion. To firmly attach solid microneedles with 140 μm in height at the end of macro-scale applicators, a transfer molding process was employed. The fabricated microneedle pens were then applied to mouse corneas. The microneedle pens successfully delivered rhodamine dye deep enough to reach the stromal layer of the cornea with small entry only about 1000 μm(2). When compared with syringes or 30 G needle tips, microneedle pens could achieve more localized and minimally invasive delivery without any chances of perforation. To investigate the efficacy of microneedle pens as a way of drug delivery, sunitinib malate proven to inhibit in vitro angiogenesis, was delivered to suture-induced angiogenesis model. When compared with delivery by a 30 G needle tip dipped with sunitinib malate, only delivery by microneedle pens could effectively inhibit corneal neovascularization in vivo. Microneedle pens could effectively deliver drugs to thin tissues without impairing merits of using microneedles: localized and minimally invasive delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. [Designer drugs and caffeine - characteristics of psychoactive substances and their impact on the organism].

    Science.gov (United States)

    Wierzejska, Regina

    2014-01-01

    For many teenagers the time of growing up is a period of trying prohibited substances. Nowadays apart from alcohol and tobacco new designed, psychoactive substances known as "smart drugs" or "legal highs" are available. Intensive development of their market is taking place in the last few years which is difficult to overcome by regulations only. Toxicological tests used now are not able to detect the presence of many such substances in the body. Designer drugs cause the interest of young people even from small towns and many times taking them give effects requiring medical help. Caffeine is also a psychoactive substance but depending on the dose it can have positive or detrimental effect. Recently there are more and more products with caffeine, especially drinks and dietary supplements, what can cause the increase of consumption of caffeine. Children are particularly exposed to the adverse effect of high consumption of caffeine because of their small body weight and development of the central nervous system. This article presents actual data about the market of designer drugs, frequency of using them, consumption of caffeine by children and teenagers and about the impact of these substances on the organism.

  2. IMPACT OF HEALTH TECHNOLOGY ASSESSMENT IN LITIGATION CONCERNING ACCESS TO HIGH-COST DRUGS.

    Science.gov (United States)

    Aleman, Alicia; Perez Galan, Ana

    2017-01-01

    The impact of health technology assessment (HTA) in the judicialization of the right of health has not been deeply studied in Latin American countries. The purpose of this study is to review the process of judicialization of the access to high cost drugs in Uruguay and assess the impact HTAs have had on this process. The methodology used for this study included a comprehensive literature search in electronic databases, local journals, internal documents developed in the Ministry of Health, as well as conducting interviews with key informants. Judicialization of the access of high cost drugs has been increasing since 2010. The strategy of the Ministry of Health of Uruguay to decrease this problem included the organization of roundtables with judges and other stakeholders on the basis of HTA, the training of defense lawyers in the use and interpretation of HTA, and the participation of a professional who develops HTA in the preparation of the defense arguments. A year after the implementation of this strategy, 25 percent of writs of protection were won by the Ministry of Health. Even though the strategy implemented was effective in reducing the loss of litigations, it was not effective in reducing the growing number of writs of protection. It is essential to address this problem in a broad debate and to promote understanding between the parties.

  3. Potential Impact of Diet on Treatment Effect from Anti-TNF Drugs in Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Hansen, Axel Kornerup; Heitmann, Berit Lilienthal

    2017-01-01

    We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such invest...... inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in prospective observational, animal and interventional studies are warranted.......We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies......% CI: 1.73-4.31, p impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic...

  4. 77 FR 28620 - Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication

    Science.gov (United States)

    2012-05-15

    ... INTERNATIONAL TRADE COMMISSION [Investigation No. 332-352] Andean Trade Preference Act: Impact on the U.S. Economy and on Andean Drug Crop Eradication AGENCY: United States International Trade... to report biennially to the Congress by September 30 of each reporting year on the economic impact of...

  5. Impact of Focused Ultrasound-enhanced Drug Delivery on Survival in Rats with Glioma

    Science.gov (United States)

    Treat, Lisa Hsu; Zhang, Yongzhi; McDannold, Nathan; Hynynen, Kullervo

    2009-04-01

    Malignancies of the brain remain difficult to treat with chemotherapy because the selective permeability of the blood-brain barrier (BBB) blocks many potent agents from reaching their target. Previous studies have illustrated the feasibility of drug and antibody delivery across the BBB using MRI-guided focused ultrasound. In this study, we investigated the impact of focused ultrasound-enhanced delivery of doxorubicin on survival in rats with aggressive glioma. Sprague-Dawley rats were implanted with 9 L gliosarcoma cells in the brain. Eight days after implantation, each rat received one of the following: (1) no treatment (control), (2) a single treatment with microbubble-enhanced MRI-guided focused ultrasound (FUS only), (3) a single treatment with i.v. liposomal doxorubicin (DOX only), or (4) a single treatment with microbubble-enhanced MRI-guided focused ultrasound and concurrent i.v. injections of liposomal doxorubicin (FUS+DOX). The survival time from implantation to death or euthanasia was recorded. We observed a modest but significant increase in median survival time in rats treated with combined MRI-guided focused ultrasound chemotherapy, compared to chemotherapy alone (p0.10). Our study demonstrates for the first time a therapeutic benefit achieved with ultrasound-enhanced drug delivery across the blood-brain barrier. This confirmation of efficacy in an in vivo tumor model indicates that targeted drug delivery using MRI-guided focused ultrasound has the potential to have a major impact on the treatment of patients with brain tumors and other neurological disorders.

  6. The effect of oral castor oil on the disposition of methyprylon in intoxicated dogs.

    Science.gov (United States)

    Gwilt, P R; Pankaskie, M C; Mitala, J J

    1982-07-01

    Clinical observations indicate that large oral doses of castor oil are effective in reducing the time of coma resulting from acute intoxication with lipophilic drugs. It has been further suggested that the rate of removal of these drugs from the body is increased by castor oil. In order to investigate the effect of castor oil on the disposition of lipophilic drugs, five dogs were given toxic doses of methyprylon by intravenous infusion. Each dog was treated with a large oral dose of castor oil in a cross-over fashion. No significant difference was observed in the sleep times of the dogs treated with castor oil, or in the methyprylon pharmacokinetics compared to controls. It was concluded that castor oil does not affect the disposition of methyprylon.

  7. NRC comprehensive records disposition schedule. Revision 3

    International Nuclear Information System (INIS)

    1998-02-01

    Title 44 US Code, ''Public Printing and Documents,'' regulations issued by the General Service Administration (GSA) in 41 CFR Chapter 101, Subchapter B, ''Management and Use of Information and Records,'' and regulations issued by the National Archives and Records Administration (NARA) in 36 CFR Chapter 12, Subchapter B, ''Records Management,'' require each agency to prepare and issue a comprehensive records disposition schedule that contains the NARA approved records disposition schedules for records unique to the agency and contains the NARA's General Records Schedules for records common to several or all agencies. The approved records disposition schedules specify the appropriate duration of retention and the final disposition for records created or maintained by the NRC. NUREG-0910, Rev. 3, contains ''NRC's Comprehensive Records Disposition Schedule,'' and the original authorized approved citation numbers issued by NARA. Rev. 3 incorporates NARA approved changes and additions to the NRC schedules that have been implemented since the last revision dated March, 1992, reflects recent organizational changes implemented at the NRC, and includes the latest version of NARA's General Records Schedule (dated August 1995)

  8. NRC comprehensive records disposition schedule. Revision 3

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-02-01

    Title 44 US Code, ``Public Printing and Documents,`` regulations issued by the General Service Administration (GSA) in 41 CFR Chapter 101, Subchapter B, ``Management and Use of Information and Records,`` and regulations issued by the National Archives and Records Administration (NARA) in 36 CFR Chapter 12, Subchapter B, ``Records Management,`` require each agency to prepare and issue a comprehensive records disposition schedule that contains the NARA approved records disposition schedules for records unique to the agency and contains the NARA`s General Records Schedules for records common to several or all agencies. The approved records disposition schedules specify the appropriate duration of retention and the final disposition for records created or maintained by the NRC. NUREG-0910, Rev. 3, contains ``NRC`s Comprehensive Records Disposition Schedule,`` and the original authorized approved citation numbers issued by NARA. Rev. 3 incorporates NARA approved changes and additions to the NRC schedules that have been implemented since the last revision dated March, 1992, reflects recent organizational changes implemented at the NRC, and includes the latest version of NARA`s General Records Schedule (dated August 1995).

  9. Estimating the budget impact of orphan drugs in Sweden and France 2013-2020.

    Science.gov (United States)

    Hutchings, Adam; Schey, Carina; Dutton, Richard; Achana, Felix; Antonov, Karolina

    2014-02-13

    The growth in expenditure on orphan medicinal products (OMP) across Europe has been identified as a concern. Estimates of future expenditure in Europe have suggested that OMPs could account for a significant proportion of total pharmaceutical expenditure in some countries, but few of these forecasts have been well validated. This analysis aims to establish a robust forecast of the future budget impact of OMPs on the healthcare systems in Sweden and France. A dynamic forecasting model was created to estimate the budget impact of OMPs in Sweden and France between 2013 and 2020. The model used historical data on OMP designation and approval rates to predict the number of new OMPs coming to the market. Average OMP sales were estimated for each year post-launch by regression analysis of historical sales data. Total forecast sales were compared with expected sales of all pharmaceuticals in each country to quantify the relative budget impact. The model predicts that by 2020, 152 OMPs will have marketing authorization in Europe. The base case OMP budget impacts are forecast to grow from 2.7% in Sweden and 3.2% in France of total drug expenditure in 2013 to 4.1% in Sweden and 4.9% in France by 2020. The principal driver of expenditure growth is the number of new OMPs obtaining OMP designation. This is tempered by the slowing success rate for new approvals and the loss of intellectual property protection on existing orphan medicines. Given the forward-looking nature of the analysis, uncertainty exists around model parameters and sensitivity analysis found peak year budget impact varying between 2% and 11%. The budget impact of OMPs in Sweden and France is likely to remain sustainable over time and a relatively small proportion of total pharmaceutical expenditure. This forecast could be affected by changes in the success rate for OMP approvals, average cost of OMPs, and the type of companies developing OMPs.

  10. Estimating the budget impact of orphan drugs in Sweden and France 2013–2020

    Science.gov (United States)

    2014-01-01

    Background The growth in expenditure on orphan medicinal products (OMP) across Europe has been identified as a concern. Estimates of future expenditure in Europe have suggested that OMPs could account for a significant proportion of total pharmaceutical expenditure in some countries, but few of these forecasts have been well validated. This analysis aims to establish a robust forecast of the future budget impact of OMPs on the healthcare systems in Sweden and France. Methods A dynamic forecasting model was created to estimate the budget impact of OMPs in Sweden and France between 2013 and 2020. The model used historical data on OMP designation and approval rates to predict the number of new OMPs coming to the market. Average OMP sales were estimated for each year post-launch by regression analysis of historical sales data. Total forecast sales were compared with expected sales of all pharmaceuticals in each country to quantify the relative budget impact. Results The model predicts that by 2020, 152 OMPs will have marketing authorization in Europe. The base case OMP budget impacts are forecast to grow from 2.7% in Sweden and 3.2% in France of total drug expenditure in 2013 to 4.1% in Sweden and 4.9% in France by 2020. The principal driver of expenditure growth is the number of new OMPs obtaining OMP designation. This is tempered by the slowing success rate for new approvals and the loss of intellectual property protection on existing orphan medicines. Given the forward-looking nature of the analysis, uncertainty exists around model parameters and sensitivity analysis found peak year budget impact varying between 2% and 11%. Conclusion The budget impact of OMPs in Sweden and France is likely to remain sustainable over time and a relatively small proportion of total pharmaceutical expenditure. This forecast could be affected by changes in the success rate for OMP approvals, average cost of OMPs, and the type of companies developing OMPs. PMID:24524281

  11. Underestimated impact of novel psychoactive substances: laboratory confirmation of recreational drug toxicity in Oslo, Norway.

    Science.gov (United States)

    Vallersnes, Odd Martin; Persett, Per Sverre; Øiestad, Elisabeth Leere; Karinen, Ritva; Heyerdahl, Fridtjof; Hovda, Knut Erik

    2017-08-01

    Recreational drug toxicity is frequent. Availability of new psychoactive substances is steadily increasing. However, data with verified analyses from clinical settings are limited. To evaluate the impact of novel psychoactive substances (NPS) on recreational drug toxicity in Oslo, Norway, we analysed samples from a selection of patients. All the patients presenting with recreational drug toxicity at the Oslo Accident and Emergency Outpatient Clinic (OAEOC) and at the Oslo University Hospital (OUH) were registered from April through September 2014. Oral fluid samples were collected at the OAEOC. Blood samples were collected at the OUH. The samples were screened using ultra-high performance liquid chromatography - tandem mass spectrometry (UHPLC-MS/MS). Nine hundred and sixty-four cases were included, 841 (87.2%) at the OAEOC and 123 (12.8%) at the OUH. A total of 55 oral fluid samples (OAEOC) and 103 blood samples (OUH) could be analysed. NPS were not clinically suspected in any of the screened cases. At the outpatient clinic, the most commonly found substances were clonazepam in 42/55 (76.4%) cases, amfetamines in 40/55 (72.7%) and heroin in 39/55 (70.9%). In seven (12.7%) cases NPS were detected: 4-methylamfetamine in three cases, dimethyltryptamine in two, methylone in one, and N,N-dimethyl-3,4-methylenedioxyamfetamine in one. Among the hospital patients, the most commonly found substances were clonazepam in 51/103 (49.5%) cases, amfetamines in 48/103 (46.6%), heroin in 31/103 (30.1%), and diazepam in 30/103 (29.1%). In five (4.9%) cases NPS were detected: JWH-210 in two cases, AM-2201 in two, and 5-EAPB in one. NPS were clinically not suspected, though found in eight percent of cases. Still, the vast majority of patients treated for recreational drug toxicity in Oslo have taken classical drugs. Management of these patients should be based on their clinical condition. However, it is highly important to be alert to atypical presentations possibly resulting from

  12. The impact of engagement in street-based income generation activities on stimulant drug use cessation among people who inject drugs.

    Science.gov (United States)

    Ti, Lianping; Richardson, Lindsey; DeBeck, Kora; Nguyen, Paul; Montaner, Julio; Wood, Evan; Kerr, Thomas

    2014-08-01

    Despite the growing prevalence of illicit stimulant drug use internationally, and the widespread involvement of people who inject drugs (IDU) within street-based drug markets, little is known about the impact of different types of street-based income generation activities on the cessation of stimulant use among IDU. Data were derived from an open prospective cohort of IDU in Vancouver, Canada. We used Kaplan-Meier methods and Cox proportional hazards regression to examine the effect of different types of street-based income generation activities (e.g., sex work, drug dealing, and scavenging) on time to cessation of stimulant use. Between December, 2005 and November, 2012, 887 IDU who use stimulant drugs (cocaine, crack cocaine, or crystal methamphetamine) were prospectively followed-up for a median duration of 47 months. In Kaplan-Meier analyses, compared to those who did not engage in street-based income generation activities, participants who reported sex work, drug dealing, scavenging, or more than one of these activities were significantly less likely to report stimulant drug use cessation (all pstreet-based income generation activity remained significantly associated with a slower time to stimulant drug cessation (all p<0.005). Our findings highlight the urgent need for strategies to address stimulant dependence, including novel pharmacotherapies. Also important, structural interventions, such as low-threshold employment opportunities, availability of supportive housing, legal reforms regarding drug use, and evidence-based approaches that reduce harm among IDU are urgently required. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. DRUG COURTS: Better DOJ Data Collection and Evaluation Efforts Needed to Measure Impact of Drug Court Programs

    National Research Council Canada - National Science Library

    2002-01-01

    .... Under this concept, in exchange for the possibility of dismissed charges or reduced sentences, defendants are diverted to drug court programs in various ways and at various stages in the judicial process...

  14. The use of crack and other illicit drugs impacts oral health-related quality of life in Brazilians.

    Science.gov (United States)

    Antoniazzi, R P; Zanatta, F B; Ardenghi, T M; Feldens, C A

    2018-04-01

    The aim of this study was to investigate the impact of the use of crack and other illicit drugs on oral health-related quality of life (OHRQoL) in young adults. This cross-sectional study evaluated 106 crack users at a public treatment center for drug addiction and 106 controls matched for gender, age, and use of tobacco. Clinical examinations were performed for dental caries and periodontal disease. The outcome was OHRQoL, which was determined using the Oral Health Impact Profile (OHIP-14). The association between OHRQoL and illicit drugs was modeled using conditional Poisson regression. Users of crack and other illicit drugs had a poorer OHRQoL than the controls (p illicit drugs. Users of crack and other illicit drugs exerted a negative impact on OHRQoL independently of socio-demographic characteristics and tobacco use, suggesting the need for special attention regarding the specific oral health needs of this population as well as drug prevention and treatment strategies. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  15. Dispositional optimism and coping with pain.

    Science.gov (United States)

    Bargiel-Matusiewicz, K; Krzyszkowska, A

    2009-12-07

    The aim of this article is to analyze the relation between dispositional optimism and coping with chronic pain. The study seeks to define the relation between life orientation (optimism vs. pessimism) and coping with pain (believes about pain control and the choice of coping strategy). The following questionnaires were used: LOT-R - Life Orientation Test, BPCQ - The Beliefs about Pain Control Questionnaire and CSQ - The Pain Coping Strategies Questionnaire. The results show that dispositional optimism correlates positively with: internal locus of pain control r=0.6, Pr=0.38, Pr = 0.93, Pr = 0.82, Pr = -0.28, P<0.05. We conclude that dispositional optimism plays a key role in forming the mechanisms of coping with chronic pain and thereby in improving the psychophysical comfort of patients.

  16. [Impact of personality disorders in a sample of 212 homeless drug users].

    Science.gov (United States)

    Combaluzier, S; Gouvernet, B; Bernoussi, A

    2009-10-01

    The impact of the mental disorders (axis I and II, according to DSM IV) on psychosocial problems (axis IV) is now a well-known fact, notably when substance abuse disorders are encountered on axis I. This leads to the conclusion that personality disorders increase the risk of substance abuse, that substance abuse increases the risk of homelessness, that dual diagnosis has a high impact on homelessness and underlines interactions between personality disorders (PD), drug abuse (DA) and homelessness. The aim of this paper is also to study these interactions. We will process the classical epidemiological measures, which have already produced interesting findings on other substance-linked disorders. We will study the multiplicative interaction (I(AB)) and the etiological fraction (EFi) linked to interaction, which evaluate the effects of two factors on another. According to the authors, the I(AB) determines whether the co-occurrence of two risk factors in a group induces more cases than each factor acting together; also if the I(AB) is greater than 1 it is possible to estimate the EFi, that proportionally measures the number of cases of the third factor that can be attributed to the co-occurrence. We will also study the interactions of homelessness and PD on DA, of the PD and DA on homelessness, and of this association DA and homelessness on PD. The data we will use in the paper deal with the prevalence of PD in general, drug users (n=226), homeless (n=999) and homeless drug abusers (n=212). The two last data are extracted from the same population and have been collected through clinical interviews, and the diagnosis follows the DSM criteria. They are comparable to Kokkevi et al.'s sample regarding the drug (heroin), the mean age (28 years for Kokkevi et al., 27 years in our sample), and the geographic origin of the populations (Mediterranean basin). The repartition of PD differs significantly (0.001) in the homeless population and the homeless drug abusers (chi(2

  17. Tramadol and o-desmethyl tramadol clearance maturation and disposition in humans

    DEFF Research Database (Denmark)

    Allegaert, Karel; Holford, Nick; Anderson, Brian J

    2015-01-01

    BACKGROUND AND OBJECTIVES: We aimed to study the impact of size, maturation and cytochrome P450 2D6 (CYP2D6) genotype activity score as predictors of intravenous tramadol disposition. METHODS: Tramadol and O-desmethyl tramadol (M1) observations in 295 human subjects (postmenstrual age 25 weeks to...

  18. Comparative plasma disposition of fenbendazole, oxfendazole and albendazole in dogs.

    Science.gov (United States)

    Gokbulut, C; Bilgili, A; Hanedan, B; McKellar, Q A

    2007-09-30

    The plasma disposition of fenbendazole (FBZ), oxfendazole (OFZ) and albendazole (ABZ); and the enantiospecific disposition of OFZ, and ABZSO produced were investigated following an oral administration (50 mg/kg) in dogs. Blood samples were collected from 1 to 120 h post-administration. The plasma samples were analysed by high performance liquid chromatography (HPLC). The plasma concentration of FBZ, OFZ, ABZ and their metabolites were significantly different from each other and depended on the drug administered. The sulphone metabolite (FBZSO2) of FBZ was not detected in any plasma samples and the parent molecule ABZ did not reach quantifiable concentrations following FBZ and ABZ administration, respectively. OFZ and its sulphone metabolite attained a significantly higher plasma concentration and remained much longer in plasma compared with FBZ and ABZ and their respective metabolites. The maximum plasma concentrations (Cmax), area under the concentration time curve (AUC) and mean residence time (MRT) of parent OFZ were more than 30, 68 and 2 times those of FBZ, respectively. The same parameters for ABZSO were also significantly greater than those of FBZSO. The ratio for total AUCs of both the parent drug and the metabolites were 1:42:7 for following FBZ, OFZ and ABZ administration, respectively. The enantiomers were never in racemic proportions and (+) enantiomers of both OFZ and ABZSO were predominant in plasma. The AUC of (+) enantiomers of OFZ and ABZSO was, respectively more than three and seven times larger than that of (-) enantiomers of both molecules. It is concluded that the plasma concentration of OFZ was substantially greater compared with FBZ and ABZ. The data on the pharmacokinetic profile of OFZ presented here may contribute to evaluate its potential as an anthelmintic drug for parasite control in dogs.

  19. Modelling Formation of a Drug Reservoir in the Stratum Corneum and Its Impact on Drug Monitoring Using Reverse Iontophoresis

    Directory of Open Access Journals (Sweden)

    Yvonne Paulley

    2010-01-01

    Full Text Available Reverse iontophoresis is a relatively new technique for non-invasive drug monitoring in the body. It involves a small electrical current being passed through the skin to facilitate the movement of small charged ions and polar molecules on the skin's surface where the amount of drug can then be measured and hence an accurate estimate of the blood concentration can be made. In vivo studies for several molecules show that initially large amounts of drug are extracted from the body, which are unrelated to the magnitude of the blood concentration; over time the fluxes of extraction decrease to a level proportional to the steady state blood concentration. This suggests that, at first, the drug is being extracted from some source other than the blood; one such candidate for this source is the dead cells which form the stratum corneum. In this paper, we construct two related mathematical models; the first describes the formation of the drug reservoir in the stratum corneum as a consequence of repeated drug intake and natural death of skin cells in the body. The output from this model provides initial conditions for the model of reverse iontophoresis in which charged ions from both the blood and the stratum corneum reservoir compete for the electric current. Model parameters are estimated from data collected for lithium monitoring. Our models will improve interpretation of reverse iontophoretic data by discriminating the subdermal from the skin contribution to the fluxes of extraction. They also suggest that analysis of the skin reservoir might be a valuable tool to investigate patients' exposure to chemicals including therapeutic drugs.

  20. Therapeutic product disposition in at-risk populations

    International Nuclear Information System (INIS)

    Foster, B. C.

    2009-01-01

    In an emergency situation, such as a chemical, biological, radionuclide, nuclear or explosion (CBRNE) event, all patient populations are at increased risk of serious adverse events. Therapeutic product (TP) safety and efficacy depend on the disposition of the product through absorption, distribution, metabolism and excretion. The ability of a patient to benefit from or merely tolerate a TP can be modified by many factors, including but not limited to culture, diet, disease, environmental contaminants, genetic predisposition, stress and socioeconomic status and recent life experiences. Metabolism is considered to have the greatest effect on safety and efficacy, as chemicals not metabolised can accumulate to toxic levels. Inter-individual variances in most drug metabolism enzymes may range up to greater than 1000-fold. The fetus, neonates, infants, individuals with hormonal change, infection or prior exposure to licit or illicit products and the elderly are more susceptible to increased risk of serious adverse health effects. The critically ill are the most at risk. The at-risk populations for a serious adverse event are dependent then on the CBRNE event, their physical and cognitive states and the inter-individual intrinsic and extrinsic factors that affect TP disposition. (authors)

  1. Repository and deep borehole disposition of plutonium

    International Nuclear Information System (INIS)

    Halsey, W.G.

    1996-02-01

    Control and disposition of excess weapons plutonium is a growing issue as both the US and Russia retire a large number of nuclear weapons> A variety of options are under consideration to ultimately dispose of this material. Permanent disposition includes tow broad categories: direct Pu disposal where the material is considered waste and disposed of, and Pu utilization, where the potential energy content of the material is exploited via fissioning. The primary alternative to a high-level radioactive waste repository for the ultimate disposal of plutonium is development of a custom geologic facility. A variety of geologic facility types have been considered, but the concept currently being assessed is the deep borehole

  2. Surplus Highly Enriched Uranium Disposition Program plan

    International Nuclear Information System (INIS)

    1996-10-01

    The purpose of this document is to provide upper level guidance for the program that will downblend surplus highly enriched uranium for use as commercial nuclear reactor fuel or low-level radioactive waste. The intent of this document is to outline the overall mission and program objectives. The document is also intended to provide a general basis for integration of disposition efforts among all applicable sites. This plan provides background information, establishes the scope of disposition activities, provides an approach to the mission and objectives, identifies programmatic assumptions, defines major roles, provides summary level schedules and milestones, and addresses budget requirements

  3. Potential Impact of Diet on Treatment Effect from Anti-TNF Drugs in Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Vibeke Andersen

    2017-03-01

    Full Text Available We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD, to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51. A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively. In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in prospective observational, animal and interventional studies are warranted.

  4. 31 CFR 501.727 - Motion for summary disposition.

    Science.gov (United States)

    2010-07-01

    ... party's arguments. Any party opposing a motion for summary disposition must file a statement setting... be supported by evidence of the same type as that submitted with the motion for summary disposition...

  5. Mapping and modelling the impact of mass drug adminstration on filariasis prevalence in Myanmar.

    Science.gov (United States)

    Aye, Ni Ni; Lin, Zaw; Lon, Khin Nan; Linn, Nay Yi Yi; Nwe, Thet Wai; Mon, Khin Mon; Ramaiah, Kapa; Betts, Hannah; Kelly-Hope, Louise A

    2018-05-31

    Lymphatic filariasis (LF) is endemic in Myanmar and targeted for elimination. To highlight the National Programme to Eliminate Lymphatic Filariasis (NPELF) progress between 2000 and 2014, this paper describes the geographical distribution of LF, the scale-up and impact of mass drug administration (MDA) implementation, and the first evidence of the decline in transmission in five districts. The LF distribution was determined by mapping historical and baseline prevalence data collected by NPELF. Data on the MDA implementation, reported coverage rates and sentinel site surveillance were summarized. A statistical model was developed from the available prevalence data to predict prevalence at township level by year of measurement. Transmission assessment survey (TAS) methods, measuring antigenemia (Ag) prevalence in children, were used to determine whether prevalence was below a level where recrudescence is unlikely to occur. The highest baseline LF prevalence was found in the Central Valley region. The MDA implementation activities scaled up to cover 45 districts, representing the majority of the endemic population, with drug coverage rates ranging from 60.0% to 98.5%. Challenges related to drug supply and local conflict were reported, and interrupted MDA in some districts. Overall, significant reductions in LF prevalence were found, especially after the first 2 to 3 rounds of MDA, which was supported by the corresponding model. The TAS activities in five districts found only two Ag positive children, resulting in all districts passing the critical threshold. Overall, the Myanmar NPELF has made positive steps forward in the elimination of LF despite several challenges, however, it needs to maintain momentum, drawing on international stakeholder support, to aim towards the national and global goals of elimination.

  6. Expansion of Viral Load Testing and the Potential Impact on HIV Drug Resistance.

    Science.gov (United States)

    Raizes, Elliot; Hader, Shannon; Birx, Deborah

    2017-12-01

    The US President's Emergency Plan for AIDS Relief (PEPFAR) supports aggressive scale-up of antiretroviral therapy (ART) in high-burden countries and across all genders and populations at risk toward global human immunodeficiency virus (HIV) epidemic control. PEPFAR recognizes the risk of HIV drug resistance (HIVDR) as a consequence of aggressive ART scale-up and is actively promoting 3 key steps to mitigate the impact of HIVDR: (1) routine access to routine viral load monitoring in all settings; (2) optimization of ART regimens; and (3) routine collection and analysis of HIVDR data to monitor the success of mitigation strategies. The transition to dolutegravir-based regimens in PEPFAR-supported countries and the continuous evolution of HIVDR surveillance strategies are essential elements of PEPFAR implementation. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  7. Rapid phospho-turnover by receptor tyrosine kinases impacts downstream signaling and drug binding.

    Science.gov (United States)

    Kleiman, Laura B; Maiwald, Thomas; Conzelmann, Holger; Lauffenburger, Douglas A; Sorger, Peter K

    2011-09-02

    Epidermal growth factor receptors (ErbB1-4) are oncogenic receptor tyrosine kinases (RTKs) that regulate diverse cellular processes. In this study, we combine measurement and mathematical modeling to quantify phospho-turnover at ErbB receptors in human cells and to determine the consequences for signaling and drug binding. We find that phosphotyrosine residues on ErbB1 have half-lives of a few seconds and therefore turn over 100-1000 times in the course of a typical immediate-early response to ligand. Rapid phospho-turnover is also observed for EGF-activated ErbB2 and ErbB3, unrelated RTKs, and multiple intracellular adaptor proteins and signaling kinases. Thus, the complexes formed on the cytoplasmic tail of active receptors and the downstream signaling kinases they control are highly dynamic and antagonized by potent phosphatases. We develop a kinetic scheme for binding of anti-ErbB1 drugs to receptors and show that rapid phospho-turnover significantly impacts their mechanisms of action. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Acute cognitive impact of antiseizure drugs in naive rodents and corneal-kindled mice.

    Science.gov (United States)

    Barker-Haliski, Melissa L; Vanegas, Fabiola; Mau, Matthew J; Underwood, Tristan K; White, H Steve

    2016-09-01

    Some antiseizure drugs (ASDs) are associated with cognitive liability in patients with epilepsy, thus ASDs without this risk would be preferred. Little comparative pharmacology exists with ASDs in preclinical models of cognition. Few pharmacologic studies exist on the acute effects in rodents with chronic seizures. Predicting risk for cognitive impact with preclinical models may supply valuable ASD differentiation data. ASDs (phenytoin [PHT]; carbamazepine [CBZ]; valproic acid [VPA]; lamotrigine [LTG]; phenobarbital [PB]; tiagabine [TGB]; retigabine [RTG]; topiramate [TPM]; and levetiracetam [LEV]) were administered equivalent to maximal electroshock median effective dose ([ED50]; mice, rats), or median dose necessary to elicit minimal motor impairment (median toxic dose [TD50]; rats). Cognition models with naive adult rodents were novel object/place recognition (NOPR) task with CF-1 mice, and Morris water maze (MWM) with Sprague-Dawley rats. Selected ASDs were also administered to rats prior to testing in an open field. The effect of chronic seizures and ASD administration on cognitive performance in NOPR was also determined with corneal-kindled mice. Mice that did not achieve kindling criterion (partially kindled) were included to examine the effect of electrical stimulation on cognitive performance. Sham-kindled and age-matched mice were also tested. No ASD (ED50) affected latency to locate the MWM platform; TD50 of PB, RTG, TPM, and VPA reduced this latency. In naive mice, CBZ and VPA (ED50) reduced time with the novel object. Of interest, no ASD (ED50) affected performance of fully kindled mice in NOPR, whereas CBZ and LEV improved cognitive performance of partially kindled mice. Standardized approaches to the preclinical evaluation of an ASD's potential cognitive impact are needed to inform drug development. This study demonstrated acute, dose- and model-dependent effects of therapeutically relevant doses of ASDs on cognitive performance of naive mice and

  9. Retrospective drug utilization review: impact of pharmacist interventions on physician prescribing

    Directory of Open Access Journals (Sweden)

    Angalakuditi M

    2011-06-01

    Full Text Available Mallik Angalakuditi1, Joseph Gomes21Georgia State University, Atlanta, GA, USA; 2Baxter Health Care, Deerfield, IL, USAObjectives: To evaluate the impact of retrospective drug utilization review (RDUR, pharmacist’s interventions on physician prescribing, and the level of spillover effect on future prescriptions following the intervention.Methods: A retrospective case–control study was conducted at a pharmacy benefits management company using the available prescription data from April 2004 to August 2005. RDUR conflicts evaluated and intervened by a clinical pharmacist served as a case group, whereas conflicts that were not evaluated and intervened by a clinical pharmacist served as a control group.Results: A total of 40,284 conflicts in cases and 13,044 in controls were identified. For cases, 32,780 interventions were considered nonrepetitive, and 529 were repetitive. There were 22,870 physicians in cases that received intervention letters and 2348 physicians in the control group that would have received intervention letters during the study period. Each physician received on average 1.4 interventions for cases vs 3.0 for controls. Among the case physicians who were intervened during the study period, 2.2% (505 were involved in a repeated intervention vs 18.2% (428 in controls (P < 0.001, which is an eight-fold difference. The most common conflict intervened on in cases was therapeutic appropriateness (8277, 25.3%, and for controls it was drug–drug interactions (1796, 25.4%. The overall interventional spillover effect in cases was 98.4% vs 89.4% in controls (P = 0.01.Conclusion: RDUR is an effective interventional program which results in decreased numbers of interventions per physician and provides a significant impact on future prescribing habits.Keywords: pharmacy management, spillover effect, RDUR, DUR

  10. Disposition of inorganic mercury in pregnant rats and their offspring

    Science.gov (United States)

    Oliveira, Cláudia S.; Joshee, Lucy; Zalups, Rudolfs K.; Pereira, Maria E.; Bridges, Christy C.

    2015-01-01

    Environmental toxicants such as methylmercury have been shown to negatively impact fetal health. Despite the prevalence of inorganic mercury (Hg2+) in the environment and the ability of methylmercury to biotransform into Hg2+, little is known about the ability of Hg2+ to cross the placenta into fetal tissues. Therefore, it is important to understand the handing and disposition of Hg2+ in the reproductive system. The purpose of the current study was to assess the disposition and transport of Hg2+ in placental and fetal tissues, and to test the hypothesis that acute renal injury in dams can alter the accumulation of Hg2+ in fetal tissues. Pregnant Wistar rats were injected intravenously with 0.5 or 2.5 μmol kg−1 HgCl2 for 6 or 48 h and the disposition of Hg2+ was measured. Accumulation of Hg2+ in the placenta was rapid and dose-dependent. Very little Hg2+ was eliminated during the initial 48 h after exposure. When dams were exposed to the low dose of HgCl2, fetal accumulation of Hg2+ increased between 6 h and 48 h, while at the higher dose, accumulation was similar at each time point. Within fetal organs, the greatest concentration of Hg2+ (nmol/g) was localized in the kidneys, followed by the liver and brain. A dose-dependent increase in the accumulation of Hg2+ in fetal organs was observed, suggesting that continued maternal exposure may lead to increased fetal exposure. Taken together, these data indicate that Hg2+ is capable of crossing the placenta and gaining access to fetal organs in a dose-dependent manner. PMID:26196528

  11. Institutional disposition and management of end-of-life electronics.

    Science.gov (United States)

    Babbitt, Callie W; Williams, Eric; Kahhat, Ramzy

    2011-06-15

    Institutions both public and private face a challenge to develop policies to manage purchase, use, and disposal of electronics. Environmental considerations play an increasing role in addition to traditional factors of cost, performance and security. Characterizing current disposition practices for end-of-life electronics is a key step in developing policies that prevent negative environmental and health impacts while maximizing potential for positive social and economic benefits though reuse. To provide a baseline, we develop the first characterization of quantity, value, disposition, and flows of end-of-life electronics at a major U.S. educational institution. Results of the empirical study indicate that most end-of-first-life electronics were resold through public auction to individuals and small companies who refurbish working equipment for resale or sell unusable products for reclamation of scrap metal. Desktop and laptop computers sold for refurbishing and resale averaged U.S. $20-100 per unit, with computers sold directly to individuals for reuse reaching $250-350 per unit. This detailed assessment was coupled with a benchmarking survey of end-of-life electronics management practices at other U.S. universities. Survey results indicate that while auctions are still commonplace, an increasing number of institutions are responding to environmental concerns by creating partnerships with local recycling and resale entities and mandating domestic recycling. We use the analyses of current disposition practices as input to discuss institutional strategies for managing electronics. One key issue is the tension between benefits of used equipment sales, in terms of income for the institution and increased reuse for society, and the environmental risks because of unknown downstream practices.

  12. 50 CFR 30.2 - Disposition of surplus range animals.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Disposition of surplus range animals. 30.2... (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM RANGE AND FERAL ANIMAL MANAGEMENT Range Animals § 30.2 Disposition of surplus range animals. Disposition shall be made only during regularly scheduled disposal...

  13. 12 CFR 34.83 - Disposition of real estate.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false Disposition of real estate. 34.83 Section 34.83 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY REAL ESTATE LENDING AND APPRAISALS Other Real Estate Owned § 34.83 Disposition of real estate. (a) Disposition. A national bank may...

  14. Mission Need Statement: Calcine Disposition Project Major Systems Acquisition Project

    International Nuclear Information System (INIS)

    J. T. Beck

    2007-01-01

    This document identifies the need to establish the Calcine Disposition Project to determine and implement the final disposition of calcine including characterization, retrieval, treatment (if necessary), packaging, loading, onsite interim storage pending shipment to a repository or interim storage facility, and disposition of related facilities

  15. Plutonium-bearing materials feed report for the DOE Fissile Materials Disposition Program alternatives

    International Nuclear Information System (INIS)

    Brough, W.G.; Boerigter, S.T.

    1995-01-01

    This report has identified all plutonium currently excess to DOE Defense Programs under current planning assumptions. A number of material categories win clearly fan within the scope of the MD (Materials Disposition) program, but the fate of the other categories are unknown at the present time. MD planning requires that estimates be made of those materials likely to be considered for disposition actions so that bounding cases for the PEIS (Programmatic Environmental Impact Statement) can be determined and so that processing which may be required can be identified in considering the various alternatives. A systematic analysis of the various alternatives in reachmg the preferred alternative requires an understanding of the possible range of values which may be taken by the various categories of feed materials. One table identifies the current total inventories excess to Defense Program planning needs and represents the bounding total of Pu which may become part of the MD disposition effort for all materials, except site return weapons. The other categories, principally irradiated fuel, rich scrap, and lean scrap, are discussed. Another table summarizes the ranges and expected quantities of Pu which could become the responsibility of the MD program. These values are to be used for assessing the impact of the various alternatives and for scaling operations to assess PEIS impact. Determination of the actual materials to be included in the disposition program will be done later

  16. Differential impact of contraceptive methods on seizures varies by antiepileptic drug category: Findings of the Epilepsy Birth Control Registry.

    Science.gov (United States)

    Herzog, Andrew G; Mandle, Hannah B; Cahill, Kaitlyn E; Fowler, Kristen M; Hauser, W Allen

    2016-07-01

    The aim of this study was to determine whether categories of contraception differ in their impact on seizures in women with epilepsy and whether the impact varies by antiepileptic drug category. Retrospective survey data came from 2712 contraceptive experiences reported by 1144 women with epilepsy. We compared risk ratios for reports of increase and decrease in seizure frequency on hormonal versus nonhormonal contraception, stratified by antiepileptic drug categories. More women with epilepsy reported a change in seizures on hormonal (28.2%) than on nonhormonal contraception (9.7%) (pcontraception (4.2%) was 4.47 (pcontraception (5.5%) was 1.71, pcontraception, the risk ratio for seizure increase was greater than for decrease (1.98, pmethod with a greater risk ratio for seizure decrease than combined pills. Seizure increase was greater for hormonal than nonhormonal contraception for each antiepileptic drug category (pcontraception, relative to the non-enzyme-inducing antiepileptic drug category which had the lowest rate, each of the other categories had significantly greater risks for seizure increase, especially the enzyme-inhibiting (valproate) category (risk ratio=2.53, p=0.0002). The findings provide community-based, epidemiological survey evidence that contraceptive methods may differ in their impact on seizures and that this impact may vary by antiepileptic drug category. Copyright © 2016. Published by Elsevier Inc.

  17. Women Faculty, Professional Identity, and Generational Disposition

    Science.gov (United States)

    Marine, Susan B.; Martínez Alemán, Ana M.

    2018-01-01

    In an exploratory qualitative study, the generational dispositions of tenured women faculty from the Boomer Generation were examined. As pioneers and now senior members in the academic profession in the Golden Era of American higher education, they exist in a common historical location characterized by cultural forces and events that helped to…

  18. Characterizing Surplus US Plutonium for Disposition - 13199

    Energy Technology Data Exchange (ETDEWEB)

    Allender, Jeffrey S. [Savannah River National Laboratory, Aiken SC 29808 (United States); Moore, Edwin N. [Moore Nuclear Energy, LLC, Savannah River Site, Aiken SC 29808 (United States)

    2013-07-01

    The United States (US) has identified 61.5 metric tons (MT) of plutonium that is permanently excess to use in nuclear weapons programs, including 47.2 MT of weapons-grade plutonium. Surplus inventories will be stored safely by the Department of Energy (DOE) and then transferred to facilities that will prepare the plutonium for permanent disposition. The Savannah River National Laboratory (SRNL) operates a Feed Characterization program for the Office of Fissile Materials Disposition (OFMD) of the National Nuclear Security Administration (NNSA) and the DOE Office of Environmental Management (DOE-EM). SRNL manages a broad program of item tracking through process history, laboratory analysis, and non-destructive assay. A combination of analytical techniques allows SRNL to predict the isotopic and chemical properties that qualify materials for disposition through the Mixed Oxide (MOX) Fuel Fabrication Facility (MFFF). The research also defines properties that are important for other disposition paths, including disposal to the Waste Isolation Pilot Plant (WIPP) as transuranic waste (TRUW) or to high-level waste (HLW) systems. (authors)

  19. 24 CFR 290.15 - Disposition plan.

    Science.gov (United States)

    2010-04-01

    ... DEVELOPMENT HUD-OWNED PROPERTIES DISPOSITION OF MULTIFAMILY PROJECTS AND SALE OF HUD-HELD MULTIFAMILY..., the sales price that is acceptable to HUD, and the assistance that HUD plans to make available to a... plan, the environmental reviews required by 24 CFR part 50. ...

  20. Disposition of surplus fissile materials via immobilization

    International Nuclear Information System (INIS)

    Gray, L.W.; Kan, T.; Sutcliffe, W.G.; McKibben, J.M.; Danker, W.

    1995-01-01

    In the Cold War aftermath, the US and Russia have agreed to large reductions in nuclear weapons. To aid in the selection of long-term management options, the USDOE has undertaken a multifaceted study to select options for storage and disposition of surplus plutonium (Pu). One disposition alternative being considered is immobilization. Immobilization is a process in which surplus Pu would be embedded in a suitable material to produce an appropriate form for ultimate disposal. To arrive at an appropriate form, we first reviewed published information on HLW immobilization technologies to identify forms to be prescreened. Surviving forms were screened using multi-attribute utility analysis to determine promising technologies for Pu immobilization. We further evaluated the most promising immobilization families to identify and seek solutions for chemical, chemical engineering, environmental, safety, and health problems; these problems remain to be solved before we can make technical decisions about the viability of using the forms for long-term disposition of Pu. All data, analyses, and reports are being provided to the DOE Office of Fissile Materials Disposition to support the Record of Decision that is anticipated in Summer of 1996

  1. Critical thinking dispositions in baccalaureate nursing students.

    Science.gov (United States)

    Shin, Kyung Rim; Lee, Ja Hyung; Ha, Ju Young; Kim, Kon Hee

    2006-10-01

    This paper reports an investigation into the critical thinking disposition of students enrolled in a baccalaureate nursing programme at a university in Korea. Critical thinking may be summarized as a skilled process that conceptualizes and applies information from observation, experience, reflection, inference and communication in a technical manner. It is more of a rational act used as an instrument rather than as a result. Critical thinking is a core competency in nursing and has been widely discussed in nursing education. However, the results of previous research on the effectiveness of nursing education in improving students' critical thinking have been inconsistent. A longitudinal design was used with a convenience sample of 60 nursing students; 32 students participated four times in completing a questionnaire each March from 1999 to 2002. The California Critical Thinking Disposition Inventory was administered to measure disposition to critical thinking. There was a statistically significant improvement in critical thinking disposition score by academic year (F = 7.54, P = 0.0001). Among the subscales, open-mindedness, self-confidence, and maturity also showed a statistically significant difference by academic year (P = 0.0194, 0.0041, 0.0044). Teaching strategies to enhance critical thinking should be developed, in addition to further research on the effect of the nursing curriculum on students' critical thinking. Moreover, survey instruments could be adjusted to incorporate characteristics of the Korean culture.

  2. Dispositional affectivity and work outcomes of expatriates

    DEFF Research Database (Denmark)

    Selmer, Jan; Lauring, Jakob

    2013-01-01

    affectivity appears to be a promising construct to explain and predict many attitudinal and behavioral outcomes in the workplace, few studies have empirically investigated dispositional affectivity and the work of expatriates. Hence, data from a net-based survey including 350 expatriates in Denmark were used...

  3. The Dispositions for Culturally Responsive Pedagogy Scale

    Science.gov (United States)

    Whitaker, Manya C.; Valtierra, Kristina Marie

    2018-01-01

    Purpose: The purpose of this study is to develop and validate the dispositions for culturally responsive pedagogy scale (DCRPS). Design/methodology/approach: Scale development consisted of a six-step process including item development, expert review, exploratory factor analysis, factor interpretation, confirmatory factor analysis and convergent…

  4. 16 CFR 5.56 - Disposition.

    Science.gov (United States)

    2010-01-01

    ... Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE STANDARDS OF CONDUCT Disciplinary Actions Concerning Postemployment Conflict of Interest § 5.56 Disposition. (a) Upon the conclusion... disciplinary committee of the bar(s) of which the attorney is a member. ...

  5. New glass material oxidation and dissolution system facility: Direct conversion of surplus fissile materials, spent nuclear fuel, and other material to high-level-waste glass. Storage and disposition of weapons-usable fissile materials programmatic environmental impact statement data report: Predecisional draft

    International Nuclear Information System (INIS)

    Forsberg, C.W.; Elam, K.R.; Reich, W.J.

    1995-01-01

    With the end of the Cold War, countries have excess plutonium and other materials from the reductions in inventories of nuclear weapons. It has been recommended that these surplus fissile materials (SFMs) be processed so that they are no more accessible than plutonium in spent nuclear fuel (SNF). This SNF standard, if adopted worldwide, would prevent rapid recovery of SFMs for the manufacture of nuclear weapons. This report provides for the PEIS the necessary input data on a new method for the disposition of SFMs: the simultaneous conversion of SFMs, SNF, and other highly radioactive materials into high-level-waste (HLW) glass. The SFMs include plutonium, neptunium, americium, and 233 U. The primary SFM is plutonium. The preferred SNF is degraded SNF, which may require processing before it can be accepted by a geological repository for disposal. The primary form of this SNF is Hanford-N SNF with preirradiation uranium enrichments between 0.95 and 1.08%. The final product is a plutonium, low-enriched-uranium, HLW, borosilicate glass for disposition in a geological repository. The proposed conversion process is the Glass Material Oxidation and Dissolution System (GMODS), which is a new process. The initial analysis of the GMODS process indicates that a MODS facility for this application would be similar in size and environmental impact to the Defense Waste Processing Facility (DWPF) at the Savannah River Site. Because of this, the detailed information available on DWPF was used as the basis for much of the GMODS input into the SFMs PEIS

  6. Impact of treatment heterogeneity on drug resistance and supply chain costs.

    Science.gov (United States)

    Spiliotopoulou, Eirini; Boni, Maciej F; Yadav, Prashant

    2013-09-01

    The efficacy of scarce drugs for many infectious diseases is threatened by the emergence and spread of resistance. Multiple studies show that available drugs should be used in a socially optimal way to contain drug resistance. This paper studies the tradeoff between risk of drug resistance and operational costs when using multiple drugs for a specific disease. Using a model for disease transmission and resistance spread, we show that treatment with multiple drugs, on a population level, results in better resistance-related health outcomes, but more interestingly, the marginal benefit decreases as the number of drugs used increases. We compare this benefit with the corresponding change in procurement and safety stock holding costs that result from higher drug variety in the supply chain. Using a large-scale simulation based on malaria transmission dynamics, we show that disease prevalence seems to be a less important factor when deciding the optimal width of drug assortment, compared to the duration of one episode of the disease and the price of the drug(s) used. Our analysis shows that under a wide variety of scenarios for disease prevalence and drug cost, it is optimal to simultaneously deploy multiple drugs in the population. If the drug price is high, large volume purchasing discounts are available, and disease prevalence is high, it may be optimal to use only one drug. Our model lends insights to policy makers into the socially optimal size of drug assortment for a given context.

  7. Newer antiepileptic drugs in the treatment of status epilepticus: impact on prognosis.

    Science.gov (United States)

    Jaques, Léonore; Rossetti, Andrea O

    2012-05-01

    Newer antiepileptic drugs (AEDs) are increasingly prescribed and seem to have a comparable efficacy as the classical AEDs; however, their impact on status epilepticus (SE) prognosis has received little attention. In our prospective SE database (2006-2010), we assessed the use of older versus newer AEDs (levetiracetam, pregabalin, topiramate, lacosamide) over time and its relationship to outcome (return to clinical baseline conditions, new handicap, or death). Newer AEDs were used more often toward the end of the study period (42% of episodes versus 30%). After adjustment for SE etiology, SE severity score, and number of compounds needed to terminate SE, newer AEDs were independently related to a reduced likelihood of return to baseline (p<0.001) but not to increased mortality. These findings seem in line with recent findings on refractory epilepsy. Also, in view of the higher price of the newer AEDs, well-designed, prospective assessments analyzing the impact of newer AEDs on efficacy and tolerability in patients with SE appear mandatory. Copyright © 2012 Elsevier Inc. All rights reserved.

  8. Analysis of disposition alternatives for radioactively contaminated scrap metal

    International Nuclear Information System (INIS)

    Nieves, L.A.; Chen, S.Y.; Kohout, E.J.; Nabelssi, B.; Tilbrook, R.W.; Wilson, S.E.

    1997-01-01

    Millions of tonnes of slightly radioactive, scrap iron and steel, stainless steel, and copper are likely to become available as nuclear and other facilities and equipment are withdrawn from service. Disposition of this material is an international policy issue under consideration currently. The major alternatives for managing this material are to either develop a regulatory process for decontamination and recycling that will safeguard human health or to dispose of the scrap and replace the metal stocks. To evaluate the alternatives, we estimate quantities of scrap arising from nuclear power plant decommissioning, evaluate potential price impacts of recycling on regional markets, and assess the health and environmental impacts of the management alternatives. We conclude that decontaminating and recycling the scrap is the superior alternative

  9. The Impact of Bubbles on Measurement of Drug Release from Echogenic Liposomes

    OpenAIRE

    Kopechek, Jonathan A.; Haworth, Kevin J.; Radhakrishnan, Kirthi; Huang, Shaoling; Klegerman, Melvin E.; McPherson, David D.; Holland, Christy K.

    2012-01-01

    Echogenic liposomes (ELIP) encapsulate gas bubbles and drugs within lipid vesicles, but the mechanisms of ultrasound-mediated drug release from ELIP are not well understood. The effect of cavitation activity on drug release from ELIP was investigated in flowing solutions using two fluorescent molecules: a lipophilic drug (rosiglitazone) and a hydrophilic drug substitute (calcein). ELIP samples were exposed to pulsed Doppler ultrasound from a clinical diagnostic ultrasound scanner at pressures...

  10. Use of the over-the-counter drugs by adults and an assessment of the impact of advertisements on consumers

    Directory of Open Access Journals (Sweden)

    Monika Szpringer

    2015-03-01

    Full Text Available Introduction: During the last few years there has been a considerable value growth in the demand for the so-called over-the-counter drugs (OTC, available without doctor’s prescription. Using OTC drugs is related to self-treatment, aimed at mitigating first symptoms of a cold, flu, or various types of pain. The omnipresent advertisements for OTC drugs encourage and contribute to the elevated demand. Unfortunately, the marketing techniques used in advertisements fail to provide reliable and objective information to the viewers about specific products. Aim of the research: To determine the respondents’ opinions on using OTC drugs and to assess how advertisements influence the consumers’ needs. Material and methods : The study was conducted by means of a diagnostic survey using a questionnaire. For the purpose of the study, the authors prepared a survey questionnaire, which was used as a research tool. The study included 114 respondents, falling within an age bracket of 18–66 years. Results : The most frequently used OTC drugs were painkillers and medicines for cold and flu symptoms (68.33% of women and 59.09% of men. The drugs were usually bought in pharmacies and grocery/convenience stores. Conclusions: Taking OTC drugs is a widespread phenomenon, both in women and men. The obtained results clearly indicate that advertisements have a considerable impact upon target groups and contribute to increased consumption of OTC drugs.

  11. Substituting cannabis for prescription drugs, alcohol and other substances among medical cannabis patients: The impact of contextual factors.

    Science.gov (United States)

    Lucas, Philippe; Walsh, Zach; Crosby, Kim; Callaway, Robert; Belle-Isle, Lynne; Kay, Robert; Capler, Rielle; Holtzman, Susan

    2016-05-01

    Recent years have witnessed increased attention to how cannabis use impacts the use of other psychoactive substances. The present study examines the use of cannabis as a substitute for alcohol, illicit substances and prescription drugs among 473 adults who use cannabis for therapeutic purposes. The Cannabis Access for Medical Purposes Survey is a 414-question cross-sectional survey that was available to Canadian medical cannabis patients online and by hard copy in 2011 and 2012 to gather information on patient demographics, medical conditions and symptoms, patterns of medical cannabis use, cannabis substitution and barriers to access to medical cannabis. Substituting cannabis for one or more of alcohol, illicit drugs or prescription drugs was reported by 87% (n = 410) of respondents, with 80.3% reporting substitution for prescription drugs, 51.7% for alcohol, and 32.6% for illicit substances. Respondents who reported substituting cannabis for prescription drugs were more likely to report difficulty affording sufficient quantities of cannabis, and patients under 40 years of age were more likely to substitute cannabis for all three classes of substance than older patients. The finding that cannabis was substituted for all three classes of substances suggests that the medical use of cannabis may play a harm reduction role in the context of use of these substances, and may have implications for abstinence-based substance use treatment approaches. Further research should seek to differentiate between biomedical substitution for prescription pharmaceuticals and psychoactive drug substitution, and to elucidate the mechanisms behind both. [Lucas P, Walsh Z, Crosby K, Callaway R, Belle-Isle L, Kay B, Capler R, Holtzman S. Substituting cannabis for prescription drugs, alcohol, and other substances among medical cannabis patients: The impact of contextual factors. Drug Alcohol Rev 2016;35:326-333]. © 2015 Australasian Professional Society on Alcohol and other Drugs.

  12. A vitrification strategy for weapons-grade plutonium disposition

    International Nuclear Information System (INIS)

    Sylvester, K.B.; Simonson, S.A.

    1995-01-01

    Excess weapons-grade plutonium (WGPu) presents a complex but welcome challenge to decision makers. High security is a clear priority but a host of concerns will impact US actions. Making disposition decisions based on a rigid set of criteria designed to identify an 'optimum' technology given immediate objectives and available technologies may delay Russian processing and unnecessarily limit US options. Attention should be given to near-term, verifiable options that may not provide an acceptable level of security in the long-term but nonetheless provide a material barrier to direct theft and immediate use, buying time to evaluate potential disposition technologies. Vitrification of WGPu in borosilicate glass was examined as one such alternative. Rare earth diluents were examined (using MCNP) for their ability to increase the compressed critical mass of the mixture. Increased critical mass complicates weapon design and increases the quantity of material necessarily diverted. Europium was effective in this regard. As Pu-239 has a 24,000 yr half-life, reactivity control in the long-term could be an environmental safety issue should the glass be placed in a repository. Rare earths were investigated as criticality controllers due to their neutron absorption capabilities and insolubility in aqueous environments. Thorium (assumed as a Pu surrogate) and the rare earths Eu, Gd, and Sm were added to a standard frit (SRL-165) and formed into glass. Aqueous leach tests were performed (using MCC-1P guidelines) to measure rare earth leaching and determine the added element's effects on glass durability

  13. A comparative assessment of the economics of plutonium disposition

    International Nuclear Information System (INIS)

    Williams, K.A.; Miller, J.W.; Reid, R.L.

    1997-01-01

    The US Department of Energy office of Fissile Materials Disposition (DOE/MD) has been evaluating three technologies for the disposition of approximately 50 metric tons of surplus plutonium from defense-related programs: reactors, immobilization, and deep boreholes. As part of the process supporting an early CY 1997 Record of Decision (ROD), a comprehensive assessment of technical viability, cost, and schedule has been conducted by DOE/MD and its national laboratory contractors. Oak Ridge National Laboratory has managed and coordinated the life-cycle cost (LCC) assessment effort for this program. This paper discusses the economic analysis methodology and the results prior to ROD. A secondary intent of the paper is to discuss major technical and economic issues that impact cost and schedule. To evaluate the economics of these technologies on an equitable basis, a set of cost-estimating guidelines and a common cost-estimating format were utilized by all three technology teams. This paper also includes the major economic analysis assumptions and the comparative constant-dollar and discounted-dollar LCCs

  14. Analysis by simulation of the disposition of nuclear fuel waste

    International Nuclear Information System (INIS)

    Turek, J.L.

    1980-09-01

    A descriptive simulation model is developed which includes all aspects of nuclear waste disposition. The model is comprised of two systems, the second system orchestrated by GASP IV. A spent fuel generation prediction module is interfaced with the AFR Program Management Information System and a repository scheduling information module. The user is permitted a wide range of options with which to tailor the simulation to any desired storage scenario. The model projects storage requirements through the year 2020. The outputs are evaluations of the impact that alternative decision policies and milestone date changes have on the demand for, the availability of, and the utilization of spent fuel storage capacities. Both graphs and detailed listings are available. These outputs give a comprehensive view of the particular scenario under observation, including the tracking, by year, of each discharge from every reactor. Included within the work is a review of the status of spent fuel disposition based on input data accurate as of August 1980. The results indicate that some temporary storage techniques (e.g., transshipment of fuel and/or additional at-reactor storage pools) must be utilized to prevent reactor shutdowns. These techniques will be required until the 1990's when several AFR facilities, and possibly one repository, can become operational

  15. 21 CFR 111.113 - What quality control operations are required for a material review and disposition decision?

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What quality control operations are required for a... Production and Process Control System: Requirements for Quality Control § 111.113 What quality control operations are required for a material review and disposition decision? (a) Quality control personnel must...

  16. Impact of drug awareness and treatment camps on attendance at a community outreach de-addiction clinic

    Directory of Open Access Journals (Sweden)

    Om Prakash Giri

    2015-01-01

    Full Text Available Background: Substance misuse is an increasing problem in urban and rural India. The utility of community-based interventions and preventive strategies are increasingly emphasized in this context. The drug de-addiction and treatment center, Department of Psychiatry, Postgraduate Institute of Medical Education and Research, has been running a drug de-addiction and treatment clinic at Kharar Civil Hospital, Kharar, District Mohali, Punjab, since 1998. As part of an effort to enhance this community outreach program, community-based drug awareness and treatment camps have been organized since March 2004 in villages in and around Tehsil Kharar of Mohali. Aim: To study the impact of the drug awareness and treatment camps on the attendance of patients at the community outreach drug de-addiction and treatment clinic at Kharar Civil Hospital. Methods: Sociodemographic and clinical variables, including treatment outcome-related variables, of patients attending the clinic at Kharar Civil Hospital, before and after the camps were compared. Discussion and Conclusion: The study showed a positive impact on drug awareness and treatment camps held in the community on outpatient attendance at a community outreach clinic, with attendance increasing more than 1.8 times.

  17. The Impact of an Indiana (United States Drug Court on Criminal Recidivism

    Directory of Open Access Journals (Sweden)

    John R. Gallagher

    2014-07-01

    Full Text Available This study evaluated a drug court located in a metropolitan area of Indiana (United States, focusing specifically on identifying variables that predicted recidivism among drug court participants and comparing criminal recidivism patterns among drug court and probation participants. Drug court participants were most likely to recidivate if they were younger, had a violation within the first 30 days of the program, had a previous criminal record, and were terminated unsuccessfully from the program. Furthermore, drug court participants were less likely to recidivate than probationers who had similar offense and demographic characteristics. Implications for drug court practice, policy advocacy, and future research are discussed.

  18. Impact of cancer diagnosis and treatment on glycaemic control among individuals with colorectal cancer using glucose lowering drugs

    NARCIS (Netherlands)

    Zanders, M.M.J.; van Herk-Sukel, M.P.P.; Herings, R.M.C.; van de Poll-Franse, L.V.; Haak, H.

    2016-01-01

    Aims This study aims to evaluate the impact of cancer and its treatment on HbA1c values among individuals with colorectal cancer (CRC) using glucose-lowering drugs (GLDs). Methods Patients with primary CRC (1998–2011) were selected from the Eindhoven Cancer Registry and linked to the PHARMO Database

  19. Correlates and Impact of Coronary Artery Calcifications in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents

    DEFF Research Database (Denmark)

    Giustino, Gennaro; Mastoris, Ioannis; Baber, Usman

    2016-01-01

    OBJECTIVES: The aim of this study was to investigate the clinical correlates and prognostic impact of coronary artery calcification (CAC) in women undergoing percutaneous coronary intervention with drug-eluting stents (DES). BACKGROUND: The clinical correlates and the prognostic significance of CAC...

  20. Impact of lipid-based drug delivery systems on the transport and uptake of insulin across Caco-2 Cell monolayers

    DEFF Research Database (Denmark)

    Li, Ping; Nielsen, Hanne Mørck; Müllertz, Anette

    2016-01-01

    Self-(nano)-emulsifying drug delivery systems (SNEDDSs) used to deliver peptides and proteins across biological barriers, such as the small intestinal membrane, represents an increasingly interesting field in nanomedicine. Hence, the present study was designed to evaluate the impact of SNEDDS...

  1. Health-Related Quality of Life in Patients with Multiple Sclerosis : Impact of Disease-Modifying Drugs

    NARCIS (Netherlands)

    Jongen, Peter Joseph

    Multiple sclerosis (MS) has a profound impact on health-related quality of life (HRQoL), a comprehensive subjective measure of the patient's health status. Assessment of HRQoL informs on the potential advantages and disadvantages of disease-modifying drugs (DMDs) beyond their effects on

  2. The impact of new insights and revised practice guidelines on prescribing drugs in the treatment of type 2 diabetes mellitus

    NARCIS (Netherlands)

    Lub, Rene; Denig, Petra; van den Berg, Paulus; Hoogenberg, Klaas; de Jong-van den Berg, Lolkje

    2006-01-01

    Aims. The aim of this study was to investigate the impact of new insights and revised guidelines on initial and follow-up treatment with antihyperglycaemic drugs over the period 1998-2003. Methods. The InterAction Database (IADB), which contains pharmacy dispensing data from 53 community pharmacies

  3. Teachers' dispositional mindfulness and the quality of their relationships with children in Head Start classrooms.

    Science.gov (United States)

    Becker, Brandon D; Gallagher, Kathleen C; Whitaker, Robert C

    2017-12-01

    The quality of teachers' relationships with children is a key predictor of children's later social emotional competence and academic achievement. Interventions to increase mindfulness among teachers have focused primarily on the impacts on teachers' subjective well-being, but not on the quality of their relationships with children. Furthermore, none of these interventions have involved preschool teachers. To consider the potential of mindfulness-based interventions to improve the quality of teachers' relationships with preschool-aged children, we examined data from an online survey of 1001 classroom teachers in 37 Pennsylvania Head Start Programs. Using path analysis we investigated the association between teachers' dispositional mindfulness and the quality of their relationships with children (conflict and closeness). We further examined whether this association was mediated by teacher depressive symptoms and moderated by perceived workplace stress. Higher levels of dispositional mindfulness among teachers were associated with higher quality relationships with children (less conflict and greater closeness). The association between greater dispositional mindfulness and less conflict was partially mediated by lower depressive symptoms, and the conditional direct effect of mindfulness on conflict was stronger when perceived workplace stress was lower. These findings suggest that preschool teachers who have higher levels of dispositional mindfulness may experience higher quality relationships with children in their classrooms. Interventions to increase levels of dispositional mindfulness among early childhood educators may improve their well-being along with the quality of their relationships with children, potentially impacting children's educational outcomes. The potential impacts of such interventions may be even stronger if structural and systemic changes are also made to reduce workplace stress. Copyright © 2017 Society for the Study of School Psychology

  4. Impact of regulatory guidances and drug regulation on risk minimization interventions in drug safety: a systematic review.

    Science.gov (United States)

    Nkeng, Lenhangmbong; Cloutier, Anne-Marie; Craig, Camille; Lelorier, Jacques; Moride, Yola

    2012-07-01

    Therapeutic risk management has received growing interest in recent years, particularly since the publication of regulatory guidances in 2005 and 2006, paralleled with a change in drug regulation. The characteristics of risk minimization interventions (RMIs) that have been implemented or approved remain inadequately explored. The aim of this study was to review RMIs published in the literature or posted on regulatory agency websites over the past 10 years, and to assess whether publication of regulatory guidances on risk management is associated with changes in the number and types of interventions. Sources were searched for RMIs published/posted between 1 January 2000 and 31 December 2009. For the literature search, MEDLINE and EMBASE databases were used using key words related to drug safety (i.e. 'drug toxicity') and the individual RMI names. The website review involved searches of major regulatory authority websites such as the European Medicines Agency, US FDA, Health Canada, the UK's Medicines and Healthcare products Regulatory Agency, Japan's Pharmaceutical and Medical Devices Agency and Australia's Therapeutic Goods Administration. The following eligibility criteria were applied for inclusion in the review: published/posted between the years 2000 and 2009, inclusive; involving drug products; use in humans; and involving RMIs, or tools used to increase the reporting of adverse events (AEs). Natural healthcare products, devices, diagnostic chemicals, pregnancy registries without follow-up, medication errors and products not used as therapy for illness were not retained. For each source, the following characteristics were extracted: nature of the intervention, target population, therapeutic area, AE(s) of special interest, country/regulatory agency and year of publication. A total of 119 unique interventions were identified in the literature (54 published in 2000-4 and 65 published in 2005-9). Interventions included educational material (n = 37; 31%), black

  5. The impact of reference pricing of nonsteroidal anti-inflammatory agents on the use and costs of analgesic drugs.

    Science.gov (United States)

    Grootendorst, Paul V; Marshall, John K; Holbrook, Anne M; Dolovich, Lisa R; O'Brien, Bernie J; Levy, Adrian R

    2005-10-01

    To estimate the effect of reference pricing (RP) of nonsteroidal anti-inflammatory drugs (NSAIDs) on drug subsidy program and beneficiary expenditures on analgesic drugs. Monthly claims data from Pharmacare, the public drug subsidy program for seniors in British Columbia, Canada, over the period of February 1993 to June 2001. RP limits drug plan reimbursement of interchangeable medicines to a reference price, which is typically equal to the price of the lowest cost interchangeable drug; any cost above that is borne by the patient. Pharmacare introduced two different forms of RP to the NSAIDs, Type 1 in April 1994 and Type 2 in November 1995. Under Type 1 RP, generic and brand versions of the same NSAID are considered interchangeable, whereas under Type 2 RP different NSAIDs are considered interchangeable. We extrapolated average reimbursement per day of NSAID therapy over the months before RP to estimate what expenditures would have been without the policies. These counterfactual predictions were compared with actual values to estimate the impact of the policies; the estimated impacts on reimbursement rates were multiplied by the postpolicy volume of NSAIDS dispensed, which appeared unaffected by the policies, to estimate expenditure changes. After Type 2 RP, program expenditures declined by $22.7 million (CAN), or $4 million (CAN), annually cutting expenditure by about half. Most savings accrued from the substitution of low-cost NSAIDs for more costly alternatives. About 20 percent of savings represented expenditures by seniors who elected to pay for partially reimbursed drugs. Type 1 RP produced one-quarter the savings of type 2 RP. Type 2 RP of NSAIDs achieved its goal of reducing drug expenditures and was more effective than Type 1 RP. The effects of RP on patient health and associated health care costs remain to be investigated.

  6. Targeting extinction and reconsolidation mechanisms to combat the impact of drug cues on addiction

    OpenAIRE

    Taylor, Jane R.; Olausson, Peter; Quinn, Jennifer J.; Torregrossa, Mary M.

    2008-01-01

    Drug addiction is a progressive and compulsive disorder, where recurrent craving and relapse to drug seeking occur even after long periods of abstinence. A major contributing factor to relapse is drug-associated cues. Here we review behavioral and pharmacological studies outlining novel methods of effective and persistent reductions in cue-induced relapse behavior in animal models. We focus on extinction and reconsolidation of cue-drug associations as the memory processes that are the most li...

  7. IMPACT OF CLINICAL-TRIALS ON THE ADOPTION OF NEW DRUGS WITHIN A UNIVERSITY HOSPITAL

    NARCIS (Netherlands)

    DENIG, P; HAAIJER-RUSKAMP, FM; WESSELING, H

    1991-01-01

    To assess the influence that clinical trials may have on the introduction of new drugs into prescribing routines, the adoption of drugs has been studied in a university hospital in the Netherlands. A significant relation was found between the testing of semi-innovative drugs in clinical trials in

  8. The power of the drug, nature of support, and their impact on homeless youth.

    Science.gov (United States)

    Hudson, Angela L; Nyamathi, Adeline; Slagle, Alexandra; Greengold, Barbara; Griffin, Deborah Koniak; Khalilifard, Farinaz; Gedzoff, Danny; Reid, Courtney

    2009-10-01

    The purpose of this study was to explore homeless youths' perspectives on the power of drugs in their lives, the preferred type of drugs used, barriers to treatment, and strategies to prevent drug initiation and abuse. This was a descriptive, qualitative study using focus groups with a purposeful sample of 24 drug-using homeless youth. The results provided insight into the lives of drug-using homeless youth. The most commonly used drugs were marijuana and alcohol. Reported reasons for drug use were parental drug use, low self-esteem, and harsh living conditions on the streets. Barriers to treatment were pleasurable enjoyment of the drug, physical dependence, and non-empathetic mental health providers. Strategies to prevent initiation and abuse of drugs were creative activities, such as art, sports, and music, and disdain for parental/family drug use and abuse. Comparative research is needed on specific personal factors that cause initiation and deterrence of drugs use/abuse among homeless youth.

  9. Impact of germline and somatic missense variations on drug binding sites.

    Science.gov (United States)

    Yan, C; Pattabiraman, N; Goecks, J; Lam, P; Nayak, A; Pan, Y; Torcivia-Rodriguez, J; Voskanian, A; Wan, Q; Mazumder, R

    2017-03-01

    Advancements in next-generation sequencing (NGS) technologies are generating a vast amount of data. This exacerbates the current challenge of translating NGS data into actionable clinical interpretations. We have comprehensively combined germline and somatic nonsynonymous single-nucleotide variations (nsSNVs) that affect drug binding sites in order to investigate their prevalence. The integrated data thus generated in conjunction with exome or whole-genome sequencing can be used to identify patients who may not respond to a specific drug because of alterations in drug binding efficacy due to nsSNVs in the target protein's gene. To identify the nsSNVs that may affect drug binding, protein-drug complex structures were retrieved from Protein Data Bank (PDB) followed by identification of amino acids in the protein-drug binding sites using an occluded surface method. Then, the germline and somatic mutations were mapped to these amino acids to identify which of these alter protein-drug binding sites. Using this method we identified 12 993 amino acid-drug binding sites across 253 unique proteins bound to 235 unique drugs. The integration of amino acid-drug binding sites data with both germline and somatic nsSNVs data sets revealed 3133 nsSNVs affecting amino acid-drug binding sites. In addition, a comprehensive drug target discovery was conducted based on protein structure similarity and conservation of amino acid-drug binding sites. Using this method, 81 paralogs were identified that could serve as alternative drug targets. In addition, non-human mammalian proteins bound to drugs were used to identify 142 homologs in humans that can potentially bind to drugs. In the current protein-drug pairs that contain somatic mutations within their binding site, we identified 85 proteins with significant differential gene expression changes associated with specific cancer types. Information on protein-drug binding predicted drug target proteins and prevalence of both somatic and

  10. Impact of doctors' resistance on success of drug utilization review system.

    Science.gov (United States)

    Choi, Jong Soo; Yun, Seong Hyeon; Kim, Dongsoo; Park, Seung Woo

    2014-04-01

    The drug utilization review (DUR) system, which checks any conflict event of medications, contributes to improve patient safety. One of the important barriers in its adoption is doctors' resistance. This study aimed to analyze the impacts of doctors' resistance on the success of the DUR system. This study adopted an augmented the DeLone and McLean Information System (D&M IS) Success Model (2003), which used doctors' resistance as a socio-technological measure. This study framework is the same as that of the D&M IS Success Model in that it is based on qualities, such as system, information, and services. The major difference is that this study excluded the variable 'use' because it was not statistically significant for mandatory systems. A survey of doctors who used computers to enter prescriptions was conducted at a Korean tertiary hospital in February 2012. This study is very meaningful in that it is the first study to explore the success factors of the DUR system associated with doctors' resistance. Doctors' resistance to the DUR system was not statistically associated with user usefulness, whereas it affected user satisfaction. The results indicate that doctors still complain of discomfort in using the DUR system in the outpatient clinical setting, even though they admit that it contributes to patient safety. To mitigate doctors' resistance and raise user satisfaction, more opinions from doctors regarding the DUR system have to be considered and have to be reflected in the system.

  11. Impact of Drug Therapy, Radiation Dose, and Dose Rate on Renal Toxicity Following Bone Marrow Transplantation

    International Nuclear Information System (INIS)

    Cheng, Jonathan C.; Schultheiss, Timothy E.; Wong, Jeffrey Y.C.

    2008-01-01

    Purpose: To demonstrate a radiation dose response and to determine the dosimetric and chemotherapeutic factors that influence the incidence of late renal toxicity following total body irradiation (TBI). Methods and Materials: A comprehensive retrospective review was performed of articles reporting late renal toxicity, along with renal dose, fractionation, dose rate, chemotherapy regimens, and potential nephrotoxic agents. In the final analysis, 12 articles (n = 1,108 patients), consisting of 24 distinct TBI/chemotherapy conditioning regimens were included. Regimens were divided into three subgroups: adults (age ≥18 years), children (age <18 years), and mixed population (both adults and children). Multivariate logistic regression was performed to identify dosimetric and chemotherapeutic factors significantly associated with late renal complications. Results: Individual analysis was performed on each population subgroup. For the purely adult population, the only significant variable was total dose. For the mixed population, the significant variables included total dose, dose rate, and the use of fludarabine. For the pediatric population, only the use of cyclosporin or teniposide was significant; no dose response was noted. A logistic model was generated with the exclusion of the pediatric population because of its lack of dose response. This model yielded the following significant variables: total dose, dose rate, and number of fractions. Conclusion: A dose response for renal damage after TBI was identified. Fractionation and low dose rates are factors to consider when delivering TBI to patients undergoing bone marrow transplantation. Drug therapy also has a major impact on kidney function and can modify the dose-response function

  12. The ultimate disposition of depleted uranium

    Energy Technology Data Exchange (ETDEWEB)

    Lemons, T.R. [Uranium Enrichment Organization, Oak Ridge, TN (United States)

    1991-12-31

    Depleted uranium (DU) is produced as a by-product of the uranium enrichment process. Over 340,000 MTU of DU in the form of UF{sub 6} have been accumulated at the US government gaseous diffusion plants and the stockpile continues to grow. An overview of issues and objectives associated with the inventory management and the ultimate disposition of this material is presented.

  13. The disposition effect and investor experience

    OpenAIRE

    Da Costa Jr, Newton; Goulart, Marco; Cupertino, Cesar; Macedo Jr, Jurandir; Da Silva, Sergio

    2013-01-01

    We examine whether investing experience can dampen the disposition effect, that is, the fact that investors seem to hold on to their losing stocks to a greater extent than they hold on to their winning stocks. To do so, we devise a computer program that simulates the stock market. We use the program in an experiment with two groups of subjects, namely experienced investors and undergraduate students (the inexperienced investors). As a control procedure, we consider random trade decisions made...

  14. Regulatory issues for deep borehole plutonium disposition

    International Nuclear Information System (INIS)

    Halsey, W.G.

    1995-03-01

    As a result of recent changes throughout the world, a substantial inventory of excess separated plutonium is expected to result from dismantlement of US nuclear weapons. The safe and secure management and eventual disposition of this plutonium, and of a similar inventory in Russia, is a high priority. A variety of options (both interim and permanent) are under consideration to manage this material. The permanent solutions can be categorized into two broad groups: direct disposal and utilization. The deep borehole disposition concept involves placing excess plutonium deep into old stable rock formations with little free water present. Issues of concern include the regulatory, statutory and policy status of such a facility, the availability of sites with desirable characteristics and the technologies required for drilling deep holes, characterizing them, emplacing excess plutonium and sealing the holes. This white paper discusses the regulatory issues. Regulatory issues concerning construction, operation and decommissioning of the surface facility do not appear to be controversial, with existing regulations providing adequate coverage. It is in the areas of siting, licensing and long term environmental protection that current regulations may be inappropriate. This is because many current regulations are by intent or by default specific to waste forms, facilities or missions significantly different from deep borehole disposition of excess weapons usable fissile material. It is expected that custom regulations can be evolved in the context of this mission

  15. DISPOSITION EFFECT AMONG BRAZILIAN EQUITY FUND MANAGERS

    Directory of Open Access Journals (Sweden)

    Eduardo Pozzi Lucchesi

    2015-01-01

    Full Text Available The disposition effect predicts that investors tend to sell winning stocks too soon and ride losing stocks too long. Despite the wide range of research evidence about this issue, the reasons that lead investors to act this way are still subject to much controversy between rational and behavioral explanations. In this article, the main goal was to test two competing behavioral motivations to justify the disposition effect: prospect theory and mean reversion bias. To achieve it, an analysis of monthly transactions for a sample of 51 Brazilian equity funds from 2002 to 2008 was conducted and regression models with qualitative dependent variables were estimated in order to set the probability of a manager to realize a capital gain or loss as a function of the stock return. The results brought evidence that prospect theory seems to guide the decision-making process of the managers, but the hypothesis that the disposition effect is due to mean reversion bias could not be confirmed.

  16. Corneal and conjunctival drug permeability: Systematic comparison and pharmacokinetic impact in the eye.

    Science.gov (United States)

    Ramsay, Eva; Del Amo, Eva M; Toropainen, Elisa; Tengvall-Unadike, Unni; Ranta, Veli-Pekka; Urtti, Arto; Ruponen, Marika

    2018-07-01

    On the surface of the eye, both the cornea and conjunctiva are restricting ocular absorption of topically applied drugs, but barrier contributions of these two membranes have not been systemically compared. Herein, we studied permeability of 32 small molecular drug compounds across an isolated porcine cornea and built a quantitative structure-property relationship (QSPR) model for the permeability. Corneal drug permeability (data obtained for 25 drug molecules) showed a 52-fold range in permeability (0.09-4.70 × 10 -6  cm/s) and the most important molecular descriptors in predicting the permeability were hydrogen bond donor, polar surface area and halogen ratio. Corneal permeability values were compared to their conjunctival drug permeability values. Ocular drug bioavailability and systemic absorption via conjunctiva were predicted for this drug set with pharmacokinetic calculations. Drug bioavailability in the aqueous humour was simulated to be drug across the conjunctiva to the blood circulation restricts significantly ocular drug bioavailability and, therefore, ocular absorption does not increase proportionally with the increasing corneal drug permeability. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Impact of injecting drug use on mortality in Danish HIV-infected patients: a nation-wide population-based cohort study

    DEFF Research Database (Denmark)

    Larsen, Mette V; Omland, Lars H; Gerstoft, Jan

    2010-01-01

    To estimate the impact of injecting drug use (IDU) on mortality in HIV-infected patients in the highly active antiretroviral therapy (HAART) era.......To estimate the impact of injecting drug use (IDU) on mortality in HIV-infected patients in the highly active antiretroviral therapy (HAART) era....

  18. Dose dependent disposition of gallium-67 in rats

    International Nuclear Information System (INIS)

    Gautam, S.R.

    1982-01-01

    Radioactive gallium-67 has been employed as a diagnostic and follow-up agent for cancer therapy. Currently gallium nitrate is undergoing Phase I clinical studies. A million fold increase in the concentration of the carrier gallium citrate over the range of carrier-free gallium-67 (pgm) to 1.0 μg caused no significant alteration in the disposition of gallium-67 in rats.Gallium-67 was eliminated from blood with a biological t1/2 of 4.1 days. A linear tissue binding profile was observed for gallium-67 over this concentration range. A multi-compartment pharmacokinetic model was developed in which all the tissues studied were treated as separate compartments. At 1.0 mg dose level, significant alteration in the disposition of gallium-67 was observed in rats, > 95% of the initial radioactivity was characteristic reappearance of the radioactivity in the blood approximately 4 hours after dosing leading to a ''hump'' in the blood concentration-time profiles. Following the 1.0 mg dose low tissue levels were observed, except for the kidneys, which contained about 8% of the administered dose per gram of the tissue one-half hour after dosing. A non-linear tissue binding profile was observed to be associated with gallium at high doses. It was hypothesized that the rapid loss of gallium-67 from the vascular system following the high doses of gallium citrate was due to the accumulation of the drug in the kidneys where it was eventually eliminated via urine. The kidneys thus would act as a temporary storage site for gallium. It was concluded that the dose-related renal toxicity associated with gallium therapy may be attributed to the kidney's role as a temporary storage site following high doses

  19. The impact of the Food and Drug Administration Modernization Act on the recruitment of children for research.

    Science.gov (United States)

    Sharav, Vera Hassner

    2003-01-01

    This article argues that contrary to the claims made by research stakeholders in industry, academia and government, the shift in public policy since the enactment of the Food and Drug Administration Modernization Act (FDAMA) of 1997 and its financial incentives to industry to test drugs on children, has had a deleterious impact on children's dignity, health and welfare. Those lucrative incentives offered an opportunity to accelerate the pace of FDA approval for pediatric drug marketing. FDAMA resulted in a radical shift in federal policy to accommodate an expansion of pediatric trials. Children who are precluded from exercising a human adult's right to informed consent to research are increasingly sought as test subjects even when the trials offer no potential benefit for them. Prior to FDAMA children were protected under federal regulations that prohibited their recruitment for experiments that were not in their best interest. This article discusses eight cases and controversies demonstrating that children have been subjected to experiments that exposed them to pain, discomfort, and serious risks of harm. Babies have died testing a lethal heartburn drug; children have been subjected to "forced dose titration" in antidepressant drug trials that resulted in several suicide attempts. Toddlers are currently being subjected to methylphenidate dose tolerance tests without evidence of any pathological condition. Healthy teenagers are being exposed to antipsychotic drugs known to induce severe pathological side effects in speculative "schizophrenia prevention" experiments.

  20. Metabolic disposition of ivermectin in tissues of cattle, sheep, and rats

    International Nuclear Information System (INIS)

    Chiu, S.H.; Sestokas, E.; Taub, R.; Buhs, R.P.; Green, M.; Sestokas, R.; Vandenheuvel, W.J.; Arison, B.H.; Jacob, T.A.

    1986-01-01

    The metabolic disposition of ivermectin, a new antiparasitic drug, has been studied in cattle, sheep, and also in rats dosed with the drug labeled with tritium in the C-22,23 positions. In the edible tissues of these animals, the unaltered drug was the major tissue residue component and was quantitated by HPLC-reverse isotope dilution assay. The depletion half-lives of the drug ranged between 1 and 6 days, similar to those of the total tissue residue in these species. Most metabolites present in the liver tissues were more polar than the parent drug. Based on spectral (NMR, mass spectrometric) analysis and chromatographic comparison with authentic compounds prepared by in vitro rat or steer microsomal incubations, three of these metabolites have been isolated and identified as the hydroxylation derivatives of ivermectin, i.e. 24-hydroxymethyl-H 2 B1a, its monosaccharide, and 24-hydroxymethyl-H 2 B1b

  1. Ultimate disposition of aluminum clad spent nuclear fuel in the United States

    International Nuclear Information System (INIS)

    Messick, C.E.; Clark, W.D.; Clapper, M.; Mustin, T.P.

    2001-01-01

    Treatment and disposition of spent nuclear fuel (SNF) in the United States has changed significantly over the last decade due to change in world climate associated with nuclear material. Chemical processing of aluminum based SNF is ending and alternate disposition paths are being developed that will allow for the ultimate disposition of the enriched uranium in this SNF. Existing inventories of aluminum based SNF are currently being stored primarily in water-filled basins at the Savannah River Site (SRS) while these alternate disposition paths are being developed and implemented. Nuclear nonproliferation continues to be a worldwide concern and it is causing a significant influence on the development of management alternatives for SNF. SRS recently completed an environmental impact statement for the management of aluminum clad SNF that selects alternatives for all of the fuels in inventory. The U.S. Department of Energy and SRS are now implementing a dual strategy of processing small quantities of 'problematic' SNF while developing an alternative technology to dispose of the remaining aluminum clad SNF in the proposed monitored geologic repository. (author)

  2. The Interpersonal Adaptiveness of Dispositional Guilt and Shame: A Meta-Analytic Investigation.

    Science.gov (United States)

    Tignor, Stefanie M; Colvin, C Randall

    2017-06-01

    Despite decades of empirical research, conclusions regarding the adaptiveness of dispositional guilt and shame are mixed. We use meta-analysis to summarize the empirical literature and clarify these ambiguities. Specifically, we evaluate how guilt and shame are uniquely related to pro-social orientation and, in doing so, highlight the substantial yet under-acknowledged impact of researchers' methodological choices. A series of meta-analyses was conducted investigating the relationship between dispositional guilt (or shame) and pro-social orientation. Two main methodological moderators of interest were tested: test format (scenario vs. checklist) and statistical analysis (semi-partial vs. zero-order correlations). Among studies employing zero-order correlations, dispositional guilt was positively correlated with pro-social orientation (k = 63, Mr = .13, p guilt studies only, with scenario measures producing significantly stronger effects. Semi-partial correlations resulted in significantly stronger effects among guilt and shame studies. Although dispositional guilt and shame are differentially related to pro-social orientation, such relationships depend largely on the methodological choices of the researcher, particularly in the case of guilt. Implications for the study of these traits are discussed. © 2016 Wiley Periodicals, Inc.

  3. The impact of cardiovascular drug innovation on the longevity of elderly residents of Switzerland, 2003-2012

    Directory of Open Access Journals (Sweden)

    Frank R Lichtenberg

    2015-03-01

    Full Text Available Previous investigators have argued that one of the two most important contributors to improved human survival is the treatment of cardiovascular disease. Among Swiss inhabitants age 65 and over, 90% of the 1994-2010 decline in the overall death rate was due to the decline in the rate of deaths from diseases of the circulatory system. Little if any of the decline in cardiovascular mortality is likely to have been due to changes in behavioral risk factors, especially tobacco use and obesity. This study examines the impact of cardiovascular drug innovation on the longevity of elderly residents of Switzerland using cross-sectional patient-level data on about 22 thousand patients insured by a major health insurer (CSS during the period 2003-2011. We investigate the effect of the vintage (world launch year of the cardiovascular drugs used by an individual in 2003 on his or her longevity (time till death, controlling for several demographic characteristics and indicators of health status. We are able to track a patient’s vital status until 12/31/2011: 8 years after the end of the period in which cardiovascular drug use (and other variables are measured. Our estimates indicate that people who used newer cardiovascular drugs in 2003 had longer time till death than people who used older cardiovascular drugs, controlling for the number of 2003 prescriptions and their distribution by main anatomical group, the number of 2003 doctor visits and their distribution by specialty, whether the person was hospitalized in 2003, sex, and age. Our most conservative estimates imply that cardiovascular drug innovation accounted for almost a quarter of the increase in longevity among elderly residents of Switzerland during 2003-2012, and that it increased their longevity by almost 3 months. Other estimates are about twice as large. All of the estimates are consistent with the hypothesis that newer classes of drugs tend to be therapeutically superior to older classes of

  4. [Impact of potentially inappropriate drug usage on health insurance business results].

    Science.gov (United States)

    Kirschke, Malin; Böhme, Jacqueline

    2014-09-01

    In Germany a list was drawn up that included 83 potentially inappropriate drugs. The PRISCUS list published in 2010 was intended to highlight certain problems in the pharmakotherapy of elderly patients and serve as a support for improved medicine safety. Almost a third of the insurance portfolio of the HALLESCHE Krankenversicherung aged over 75 years takes drugs that are on the PRISCUS list. Benzodiazepine and Z-drugs are taken most frequently. The costs per insurant with potentially inappropriate medication are on average higher than for policyholders who do not take drugs on the PRISCUS list. The costs per insurant are rising, with an increase in the number of PRISCUS agents being taken as well. However, there is still no scientific proof that potentially inappropriate drugs lead to adverse drug events.

  5. Impact of sampling resolution on estimation of community-wide daily illicit drug use

    DEFF Research Database (Denmark)

    Ramin, Pedram; Baz Lomba, J. A.; Reid, M.

    It is a common approach to report daily community-wide drug consumption, based on single daily measurements of the influent from a treatment plant. This article suggests that neglecting diurnal variations of loads and flow can result in misestimating daily drug consumption.......It is a common approach to report daily community-wide drug consumption, based on single daily measurements of the influent from a treatment plant. This article suggests that neglecting diurnal variations of loads and flow can result in misestimating daily drug consumption....

  6. Impact assessment of an automated drug-dispensing system in a tertiary hospital

    Directory of Open Access Journals (Sweden)

    Débora de-Carvalho

    Full Text Available OBJECTIVE: To evaluate the costs and patient safety of a pilot implementation of an automated dispensing cabinet in a critical care unit of a private tertiary hospital in São Paulo/Brazil. METHODS: This study considered pre- (January-August 2013 and post- (October 2013-October 2014 intervention periods. We considered the time and cost of personnel, number of adverse events, audit adjustments to patient bills, and urgent requests and returns of medications to the central pharmacy. Costs were evaluated based on a 5-year analytical horizon and are reported in Brazilian Reals (R$ and US dollars (USD. RESULTS: The observed decrease in the mean number of events reported with regard to the automated drug-dispensing system between pre- and post-implementation periods was not significant. Importantly, the numbers are small, which limits the power of the mean comparative analysis between the two periods. A reduction in work time was observed among the nurses and administrative assistants, whereas pharmacist assistants showed an increased work load that resulted in an overall 6.5 hours of work saved/day and a reduction of R$ 33,598 (USD 14,444 during the first year. The initial investment (R$ 206,065; USD 88,592 would have been paid off in 5 years considering only personnel savings. Other findings included significant reductions of audit adjustments to patient hospital bills and urgent requests and returns of medications to the central pharmacy. CONCLUSIONS: Evidence of the positive impact of this technology on personnel time and costs and on other outcomes of interest is important for decision making by health managers.

  7. Validation of a microdose probe drug cocktail for clinical drug interaction assessments for drug transporters and CYP3A.

    Science.gov (United States)

    Prueksaritanont, T; Tatosian, D A; Chu, X; Railkar, R; Evers, R; Chavez-Eng, C; Lutz, R; Zeng, W; Yabut, J; Chan, G H; Cai, X; Latham, A H; Hehman, J; Stypinski, D; Brejda, J; Zhou, C; Thornton, B; Bateman, K P; Fraser, I; Stoch, S A

    2017-04-01

    A microdose cocktail containing midazolam, dabigatran etexilate, pitavastatin, rosuvastatin, and atorvastatin has been established to allow simultaneous assessment of a perpetrator impact on the most common drug metabolizing enzyme, cytochrome P450 (CYP)3A, and the major transporters organic anion-transporting polypeptides (OATP)1B, breast cancer resistance protein (BCRP), and MDR1 P-glycoprotein (P-gp). The clinical utility of these microdose cocktail probe substrates was qualified by conducting clinical drug interaction studies with three inhibitors with different in vitro inhibitory profiles (rifampin, itraconazole, and clarithromycin). Generally, the pharmacokinetic profiles of the probe substrates, in the absence and presence of the inhibitors, were comparable to their reported corresponding pharmacological doses, and/or in agreement with theoretical expectations. The exception was dabigatran, which resulted in an approximately twofold higher magnitude for microdose compared to conventional dosing, and, thus, can be used to flag a worst-case scenario for P-gp. Broader application of the microdose cocktail will facilitate a more comprehensive understanding of the roles of drug transporters in drug disposition and drug interactions. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  8. The Dual Effects of Critical Thinking Disposition on Worry

    Science.gov (United States)

    Sugiura, Yoshinori

    2013-01-01

    This study investigated the relationship between disposition (people’s consistent motivation) toward critical thinking (CT) and worrying. In spite of its connection to psychopathology, worry is thought to represent an effort at problem-solving. Moreover, worry has been found to be underpinned by cognitive development, leading us to predict a positive relationship between worry and CT disposition. On the other hand, cognitive behavioral therapy, which involves techniques similar to CT, has been shown to be effective in reducing worrying, suggesting that increasing CT disposition decreases worrying. This study attempted to reconcile these seemingly contrasting predictions about the relationship between CT disposition and worrying by using multiple mediator analysis. A model was proposed wherein the mediators, responsibility to continue thinking and detached awareness of negative thinking, were related to two opposing predictions. The former is thought to lead to enhanced worrying and the latter to reduced worrying, with both positively related to CT disposition. A questionnaire study with university students (N = 760) revealed that CT disposition enhanced worrying by obliging people to continue thinking about a problem, but that it also reduced worrying by enhancing the detached and objective awareness of their negative thoughts. This study thus demonstrated the dual effects of CT disposition on worrying through different mediators. Thus, when enhancing CT disposition, it is important for educators to be aware of possible disadvantages apart from its worry-reducing effect. Future studies should therefore examine the underlying mechanisms of these two effects of CT disposition. PMID:24278160

  9. Dispositional Optimism and Therapeutic Expectations in Early Phase Oncology Trials

    Science.gov (United States)

    Jansen, Lynn A.; Mahadevan, Daruka; Appelbaum, Paul S.; Klein, William MP; Weinstein, Neil D.; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P.

    2016-01-01

    Purpose Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early phase oncology trials. Optimism, however, is not a unitary construct – it can also be defined as a general disposition, or what is called dispositional optimism. We assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. We also assessed how dispositional optimism related to unrealistic optimism. Methods Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Results Dispositional optimism was significantly associated with higher expectations for personal therapeutic benefit (Spearman r=0.333, poptimism was weakly associated with unrealistic optimism (Spearman r=0.215, p=0.005). In multivariate analysis, both dispositional optimism (p=0.02) and unrealistic optimism (poptimism (p=.0001), but not dispositional optimism, was independently associated with the therapeutic misconception. Conclusion High expectations for therapeutic benefit among patient-subjects in early phase oncology trials should not be assumed to result from misunderstanding of specific information about the trials. Our data reveal that these expectations are associated with either a dispositionally positive outlook on life or biased expectations about specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early phase oncology research. PMID:26882017

  10. The environmental assessment of nuclear materials disposition options: A transportation perspective

    International Nuclear Information System (INIS)

    Wilson, R.K.; Clauss, D.B.; Moyer, J.W.

    1994-01-01

    The US Department of Energy has undertaken a program to evaluate and select options for the long-term storage and disposition of fissile materials declared surplus to defense needs as a result of the end of the Cold War. The transport of surplus fissile material will be an important and highly visible aspect of the environmental impact studies and other planning documents required for implementation of the disposition options. This report defines the roles and requirements for transportation of fissile materials in the program, and discusses an existing methodology for determining the environmental impact in terms of risk. While it will be some time before specific alternatives are chosen that will permit the completion of detailed risk calculations, the analytical models for performing the probabilistic risk assessments already exist with much of the supporting data related to the transportation system. This report summarizes the various types of data required and identifies sources for that data

  11. In vivo assessment of the impact of efflux transporter on oral drug absorption using portal vein-cannulated rats.

    Science.gov (United States)

    Matsuda, Yoshiki; Konno, Yoshihiro; Hashimoto, Takashi; Nagai, Mika; Taguchi, Takayuki; Satsukawa, Masahiro; Yamashita, Shinji

    2013-08-01

    The purpose of this study was to evaluate the impact of intestinal efflux transporters on the in vivo oral absorption process. Three model drugs-fexofenadine (FEX), sulfasalazine (SASP), and topotecan (TPT)-were selected as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and P-gp and BCRP substrates, respectively. The drugs were orally administered to portal vein-cannulated rats after pretreatment with zosuquidar (ZSQ), P-gp inhibitor, and/or Ko143, BCRP inhibitor. Intestinal availability (Fa·Fg) of the drugs was calculated from the difference between portal and systemic plasma concentrations. When rats were orally pretreated with ZSQ, Fa·Fg of FEX increased 4-fold and systemic clearance decreased to 75% of the control. In contrast, intravenous pretreatment with ZSQ did not affect Fa·Fg of FEX, although systemic clearance decreased significantly. These data clearly show that the method presented herein using portal vein-cannulated rats can evaluate the effects of intestinal transporters on Fa·Fg of drugs independently of variable systemic clearance. In addition, it was revealed that 71% of FEX taken up into enterocytes underwent selective efflux via P-gp to the apical surface, while 79% of SASP was effluxed by Bcrp. In the case of TPT, both transporters were involved in its oral absorption. Quantitative analysis indicated a 3.5-fold higher contribution from Bcrp than P-gp. In conclusion, the use of portal vein-cannulated rats enabled the assessment of the impact of efflux transporters on intestinal absorption of model drugs. This experimental system is useful for clarifying the cause of low bioavailability of various drugs.

  12. The Impact of Parenting Factors, Deviant Peers, and Coping Style upon Adolescent Drug Use.

    Science.gov (United States)

    Simons, Ronald L.; Robertson, Joan F.

    1989-01-01

    Developed and tested adolescent drug use model integrating social learning theory and recent stress and coping studies. Interviewed adolescents (N=343) aged 13-17 and found increase in adolescent drug use with presence of parental rejection, deviant peers, and combination of low self-esteem and avoidant coping style. Suggests both individual…

  13. Drug Safety Monitoring in Children: Performance of Signal Detection Algorithms and Impact of Age Stratification

    NARCIS (Netherlands)

    O.U. Osokogu (Osemeke); C. Dodd (Caitlin); A.C. Pacurariu (Alexandra C.); F. Kaguelidou (Florentia); D.M. Weibel (Daniel); M.C.J.M. Sturkenboom (Miriam)

    2016-01-01

    textabstractIntroduction: Spontaneous reports of suspected adverse drug reactions (ADRs) can be analyzed to yield additional drug safety evidence for the pediatric population. Signal detection algorithms (SDAs) are required for these analyses; however, the performance of SDAs in the pediatric

  14. Extended and targeted Drug Information at Pharmacies: Attitudes to the Concept and Barriers to Impact.

    DEFF Research Database (Denmark)

    Søndergaard, Jens; Foged, Anette; Andersen, Morten

    2004-01-01

    20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:178......20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:178...

  15. The Impact of Science Education Games on Prescription Drug Abuse Attitudes among Teens: A Case Study

    Science.gov (United States)

    Klisch, Yvonne; Bowling, Kristi G.; Miller, Leslie M.; Ramos, Miguel A.

    2013-01-01

    Two online science education games, in which players learn about the risks of prescription drug abuse in the context of investigating crimes, were evaluated to determine shifts of prescription drug abuse attitudes attributable to game exposure. High school students from grades 11 and 12 (n = 179) were assigned to one of the games and participated…

  16. The Longitudinal Impact of Adolescent Drug Use on Socioeconomic Outcomes in Young Adulthood

    Science.gov (United States)

    Broman, Clifford L.

    2009-01-01

    This study investigates how drug use in adolescence contributes to socioeconomic outcomes in young adulthood. Several studies have investigated whether drug problems alter the life course in ways that are detrimental to young adult achievement, but findings are inconsistent. We use data from the National Longitudinal Study of Adolescent Health to…

  17. Transmission of drug resistant HIV and its potential impact on mortality and treatment outcomes in resource-limited settings

    DEFF Research Database (Denmark)

    Cambiano, Valentina; Bertagnolio, Silvia; Jordan, Michael R

    2013-01-01

    is the most cost-effective. Mathematical models can contribute to answer these questions. In order to estimate the potential long-term impact of TDR on mortality in people on ART we used the Synthesis transmission model. TDR is predicted to have potentially significant impact on future HIV mortality...... periods of unrecognized viral failure, during which drug-resistant virus can be transmitted and this could compromise the long-term effectiveness of currently available first-line regimens. In response to this concern, the World Health Organization recommends population-based surveys to detect whether...... the prevalence of resistance in ART-naive people is reaching alerting levels. Whereas adherence counseling has to be an integral component of any treatment program, it is still unclear which threshold of transmitted drug resistance (TDR) should trigger additional targeted public health actions and which action...

  18. Impact of use of alcohol and illicit drugs by AIDS patients on adherence to antiretroviral therapy in Bahia, Brazil.

    Science.gov (United States)

    Teixeira, Celia; Dourado, Maria De Lourdes; Santos, Marcio P; Brites, Carlos

    2013-05-01

    Use of alcohol and illicit drugs is a common finding among HIV-infected individuals, but there are many open questions about its impact on adherence to antiretroviral therapy and virological outcomes. Our study aimed to evaluate the impact of the use of alcohol and illicit drugs on the adherence to antiretroviral therapy (ART) among patients starting ART in Salvador, Brazil. We followed up 144 AIDS patients initiating ART for a 6-month period. At baseline, they were interviewed about demographics, behavior, and use of illicit drugs and alcohol. All of them had HIV-1 RNA plasma viral load and CD4(+)/CD8(+) cells count measured before starting therapy. After 60 days of treatment they were asked to answer a new questionnaire on adherence to ART. All patients were monitored during the following months, and new CD4(+) cell count/HIV-1 RNA plasma viral load determinations were performed after 6 months of therapy. Optimal adherence to therapy was defined by self-reported questionnaire, by 95% use of prescribed drug doses, and by using plasma HIV-1 RNA viral load as a biological marker. A total of 61 (42.4%) patients reported alcohol use, 7 (4.9%) used illicit drugs, and 17 (11.8%) used both alcohol and illicit drugs. Being in a steady relationship was protective to nonadherence (95% CI: 0.18-0.84). Missing more than two medical visits was also associated with a 68% higher likelihood of nonadherence (95% CI: 0.10-1.02). After logistic regression we detected a higher risk of nonadherence for patients declaring use of alcohol plus illicit drugs (odds ratio=6.0; 95% CI: 1.78-20.28) or high-intensity use of alcohol (odds ratio=3.29; 95% CI: 1.83-5.92). AIDS patients using alcohol and/or illicit drugs are socially vulnerable, and need specific and flexible programs, combining mental health care, harm reduction strategies, and assisted drug therapy to maximize the chances of successful use of ART.

  19. The Impact of Drug Trafficking on Informal Security Actors in Kenya

    Directory of Open Access Journals (Sweden)

    Moritz Schuberth

    2014-01-01

    Full Text Available The Kenyan state is currently under pressure from two sides: First, numerous non-state armed groups have taken over the provision of security in areas where the state is practically absent. Second, drug-trafficking organizations are gaining ground as the country is increasingly being used as a major transit hub for narcotics. This article investigates the relationship between drug trafficking and informal security provision in Kenya and draws analogies from comparable experiences in Latin America and West Africa. Field research in Kenya has demonstrated that profit-oriented, informal security actors in Mombasa work for drug lords, while their counterparts in Nairobi are more likely to be hired by politicians. Moreover, faith-based vigilante groups in both cities appear to be less susceptible to external manipulation by drug traffickers. The article concludes by considering the potential consequences of an expansion of the drug trade in Kenya.

  20. The impact of assay technology as applied to safety assessment in reducing compound attrition in drug discovery.

    Science.gov (United States)

    Thomas, Craig E; Will, Yvonne

    2012-02-01

    Attrition in the drug industry due to safety findings remains high and requires a shift in the current safety testing paradigm. Many companies are now positioning safety assessment at each stage of the drug development process, including discovery, where an early perspective on potential safety issues is sought, often at chemical scaffold level, using a variety of emerging technologies. Given the lengthy development time frames of drugs in the pharmaceutical industry, the authors believe that the impact of new technologies on attrition is best measured as a function of the quality and timeliness of candidate compounds entering development. The authors provide an overview of in silico and in vitro models, as well as more complex approaches such as 'omics,' and where they are best positioned within the drug discovery process. It is important to take away that not all technologies should be applied to all projects. Technologies vary widely in their validation state, throughput and cost. A thoughtful combination of validated and emerging technologies is crucial in identifying the most promising candidates to move to proof-of-concept testing in humans. In spite of the challenges inherent in applying new technologies to drug discovery, the successes and recognition that we cannot continue to rely on safety assessment practices used for decades have led to rather dramatic strategy shifts and fostered partnerships across government agencies and industry. We are optimistic that these efforts will ultimately benefit patients by delivering effective and safe medications in a timely fashion.

  1. Impact of the zero-markup drug policy on hospitalisation expenditure in western rural China: an interrupted time series analysis.

    Science.gov (United States)

    Yang, Caijun; Shen, Qian; Cai, Wenfang; Zhu, Wenwen; Li, Zongjie; Wu, Lina; Fang, Yu

    2017-02-01

    To assess the long-term effects of the introduction of China's zero-markup drug policy on hospitalisation expenditure and hospitalisation expenditures after reimbursement. An interrupted time series was used to evaluate the impact of the zero-markup drug policy on hospitalisation expenditure and hospitalisation expenditure after reimbursement at primary health institutions in Fufeng County of Shaanxi Province, western China. Two regression models were developed. Monthly average hospitalisation expenditure and monthly average hospitalisation expenditure after reimbursement in primary health institutions were analysed covering the period 2009 through to 2013. For the monthly average hospitalisation expenditure, the increasing trend was slowed down after the introduction of the zero-markup drug policy (coefficient = -16.49, P = 0.009). For the monthly average hospitalisation expenditure after reimbursement, the increasing trend was slowed down after the introduction of the zero-markup drug policy (coefficient = -10.84, P = 0.064), and a significant decrease in the intercept was noted after the second intervention of changes in reimbursement schemes of the new rural cooperative medical insurance (coefficient = -220.64, P markup drug policy in western China. However, hospitalisation expenditure and hospitalisation expenditure after reimbursement were still increasing. More effective policies are needed to prevent these costs from continuing to rise. © 2016 John Wiley & Sons Ltd.

  2. CETA and pharmaceuticals: impact of the trade agreement between Europe and Canada on the costs of prescription drugs.

    Science.gov (United States)

    Lexchin, Joel; Gagnon, Marc-André

    2014-05-06

    On a per capita basis, Canadian drug costs are already the second highest in the world after the United States and are among the fastest rising in the Organization for Economic Co-Operation and Development. The Comprehensive Economic and Trade Agreement (CETA) between the European Union (EU) and Canada will further exacerbate the rise in costs by:  Committing Canada to creating a new system of patent term restoration thereby delaying entry of generic medicines by up to two years; Locking in Canada's current term of data protection, and creating barriers for future governments wanting to reverse it;  Implementing a new right of appeal under the patent linkage system that will create further delays for the entry of generics.CETA will only affect intellectual property rights in Canada-not the EU. This analysis estimates that CETA's provisions will increase Canadian drug costs by between 6.2% and 12.9% starting in 2023. The Canadian government committed to compensating provinces for the rise in costs for their public drug plans. Importantly, this means that people paying out-of-pocket for their drugs or receiving them through private insurance, will be charged twice: once through higher drug costs and once more through their federal taxes.As drug costs continue to grow, there are limited options available for provincial/territorial governments: restrict the choice of medicines in public drug plans; transfer costs to patients who typically are either elderly or sick; or take money from other places in the health system, and threaten the viability of Canada's single payer system. CETA will therefore negatively impact the ability of Canada to offer quality health care.

  3. Considerations for Disposition of Dry Cask Storage System Materials at End of Storage System Life

    International Nuclear Information System (INIS)

    Howard, Rob; Van den Akker, Bret

    2014-01-01

    Dry cask storage systems are deployed at nuclear power plants for used nuclear fuel (UNF) storage when spent fuel pools reach their storage capacity and/or the plants are decommissioned. An important waste and materials disposition consideration arising from the increasing use of these systems is the management of the dry cask storage systems' materials after the UNF proceeds to disposition. Thermal analyses of repository design concepts currently under consideration internationally indicate that waste package sizes for the geologic media under consideration may be significantly smaller than the canisters being used for on-site dry storage by the nuclear utilities. Therefore, at some point along the UNF disposition pathway, there could be a need to repackage fuel assemblies already loaded into the dry storage canisters currently in use. In the United States, there are already over 1650 of these dry storage canisters deployed and approximately 200 canisters per year are being loaded at the current fleet of commercial nuclear power plants. There is about 10 cubic meters of material from each dry storage canister system that will need to be dispositioned. The concrete horizontal storage modules or vertical storage overpacks will need to be reused, re-purposed, recycled, or disposed of in some manner. The empty metal storage canister/cask would also have to be cleaned, and decontaminated for possible reuse or recycling or disposed of, likely as low-level radioactive waste. These material disposition options can have impacts of the overall used fuel management system costs. This paper will identify and explore some of the technical and interface considerations associated with managing the dry cask storage system materials. (authors)

  4. Used fuel disposition in crystalline rocks

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Y. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hadgu, Teklu [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Kalinina, Elena Arkadievna [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Jerden, James L. [Argonne National Lab. (ANL), Argonne, IL (United States); Copple, Jacqueline M. [Argonne National Lab. (ANL), Argonne, IL (United States); Cruse, T. [Argonne National Lab. (ANL), Argonne, IL (United States); Ebert, W. [Argonne National Lab. (ANL), Argonne, IL (United States); Buck, E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Eittman, R. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Tinnacher, R. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Tournassat, Christophe. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Davis, J. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Viswanathan, H. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Chu, S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Dittrich, T. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Hyman, F. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Karra, S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Makedonska, N. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Reimus, P. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Zavarin, Mavrik [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Joseph, C. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2016-09-01

    The U.S. Department of Energy Office of Nuclear Energy, Office of Fuel Cycle Technology established the Used Fuel Disposition Campaign (UFDC) in fiscal year 2010 (FY10) to conduct the research and development (R&D) activities related to storage, transportation and disposal of used nuclear fuel and high level nuclear waste. The objective of the Crystalline Disposal R&D Work Package is to advance our understanding of long-term disposal of used fuel in crystalline rocks and to develop necessary experimental and computational capabilities to evaluate various disposal concepts in such media.

  5. KEWB facilities decontamination and disposition. Final report

    International Nuclear Information System (INIS)

    Ureda, B.F.

    1976-01-01

    The decontamination and disposition of the KEWB facilities, Buildings 073, 643, 123, and 793, are complete. All of the facility equipment, including reactor enclosure, reactor vessel, fuel handling systems, controls, radioactive waste systems, exhaust systems, electrical services, and protective systems were removed from the site. Buildings 643, 123, and 793 were completely removed, including foundations. The floor and portions of the walls of Building 073 were covered over by final grading. Results of the radiological monitoring and the final survey are presented. 9 tables, 19 figures

  6. The impact of medicinal drugs on traffic safety: a systematic review of epidemiological studies.

    Science.gov (United States)

    Orriols, Ludivine; Salmi, Louis-Rachid; Philip, Pierre; Moore, Nicholas; Delorme, Bernard; Castot, Anne; Lagarde, Emmanuel

    2009-08-01

    To evaluate the quality of epidemiological research into effects of medicinal drugs on traffic safety and the current knowledge in this area. The bibliographic search was done in Medline electronic database using the keywords: ((accident* or crash*) and traffic and drug*) leading to 1141 references. Additional references were retrieved from the Safetylit website and the reference lists of selected studies. Original articles published in English or French, between 1 April 1979 and 31 July 2008, were considered for inclusion. We excluded descriptive studies, studies limited to alcohol or illicit drug involvement and investigations of injuries other than from traffic crashes. Studies based on laboratory tests, driving simulators or on-the-road driving tests were also excluded. Eligible studies had to evaluate the causal relationship between the use of medicinal drugs and the risk of traffic crashes. Study quality was assessed by two independent experts, according to a grid adapted from the strengthening the reporting of observational studies in epidemiology (STROBE) statement. Twenty two studies of variable methodological quality were included. Definition of drug exposure varied across studies and depended on the data sources. Potential confounding due to the interaction between the effects of the medicinal drug and disease-related symptoms was often not controlled. The risk of motor-vehicle crashes related to benzodiazepines has been amply studied and demonstrated. Results for other medicinal drugs remain controversial. There is a need for large studies, investigating the role of individual substances in the risk of road traffic crashes. Copyright 2009 John Wiley & Sons, Ltd.

  7. Hydrodynamic Impacts on Dissolution, Transport and Absorption from Thousands of Drug Particles Moving within the Intestines

    Science.gov (United States)

    Behafarid, Farhad; Brasseur, James G.

    2017-11-01

    Following tablet disintegration, clouds of drug particles 5-200 μm in diameter pass through the intestines where drug molecules are absorbed into the blood. Release rate depends on particle size, drug solubility, local drug concentration and the hydrodynamic environment driven by patterned gut contractions. To analyze the dynamics underlying drug release and absorption, we use a 3D lattice Boltzmann model of the velocity and concentration fields driven by peristaltic contractions in vivo, combined with a mathematical model of dissolution-rate from each drug particle transported through the grid. The model is empirically extended for hydrodynamic enhancements to release rate by local convection and shear-rate, and incorporates heterogeneity in bulk concentration. Drug dosage and solubility are systematically varied along with peristaltic wave speed and volume. We predict large hydrodynamic enhancements (35-65%) from local shear-rate with minimal enhancement from convection. With high permeability boundary conditions, a quasi-equilibrium balance between release and absorption is established with volume and wave-speed dependent transport time scale, after an initial transient and before a final period of dissolution/absorption. Supported by FDA.

  8. Targeting extinction and reconsolidation mechanisms to combat the impact of drug cues on addiction.

    Science.gov (United States)

    Taylor, Jane R; Olausson, Peter; Quinn, Jennifer J; Torregrossa, Mary M

    2009-01-01

    Drug addiction is a progressive and compulsive disorder, where recurrent craving and relapse to drug-seeking occur even after long periods of abstinence. A major contributing factor to relapse is drug-associated cues. Here we review behavioral and pharmacological studies outlining novel methods of effective and persistent reductions in cue-induced relapse behavior in animal models. We focus on extinction and reconsolidation of cue-drug associations as the memory processes that are the most likely targets for interventions. Extinction involves the formation of new inhibitory memories rather than memory erasure; thus, it should be possible to facilitate the extinction of cue-drug memories to reduce relapse. We propose that context-dependency of extinction might be altered by mnemonic agents, thereby enhancing the efficacy of cue-exposure therapy as treatment strategy. In contrast, interfering with memory reconsolidation processes can disrupt the integrity or strength of specific cue-drug memories. Reconsolidation is argued to be a distinct process that occurs over a brief time period after memory is reactivated/retrieved - when the memory becomes labile and vulnerable to disruption. Reconsolidation is thought to be an independent, perhaps opposing, process to extinction and disruption of reconsolidation has recently been shown to directly affect subsequent cue-drug memory retrieval in an animal model of relapse. We hypothesize that a combined approach aimed at both enhancing the consolidation of cue-drug extinction and interfering with the reconsolidation of cue-drug memories will have a greater potential for persistently inhibiting cue-induced relapse than either treatment alone.

  9. From "Kickeando las malias" (kicking the withdrawals) to "Staying clean": The impact of cultural values on cessation of injection drug use in aging Mexican-American men.

    Science.gov (United States)

    Flores, David V; Torres, Luis R; Torres-Vigil, Isabel; Bordnick, Patrick S; Ren, Yi; Torres, Melissa I M; Deleon, Freddie; Pericot-Valverde, Irene; Lopez, Tenee

    2014-06-01

    Drug use among older adults is a growing concern, particularly for the burgeoning Hispanic population. Older adults seeking drug treatment will double over the next decade to almost 6 million. Cultural factors influence drug use, and more specifically, Hispanic cultural values influence heroin use. This study explored Mexican-American injection drug users' adherence to traditional Hispanic cultural values and their impact on cessation. Ethnographic interviews endorsed contextualized influences of values on heroin use. Cultural values functioned dichotomously, influencing both initiation and cessation. Understanding the impact of cultural values on substance abuse is critical given the changing demographics in American society.

  10. How excluding some benefits from value assessment of new drugs impacts innovation.

    Science.gov (United States)

    Cook, Joseph P; Golec, Joseph

    2017-12-01

    Payers often assess the benefits of new drugs relative to costs for reimbursement purposes, but they frequently exclude some drugs' option-related benefits, reducing their reimbursement chances, and making them less attractive R&D investments. We develop and test a real options model of R&D investment that shows that excluding option-related benefits heightens drug developers' incentives to avoid high-risk (volatile) R&D investments and instead encourages them to focus on "safer" (positively skewed) investments. Our model and empirical results could partly explain the decline in the number of risky new molecular entities. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Drug discovery and the impact of the safe harbor provision of the Hatch- Waxman Act.

    Science.gov (United States)

    Goodson, Susanne H

    2010-01-01

    Many facets of drug discovery involve the use of patented materials and methods, subjecting the researcher to potential liability from infringement of the underlying patents. Enacted in 1984, the Hatch-Waxman Act established a “safe harbor” for activities that would otherwise constitute infringement of a patented invention, if those activities were “solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products”. This article examines the major court decisions interpreting the scope of the safe harbor and their application to various activities in drug development.

  12. Measuring the impact of pharmacoepidemiologic research using altmetrics: A case study of a CNODES drug-safety article.

    Science.gov (United States)

    Gamble, J M; Traynor, Robyn L; Gruzd, Anatoliy; Mai, Philip; Dormuth, Colin R; Sketris, Ingrid S

    2018-03-24

    To provide an overview of altmetrics, including their potential benefits and limitations, how they may be obtained, and their role in assessing pharmacoepidemiologic research impact. Our review was informed by compiling relevant literature identified through searching multiple health research databases (PubMed, Embase, and CIHNAHL) and grey literature sources (websites, blogs, and reports). We demonstrate how pharmacoepidemiologists, in particular, may use altmetrics to understand scholarly impact and knowledge translation by providing a case study of a drug-safety study conducted by the Canadian Network of Observational Drug Effect Studies. A common approach to measuring research impact is the use of citation-based metrics, such as an article's citation count or a journal's impact factor. "Alternative" metrics, or altmetrics, are increasingly supported as a complementary measure of research uptake in the age of social media. Altmetrics are nontraditional indicators that capture a diverse set of traceable, online research-related artifacts including peer-reviewed publications and other research outputs (software, datasets, blogs, videos, posters, policy documents, presentations, social media posts, wiki entries, etc). Compared with traditional citation-based metrics, altmetrics take a more holistic view of research impact, attempting to capture the activity and engagement of both scholarly and nonscholarly communities. Despite the limited theoretical underpinnings, possible commercial influence, potential for gaming and manipulation, and numerous data quality-related issues, altmetrics are promising as a supplement to more traditional citation-based metrics because they can ingest and process a larger set of data points related to the flow and reach of scholarly communication from an expanded pool of stakeholders. Unlike citation-based metrics, altmetrics are not inherently rooted in the research publication process, which includes peer review; it is unclear to

  13. A preliminary investigation of the relationship between dispositional mindfulness and eating disorder symptoms among men in residential substance use treatment.

    Science.gov (United States)

    Elmquist, JoAnna; Shorey, Ryan C; Anderson, Scott E; Stuart, Gregory L

    2017-01-01

    The comorbidity between eating disorders (EDs) and substance use disorders (SUDs) is of particular concern given the high rates of mortality, relapse and poor treatment outcomes associated with both disorders. As a result, there has been a growing impetus within the field to elucidate factors that might influence and aid treatment for this comorbidity. One such factor is dispositional mindfulness, as past literature has demonstrated a significant relationship between mindfulness and both EDs and SUDs. However, we are unaware of any research that has examined the relationship between dispositional mindfulness and ED symptoms in a sample of men in residential treatment for SUDs. Medical records from 152 men were included in the current study. Alcohol and drug use and problems, ED symptoms, and dispositional mindfulness were assessed with self-report measures. Hierarchical regression analysis indicated that dispositional mindfulness was inversely related to ED symptoms after controlling for alcohol use, drug use, and age. Although results are preliminary and continued research in this area is needed, our findings suggest that there may be potential usefulness in targeting and enhancing mindfulness among patients in residential treatment for SUDs with co-occurring psychiatric symptoms (e.g., EDs).

  14. Impact of the new handling recommendations for hazardous drugs in a hospital pharmacy service.

    Science.gov (United States)

    García-Alcántara, Beatriz G; Perelló Alomar, Catalina; Moreno Centeno, Elena; Modamio, Pilar; Mariño, Eduardo L; Delgado Sánchez, Olga

    2017-03-01

    To describe the actions taken by the Pharmacy Unit in a tertiary hospital in order to adapt to the recommendations established by NIOSH 2014 for handling Hazardous Drugs. Method: A retrospective observational study. A list was prepared including all hazardous drugs according to NIOSH 2014 that were available at the hospital as marketed or foreign drugs, or used in clinical trials, and there was a review of the processes of acquisition, repackaging, preparation, circuits, organizational, dispensing and identification. Results: After the analysis, a report including all needs was prepared and sent to the Hospital Management. Any relevant information about the handling and administration of hazardous drugs was included in the prescription computer program. There were changes in the acquisition process of two drugs, in order to avoid splitting and multi-dose formulations. An alternative or improvement was found for 35 253 of the 75 779 units of hazardous drugs repackaged in one year. The Pharmacy Unit took over the preparation of four non-sterile medications, as well as the preparation of all sterile parenteral medications included in Lists 1 and 2 that were not previously prepared there, as well as one from List 3. Information was also included about the preparation processes of Magistral Formulations that involved hazardous drugs from Lists 2 or 3. The adaptation to the recommendations by NIOSH 2014 has represented a change, but also a significant reduction in the handling process of hazardous drugs by the healthcare staff, therefore reducing the risk of occupational exposure. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  15. G-protein-coupled receptors: new approaches to maximise the impact of GPCRS in drug discovery.

    Science.gov (United States)

    Davey, John

    2004-04-01

    IBC's Drug Discovery Technology Series is a group of conferences highlighting technological advances and applications in niche areas of the drug discovery pipeline. This 2-day meeting focused on G-protein-coupled receptors (GPCRs), probably the most important and certainly the most valuable class of targets for drug discovery. The meeting was chaired by J Beesley (Vice President, European Business Development for LifeSpan Biosciences, Seattle, USA) and included 17 presentations on various aspects of GPCR activity, drug screens and therapeutic analyses. Keynote Addresses covered two of the emerging areas in GPCR regulation; receptor dimerisation (G Milligan, Professor of Molecular Pharmacology and Biochemistry, University of Glasgow, UK) and proteins that interact with GPCRs (J Bockaert, Laboratory of Functional Genomics, CNRS Montpellier, France). A third Keynote Address from W Thomsen (Director of GPCR Drug Screening, Arena Pharmaceuticals, USA) discussed Arena's general approach to drug discovery and illustrated this with reference to the development of an agonist with potential efficacy in Type II diabetes.

  16. Recent advances in fluorination techniques and their anticipated impact on drug metabolism and toxicity.

    Science.gov (United States)

    Murphy, Cormac D; Sandford, Graham

    2015-04-01

    Fluorine's unique physicochemical properties make it a key element for incorporation into pharmacologically active compounds. Its presence in a drug can alter a number of characteristics that affect ADME-Tox, which has prompted efforts at improving synthetic fluorination procedures. This review describes the influence of fluorine on attributes such as potency, lipophilicity, metabolic stability and bioavailablility and how the effects observed are related to the physicochemical characteristics of the element. Examples of more recently used larger scale synthetic methods for introduction of fluorine into drug leads are detailed and the potential for using biological systems for fluorinated drug production is discussed. The synthetic procedures for carbon-fluorine bond formation largely still rely on decades-old technology for the manufacturing scale and new reagents and methods are required to meet the demands for the preparation of structurally more complex drugs. The improvement of in vitro and computational methods should make fluorinated drug design more efficient and place less emphasis on approaches such as fluorine scanning and animal studies. The introduction of new fluorinated drugs, and in particular those that have novel fluorinated functional groups, should be accompanied by rigorous environmental assessment to determine the nature of transformation products that may cause ecological damage.

  17. Hepatic Disposition of Gemfibrozil and Its Major Metabolite Gemfibrozil 1-O-β-Glucuronide.

    Science.gov (United States)

    Kimoto, Emi; Li, Rui; Scialis, Renato J; Lai, Yurong; Varma, Manthena V S

    2015-11-02

    Gemfibrozil (GEM), which decreases serum triglycerides and low density lipoprotein, perpetrates drug-drug interactions (DDIs) with several drugs. These DDIs are primarily attributed to the inhibition of drug transporters and metabolic enzymes, particularly cytochrome P450 (CYP) 2C8 by the major circulating metabolite gemfibrozil 1-O-β-glucuronide (GG). Here, we characterized the transporter-mediated hepatic disposition of GEM and GG using sandwich-cultured human hepatocytes (SCHH) and transporter-transfect systems. Significant active uptake was noted in SCHH for the metabolite. GG, but not GEM, showed substrate affinity to organic anion transporting polypeptide (OATP) 1B1, 1B3, and 2B1. In SCHH, glucuronidation was characterized affinity constants (Km) of 7.9 and 61.4 μM, and biliary excretion of GG was observed. Furthermore, GG showed active basolateral efflux from preloaded SCHH and ATP-dependent uptake into membrane vesicles overexpressing multidrug resistance-associated protein (MRP) 2, MRP3, and MRP4. A mathematical model was developed to estimate hepatic uptake and efflux kinetics of GEM and GG based on SCHH studies. Collectively, the hepatic transporters play a key role in the disposition and thus determine the local concentrations of GEM and more so for GG, which is the predominant inhibitory species against CYP2C8 and OATP1B1.

  18. Extent, quality and impact of patient and public involvement in antimicrobial drug development research: A systematic review.

    Science.gov (United States)

    Evans, David; Bird, Emma; Gibson, Andy; Grier, Sally; Chin, Teh Li; Stoddart, Margaret; MacGowan, Alasdair

    2018-02-01

    Patient and public involvement (PPI) is increasingly recognized as bringing a range of benefits to clinical and health services research. Recent systematic reviews have identified and synthesized many benefits (eg higher recruitment rates) and some costs (eg extra time need). Much of the literature focuses on PPI in long-term conditions rather than more acute health care in which the majority of microbiological research is undertaken. The aim was to identify the extent, quality and impact of PPI in antimicrobial drug development research. Objectives were to identify any relevant reporting of PPI in antimicrobial research; appraise the quality of reporting on PPI using recognized PPI reporting and critical appraisal tools; and extract and synthesize data on the impact of PPI. A systematic review was undertaken with a search strategy based on four word groups (PPI, patients, antimicrobial drug development and outcomes). Eight online databases were searched. English language publication, publication between 1996 and 2016 and studies describing PPI in antimicrobial drug development research. No studies were found through online searching that met the search strategy and inclusion criteria. One relevant protocol paper with a brief mention of PPI was identified through expert recommendation. Commentary papers recommending PPI were identified through website searching and expert opinion. Despite strong policy guidance encouraging PPI at the international and national levels, and anecdotal accounts of PPI taking place, evidence for the extent, quality and impact of PPI in antimicrobial drug development research has not yet appeared in the peer-reviewed literature. © 2017 The Authors Health Expectations Published by John Wiley & Sons Ltd.

  19. Tissue distribution, disposition, and metabolism of cyclosporine in rats

    International Nuclear Information System (INIS)

    Wagner, O.; Schreier, E.; Heitz, F.; Maurer, G.

    1987-01-01

    Tissue distribution, disposition, and metabolism of 3 H-cyclosporine were studied in rats after single and repeated oral doses of 10 and 30 mg/kg and after an iv dose of 3 mg/kg. The oral doses of 10 and 30 mg/kg were dissolved in polyethylene glycol 200/ethanol or in olive oil/Labrafil/ethanol. Absorption from both formulations was slow and incomplete, with peak 3 H blood levels at 3-4 hr. Approximately 30% of the radioactive dose was absorbed, which is consistent with oral bioavailability data for cyclosporine. More than 70% of the radioactivity was excreted in feces and up to 15% in urine. Elimination via the bile accounted for 10 and 60% of the oral and iv doses, respectively. Since unchanged cyclosporine predominated in both blood and tissues at early time points, the half-lives of the distribution phases (t 1/2 alpha) of parent drug and of total radioactivity were similar. In blood, kidney, liver, and lymph nodes, t 1/2 alpha of cyclosporine ranged from 6-10 hr. Elimination of radioactivity from the systemic circulation was multiphasic, with a terminal half-life of 20-30 hr. 3 H-Cyclosporine was extensively distributed throughout the body, with highest concentrations in liver, kidney, endocrine glands, and adipose tissue. The concentrations of both total radioactivity and parent drug were greater in tissues than in blood, which is consistent with the high lipid solubility of cyclosporine and some of its metabolites. Skin and adipose tissue were the main storage sites for unchanged cyclosporine. Elimination half-lives were slower for most tissues than for blood and increased with multiple dosing. The amount of unchanged drug was negligible in urine and bile

  20. Disposition of citral in male Fischer rats

    International Nuclear Information System (INIS)

    Diliberto, J.J.; Usha, G.; Birnbaum, L.S.

    1988-01-01

    The disposition of citral, an essential oil occurring in many foods and fragrances, was studied in male Fischer rats after iv, po, and dermal treatments. The pattern of distribution and elimination was the same after iv or oral exposure. Urine was the major route of elimination of citral-derived radioactivity, followed by feces, 14 CO 2 , and expired volatiles. However, after dermal exposure, relatively less of the material was eliminated in the urine and more in the feces, suggesting a role for first-pass metabolism through the skin. Citral was almost completely absorbed orally; due to its extreme volatility, much of an applied dermal dose was lost. The citral remaining on the skin was fairly well absorbed. No effect of oral dose, from 5 to 500 mg/kg, was detected on disposition. Although the feces was a minor route of excretion, approximately 25% of the administered dose was eliminated via the bile within 4 hr of an iv dose. The metabolism of citral was both rapid and extensive. Within 5 min of an iv dose, no unmetabolized citral could be detected in the blood. Repeated exposure to citral resulted in an increase in biliary elimination, without any significant change in the pattern of urinary, fecal, or exhaled excretion. This suggests that citral may induce at least one pathway of its own metabolism. The rapid metabolism and excretion of this compound suggest that significant bioaccumulation of citral would not occur

  1. 30 CFR 879.15 - Disposition of reclaimed land.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Disposition of reclaimed land. 879.15 Section 879.15 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR ABANDONED MINE LAND RECLAMATION ACQUISITION, MANAGEMENT, AND DISPOSITION OF LANDS AND WATER § 879...

  2. 50 CFR 30.12 - Disposition of feral animals.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Disposition of feral animals. 30.12... (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM RANGE AND FERAL ANIMAL MANAGEMENT Feral Animals § 30.12 Disposition of feral animals. Feral animals taken on wildlife refuge areas may be disposed of by sale on the...

  3. Digital Reading Disposition Scale: A Study of Validity and Reliability

    Science.gov (United States)

    Bulut, Berker; Karasakaloglu, Nuri

    2018-01-01

    In this study, "a Digital Reading Disposition Scale" was developed to determine undergraduate pre-service teacher students' dispositions towards digital reading, opposed to a preference for printed reading material. Initially, a 20-items trial version of the scale was administered to a total sample of N = 301 undergraduate pre-service…

  4. 47 CFR 76.802 - Disposition of cable home wiring.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Disposition of cable home wiring. 76.802... MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cable Inside Wiring § 76.802 Disposition of cable home wiring. (a)(1) Upon voluntary termination of cable service by a subscriber in a single unit installation, a...

  5. 38 CFR 12.22 - Disposition of personal property.

    Science.gov (United States)

    2010-07-01

    ... converted into cash, except that articles of personal adornment which are obviously of sentimental value... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Disposition of personal... DISPOSITION OF VETERAN'S PERSONAL FUNDS AND EFFECTS Under Pub. L. 382, 77th Congress, December 26, 1941...

  6. Building a Conceptual Framework for Online Educator Dispositions

    Science.gov (United States)

    Kirwan, Jeral R.; Roumell, Elizabeth Anne

    2015-01-01

    It has been argued that online instruction is distinctive from the conventional classroom. If an effective online practice is to emerge, the roles, characteristics and dispositions of the educators themselves should be studied more closely. The aim of this paper was to present an online educator dispositions model that addresses the underlying…

  7. 45 CFR 95.707 - Equipment management and disposition.

    Science.gov (United States)

    2010-10-01

    ... participation in the costs of replacement equipment shall be limited to the additional outlay. (4) If the... 45 Public Welfare 1 2010-10-01 2010-10-01 false Equipment management and disposition. 95.707... PROGRAMS) Equipment Acquired Under Public Assistance Programs § 95.707 Equipment management and disposition...

  8. 7 CFR 3565.453 - Disposition of the property.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Disposition of the property. 3565.453 Section 3565....453 Disposition of the property. (a) Submission of the liquidation plan. The lender will, within 30... the interest. (3) A full and complete list of all collateral including any personal and corporate...

  9. 7 CFR 1779.90 - Disposition of acquired property.

    Science.gov (United States)

    2010-01-01

    ... Disposition of acquired property. (a) General. When the lender acquires title to the collateral and the final... 7 Agriculture 12 2010-01-01 2010-01-01 false Disposition of acquired property. 1779.90 Section... develop a plan to fully protect the collateral, and the lender must dispose of the collateral without...

  10. Critical Thinking Dispositions of Pre-Service Teachers

    Science.gov (United States)

    Bakir, Selda

    2015-01-01

    This study investigated the critical thinking dispositions of pre-service teachers in terms of various variables. The study included 1106 participants and used the survey model and the Turkish version (CCTDI-T) of the California Critical Thinking Disposition Inventory (CCTDI). The reliability of the scale for this study was found to be 0.82. The…

  11. 25 CFR 242.5 - Disposition of unmarketable fish.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Disposition of unmarketable fish. 242.5 Section 242.5 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FISH AND WILDLIFE COMMERCIAL FISHING ON RED LAKE INDIAN RESERVATION § 242.5 Disposition of unmarketable fish. All unmarketable live fish taken...

  12. Identifying and Assessing Dispositions of Educational Leadership Candidates

    Science.gov (United States)

    Melton, Teri; Mallory, Barbara J.; Green, James

    2010-01-01

    The purpose of this study was to identify educational leadership programs' procedures for the identification and assessment of leadership dispositions. The findings of this cross sectional survey indicated that there is little consistency in practice in defining and assessing dispositions of leadership candidates. While findings indicated that the…

  13. Urban High School Teachers' Beliefs Concerning Essential Science Teaching Dispositions

    Science.gov (United States)

    Miranda, Rommel

    2012-01-01

    This qualitative study addresses the link between urban high school science teachers' beliefs about essential teaching dispositions and student learning outcomes. The findings suggest that in order to help students to do well in science in urban school settings, science teachers should possess essential teaching dispositions which include…

  14. 31 CFR 10.23 - Prompt disposition of pending matters.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Prompt disposition of pending matters. 10.23 Section 10.23 Money and Finance: Treasury Office of the Secretary of the Treasury PRACTICE... Revenue Service § 10.23 Prompt disposition of pending matters. A practitioner may not unreasonably delay...

  15. 31 CFR 8.32 - Prompt disposition of pending matters.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Prompt disposition of pending matters. 8.32 Section 8.32 Money and Finance: Treasury Office of the Secretary of the Treasury PRACTICE... Prompt disposition of pending matters. No attorney, certified public accountant, or enrolled practitioner...

  16. 5 CFR 2635.205 - Proper disposition of prohibited gifts.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Proper disposition of prohibited gifts... STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE EXECUTIVE BRANCH Gifts From Outside Sources § 2635.205 Proper disposition of prohibited gifts. (a) An employee who has received a gift that cannot be accepted...

  17. Prediction of critical thinking disposition based on mentoring among ...

    African Journals Online (AJOL)

    The results of study showed that there was a significantly positive correlation between Mentoring and Critical thinking disposition among faculty members. The findings showed that 67% of variance of critical thinking disposition was defined by predictive variables. The faculty members evaluated themselves in all mentoring ...

  18. 46 CFR Sec. 12 - Disposition of removed equipment and scrap.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 8 2010-10-01 2010-10-01 false Disposition of removed equipment and scrap. Sec. 12... CONTRACT-NSA-LUMPSUMREP Sec. 12 Disposition of removed equipment and scrap. (a) Article 8 of the NSA-LUMPSUMREP Contract provides that any ship equipment, fuel, lube oil, supplies, stores, furniture, fixtures...

  19. 48 CFR 945.570-7 - Disposition of motor vehicles.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Disposition of motor... Disposition of motor vehicles. (a) The contractor shall dispose of DOE-owned motor vehicles as directed by the contracting officer. (b) DOE-owned motor vehicles may be disposed of as exchange/sale items when directed by...

  20. 78 FR 57547 - Guidance Regarding Dispositions of Tangible Depreciable Property

    Science.gov (United States)

    2013-09-19

    ... definition of a qualifying disposition under Sec. 1.168(i)- 1T(e)(3)(iii). The purpose of a general asset...) Dispositions from a general asset account--(1) Scope and Definition--(i) In general. This paragraph (e... Accelerated Cost Recovery System (MACRS) property). The proposed regulations also amend the general asset...

  1. Patent extension policy for paediatric indications: an evaluation of the impact within three drug classes in a state Medicaid programme.

    Science.gov (United States)

    Nelson, Richard E; McAdam-Marx, Carrie; Evans, Megan L; Ward, Robert; Campbell, Benjamin; Brixner, Diana; Lafleur, Joanne

    2011-05-01

    The Food and Drug Administration Modernization Act (FDAMA) of 1997, Best Pharmaceuticals for Children Act (BPCA) of 2002 and Pediatric Research Equity Act of 2007 provide an extended period of 6 months of marketing exclusivity (i.e. patent extension) to prescription drug manufacturers that conduct paediatric studies. Branded drugs in the statin, ACE inhibitor and selective serotonin reuptake inhibitor (SSRI) classes were three of many classes with drugs granted patent extensions. We estimated the cost impact of the 6-month exclusivity extension policy on the Utah Medicaid drug programme by comparing actual costs to projected costs had the 6-month exclusivity extension not been granted for these drugs and thus less expensive generic alternatives been available sooner. Using these results, we then projected the cost impact of this policy on Medicaid programmes in the US during the 18 months following patent expiration. The Utah Medicaid prescription claims obtained for statins, ACE inhibitors and SSRIs included reimbursement amount, number of units dispensed, days supplied, date of service and drug strength. Actual expenditures for each drug were calculated for the 6 months before and 12 months after generic availability. The percentage difference between the brand name prescription reimbursement amount to Medicaid in the last 2 months of the 6-month extension and the generic prescription reimbursement amount to Medicaid in the first 2 months following exclusivity expiration was then calculated for each drug. This was done using data from the 5 months surrounding the exclusivity expiration by regressing the log-transformed Utah Medicaid reimbursement amount on an indicator for patent expiration, controlling for number of units, volume of sales, month filled and strength. This was used to estimate what the initial generic prescription price would have been without the 6-month patent extension and what costs would have been in the 18 months following the original

  2. Contribution of Emotional Intelligence towards Graduate Students’ Critical Thinking Disposition

    Directory of Open Access Journals (Sweden)

    Fong-Luan Kang

    2015-10-01

    Full Text Available Good critical thinkers possess a core set of cognitive thinking skills, and a disposition towards critical thinking. They are able to think critically to solve complex, real-world problems effectively. Although personal emotion is important in critical thinking, it is often a neglected issue. The emotional intelligence in this study concerns our sensitivity to and artful handling of our own and others’ emotions. Engaging students emotionally is the key to strengthening their dispositions toward critical thinking. Hence, a study involving 338 male and female graduate students from a public university was carried out. They rated the Emotional Intelligence Scale and Critical Thinking Disposition Scale. Findings suggested that emotional intelligence and critical thinking disposition were positively correlated (r=.609. Differences in terms of age, gender, and course of study also formed part of the analysis. Keywords: emotional intelligence, critical thinking disposition, graduate students

  3. Design and development of a cross-cultural disposition inventory

    Science.gov (United States)

    Davies, Randall; Zaugg, Holt; Tateishi, Isaku

    2015-01-01

    Advances in technology have increased the likelihood that engineers will have to work in a global, culturally diverse setting. Many schools of engineering are currently revising their curricula to help students to develop cultural competence. However, our ability to measure cultural dispositions can be a challenge. The purpose of this project was to develop and test an instrument that measures the various aspects of cultural disposition. The results of the validation process verified that the hypothesised model adequately represented the data. The refined instrument produced a four-factor model for the overall construct. The validation process for the instrument verified the existence of specific subcomponents that form the overall cultural disposition construct. There also seems to be a hierarchical relationship within the subcomponents of cultural disposition. Additional research is needed to explore which aspects of cultural disposition affect an individual's ability to work effectively in a culturally diverse engineering team.

  4. Non-authoritative parents and impact on drug use: the perception of adolescent children.

    Science.gov (United States)

    Benchaya, Mariana C; Bisch, Nadia K; Moreira, Taís C; Ferigolo, Maristela; Barros, Helena M T

    To evaluate the association between drug use and parenting styles perceived by Brazilian adolescent children. This cross-sectional study enrolled adolescents aged 14 to 19 years that used the Serviço Nacional de Orientações e Informações sobre a Prevenção do Uso Indevido de Drogas (VIVAVOZ). A total of 232 adolescents participated in the study. Phone interviews were conducted using the Parental Responsiveness and Demandingness Scale, which classifies maternal and paternal styles perceived by adolescent children as authoritative, neglectful, indulgent or authoritarian. Sociodemographic variables were collected and an instrument was used to assess monthly drug use and abuse. Maternal and paternal parenting styles perceived as neglectful, indulgent or authoritarian (non-authoritative) were significantly associated with drug use (odds ratio [OR] = 2.8; 95% confidence interval [95%CI], 1.3-5.7 for mothers and OR = 2.8; 95%CI, 1.3-6.3 for fathers). Non-authoritative styles also had a significant association with tobacco use in the previous month in the analysis of maternal (OR = 2.7; 95%CI, 1.2-6.5) and paternal (OR = 3.9; 95%CI, 1.4-10.7) styles, and use of cocaine/crack in the previous month (OR = 3.9; 95%CI, 1.1-13.8) and abuse of any drug (OR = 2.2; 95%CI, 1.0-5.1) only for the paternal style. Logistic regression revealed that maternal style (OR = 3.3; 95%CI, 1.1-9.8), adolescent sex (OR = 3.2; 95%CI, 1.5-7.2) and age (OR = 2.8; 95%CI, 1.2-6.2) were associated with drug use. Adolescents that perceived their mothers as non-authoritative had greater chances of using drugs. There was a strong association between non-authoritative paternal styles and adolescent drug abuse.

  5. Development of Prescription Drug Information Leaflets: Impact of Cognitive Effort and Patient Involvement on Prescription Medication Information Processing.

    Science.gov (United States)

    Patel, Harshali K; Bapat, Shweta S; Bhansali, Archita H; Sansgiry, Sujit S

    2018-01-01

    The objective of this study was to develop a one-page (1-page) prescription drug information leaflet (PILs) and assess their impact on the information processing variables, across 2 levels of patient involvement. One-page PILs were developed using cognitive principles to lower mental effort and improve comprehension. An experimental, 3 × 2 repeated measures study was conducted to determine the impact of cognitive effort, manipulated using leaflet type on comprehension across 2 levels (high/low) of patient involvement. Adults (≥18 years) in a university setting in Houston were recruited for the study. Each participant was exposed to 3 different types of prescription drug information leaflet (the current practice, preexisting 1-page text-only, and 1-page PILs) for the 3 drugs (Celebrex, Ventolin HFA, Prezista) for a given involvement scenario. A prevalidated survey instrument was used to measure product knowledge, attitude toward leaflet, and intention to read. Multivariate analysis of variance indicated significant positive effect of cognitive effort, involvement, and their interaction effect across all measured variables. Mean scores for product knowledge, attitude toward leaflet, and intention to read were highest for PILs ( P information processing for consumers by reducing their cognitive effort.

  6. Narrative of a drug user's daughter: impact on family daily routine

    Directory of Open Access Journals (Sweden)

    Lúcia Margarete dos Reis

    2017-08-01

    Full Text Available Abstract Objective: To understand the repercussions of coexisting with the drug use in a family based on the daughter's narrative of a woman who is a multiple drugs user. Method: A case study with a family accessed in 2014, through the records of a Poison Control Center in the North of Paraná. It was used a semi-structured interview and field journal, and resources of thematic oral history to apprehend the story, from the question "How is/was for you and your family to live with a mother who is a drug user?” Results: The daughter's memories emphasized repercussions in the family context: long-term of living with drug abuse; absence or transience of the motherly figure, with rupture processes for homeless situation; cycle of parental disruption/forgiveness and continued presence and fatherly support. Final considerations: The narrative indicated a family that could be added to the process of rehabilitation and social reintegration of the female drug user.

  7. Phenobarbital increases monkey in vivo nicotine disposition and induces liver and brain CYP2B6 protein

    Science.gov (United States)

    Lee, Anna M; Miksys, Sharon; Tyndale, Rachel F

    2006-01-01

    CYP2B6 is a drug-metabolizing enzyme expressed in the liver and brain that can metabolize bupropion (Zyban®, a smoking cessation drug), activate tobacco-smoke nitrosamines, and inactivate nicotine. Hepatic CYP2B6 is induced by phenobarbital and induction may affect in vivo nicotine disposition, while brain CYP2B6 induction may affect local levels of centrally acting substrates. We investigated the effect of chronic phenobarbital treatment on induction of in vivo nicotine disposition and CYP2B6 expression in the liver and brain of African Green (Vervet) monkeys. Monkeys were split into two groups (n=6 each) and given oral saccharin daily for 22 days; one group was supplemented with 20 mg kg−1 phenobarbital. Monkeys were given a 0.1 mg kg−1 nicotine dose subcutaneously before and after treatment. Phenobarbital treatment resulted in a significant, 56%, decrease (P=0.04) in the maximum nicotine plasma concentration and a 46% decrease (P=0.003) in the area under the concentration–time curve. Phenobarbital also increased hepatic CYP2B6 protein expression. In monkey brain, significant induction (Pphenobarbital treatment in monkeys resulted in increased in vivo nicotine disposition, and induced hepatic and brain CYP2B6 protein levels and cellular expression. This induction may alter the metabolism of CYP2B6 substrates including peripherally acting drugs such as cyclophosphamide and centrally acting drugs such as bupropion, ecstasy and phencyclidine. PMID:16751792

  8. A review of formulation techniques that impact the disintegration and mechanical properties of oradispersible drug delivery technologies.

    Science.gov (United States)

    Manyikana, Martina; Choonara, Yahya E; Tomar, Lomas K; Tyagi, Charu; Kumar, Pradeep; du Toit, Lisa C; Pillay, Viness

    2016-01-01

    The drug treatment of acute disorders such as neuropathic pain, migraines, insomnia, vomiting, allergic rhinitis or erectile dysfunction requires an immediate pharmacological effect that may be achieved through parenteral drug administration. However, the parenteral route is not always convenient for reasons that are well known. Therefore, in the recent past there has been a barrage of interest in formulating new, non-invasive, reliable and convenient oradispersible drug delivery technologies (ODDTs). Research in this area has focused extensively on developing ODDTs that are capable of releasing drugs immediately when they come into contact with saliva. This disregards the necessity of water during administration and several other advantages that is an attribute that makes this technology lucrative for groups such as pediatrics, geriatrics, psychiatrics and unconscious patients. Many reviews have been compiled on the salient features of ODDTs. However, none to date has focused on the actual formulation techniques used to produce these technologies and how this may impact their disintegration and physical stability for fulfilling their purpose. Therefore this review provides a concise incursion on the recent formulation techniques, excipients used as well as methods of testing the performance of ODDTs and critically assesses these in terms of improving their performance.

  9. Expected impacts of the Cannabis Infringement Notice scheme in Western Australia on attitudes and drug use of school children.

    Science.gov (United States)

    Lenton, Simon; Farringdon, Fiona

    2005-07-01

    Western Australia (WA) became the fourth Australian jurisdiction to adopt a prohibition with civil penalties scheme for minor cannabis offences when its Cannabis Infringement Notice (CIN) scheme came into effect on 22 March 2004. This study, part of the pre--post evaluation of the legislative reforms, aimed to measure the impact of the changes on attitudes and drug use of school children. A self-completion survey was conducted of 2,638 students in years 9 and 12 from a selection of 11 government secondary schools in Perth. The students knew more about the risks and harms associated with cannabis than they did about prevalence of use and cannabis law. Half the year 12s and 28% of the year 9s had used the drug. Only 32% of students understood the term 'prohibition with civil penalties'. Once explained, 70% of those who had never used the drug said they would not try it if such a scheme were introduced, 5% said they would try it and 24% did not know. Significantly more (11%) said that they would try the drug if it were legalized. Although the CIN scheme applies only to adults there was a concern that such a change would indirectly affect cannabis use by children. This pre-change study suggests this is unlikely, but this will be monitored in the post-change phase of the research.

  10. Impact of a longitudinal community HIV intervention targeting injecting drug users' stage of change for condom and bleach use.

    Science.gov (United States)

    Jamner, M S; Wolitski, R J; Corby, N H

    1997-01-01

    To evaluate the impact of the Long Beach AIDS Community Demonstration Project, a community-based HIV-prevention intervention incorporating principles from the Transtheoretical model in its design and evaluation. Repeated cross-sectional sampling with matched intervention and comparison communities. Neighborhoods in Long Beach, California, having a high prevalence of drug abuse and prostitution. 3081 injecting drug users who were sexually active and/or shared injection equipment. Trained peer volunteers distributed fliers featuring role model stories targeted to the population's stage of change. Fliers were packaged with bleaching kits and/or condoms. Primary outcome measures were exposure to the intervention, condom carrying, and stage of change for disinfecting injection equipment with bleach and for using condoms with main and other partners. Toward the end of the study, 77% of injection drug users in the intervention area reported being exposed to the intervention. In the intervention area, rates of condom carrying increased from 10 to 27% (p project exposure had higher stage-of-change scores for using condoms with a main partner (p Project intervention for reaching injecting drug users in the community and for motivating the adoption of risk-reducing practices.

  11. Stereoselectivity in the disposition and metabolism of the uricosuric-diuretic agent, indacrinone, in Rhesus monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Zacchei, A.G.; Dobrinska, M.R.; Wishousky, T.I.; Kwan, K.C.; White, S.D.

    The physiological disposition following intravenous dosing of the separate enantiomers of indacrinone-/sup 14/C (I), and of their major metabolite, 4'-hydroxyindacrinone-/sup 14/C (M), was studied in the rhesus monkey. Pharmacokinetic analysis indicated that the disposition of I and M was stereoselective. In the case of the enantiomers of I, the areas under the curves of plasma concentration vs. time were about sevenfold greater for the (S)(+)- as compared to the (R)(-)-enantiomer. Renal and plasma clearances of (R)(-)-I were five to seven times greater than those of (S)(+)-I. Total urinary recovery of unchanged drug and metabolite accounted for 70% of the administered dose of either enantiomer. The systemic availability of (R)(-)-M from (R)(-)-I was approximately 21% of the dose, whereas that of (S)(+)-M from (S)(+)-I was only 4%. More pronounced differences were noted in the kinetics of metabolite disposition. The AUC values were about 27 times greater for (S)(+)-M than (R)(-)-M, and the renal and plasma clearances were approximately 25-fold higher for (R)(-)-M as compared to (S)(+)-M. The volume of distribution of (S)(+)-M was only 12% of that observed with (R)(+)-M. There was no evidence of glucuronide or sulfate conjugates of any of the enantiomers. These findings are consistent with the pharmacological activity attributed to the different enantiomers.

  12. Drugs and Medical Devices: Adverse Events and the Impact on Women's Health.

    Science.gov (United States)

    Carey, Jennifer L; Nader, Nathalie; Chai, Peter R; Carreiro, Stephanie; Griswold, Matthew K; Boyle, Katherine L

    2017-01-01

    A large number of medications and medical devices removed from the market by the US Food and Drug Administration over the past 4 decades specifically posed greater health risks to women. This article reviews the historical background of sex and gender in clinical research policy and describes several approved drugs and devices targeted for use in women that have caused major morbidity and mortality. The intended population for the medications and devices, population affected, approval process, and the basic and legal actions taken against the medication/drug company are also discussed. It is recognized that women are still at risk for harm from unsafe medications and devices, and continued improvements in legislation that promotes inclusion of sex and gender into the design and analysis of research will improve safety for both men and women. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  13. Mixing monoclonal antibody formulations using bottom-mounted mixers: impact of mechanism and design on drug product quality.

    Science.gov (United States)

    Gikanga, Benson; Chen, Yufei; Stauch, Oliver B; Maa, Yuh-Fun

    2015-01-01

    Using bottom-mounted mixers, particularly those that are magnetically driven, is becoming increasingly common during the mixing process in pharmaceutical and biotechnology manufacturing because of their associated low risk of contamination, ease of use, and ability to accommodate low minimum mixing volumes. Despite these benefits, the impact of bottom-mounted mixers on biologic drug product is not yet fully understood and is scarcely reported. This study evaluated four bottom-mounted mixers to assess their impact on monoclonal antibody formulations. Changes in product quality (size variants, particles, and turbidity) and impact on process performance (sterile filtration) were evaluated after mixing. The results suggested that mixers that are designed to function with no contact between the impeller and the drive unit are the most favorable and gentle to monoclonal antibody molecules. Designs with contact or a narrow clearance tended to shear and grind the protein and resulted in high particle count in the liquid, which would subsequently foul a filter membrane during sterile filtration using a 0.22 μm pore size filter. Despite particle formation, increases in turbidity of the protein solution and protein aggregation/fragmentation were not detected. Further particle analysis indicated particles in the range of 0.2-2 μm are responsible for filter fouling. A small-scale screening model was developed using two types of magnetic stir bars mimicking the presence or absence of contact between the impeller and drive unit in the bottom-mounted mixers. The model is capable of differentiating the sensitivity of monoclonal antibody formulations to bottom-mounted mixers with a small sample size. This study fills an important gap in understanding a critical bioprocess unit operation. Mixing is an important unit operation in drug product manufacturing for compounding (dilution, pooling, homogenization, etc.). The current trend in adopting disposable bottom-mounted mixers has

  14. Safeguards and security in the face of nonproliferation, material storage and material disposition

    International Nuclear Information System (INIS)

    Rivers, J.D.; Kohen, M.D.

    1996-01-01

    Change is everywhere: society, domestic and international business, the US Government. As the world becomes smaller and more interconnected, the task of protecting the US'' most sensitive assets will become more complex. International obligations resulting from treaties and agreements will increasingly impact the Department of Energy (DOE), to include the dismantlement of nuclear weapons, and the safe, secure storage and disposition of special nuclear material that is a product of dismantlement. Two of the most urgent topics facing DOE are the prevention of proliferation of weapons of mass destruction and the future disposition of special nuclear material. This paper discusses how the DOE safeguards and security community is responding to the increasing challenges imposed by these two issues

  15. Disposition and transportation of surplus radioactive low specific activity nitric acid. Volume 1, Environmental Assessment

    International Nuclear Information System (INIS)

    1995-05-01

    DOE is deactivating the PUREX plant at Hanford; this will involve the disposition of about 692,000 liters (183,000 gallons) of surplus nitric acid contaminated with low levels of U and other radionuclides. The nitric acid, designated as low specific activity, is stored in 4 storage tanks at PUREX. Five principal alternatives were evaluated: transfer for reuse (sale to BNF plc), no action, continued storage in Hanford upgraded or new facility, consolidation of DOE surplus acid, and processing the LSA nitric acid as waste. The transfer to BNF plc is the preferred alternative. From the analysis, it is concluded that the proposed disposition and transportation of the acid does not constitute a major federal action significantly affecting the quality of the human environment within the meaning of NEPA; therefore an environmental impact statement is not required

  16. Fast dissolution of poorly water soluble drugs from fluidized bed coated nanocomposites: Impact of carrier size.

    Science.gov (United States)

    Azad, Mohammad; Moreno, Jacqueline; Bilgili, Ecevit; Davé, Rajesh

    2016-11-20

    Formation of core-shell nanocomposites of Fenofibrate and Itraconazole, model poorly water soluble drugs, via fluidized bed (FB) coating of their well-stabilized high drug loaded nanosuspensions is investigated. Specifically, the extent of dissolution enhancement, when fine carrier particles (sub-50μm) as opposed to the traditional large carrier particles (>300μm) are used, is examined. This allows testing the hypothesis that greatly increased carrier surface area and more importantly, thinner shell for finer carriers at the same drug loading can significantly increase the dissolution rate when spray-coated nanosuspensions are well-stabilized. Fine sub-50μm lactose (GranuLac ® 200) carrier particles were made fluidizable via dry coating with nano-silica, enabling decreased cohesion, fluidization and subsequent nanosuspension coating. For both drugs, 30% drug loaded suspensions were prepared via wet-stirred media milling using hydroxypropyl methyl cellulose and sodium dodecyl sulfate as stabilizers. The stabilizer concentrations were varied to affect the milled particle size and prepare a stable nanosuspension. The suspensions were FB coated onto hydrophilic nano-silica (M-5P) dry coated sub-50μm lactose (GranuLac ® 200) carrier particles or larger carrier particles of median size >300μm (PrismaLac ® 40). The resulting finer composite powders (sub-100μm) based on GranuLac ® 200 were freely flowing, had high bulk density, and had much faster, immediate dissolution of the poorly water-soluble drugs, in particular for Itraconazole. This is attributed to a much higher specific surface area of the carrier and corresponding thinner coating layer for fine carriers as opposed to those for large carrier particles. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Enantioselective Effect of Flurbiprofen on Lithium Disposition in Rats.

    Science.gov (United States)

    Uwai, Yuichi; Matsumoto, Masashi; Kawasaki, Tatsuya; Nabekura, Tomohiro

    2017-01-01

    Lithium is administered for treating bipolar disorders and is mainly excreted into urine. Nonsteroidal anti-inflammatory drugs inhibit this process. In this study, we examined the enantioselective effect of flurbiprofen on the disposition of lithium in rats. Pharmacokinetic experiments with lithium were performed. Until 60 min after the intravenous administration of lithium chloride at 30 mg/kg as a bolus, 17.8% of lithium injected was recovered into the urine. Its renal clearance was calculated to be 1.62 mL/min/kg. Neither creatinine clearance (Ccr) nor pharmacokinetics of lithium was affected by the simultaneous injection of (R)-flurbiprofen at 20 mg/kg. (S)-flurbiprofen impaired the renal function and interfered with the urinary excretion of lithium. The ratio of renal clearance of lithium to Ccr was decreased by the (S)-enantiomer. This study clarified that the (S)-flurbiprofen but not (R)-flurbiprofen inhibited the renal excretion of lithium in rats. © 2017 S. Karger AG, Basel.

  18. The Impact of Restricting Over-the-Counter Sales of Antimicrobial Drugs: Preliminary Analysis of National Data.

    Science.gov (United States)

    Moura, Maria Luísa; Boszczowski, Icaro; Mortari, Naíma; Barrozo, Lígia Vizeu; Chiaravalloti Neto, Francisco; Lobo, Renata Desordi; Pedroso de Lima, Antonio Carlos; Levin, Anna S

    2015-09-01

    To describe the nationwide impact of a restrictive law on over-the-counter sales of antimicrobial drugs, implemented in Brazil in November 2010. Approximately 75% of the population receives healthcare from the public health system and receives free-of-charge medication if prescribed. Total sales in private pharmacies as compared with other channels of sales of oral antibiotics were evaluated in this observational study before and after the law (2008-2012). Defined daily dose per 1000 inhabitants per day (DDD/TID) was used as standard unit. In private pharmacies the effect of the restrictive law was statistically significant (P sales was observed (P = 0.643). The impact in the South and Southeast (more developed) regions was higher than in the North, Northeast, and Mid-West. The state capitals had a 19% decrease, compared with 0.8% increase in the rest of the states. Before the law, the sales of antimicrobial drugs were steadily increasing. From November 2010, with the restrictive law, there was an abrupt drop in sales followed by an increase albeit at a significantly lower rate. The impact was higher in regions with better socio-economic status.

  19. Dispositional hope and life satisfaction among older adults attending lifelong learning programs.

    Science.gov (United States)

    Oliver, A; Tomás, J M; Montoro-Rodriguez, J

    2017-09-01

    The aim of this study is to explore the indirect effects of dispositional hope in the life satisfaction of older adults attending a lifelong learning program at the University of Valencia, Spain. We examine the mediating impact of dispositional hope regarding its ability to impact life satisfaction while considering affective and confidant social support, perceived health and leisure activities, consciousness and spirituality as predictors. Analysis were based on survey data (response rate 77.4%) provided by 737 adults 55 years old or more (Mean age=65.41, SD=6.60; 69% woman). A structural model with latent variables was specified and estimated in Mplus. The results show the ability of just a few variables to sum up a reasonable model to apply to successful aging population. All these variables are correlated and significantly predict hope with the exception of health. The model additionally includes significant positive indirect effects from spirituality, affective support and consciousness on satisfaction. The model has a good fit in terms of both the measurement and structural model. Regarding predictive power, these comprehensive four main areas of successful aging account for 42% of hope and finally for one third of the life satisfaction variance. Results support the mediating role of dispositional hope on the life satisfaction among older adults attending lifelong learning programs. These findings also support the MacArthur model of successful aging adapted to older adults with high levels of functional, social and cognitive ability. Dispositional hope, perceived health, and social support were the strongest predictors of satisfaction with life. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Weapons-grade plutonium dispositioning. Volume 2: Comparison of plutonium disposition options

    Energy Technology Data Exchange (ETDEWEB)

    Brownson, D.A.; Hanson, D.J.; Blackman, H.S. [and others

    1993-06-01

    The Secretary of Energy requested the National Academy of Sciences (NAS) Committee on International Security and Arms Control to evaluate disposition options for weapons-grade plutonium. The Idaho National Engineering Laboratory (INEL) offered to assist the NAS in this evaluation by investigating the technical aspects of the disposition options and their capability for achieving plutonium annihilation levels greater than 90%. This report was prepared for the NAS to document the gathered information and results from the requested option evaluations. Evaluations were performed for 12 plutonium disposition options involving five reactor and one accelerator-based systems. Each option was evaluated in four technical areas: (1) fuel status, (2) reactor or accelerator-based system status, (3) waste-processing status, and (4) waste disposal status. Based on these evaluations, each concept was rated on its operational capability and time to deployment. A third rating category of option costs could not be performed because of the unavailability of adequate information from the concept sponsors. The four options achieving the highest rating, in alphabetical order, are the Advanced Light Water Reactor with plutonium-based ternary fuel, the Advanced Liquid Metal Reactor with plutonium-based fuel, the Advanced Liquid Metal Reactor with uranium-plutonium-based fuel, and the Modular High Temperature Gas-Cooled Reactor with plutonium-based fuel. Of these four options, the Advanced Light Water Reactor and the Modular High Temperature Gas-Cooled Reactor do not propose reprocessing of their irradiated fuel. Time constraints and lack of detailed information did not allow for any further ratings among these four options. The INEL recommends these four options be investigated further to determine the optimum reactor design for plutonium disposition.

  1. Weapons-grade plutonium dispositioning. Volume 2: Comparison of plutonium disposition options

    International Nuclear Information System (INIS)

    Brownson, D.A.; Hanson, D.J.; Blackman, H.S.

    1993-06-01

    The Secretary of Energy requested the National Academy of Sciences (NAS) Committee on International Security and Arms Control to evaluate disposition options for weapons-grade plutonium. The Idaho National Engineering Laboratory (INEL) offered to assist the NAS in this evaluation by investigating the technical aspects of the disposition options and their capability for achieving plutonium annihilation levels greater than 90%. This report was prepared for the NAS to document the gathered information and results from the requested option evaluations. Evaluations were performed for 12 plutonium disposition options involving five reactor and one accelerator-based systems. Each option was evaluated in four technical areas: (1) fuel status, (2) reactor or accelerator-based system status, (3) waste-processing status, and (4) waste disposal status. Based on these evaluations, each concept was rated on its operational capability and time to deployment. A third rating category of option costs could not be performed because of the unavailability of adequate information from the concept sponsors. The four options achieving the highest rating, in alphabetical order, are the Advanced Light Water Reactor with plutonium-based ternary fuel, the Advanced Liquid Metal Reactor with plutonium-based fuel, the Advanced Liquid Metal Reactor with uranium-plutonium-based fuel, and the Modular High Temperature Gas-Cooled Reactor with plutonium-based fuel. Of these four options, the Advanced Light Water Reactor and the Modular High Temperature Gas-Cooled Reactor do not propose reprocessing of their irradiated fuel. Time constraints and lack of detailed information did not allow for any further ratings among these four options. The INEL recommends these four options be investigated further to determine the optimum reactor design for plutonium disposition

  2. A review of the impact of commercial drug advertising on the ...

    African Journals Online (AJOL)

    Introduction: Today, the phenomenon of commercial advertising is not a simple information tool to link consumer to producers. The pharmaceutical industry is increasingly influenced by commercial advertising. Self-medication may be one of the major consequences of drug advertising. Methodology: This review article was ...

  3. Fertility, pregnancy and childbirth in patients with multiple sclerosis: impact of disease-modifying drugs.

    Science.gov (United States)

    Amato, Maria Pia; Portaccio, Emilio

    2015-03-01

    In recent decades, pregnancy-related issues in multiple sclerosis (MS) have received growing interest. MS is more frequent in women than in men and typically starts during child-bearing age. An increasing number of disease-modifying drugs (DMDs) for the treatment of MS are becoming available. Gathering information on their influences on pregnancy-related issues is of crucial importance for the counselling of MS patients. As for the immunomodulatory drugs (interferons and glatiramer acetate), accumulating evidence points to the relative safety of pregnancy exposure in terms of maternal and foetal outcomes. In case of higher clinical disease activity before pregnancy, these drugs could be continued until conception. As for the 'newer' drugs (fingolimod, natalizumab, teriflunomide, dimethyl fumarate and alemtuzumab), the information is more limited. Whereas fingolimod and teriflunomide are likely associated with an increased risk of foetal malformations, the effects of natalizumab, dimethyl fumarate and alemtuzumab still need to be ascertained. This article provides a review of the available information on the use of DMDs during pregnancy, with a specific focus on fertility, foetal development, delivery and breast-feeding.

  4. Physicians' decision process for drug prescription and the impact of pharmaceutical marketing mix instruments.

    Science.gov (United States)

    Campo, Katia; De Staebel, Odette; Gijsbrechts, Els; van Waterschoot, Walter

    2005-01-01

    This paper provides an in-depth, qualitative analysis of the physicians' decision process for drug prescription. Drugs in the considered therapeutic classes are mainly prescribed by specialists, treating patients with obligatory medical insurance, for a prolonged period of time. The research approach is specifically designed to capture the full complexity and sensitive nature of the physician's choice behavior, which appears to be more hybrid and less rational in nature than is often assumed in quantitative, model-based analyses of prescription behavior. Several interesting findings emerge from the analysis: (i) non-compensatory decision rules seem to dominate the decision process, (ii) consideration sets are typically small and change-resistant, (iii) drug cost is not a major issue for most physicians, (iv) detailing remains one of the most powerful pharmaceutical marketing instruments and is highly appreciated as a valuable and quick source of information, and (v) certain types of non-medical marketing incentives (such as free conference participation) may in some situations also influence drug choices.

  5. Pharmacogenetics of taxanes: impact of gene polymorphisms of drug transporters on pharmacokinetics and toxicity.

    Science.gov (United States)

    Jabir, Rafid Salim; Naidu, Rakesh; Annuar, Muhammad Azrif Bin Ahmad; Ho, Gwo Fuang; Munisamy, Murali; Stanslas, Johnson

    2012-12-01

    Interindividual variability in drug response and the emergence of adverse drug effects are the main causes of treatment failure in cancer therapy. Functional membrane drug transporters play important roles in altering pharmacokinetic profile, resistance to treatment, toxicity and patient survival. Pharmacogenetic studies of these transporters are expected to provide new approaches for optimizing therapy. Taxanes are approved for the treatment of various cancers. Circulating taxanes are taken up by SLCO1B3 into hepatocytes. The CYP450 enzymes CYP3A4, CYP3A5 and CYP2C8 are responsible for the conversion of taxanes into their metabolites. Ultimately, ABCB1 and ABCC2 will dispose the metabolites into bile canaliculi. Polymorphisms of genes encoding for proteins involved in the transport and clearance of taxanes reduce excretion of the drugs, leading to development of toxicity in patients. This review addresses current knowledge on genetic variations of transporters affecting taxanes pharmacokinetics and toxicity, and provides insights into future direction for personalized medicine.

  6. The impact of nanobiotechnology on the development of new drug delivery systems

    NARCIS (Netherlands)

    Kayser, Oliver; Lemke, A.; Hernandez-Trejo, N.

    2005-01-01

    Nanotechnology, or systems/devices manufactured at the molecular level, is a multidisciplinary scientific field undergoing explosive development. A part of this field is the development of nanoscaled drug delivery devices. Nanoparticles have been developed as an important strategy to deliver

  7. Voluntary, Randomized, Student Drug-Testing: Impact in a Rural, Low-Income, Community

    Science.gov (United States)

    Barrington, Kyle D.

    2008-01-01

    Illegal drug use and abuse by the nation's secondary school students is a continuing public health issue and this is especially true for students living in rural, low-income areas where access to intervention and treatment services is often limited. To address this issue, some school districts have implemented voluntary, randomized, student …

  8. Neutron Assay System for Confinement Vessel Disposition

    International Nuclear Information System (INIS)

    Frame, Katherine C.; Bourne, Mark M.; Crooks, William J.; Evans, Louise; Mayo, Douglas R.; Miko, David K.; Salazar, William R.; Stange, Sy; Valdez, Jose I.; Vigil, Georgiana M.

    2012-01-01

    Los Alamos National Laboratory has a number of spherical confinement vessels (CVs) remaining from tests involving nuclear materials. These vessels have an inner diameter of 6 feet with 1-inch thick steel walls. The goal of the Confinement Vessel Disposition (CVD) project is to remove debris and reduce contamination inside the CVs. The Confinement Vessel Assay System (CVAS) was developed to measure the amount of special nuclear material (SNM) in CVs before and after cleanout. Prior to cleanout, the system will be used to perform a verification measurement of each vessel. After cleanout, the system will be used to perform safeguards-quality assays of (le)100-g 239 Pu equivalent in a vessel for safeguards termination. The CVAS has been tested and calibrated in preparation for verification and safeguards measurements.

  9. The mind as skills and dispositions

    DEFF Research Database (Denmark)

    Brinkmann, Svend

    2012-01-01

    On the occasion of the critique of Alfredo Gaete and Carlos Cornejo, this article explains and extends the hybrid theory of the mind that I recently presented in this journal. Taking inspiration from Rom Harré’s program for a hybrid psychology, the theory is supposed to be integrative and aims...... to broaden Harré’s hybrid psychology by including not just the brain, but also the body, social practices, and technological artifacts as mediators of the mind. The mind is understood not as a substance of any kind, but as a set of skills and dispositions to act, think, and feel. This implies a normative...... view of the mind, according to which psychological phenomena do not simply happen, but are done, and can consequently be done more or less well. I provide arguments in favor of grounding psychology in normativity rather than conscious experience, and I explain why the emphasis on mediators does...

  10. SOCIAL NETWORKS AS DISPOSITIVES OF NEOLIBERAL GOVERNMENTALITY

    Directory of Open Access Journals (Sweden)

    Julio Cesar Lemes de Castro

    2016-10-01

    Full Text Available This article of theoretical reflection investigates the social networks that emerge in the context of Web 2.0, such as Facebook, as dispositives of neoliberal governmentality in the sense proposed by Foucault. From the standpoint of government of self, the design of social networks establishes a competition for attention that tends to favor the neoliberal culture of performance. In terms of social organization, the way in which users intertwine their connections is paralleled by the neoliberal paradigm of spontaneous market order. Furthermore, the use of personal information on these users, encompassing all their activities within the networks, in order to set up databases to attract advertisers reflects the neoliberal tendency of colonization of the different realms of existence by economic forces. However, the tensions that accompany neoliberal governmentality in social networks reveal its limitations, opening the possibility for these networks to also act as instruments of resistance to neoliberalism.

  11. Cancer drug funding decisions in Scotland: impact of new end-of-life, orphan and ultra-orphan processes.

    Science.gov (United States)

    Morrell, Liz; Wordsworth, Sarah; Fu, Howell; Rees, Sian; Barker, Richard

    2017-08-30

    The Scottish Medicines Consortium evaluates new drugs for use in the National Health Service in Scotland. Reforms in 2014 to their evaluation process aimed to increase patient access to new drugs for end-of-life or rare conditions; the changes include additional steps in the process to gain further information from patients and clinicians, and for revised commercial agreements. This study examines the extent of any impact of the reforms on funding decisions. Data on the Scottish Medicines Consortium's funding decisions during 24 months post-reform were extracted from published Advice, for descriptive statistics and thematic analysis. Comparison data were extracted for the 24 months pre-reform. Data on decisions for England by the National Institute for Clinical and Health Excellence for the same drugs were extracted from published Technology Appraisals. The new process was used by 90% (53/59) of cancer submissions. It is triggered if the initial advice is not to recommend, and this risk-of-rejection level is higher than in the pre-period. Thirty-eight cancer drugs obtained some level of funding through the new process, but there was no significant difference in the distribution of decision types compared to the pre-reform period. Thematic analysis of patient and clinician input showed no clear relationship between issues raised and funding decision. Differences between SMC's and NICE's definitions of End-of-Life did not fully explain differences in funding decisions. The Scottish Medicines Consortium's reforms have allowed funding of up to 38 cancer drugs that might previously have been rejected. However, the contribution of specific elements of the reforms to the final decision is unclear. The process could be improved by increased transparency in how the non-quantitative inputs influence decisions. Some disparities in funding decisions between England and Scotland are likely to remain despite recent process convergence.

  12. Randomized clinical trial on the use of antispasmodic drugs in barium enema: impact on radiological practice

    International Nuclear Information System (INIS)

    Goei, Reginald; Kessels, Alphons H.; Nix, Maarten; Knipschild, Paul G.

    2000-01-01

    Purpose: To assess the willingness of radiologists to change their practice when the results of a randomized clinical trial (RCT) on the use of antispasmodic drugs in barium enema are presented. Materials and Methods: During the years 1994 and 1995 two postal questionnaires were sent to 481 practicing radiologists who were all members of the Netherlands Society of Radiology. In the first questionnaire the respondents were asked to give the characteristics of their practices in performing daily barium enema. The data from this questionnaire was used as a reference. The second questionnaire was sent to the respondents together with an abstract on the randomized clinical trial supporting the use of antispasmodic drugs in barium enema. We also indicated a preference for Buscopan over Glucagon as the antispasmodic drug. The willingness to change prescription habits was measured by comparing the data of the two questionnaires. Results: Of 481 practicing radiologists, 312 responded to the first questionnaire and gave information of their prescription habits (response rate 64%). These 312 responders were sent an abstract of the RCT and were asked to fill out a second questionnaire to determine their willingness to change their practice. Two hundred and sixty-seven radiologists responded (response rate 86%). A significant number of 119 (51%) were willing to increase the use of antispasmodic drugs. A significant number of 128 (55%) chose to increase the use of Buscopan, while a significant number of 81 (32%) were willing to decrease the use of Glucagon. Conclusion: Direct exposure to the results of an RCT recommending the use of antispasmodic drugs in barium enema, especially Buscopan, is likely to increase its use by practicing radiologists

  13. The ultimate disposition of depleted uranium

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-01

    Significant amounts of the depleted uranium (DU) created by past uranium enrichment activities have been sold, disposed of commercially, or utilized by defense programs. In recent years, however, the demand for DU has become quite small compared to quantities available, and within the US Department of Energy (DOE) there is concern for any risks and/or cost liabilities that might be associated with the ever-growing inventory of this material. As a result, Martin Marietta Energy Systems, Inc. (Energy Systems), was asked to review options and to develop a comprehensive plan for inventory management and the ultimate disposition of DU accumulated at the gaseous diffusion plants (GDPs). An Energy Systems task team, under the chairmanship of T. R. Lemons, was formed in late 1989 to provide advice and guidance for this task. This report reviews options and recommends actions and objectives in the management of working inventories of partially depleted feed (PDF) materials and for the ultimate disposition of fully depleted uranium (FDU). Actions that should be considered are as follows. (1) Inspect UF{sub 6} cylinders on a semiannual basis. (2) Upgrade cylinder maintenance and storage yards. (3) Convert FDU to U{sub 3}O{sub 8} for long-term storage or disposal. This will include provisions for partial recovery of costs to offset those associated with DU inventory management and the ultimate disposal of FDU. Another recommendation is to drop the term tails'' in favor of depleted uranium'' or DU'' because the tails'' label implies that it is waste.'' 13 refs.

  14. The association between resting functional connectivity and dispositional optimism.

    Science.gov (United States)

    Ran, Qian; Yang, Junyi; Yang, Wenjing; Wei, Dongtao; Qiu, Jiang; Zhang, Dong

    2017-01-01

    Dispositional optimism is an individual characteristic that plays an important role in human experience. Optimists are people who tend to hold positive expectations for their future. Previous studies have focused on the neural basis of optimism, such as task response neural activity and brain structure volume. However, the functional connectivity between brain regions of the dispositional optimists are poorly understood. Previous study suggested that the ventromedial prefrontal cortex (vmPFC) are associated with individual differences in dispositional optimism, but it is unclear whether there are other brain regions that combine with the vmPFC to contribute to dispositional optimism. Thus, the present study used the resting-state functional connectivity (RSFC) approach and set the vmPFC as the seed region to examine if differences in functional brain connectivity between the vmPFC and other brain regions would be associated with individual differences in dispositional optimism. The results found that dispositional optimism was significantly positively correlated with the strength of the RSFC between vmPFC and middle temporal gyrus (mTG) and negativly correlated with RSFC between vmPFC and inferior frontal gyrus (IFG). These findings may be suggested that mTG and IFG which associated with emotion processes and emotion regulation also play an important role in the dispositional optimism.

  15. The association between resting functional connectivity and dispositional optimism.

    Directory of Open Access Journals (Sweden)

    Qian Ran

    Full Text Available Dispositional optimism is an individual characteristic that plays an important role in human experience. Optimists are people who tend to hold positive expectations for their future. Previous studies have focused on the neural basis of optimism, such as task response neural activity and brain structure volume. However, the functional connectivity between brain regions of the dispositional optimists are poorly understood. Previous study suggested that the ventromedial prefrontal cortex (vmPFC are associated with individual differences in dispositional optimism, but it is unclear whether there are other brain regions that combine with the vmPFC to contribute to dispositional optimism. Thus, the present study used the resting-state functional connectivity (RSFC approach and set the vmPFC as the seed region to examine if differences in functional brain connectivity between the vmPFC and other brain regions would be associated with individual differences in dispositional optimism. The results found that dispositional optimism was significantly positively correlated with the strength of the RSFC between vmPFC and middle temporal gyrus (mTG and negativly correlated with RSFC between vmPFC and inferior frontal gyrus (IFG. These findings may be suggested that mTG and IFG which associated with emotion processes and emotion regulation also play an important role in the dispositional optimism.

  16. The Relationship between Critical Thinking Disposition and Self-Esteem

    Directory of Open Access Journals (Sweden)

    Shirin Iranfar

    2013-12-01

    Full Text Available Introduction: Critical Thinking Disposition indicates individual’s inclination to Critical Thinking, which is one of the domains of personality. Individual characteristics are important and influential factors in the growth and development of students’ Critical Thinking. One of these influential characteristics might be self-esteem, thus this study was to determine the correlation between Critical Thinking Disposition and self-esteem in medical students. Methods: In an analytical cross-sectional study, 289 medical students were selected through stratified random sampling method in Kermanshah University of Medical Sciences in 2011. The instrument for data collection was a questionnaire containing 3 parts: demographic data, California Critical Thinking Disposition Inventory, and Cooper-Smith Self-Esteem Inventory. The results were analyzed by SPSS-16 using descriptive statistics, Pearson and Spearman Correlation Coefficient, ANOVA, Chi-Square and Fisher exact test. Results: Results showed that 98.6% (285 of students had deficiency, 1.4% (4 ambivalence and nobody had positive critical thinking disposition. There was a significantly negative correlation between Critical Thinking Disposition and self-esteem (r=-0.462, P<0.001. Also, there was no a significant relationship between two groups of low self-esteem , high self-esteem , negative and ambivalent Critical Thinking Disposition. Conclusion: It seems that Critical Thinking Disposition, like other psychological variables, is influenced by social factors and social environment plays a role in promoting or undermining it. So, similar studies are recommended to investigate the factors affecting Critical Thinking in medical students.

  17. 14 CFR 61.15 - Offenses involving alcohol or drugs.

    Science.gov (United States)

    2010-01-01

    ... the growing, processing, manufacture, sale, disposition, possession, transportation, or importation of... influence of alcohol or a drug; (2) The cancellation, suspension, or revocation of a license to operate a... intoxicated by alcohol or a drug, while impaired by alcohol or a drug, or while under the influence of alcohol...

  18. Effect of perceived social support and dispositional optimism on the depression of burn patients.

    Science.gov (United States)

    He, Fei; Zhou, Qin; Zhao, Zhijing; Zhang, Yuan; Guan, Hao

    2016-06-01

    Burn wounds have a significant impact on the mental health of patients. This study aimed to investigate the impact of perceived social support and dispositional optimism on depression of burn patients. A total of 246 burn patients accomplished the Multidimensional Scale of Perceived Social Support, the Revised Life Orientation Test, and Depression Scale. The results revealed that both perceived social support and optimism were significantly correlated with depression. Structural equation modeling indicated that optimism partially mediated the relationship between perceived social support and depression. Implications for prevention of depression in burn patients were discussed. © The Author(s) 2014.

  19. Impact of concentration and rate of intraluminal drug delivery on absorption and gut wall metabolism of verapamil in humans.

    Science.gov (United States)

    Glaeser, Hartmut; Drescher, Siegfried; Hofmann, Ute; Heinkele, Georg; Somogyi, Andrew A; Eichelbaum, Michel; Fromm, Martin F

    2004-09-01

    In humans gut wall metabolism can be quantitatively as important as hepatic drug metabolism in limiting the systemic exposure to drugs after oral administration. However, it has been proposed that the role of gut wall metabolism might be overemphasized, because high luminal drug concentrations would lead to a saturation of gut wall metabolism. Therefore we investigated the impact of concentration and rate of intraluminal drug delivery on absorption (F(abs)) and gastrointestinal extraction (E(GI)) of a luminally administered cytochrome P450 (CYP) 3A4 substrate (verapamil) using a multilumen perfusion catheter in combination with a stable isotope technique. Two 20-cm-long, adjacent jejunal segments were isolated with the multilumen perfusion catheter in 7 subjects. In this study 80 mg of unlabeled verapamil (d0-verapamil 15 min) was infused into one segment over a 15-minute period, 80 mg of 3-fold deuterated verapamil (d3-verapamil 240 min) was administered over a 240-minute period into the other segment, and simultaneously, 5 mg of 7-fold deuterated verapamil (d7-verapamil) was injected intravenously over a 15-minute period. The rate of intraluminal drug delivery had only a modest effect on bioavailability of the verapamil isotopes (after correction for F abs ) (F/F abs d3-verapamil 240 min versus d0-verapamil 15 min, 0.24 +/- 0.10 versus 0.20 +/- 0.09; P d3-verapamil 240 min was 0.50 +/- 0.18 compared with 0.59 +/- 0.14 for d0 -verapamil 15 min ( P d0-verapamil 15 min ) correlated strongly with E GI (d3-verapamil 240 min ) (r = 0.94, P d0-verapamil 15 min /d3-verapamil 240 min (r = 0.62, P =.03). Substantial gut wall metabolism of verapamil occurs in humans and can be predicted from ex vivo data by use of shed enterocytes. The different intraluminal concentrations and rates of intraluminal drug delivery did not lead to a pronounced saturation of intestinal drug metabolism.

  20. Prediction of solubility and permeability class membership: provisional BCS classification of the world's top oral drugs.

    Science.gov (United States)

    Dahan, Arik; Miller, Jonathan M; Amidon, Gordon L

    2009-12-01

    The Biopharmaceutics Classification System (BCS) categorizes drugs into one of four biopharmaceutical classes according to their water solubility and membrane permeability characteristics and broadly allows the prediction of the rate-limiting step in the intestinal absorption process following oral administration. Since its introduction in 1995, the BCS has generated remarkable impact on the global pharmaceutical sciences arena, in drug discovery, development, and regulation, and extensive validation/discussion/extension of the BCS is continuously published in the literature. The BCS has been effectively implanted by drug regulatory agencies around the world in setting bioavailability/bioequivalence standards for immediate-release (IR) oral drug product approval. In this review, we describe the BCS scientific framework and impact on regulatory practice of oral drug products and review the provisional BCS classification of the top drugs on the global market. The Biopharmaceutical Drug Disposition Classification System and its association with the BCS are discussed as well. One notable finding of the provisional BCS classification is that the clinical performance of the majority of approved IR oral drug products essential for human health can be assured with an in vitro dissolution test, rather than empirical in vivo human studies.

  1. Proliferation resistance criteria for fissile material disposition issues

    International Nuclear Information System (INIS)

    Rutherford, D.A.; Fearey, B.L.; Markin, J.T.; Close, D.A.; Tolk, K.M.; Mangan, D.L.; Moore, L.

    1995-01-01

    The 1994 National Acdaemy of Sciences study ''Management and Disposition of Excess Weapons Plutonium'' defined options for reducing the national and international proliferation risks of materials declared excess to the nuclear weapons program. This paper proposes criteria for assessing the proliferation resistance of these options as well defining the ''Standards'' from the report. The criteria are general, encompassing all stages of the disposition process from storage through intermediate processing to final disposition including the facilities, processing technologies and materials, the level of safeguards for these materials, and the national/subnational threat to the materials

  2. The impact of non-steroidal anti-inflammatory drugs on the small intestinal epithelium

    OpenAIRE

    Handa, Osamu; Naito, Yuji; Fukui, Akifumi; Omatsu, Tatsushi; Yoshikawa, Toshikazu

    2013-01-01

    The small intestine has been called as a dark continent of digestive tract and it had been very difficult to diagnose or treat the disease of small intestine. However recent technological development including video capsule endoscopy or balloon-assisted endoscopy has made us to aware the various diseases of small intestine. By using capsule endoscopy, many researchers reported that more than 70% of patients treated continuously with non-steroidal anti-inflammatory drugs (NSAID) exhibit the mu...

  3. Recent advances in fluorination techniques and their anticipated impact on drug metabolism and toxicity

    OpenAIRE

    Murphy, Cormac D.; Sandford, Graham

    2015-01-01

    Introduction: Fluorine’s unique physicochemical properties make it a key element for incorporation into pharmacologically active compounds. Its presence in a drug can alter a number of characteristics that affect ADME-Tox, which has prompted efforts at improving synthetic fluorination procedures. Areas covered: This review describes the influence of fluorine on attributes such as potency, lipophilicity, metabolic stability and bioavailablility and how the effects observed are related to the p...

  4. The impact of anti-diabetic drugs on colorectal cancer risk in a large ...

    African Journals Online (AJOL)

    risk of cancers (1Б4). In Decensi et al.'s meta-analysis, a. 31% reduction of overall cancer risk (95% CI00.61Б0.79) is found in patients using metformin compared with the other anti-diabetic drugs (2). The present study also showed women with ever-use of metformin could have a. 58% reduced risk of colorectal cancer.

  5. Impact of polymer type on bioperformance and physical stability of hot melt extruded formulations of a poorly water soluble drug.

    Science.gov (United States)

    Mitra, Amitava; Li, Li; Marsac, Patrick; Marks, Brian; Liu, Zhen; Brown, Chad

    2016-05-30

    Amorphous solid dispersion formulations have been widely used to enhance bioavailability of poorly soluble drugs. In these formulations, polymer is included to physically stabilize the amorphous drug by dispersing it in the polymeric carrier and thus forming a solid solution. The polymer can also maintain supersaturation and promote speciation during dissolution, thus enabling better absorption as compared to crystalline drug substance. In this paper, we report the use of hot melt extrusion (HME) to develop amorphous formulations of a poorly soluble compound (FaSSIF solubility=1μg/mL). The poor solubility of the compound and high dose (300mg) necessitated the use of amorphous formulation to achieve adequate bioperformance. The effect of using three different polymers (HPMCAS-HF, HPMCAS-LF and copovidone), on the dissolution, physical stability, and bioperformance of the formulations was demonstrated. In this particular case, HPMCAS-HF containing HME provided the highest bioavailability and also had better physical stability as compared to extrudates using HPMCAS-LF and copovidone. The data demonstrated that the polymer type can have significant impact on the formulation bioperformance and physical stability. Thus a thorough understanding of the polymer choice is imperative when designing an amorphous solid dispersion formulation, such that the formulation provides robust bioperformance and has adequate shelf life. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Fluorinated ionic liquids for protein drug delivery systems: Investigating their impact on the structure and function of lysozyme.

    Science.gov (United States)

    Alves, Márcia; Vieira, Nicole S M; Rebelo, Luís Paulo N; Araújo, João M M; Pereiro, Ana B; Archer, Margarida

    2017-06-30

    Since the approval of recombinant human insulin by FDA in 1982, more than 200 proteins are currently available for pharmaceutical use to treat a wide range of diseases. However, innovation is still required to develop effective approaches for drug delivery. Our aim is to investigate the potential use of fluorinated ionic liquids (FILs) as drug delivery systems (DDS) for therapeutic proteins. Some initial parameters need to be assessed before further studies can proceed. This work evaluates the impact of FILs on the stability, function, structure and aggregation state of lysozyme. Different techniques were used for this purpose, which included differential scanning fluorimetry (DSF), spectrophotometric assays, circular dichroism (CD), dynamic light scattering (DLS), and scanning and transmission electron microscopy (SEM/TEM). Ionic liquids composed of cholinium-, imidazolium- or pyridinium- derivatives were combined with different anions and analysed at different concentrations in aqueous solutions (below and above the critical aggregation concentration, CAC). The results herein presented show that the addition of ionic liquids had no significant effect on the stability and hydrolytic activity of lysozyme. Moreover, a distinct behaviour was observed in DLS experiments for non-surfactant and surfactant ionic liquids, with the latter encapsulating the protein at concentrations above the CAC. These results encourage us to further study ionic liquids as promising tools for DDS of protein drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Impact of salt form and molecular weight of chitosan on swelling and drug release from chitosan matrix tablets.

    Science.gov (United States)

    Huanbutta, Kampanart; Cheewatanakornkool, Kamonrak; Terada, Katsuhide; Nunthanid, Jurairat; Sriamornsak, Pornsak

    2013-08-14

    Magnetic resonance imaging (MRI) and gravimetric techniques were used to assess swelling and erosion behaviors of hydrophilic matrix tablets made of chitosan. The impact of salt form, molecular weight (MW) and dissolution medium on swelling behavior and drug (theophylline) release was studied. The matrix tablets made of chitosan glycolate (CGY) showed the greatest swelling in both acid and neutral media, compared to chitosan aspartate, chitosan glutamate and chitosan lactate. MRI illustrated that swelling region of CGY in both media was not different in the first 100 min but glassy region (dry core) in 0.1N HCl was less than in pH 6.8 buffer. The tablets prepared from chitosan with high MW swelled greater than those of low MW. Moreover, CGY can delay drug release in the acid condition due to thick swollen gel and low erosion rate. Therefore, CGY may be suitably applied as sustained drug release polymer or enteric coating material. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Summary report of the screening process to determine reasonable alternatives for long-term storage and disposition of weapons-usable fissile materials

    International Nuclear Information System (INIS)

    1995-01-01

    Significant quantities of weapons-usable fissile materials (primarily plutonium and highly enriched uranium) have become surplus to national defense needs both in the US and Russia. These stocks of fissile materials pose significant dangers to national and international security. The dangers exist not only in the potential proliferation of nuclear weapons but also in the potential for environmental, safety and health consequences if surplus fissile materials are not properly managed. As announced in the Notice of Intent (NOI) to prepare a Programmatic Environmental Impact Statement (PEIS), the Department of Energy is currently conducting an evaluation process for disposition of surplus weapons-usable fissile materials determined surplus to National Security needs, and long-term storage of national security and programmatic inventories, and surplus weapons-usable fissile materials that are not able to go directly from interim storage to disposition. An extensive set of long-term storage and disposition options was compiled. Five broad long-term storage options were identified; thirty-seven options were considered for plutonium disposition; nine options were considered for HEU disposition; and eight options were identified for Uranium-233 disposition. Section 2 discusses the criteria used in the screening process. Section 3 describes the options considered, and Section 4 provides a detailed summary discussions of the screening results

  9. Summary report of the screening process to determine reasonable alternatives for long-term storage and disposition of weapons-usable fissile materials

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-03-29

    Significant quantities of weapons-usable fissile materials (primarily plutonium and highly enriched uranium) have become surplus to national defense needs both in the US and Russia. These stocks of fissile materials pose significant dangers to national and international security. The dangers exist not only in the potential proliferation of nuclear weapons but also in the potential for environmental, safety and health consequences if surplus fissile materials are not properly managed. As announced in the Notice of Intent (NOI) to prepare a Programmatic Environmental Impact Statement (PEIS), the Department of Energy is currently conducting an evaluation process for disposition of surplus weapons-usable fissile materials determined surplus to National Security needs, and long-term storage of national security and programmatic inventories, and surplus weapons-usable fissile materials that are not able to go directly from interim storage to disposition. An extensive set of long-term storage and disposition options was compiled. Five broad long-term storage options were identified; thirty-seven options were considered for plutonium disposition; nine options were considered for HEU disposition; and eight options were identified for Uranium-233 disposition. Section 2 discusses the criteria used in the screening process. Section 3 describes the options considered, and Section 4 provides a detailed summary discussions of the screening results.

  10. Life cycle costs for the domestic reactor-based plutonium disposition option

    International Nuclear Information System (INIS)

    Williams, K.A.

    1999-01-01

    Projected constant dollar life cycle cost (LCC) estimates are presented for the domestic reactor-based plutonium disposition program being managed by the US Department of Energy Office of Fissile Materials Disposition (DOE/MD). The scope of the LCC estimate includes: design, construction, licensing, operation, and deactivation of a mixed-oxide (MOX) fuel fabrication facility (FFF) that will be used to purify and convert weapons-derived plutonium oxides to MOX fuel pellets and fabricate MOX fuel bundles for use in commercial pressurized-water reactors (PWRs); fuel qualification activities and modification of facilities required for manufacture of lead assemblies that will be used to qualify and license this MOX fuel; and modification, licensing, and operation of commercial PWRs to allow irradiation of a partial core of MOX fuel in combination with low-enriched uranium fuel. The baseline cost elements used for this document are the same as those used for examination of the preferred sites described in the site-specific final environmental impact statement and in the DOE Record of Decision that will follow in late 1999. Cost data are separated by facilities, government accounting categories, contract phases, and expenditures anticipated by the various organizations who will participate in the program over a 20-year period. Total LCCs to DOE/MD are projected at approximately $1.4 billion for a 33-MT plutonium disposition mission

  11. Life Cycle Analysis for D and D Decision Making: Disposition of Hanford Railcars

    Energy Technology Data Exchange (ETDEWEB)

    Yuracko, K.L.

    2001-01-11

    This report summarizes a joint venture between the U.S. Department of Energy (DOE) Deactivation and Decommissioning Focus Area and the Oak Ridge Operations Assets Utilization (AU) Facilities and Materials Reuse Division (FMRD) in its role as the DOE National Center of Excellence for Metals Recycle (NMR), to better address problems in the DOE complex. This task was initially developed to meet a request from the Richland Operations Office (RL) to AU FMRD for assistance in analyzing equipment reuse and metals recycling opportunities at RL, utilizing expertise and experience related to life cycle analysis (LCA), technology, and planning. Oak Ridge National Laboratory (ORNL) has developed an LCA system to assist DOE in identifying and analyzing opportunities for equipment and materials reuse and recycle. This report presents the use of the LCA system to identify and analyze methods for disposition of surplus railcars at the Hanford site. Alternative possible disposition pathways were evaluated for their financial, health and safety, environmental, programmatic, and institutional impacts; and a preferred disposition pathway was identified.

  12. Development and implementation of attractiveness Level E criteria and the plutonium disposition methodology

    International Nuclear Information System (INIS)

    Christensen, D.C.; Robinson, M.A.

    1998-03-01

    Historically, the Department of Energy used the Economic Discard Limits (EDLs), those Special Nuclear Material (SNM) concentrations in residue matrices below which production of new SNM was more economic than SNM recovery, as a basis for discard decisions. In 1994, a joint team from DOE Defense Programs (DP) and Environmental Management (EM) determined that the EDLs were no longer a valid discriminator and directed that SNM disposition consider instead 12 specific criteria, foremost of which are waste minimization, environmental impacts, safety, proliferation concerns, and cost. In response, the Los Alamos National Laboratory developed a technical basis for determining SNM bearing materials unattractive for proliferation purposes and a quantitative method for predicting materials disposition consequences as a basis for decision making called the plutonium disposition methodology. The objective of attractiveness Level E criteria is to insure that waste is unattractive for proliferation or terrorist purposes. Level E criteria is about 0.17 kg Pu per 208 liter drum (requiring diversion of a minimum of 54 drums, assuming 100% recovery efficiency)

  13. A Cluster Randomised Trial Introducing Rapid Diagnostic Tests into Registered Drug Shops in Uganda: Impact on Appropriate Treatment of Malaria

    Science.gov (United States)

    Mbonye, Anthony K.; Magnussen, Pascal; Lal, Sham; Hansen, Kristian S.; Cundill, Bonnie; Chandler, Clare; Clarke, Siân E.

    2015-01-01

    Background Inappropriate treatment of malaria is widely reported particularly in areas where there is poor access to health facilities and self-treatment of fevers with anti-malarial drugs bought in shops is the most common form of care-seeking. The main objective of the study was to examine the impact of introducing rapid diagnostic tests for malaria (mRDTs) in registered drug shops in Uganda, with the aim to increase appropriate treatment of malaria with artemisinin-based combination therapy (ACT) in patients seeking treatment for fever in drug shops. Methods A cluster-randomized trial of introducing mRDTs in registered drug shops was implemented in 20 geographical clusters of drug shops in Mukono district, central Uganda. Ten clusters were randomly allocated to the intervention (diagnostic confirmation of malaria by mRDT followed by ACT) and ten clusters to the control arm (presumptive treatment of fevers with ACT). Treatment decisions by providers were validated by microscopy on a reference blood slide collected at the time of consultation. The primary outcome was the proportion of febrile patients receiving appropriate treatment with ACT defined as: malaria patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving ACT or rectal artesunate, and patients with no malaria parasites not given ACT. Findings A total of 15,517 eligible patients (8672 intervention and 6845 control) received treatment for fever between January-December 2011. The proportion of febrile patients who received appropriate ACT treatment was 72·9% versus 33·7% in the control arm; a difference of 36·1% (95% CI: 21·3 – 50·9), pshop vendors adhered to the mRDT results, reducing over-treatment of malaria by 72·6% (95% CI: 46·7– 98·4), pshop vendors using presumptive diagnosis (control arm). Conclusion Diagnostic testing with mRDTs compared to presumptive treatment of fevers implemented in registered drug shops substantially improved appropriate

  14. Prevalence of transmitted drug resistance and impact of transmitted resistance on treatment success in the German HIV-1 Seroconverter Cohort.

    Directory of Open Access Journals (Sweden)

    Barbara Bartmeyer

    Full Text Available BACKGROUND: The aim of this study is to analyse the prevalence of transmitted drug resistance, TDR, and the impact of TDR on treatment success in the German HIV-1 Seroconverter Cohort. METHODS: Genotypic resistance analysis was performed in treatment-naïve study patients whose sample was available 1,312/1,564 (83.9% October 2008. A genotypic resistance result was obtained for 1,276/1,312 (97.3%. The resistance associated mutations were identified according to the surveillance drug resistance mutations list recommended for drug-naïve patients. Treatment success was determined as viral suppression below 500 copies/ml. RESULTS: Prevalence of TDR was stable at a high level between 1996 and 2007 in the German HIV-1 Seroconverter Cohort (N = 158/1,276; 12.4%; CI(wilson 10.7-14.3; p(for trend = 0.25. NRTI resistance was predominant (7.5% but decreased significantly over time (CI(Wilson: 6.2-9.1, p(for trend = 0.02. NNRTI resistance tended to increase over time (NNRTI: 3.5%; CI(Wilson: 2.6-4.6; p(for trend= 0.07, whereas PI resistance remained stable (PI: 3.0%; CI(Wilson: 2.1-4.0; p(for trend = 0.24. Resistance to all drug classes was frequently caused by singleton resistance mutations (NRTI 55.6%, PI 68.4%, NNRTI 99.1%. The majority of NRTI-resistant strains (79.8% carried resistance-associated mutations selected by the thymidine analogues zidovudine and stavudine. Preferably 2NRTI/1PIr combinations were prescribed as first line regimen in patients with resistant HIV as well as in patients with susceptible strains (susceptible 45.3%; 173/382 vs. resistant 65.5%; 40/61. The majority of patients in both groups were treated successfully within the first year after ART-initiation (susceptible: 89.9%; 62/69; resistant: 7/9; 77.8%. CONCLUSION: Overall prevalence of TDR remained stable at a high level but trends of resistance against drug classes differed over time. The significant decrease of NRTI-resistance in patients newly infected

  15. Impact of the CYP2C8 *3 polymorphism on the drug–drug interaction between gemfibrozil and pioglitazone

    Science.gov (United States)

    Aquilante, Christina L; Kosmiski, Lisa A; Bourne, David W A; Bushman, Lane R; Daily, Elizabeth B; Hammond, Kyle P; Hopley, Charles W; Kadam, Rajendra S; Kanack, Alexander T; Kompella, Uday B; Le, Merry; Predhomme, Julie A; Rower, Joseph E; Sidhom, Maha S

    2013-01-01

    AIM The objective of this study was to determine the extent to which the CYP2C8*3 allele influences pharmacokinetic variability in the drug–drug interaction between gemfibrozil (CYP2C8 inhibitor) and pioglitazone (CYP2C8 substrate). METHODS In this randomized, two phase crossover study, 30 healthy Caucasian subjects were enrolled based on CYP2C8*3 genotype (n = 15, CYP2C8*1/*1; n = 15, CYP2C8*3 carriers). Subjects received a single 15 mg dose of pioglitazone or gemfibrozil 600 mg every 12 h for 4 days with a single 15 mg dose of pioglitazone administered on the morning of day 3. A 48 h pharmacokinetic study followed each pioglitazone dose and the study phases were separated by a 14 day washout period. RESULTS Gemfibrozil significantly increased mean pioglitazone AUC(0,∞) by 4.3-fold (P gemfibrozil administration was significantly influenced by CYP2C8 genotype. Specifically, CYP2C8*3 carriers had a 5.2-fold mean increase in pioglitazone AUC(0,∞) compared with a 3.3-fold mean increase in CYP2C8*1 homozygotes (P= 0.02). CONCLUSION CYP2C8*3 is associated with decreased pioglitazone plasma exposure in vivo and significantly influences the pharmacokinetic magnitude of the gemfibrozil–pioglitazone drug-drug interaction. Additional studies are needed to evaluate the impact of CYP2C8 genetics on the pharmacokinetics of other CYP2C8-mediated drug–drug interactions. PMID:22625877

  16. Impact of Cost-Sharing Increases on Continuity of Specialty Drug Use: A Quasi-Experimental Study.

    Science.gov (United States)

    Li, Pengxiang; Hu, Tianyan; Yu, Xinyan; Chahin, Salim; Dahodwala, Nabila; Blum, Marissa; Pettit, Amy R; Doshi, Jalpa A

    2017-07-24

    To examine the impact of cost-sharing increases on continuity of specialty drug use in Medicare beneficiaries with multiple sclerosis (MS) or rheumatoid arthritis (RA). Five percent Medicare claims data (2007-2010). Quasi-experimental study examining changes in specialty drug use among a group of Medicare Part D beneficiaries without low-income subsidies (non-LIS) as they transitioned from a 5 percent cost-sharing preperiod to a ≥25 percent cost-sharing postperiod, as compared to changes among a disease-matched contemporaneous control group of patients eligible for full low-income subsidies (LIS), who faced minor cost sharing (≤$6.30 copayment) in both the pre- and postperiods. Key variables were extracted from Medicare data. Relative to the LIS group, the non-LIS group had a greater increase in incidence of 30-day continuous gaps in any Part D treatment from the lower cost-sharing period to the higher cost-sharing period (MS, absolute increase = 10.1 percent, OR = 1.61, 95% CI 1.19-2.17; RA, absolute increase = 21.9 percent, OR = 2.75, 95% CI 2.15-3.51). The increase in Part D treatment gaps was not offset by increased Part B specialty drug use. Cost-sharing increases due to specialty tier-level cost sharing were associated with interruptions in MS and RA specialty drug treatments. © Health Research and Educational Trust.

  17. Rifampicin and anti-hypertensive drugs in chronic kidney disease: Pharmacokinetic interactions and their clinical impact

    Directory of Open Access Journals (Sweden)

    A Agrawal

    2016-01-01

    Full Text Available Patients on dialysis have an increased incidence of tuberculosis (TB. Rifampicin, a first-line antitubercular therapy (ATT drug, is a potent inducer of hepatic cytochrome P450 (CYP. There is potential for pharmacokinetic interaction between rifampicin and anti-hypertensives that are CYP substrates: amlodipine and metoprolol. Therefore, hypertensive patients receiving rifampicin-based ATT are at risk for worsening of hypertension. However, this hypothesis has not yet been systematically studied. In this prospective study, hypertensive CKD 5D patients with TB were followed after rifampicin initiation. Blood pressure (BP was ≤140/90 mmHg with stable anti-HT requirement at inclusion. Serum amlodipine, metoprolol, and prazosin levels were estimated by high-performance liquid chromatography at baseline and 3, 7, 10, and 14 days after rifampicin initiation. BP and anti-HT requirement were monitored for 2 weeks or until stabilization. All 24 patients in the study had worsening of hypertension after rifampicin and 83.3% required increase in drugs to maintain BP 50% in all patients and became undetectable in 50-75%. Drug requirement increased from 4.5 ± 3.6 to 8.5 ± 6.4 units (P < 0.0001. Mean time to first increase in dose was 6.5 ± 3.6 days. Eleven (46% patients experienced a hypertensive crisis at 9.1 ± 3.8 days. Three of them had a hypertensive emergency with acute pulmonary edema. In two patients, rifampicin had to be discontinued to achieve BP control. In conclusion, rifampicin caused a significant decrease in blood levels of commonly used anti hypertensives. This decrease in levels correlated well with worsening of hypertension. Thus, we suggest very close BP monitoring in CKD patients after rifampicin initiation.

  18. Impact of cannabis and other drugs on age at onset of psychosis.

    Science.gov (United States)

    González-Pinto, Ana; Vega, Patricia; Ibáñez, Berta; Mosquera, Fernando; Barbeito, Sara; Gutiérrez, Miguel; Ruiz de Azúa, Sonia; Ruiz, Iván; Vieta, Eduard

    2008-08-01

    The aim of this study was to investigate the relationship between age and cannabis use in patients with a first psychotic episode, and to analyze the mediating effect of comorbid use of other drugs and sex on age at onset of psychosis. All consenting patients (aged 15 to 65 years) with a first psychotic episode needing inpatient psychiatric treatment during a 2-year period between February 1997 and January 1999 were considered, confirming a total of 131 patients. Subjects were interviewed using the Structured Clinical Interview for DSM-IV Axis I Disorders, and clinical and demographic data were collected. We used general linear models with age at onset as the response variable and survival Cox models to confirm the results. Both a multivariate linear model and the corresponding Cox model were fitted with a covariate that summarizes the most significant contributors that seemed to decrease age at onset. Regarding the effect of cannabis use, a significant gradual reduction on age at onset was found as dependence on cannabis increased, consisting in a decrement of 7, 8.5, and 12 years for users, abusers, and dependents, respectively, with respect to nonusers (p = .004, p drugs or by gender. The finding was similar in the youngest patients, suggesting that this effect was not due to chance. The major contribution of this investigation is the independent and strong link between cannabis use and early age at onset of psychosis, and the slight or nonexistent effect of sex and comorbid substance abuse in this variable. These results point to cannabis as a dangerous drug in young people at risk of developing psychosis.

  19. Improving reticle defect disposition via fully automated lithography simulation

    Science.gov (United States)

    Mann, Raunak; Goodman, Eliot; Lao, Keith; Ha, Steven; Vacca, Anthony; Fiekowsky, Peter; Fiekowsky, Dan

    2016-03-01

    Most advanced wafer fabs have embraced complex pattern decoration, which creates numerous challenges during in-fab reticle qualification. These optical proximity correction (OPC) techniques create assist features that tend to be very close in size and shape to the main patterns as seen in Figure 1. A small defect on an assist feature will most likely have little or no impact on the fidelity of the wafer image, whereas the same defect on a main feature could significantly decrease device functionality. In order to properly disposition these defects, reticle inspection technicians need an efficient method that automatically separates main from assist features and predicts the resulting defect impact on the wafer image. Analysis System (ADAS) defect simulation system[1]. Up until now, using ADAS simulation was limited to engineers due to the complexity of the settings that need to be manually entered in order to create an accurate result. A single error in entering one of these values can cause erroneous results, therefore full automation is necessary. In this study, we propose a new method where all needed simulation parameters are automatically loaded into ADAS. This is accomplished in two parts. First we have created a scanner parameter database that is automatically identified from mask product and level names. Second, we automatically determine the appropriate simulation printability threshold by using a new reference image (provided by the inspection tool) that contains a known measured value of the reticle critical dimension (CD). This new method automatically loads the correct scanner conditions, sets the appropriate simulation threshold, and automatically measures the percentage of CD change caused by the defect. This streamlines qualification and reduces the number of reticles being put on hold, waiting for engineer review. We also present data showing the consistency and reliability of the new method, along with the impact on the efficiency of in

  20. Impact of probiotic drugs, based on Enterobacter faecium autostrains, on human intestinal microflora in confined habitat

    Science.gov (United States)

    Viacheslav, Ilyin; Batov, Alexey; Usanova, Nonna

    The aim of research: Investigation of influence of probiotic drugs based on autostrains of Enter-obacter faecium, selected from the crew in long term isolation experiment in confined habitat. It is known that during long-term presence in confined habitat the risk of infectious diseases increases. One of the main infectious risk occurs during first 20 days of isolation as a result of exchange of strains and stress-mediated disbacterioses. Therefore it is necessary to evaluate activities of probiotics to avoid this risk. Furthermore, in case of super long term autonomous flight there should be possibilities of application of autochthonous microflora strains as pro-biotics to strengthen colonial resistance of crews. Materials and methods: In the experiment there were used probiotic drugs based on autostrains of E. faecium, selected from the crew before the experiment. Probiotic drugs were consumed during 30 days since the beginning of the experiment with the break of consumption between 10th to 19th day. Results: Comparing the state of intestinal microflora of the crew on the baseline and 14th day of experiment re-vealed remarkable changes of microflora: the increasing of concentration of bifidobacteria and E. faecium (approximately 10 times), elimination of hemolytic streptococcus, yeasts, reduction of the rate of S.aureus, hemolytic gramnegative non-fermenting rods, lactobacilli and normal E.coli. On the 45th day of isolation, 15 days after finishing of auto-strains administration, there fere signs of restoration of disbacteriosis: the quantitative decreasing lactobacilli, bifidobacteria and normal E.coli, increasing of the rate of S.aureus, hemolytic gramnegative nonfermentive rods. Conclusion: Thus we managed to avoid risk of pathogenicity potential growth in first 2 decades of isolation. Application of probiotic, based on the autostrains of E. faecium leads to insignificant changes of concentration of lactobacteries, bifidobacteries, normal E. coli and to

  1. Rapid Phospho-Turnover by Receptor Tyrosine Kinases Impacts Downstream Signaling and Drug Binding

    OpenAIRE

    Kleiman, Laura B.; Maiwald, Thomas; Conzelmann, Holger; Lauffenburger, Douglas A.; Sorger, Peter K.

    2011-01-01

    Epidermal growth factor receptors (ErbB1–4) are oncogenic receptor tyrosine kinases (RTKs) that regulate diverse cellular processes. In this study, we combine measurement and mathematical modeling to quantify phospho-turnover at ErbB receptors in human cells and to determine the consequences for signaling and drug binding. We find that phosphotyrosine residues on ErbB1 have half-lives of a few seconds and therefore turn over 100–1000 times in the course of a typical immediate-early response t...

  2. Highly enriched uranium (HEU) storage and disposition program plan

    International Nuclear Information System (INIS)

    Arms, W.M.; Everitt, D.A.; O'Dell, C.L.

    1995-01-01

    Recent changes in international relations and other changes in national priorities have profoundly affected the management of weapons-usable fissile materials within the United States (US). The nuclear weapon stockpile reductions agreed to by the US and Russia have reduced the national security requirements for these fissile materials. National policies outlined by the US President seek to prevent the accumulation of nuclear weapon stockpiles of plutonium (Pu) and HEU, and to ensure that these materials are subjected to the highest standards of safety, security and international accountability. The purpose of the Highly Enriched Uranium (HEU) Storage and Disposition Program Plan is to define and establish a planned approach for storage of all HEU and disposition of surplus HEU in support of the US Department of Energy (DOE) Fissile Material Disposition Program. Elements Of this Plan, which are specific to HEU storage and disposition, include program requirements, roles and responsibilities, program activities (action plans), milestone schedules, and deliverables

  3. Hearing Office Dispositions Per ALJ Per Day Rate Ranking Report

    Data.gov (United States)

    Social Security Administration — A ranking of ODAR hearing offices by the average number of hearings dispositions per ALJ per day. The average shown will be a combined average for all ALJs working...

  4. Legacy sample disposition project. Volume 2: Final report

    International Nuclear Information System (INIS)

    Gurley, R.N.; Shifty, K.L.

    1998-02-01

    This report describes the legacy sample disposition project at the Idaho Engineering and Environmental Laboratory (INEEL), which assessed Site-wide facilities/areas to locate legacy samples and owner organizations and then characterized and dispositioned these samples. This project resulted from an Idaho Department of Environmental Quality inspection of selected areas of the INEEL in January 1996, which identified some samples at the Test Reactor Area and Idaho Chemical Processing Plant that had not been characterized and dispositioned according to Resource Conservation and Recovery Act (RCRA) requirements. The objective of the project was to manage legacy samples in accordance with all applicable environmental and safety requirements. A systems engineering approach was used throughout the project, which included collecting the legacy sample information and developing a system for amending and retrieving the information. All legacy samples were dispositioned by the end of 1997. Closure of the legacy sample issue was achieved through these actions

  5. Americium/Curium Disposition Life Cycle Planning Study

    International Nuclear Information System (INIS)

    Jackson, W.N.; Krupa, J.; Stutts, P.; Nester, S.; Raimesch, R.

    1998-01-01

    At the request of the Department of Energy Savannah River Office (DOE- SR), Westinghouse Savannah River Company (WSRC) evaluated concepts to complete disposition of Americium and Curium (Am/Cm) bearing materials currently located at the Savannah River Site (SRS)

  6. ACCELERATION OF LOS ALAMOS NATIONAL LABORATORY TRANSURANIC WASTE DISPOSITION

    International Nuclear Information System (INIS)

    O'Leary, Gerald A.

    2007-01-01

    -handled transuranic waste inventory. Building 412 Decontamination and Volume Facility and Dome 231 Permacon will be reconfigured to remediate and repackage oversized containers. Actions are underway to stage the inventory in a manner that facilitiates handling and processing, and builds a backlog at key process steps to improve efficienty and minimize the impact of operational slowdown elsewhere in the process. Several initiatives will improve safety and strengthen disciplined operations and compliance with established requirements. Retrieval is a critical element in dispositioning the below-ground contact-handled and remote-handled transuranic waste inventory and will be subcontracted to a firm(s) with the experience and specialized capability to retrieve the contact-handled and remote-handled inventories. Performance specifications consider likely container integrity issues and anticipated challenges recoveirng the waste from storage in pits, trenches, and lined shafts.

  7. URGENSI STRATEGI DISPOSITION HABITS OF MIND MATEMATIS

    Directory of Open Access Journals (Sweden)

    Bety Miliyawati

    2014-09-01

    Full Text Available ABSTRAK Kebiasaan berpikir (habits of mind memiliki peranan penting dalam proses pembelajaran dan perkembangan individu dalam membantu memecahkan masalah. Habits Of Mind (HOM adalah kebiasaan berpikir secara fleksibel, mengelola secara empulsif, mendengarkan dengan empati, membiasakan mengajukan pertanyaan, kebiasaan menyelesaikan masalah secara efektif, membiasakan menggunakan pengetahuan masa lalu untuk situasi baru, membiasakan berkomunikasi, berpikir jernih dengan tepat, menggunakan semua indera ketika mengumpulkan informasi, mencoba cara berbeda dan menghasilkan ide-ide yang baru, kebiasaan untuk merespon, kebiasaan untuk mengambil resiko, biasa bertanggung jawab, memiliki rasa humor, membiasakan berpikir interaktif dengan orang lain, bersikap terbuka dan mencoba terus-menerus. Hal ini sejalan dengan tujuan Kurikulum 2013, yaitu mempersiapkan generasi bangsa agar memiliki kemampuan hidup sebagai pribadi dan warga negara yang produktif, kreatif, inovatif, dan afektif. Artikel ini dikaji didasarkan atas analisis terhadap: (1 karakteristik matematika, (2 habits of mind matematis, dan (3 disposition contoh strategi HOM dalam pembelajaran matematika yang dikembangkan pada siswa. Kata Kunci    : Pembelajaran, Karakteristik Matematika, Habits of Mind Matematis   ABSTRACT Habits of mind have an important role in the learning process and the development of individuals in helping to solve the problem. Habits Of Mind (HOM is the habit of thinking flexibly, manage empulsif, listening with empathy, get used to ask questions, solve problems effectively habit, the habit of using past knowledge to new situations, to get used to communicate, think clearly, precisely, using all the senses when gathering information, trying different ways and generate new ideas, habits to respond, the habit to take risks, the usual charge, have a sense of humor, familiarize interactive thinking with others, be open and try constantly. This is in line with the curriculum

  8. Salt disposition alternatives filtration at SRTC

    International Nuclear Information System (INIS)

    Walker, B. W.; Hobbs, D.

    2000-01-01

    Several of the prospective salt disposition alternative technologies require a monosodium titanate (MST) contact to remove strontium and actinides from inorganic salt solution feedstock. This feedstock also contains sludge solids from waste removal operations and may contain defoamers added in the evaporator systems. Filtration is required to remove the sludge and MST solids before sending the salt solution for further processing. This report describes testing performed using the Parallel Theological Experimental Filter (PREF). The PREF contains two single tube Mott sintered metal crossflow filters. For this test one filter was isolated so that the maximum velocities could be achieved. Previous studies showed slurries of MST and sludge in the presence of sodium tetraphenylborate (NaTPB) were filterable since the NaTPB slurry formed a filter cake which aided in removing the smaller MST and sludge particles. Some of the salt disposition alternative technologies do not use NaTPB raising the question of how effective crossflow filtration is with a feed stream containing only sludge and MST. Variables investigated included axial velocity, transmembrane pressure, defoamer effects, and solids concentration (MST and sludge). Details of the tests are outlined in the technical report WSRC-RP-98-O0691. Key conclusions from this study are: (1) Severe fouling of the Mott sintered metal filter did not occur with any of the solutions filtered. (2) The highest fluxes, in the range of .46 to 1.02 gpm/f 2 , were obtained when salt solution decanted from settled solids was fed to the filter. These fluxes would achieve 92 to 204 gpm filtrate production for the current ITP filters. The filtrate fluxes were close to the flux of 0.42 gpm/f 2 reported for In Tank Precipitation Salt Solution by Morrisey. (3) For the range of solids loading studied, the filter flux ranged from .04 to .17 gpm/f 2 which would result in a filtrate production rate of 9 to 31 gpm for the current HP filter. (4

  9. Guide for disposition of radioactive-material sources

    International Nuclear Information System (INIS)

    Taylor, J.M.; Selby, J.M.

    1983-04-01

    This guide has been prepared to assist DOE Energy Technology Centers in disposing of radioactive-material sources. The guide describes the steps and requirements necessary to dispose of unwanted sources. The steps include obtaining approvals, source characterization, source disposition, packaging requirements, and shipment preparation. A flow chart is provided in the guide to assist the user in the necessary sequential steps of source disposition

  10. Regulatory Notes on Impact of Excipients on Drug Products and the Maillard Reaction.

    Science.gov (United States)

    Chowdhury, Dipak K; Sarker, Haripada; Schwartz, Paul

    2018-02-01

    In general, it is an important criterion that excipients remain inert throughout the shelf life of the formulated pharmaceutical product. However, depending on the functionality in chemical structure of active drug and excipients, they may undergo interaction. The well-known Maillard reaction occurs between a primary amine with lactose at high temperature to produce brown pigments. The reactivity of Maillard reaction may vary depending on the concentration as well as other conditions. Commercially, there are products where the active pharmaceutical ingredient is a primary amine and contains less than 75% lactose along with inactive excipients. This product does not show Maillard reaction during its shelf life of around 2 years at ambient conditions. However, when the same type of product contains more than 95 % lactose as an excipient, then there is a possibility of interactions though it is not visible in the initial year. Therefore, this regulatory note discusses involvement of different factors of a known drug-excipient interactions with case studies and provides an overview on how the concentration of lactose in the pharmaceutical product is important in addition to temperature and moisture in Maillard reaction.

  11. The impact of currently used oral antihyperglycemic drugs on dysfunctional adipose tissue

    Directory of Open Access Journals (Sweden)

    Tomić-Naglić Dragana

    2017-01-01

    Full Text Available Obesity is a disease with pandemic frequency, often accompanied by chronic metabolic and organic complications. Type 2 diabetes mellitus (T2DM is among the most common metabolic complications of obesity. The first step in the treatment of T2DM is medical nutrition therapy combined with moderate physical activity and with advice to patients to reduce their body weight. Pharmacotherapy starts with metformin, and in the case of inadequate therapeutic response, another antihyperglycemic agent should be added. The most clinical experience exists with sulfonylurea agents, but their use is limited due to high incidence of hypoglycemia and increase in body weight. Based on the fact that dysfunction of adipose tissue can lead to the development of chronic degenerative complications, precise use of drugs with a favorable effect on the functionality of adipose tissue represents an imperative of modern T2DM treatment. Antihyperglycemic drugs of choice in obese individuals are those which cause maturation of adipocytes, improvement of secretion of protective adipokines, and redistribution of fat mass from visceral to subcutaneous depots. Oral antihyperglycemic agents that can affect the functionality of adipose tissue are metformin, SGLT-2 inhibitors, DPP-4 inhibitors, and thiazolidinediones.

  12. The impact of parameter identification methods on drug therapy control in an intensive care unit

    NARCIS (Netherlands)

    Hann, C.E.; Chase, J.G.; Ypma, M.F.; Elfring, J.; Nor, N.H.M.; Lawrence, P.; Shaw, G.M.

    2008-01-01

    This paper investigates the impact of fast parameter identification methods, which do not require any forward simulations, on model-based glucose control, using retrospective data in the Christchurch Hospital Intensive Care Unit. The integral-based identification method has been previously

  13. Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes

    NARCIS (Netherlands)

    Falzon, Dennis; Gandhi, Neel; Migliori, Giovanni B.; Sotgiu, Giovanni; Cox, Helen S.; Holtz, Timothy H.; Hollm-Delgado, Maria-Graciela; Keshavjee, Salmaan; Deriemer, Kathryn; Centis, Rosella; D'Ambrosio, Lia; Lange, Christoph G.; Bauer, Melissa; Menzies, Dick; Ahuja, S. D.; Ashkin, D.; Avendaño, M.; Banerjee, R.; Bauer, M.; Becerra, M. C.; Benedetti, A.; Burgos, M.; Centis, R.; Chan, E. D.; Chiang, C. Y.; Cobelens, F.; Cox, H.; D'Ambrosio, L.; de Lange, W. C. M.; DeRiemer, K.; Enarson, D.; Falzon, D.; Flanagan, K. L.; Flood, J.; Gandhi, N.; Garcia-Garcia, M. L.; Granich, R. M.; Hollm-Delgado, M. G.; Holtz, T. H.; Hopewell, P.; Iseman, M. D.; Jarlsberg, L. G.; Keshavjee, S.; Kim, H. R.; Koh, W. J.; Lancaster, J. L.; Lange, C.; Leimane, V.; Leung, C. C.; Li, J.

    2013-01-01

    A meta-analysis for response to treatment was undertaken using individual data of multidrug-resistant tuberculosis (MDR-TB) (resistance to isoniazid and rifampicin) patients from 26 centres. The analysis assessed the impact of additional resistance to fluoroquinolones and/or second-line injectable

  14. Accessing and assessing young learner’s mathematical dispositions

    Directory of Open Access Journals (Sweden)

    mellony Graven

    2012-07-01

    Full Text Available It is argued in this paper that there is an absence of literature relating to research on learner mathematical dispositions, particularly with young learners. Drawing on Kilpatrick, Swafford and Findell’s (2001 five interrelated strands of mathematical proficiency, which include: conceptual understanding, procedural fluency, strategic competence, adaptive reasoning and productive disposition, it is argued that there has been little engagement with productive disposition in the field of mathematics education and how we might access and assess this strand. Despite competence in all strands being essential for mathematical proficiency, literature and assessments that seek to establish learner levels of mathematical proficiency have tended to focus on the first four and have neglected the last; productive disposition. Finding ways in which to access student mathematical learning dispositions can be challenging, especially with young learners who struggle to articulate their views. An instrument is shared that the author has designed with doctoral fellow, Debbie Stott, in order to access and assess the productive disposition of learners participating in maths clubs run within the South African Numeracy Chair. The findings that emerge in one Grade 3 club with six learners is shared. These findings are related to the data collected through instruments that assess the other four strands of mathematical proficiency. This enables a holistic picture of learner’s mathematical proficiency as intended in the conceptualisation of the interrelated five strands of proficiency.

  15. Disposition of excess weapons plutonium from dismantled weapons

    International Nuclear Information System (INIS)

    Jardine, L.J.

    1997-01-01

    With the end of the Cold War and the implementation of various nuclear arms reduction agreements, US and Russia have been actively dismantling tens of thousands of nuclear weapons. As a result,large quantities of fissile materials, including more than 100 (tonnes?) of weapons-grade Pu, have become excess to both countries' military needs. To meet nonproliferation goals and to ensure the irreversibility of nuclear arms reductions, this excess weapons Pu must be placed in secure storage and then, in timely manner, either used in nuclear reactors as fuel or discarded in geologic repositories as solid waste. This disposition in US and Russia must be accomplished in a safe, secure manner and as quickly as practical. Storage of this Pu is a prerequisite to any disposition process, but the length of storage time is unknown. Whether by use as fuel or discard as solid waste, disposition of that amount of Pu will require decades--and perhaps longer, if disposition operations encounter delays. Neither US nor Russia believes that long-term secure storage is a substitute for timely disposition of excess Pu, but long-term, safe, secure storage is a critical element of all excess Pu disposition activities

  16. ISS Logistics Hardware Disposition and Metrics Validation

    Science.gov (United States)

    Rogers, Toneka R.

    2010-01-01

    I was assigned to the Logistics Division of the International Space Station (ISS)/Spacecraft Processing Directorate. The Division consists of eight NASA engineers and specialists that oversee the logistics portion of the Checkout, Assembly, and Payload Processing Services (CAPPS) contract. Boeing, their sub-contractors and the Boeing Prime contract out of Johnson Space Center, provide the Integrated Logistics Support for the ISS activities at Kennedy Space Center. Essentially they ensure that spares are available to support flight hardware processing and the associated ground support equipment (GSE). Boeing maintains a Depot for electrical, mechanical and structural modifications and/or repair capability as required. My assigned task was to learn project management techniques utilized by NASA and its' contractors to provide an efficient and effective logistics support infrastructure to the ISS program. Within the Space Station Processing Facility (SSPF) I was exposed to Logistics support components, such as, the NASA Spacecraft Services Depot (NSSD) capabilities, Mission Processing tools, techniques and Warehouse support issues, required for integrating Space Station elements at the Kennedy Space Center. I also supported the identification of near-term ISS Hardware and Ground Support Equipment (GSE) candidates for excessing/disposition prior to October 2010; and the validation of several Logistics Metrics used by the contractor to measure logistics support effectiveness.

  17. Interactions between estrogen receptors and metabotropic glutamate receptors and their impact on drug addiction in females.

    Science.gov (United States)

    Tonn Eisinger, Katherine R; Gross, Kellie S; Head, Brian P; Mermelstein, Paul G

    2018-03-10

    Estrogen receptors α and β (ERα and ERβ) have a unique relationship with metabotropic glutamate receptors (mGluRs) in the female rodent brain such that estradiol is able to recruit intracellular G-protein signaling cascades to influence neuronal physiology, structure, and ultimately behavior. While this association between ERs and mGluRs exists in many cell types and brain regions, its effects are perhaps most striking in the nucleus accumbens (NAc). This review will discuss the original characterization of ER/mGluR signaling and how estradiol activity in the NAc confers increased sensitivity to drugs of abuse in females through this mechanism. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Modeling the impact and costs of semiannual mass drug administration for accelerated elimination of lymphatic filariasis.

    Directory of Open Access Journals (Sweden)

    Wilma A Stolk

    Full Text Available The Global Program to Eliminate Lymphatic Filariasis (LF has a target date of 2020. This program is progressing well in many countries. However, progress has been slow in some countries, and others have not yet started their mass drug administration (MDA programs. Acceleration is needed. We studied how increasing MDA frequency from once to twice per year would affect program duration and costs by using computer simulation modeling and cost projections. We used the LYMFASIM simulation model to estimate how many annual or semiannual MDA rounds would be required to eliminate LF for Indian and West African scenarios with varied pre-control endemicity and coverage levels. Results were used to estimate total program costs assuming a target population of 100,000 eligibles, a 3% discount rate, and not counting the costs of donated drugs. A sensitivity analysis was done to investigate the robustness of these results with varied assumptions for key parameters. Model predictions suggested that semiannual MDA will require the same number of MDA rounds to achieve LF elimination as annual MDA in most scenarios. Thus semiannual MDA programs should achieve this goal in half of the time required for annual programs. Due to efficiency gains, total program costs for semiannual MDA programs are projected to be lower than those for annual MDA programs in most scenarios. A sensitivity analysis showed that this conclusion is robust. Semiannual MDA is likely to shorten the time and lower the cost required for LF elimination in countries where it can be implemented. This strategy may improve prospects for global elimination of LF by the target year 2020.

  19. THE POPULATION IMPACT OF ELIMINATING HOMELESSNESS ON HIV VIRAL SUPPRESSION AMONG PEOPLE WHO USE DRUGS

    Science.gov (United States)

    Marshall, Brandon D.L.; Elston, Beth; Dobrer, Sabina; Parashar, Surita; Hogg, Robert S.; Montaner, Julio S.G.; Kerr, Thomas; Wood, Evan; Milloy, M-J

    2015-01-01

    Objective We sought to estimate the change in viral suppression prevalence if homelessness were eliminated from a population of HIV-infected people who use drugs (PWUD). Design Community-recruited prospective cohort of HIV-infected PWUD in Vancouver, Canada. Behavioral information was collected at baseline and linked to a province-wide HIV/AIDS treatment database. The primary outcome was viral suppression (<50 copies/mL) measured during subsequent routine clinical care. Methods We employed an imputation-based marginal modelling approach. First, we used modified Poisson regression to obtain effect estimates (adjusting for sociodemographics, substance use, addiction treatment, and other confounders). Then, we imputed an outcome probability for each individual while manipulating the exposure (homelessness). Population viral suppression prevalence under realized and “housed” scenarios were obtained by averaging these probabilities across the population. Bootstrapping was conducted to calculate 95% confidence limits. Results Of 706 individuals interviewed between January 2005 and December 2015, the majority was male (66.0%), of Caucasian race/ethnicity (55.1%), and had a history of injection (93.6%). At first study visit, 223 (31.6%) reported recent homelessness, and 37.8% were subsequently identified as virally suppressed. Adjusted marginal models estimated a 15.1% relative increase (95%CI: 9.0%, 21.7%) in viral suppression in the entire population—to 43.5% (95%CI: 39.4%, 48.2%)—if all homeless individuals were housed. Among those homeless, eliminating this exposure would increase viral suppression from 22.0% to 40.1% (95%CI: 35.1%, 46.1%), an 82.3% relative increase. Conclusions Interventions to house homeless, HIV-positive individuals who use drugs could significantly increase population viral suppression. Such interventions should be implemented as a part of renewed HIV/AIDS prevention and treatment efforts. PMID:26636924

  20. Plasma and Ocular Prednisolone Disposition after Oral Treatment in Cats

    Directory of Open Access Journals (Sweden)

    María J. Del Sole

    2013-01-01

    Full Text Available Objective. To evaluate the plasma and aqueous humor disposition of prednisolone after oral administration in cats. Methods. Six cats were administered with a single oral dose of prednisolone (10 mg. Blood and aqueous humor samples were serially collected after drug administration. Prednisolone concentrations in plasma and aqueous humor were measured at 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, and 5.0 h after administration by a high-performance liquid chromatographic analytical method developed and validated for this purpose. Results. Mean ± standard error (SE of maximum plasma prednisolone concentration (300.8 ± 67.3 ng/mL was reached at 1 h after administration. Prednisolone was distributed to the aqueous humor reaching a mean peak concentration of 100.9 ± 25.5 ng/mL at 1.25 h after administration. The mean ± SE systemic and aqueous humor exposure (AUC was 553.3 ± 120.0 ng*h/mL and 378.8 ± 64.9 ng*h/mL, respectively. A high AUCaqueous humor/AUCplasma ratio was observed (0.68 ± 0.13. The mean half-life time of elimination in plasma and aqueous humor was 0.87 ± 0.16 h and 2.25 ± 0.44 h, respectively. Clinical Significance. The observed high ratio between aqueous humor and plasma prednisolone concentrations indicates that extensive penetration of prednisolone to the anterior segment of the eye may occur. This is the first step that contributes to the optimization of the pharmacological therapeutics for the clinical treatment of uveitis.

  1. The potential impact of density dependent fecundity on the use of the faecal egg count reduction test for detecting drug resistance in human hookworms.

    Directory of Open Access Journals (Sweden)

    Andrew C Kotze

    Full Text Available Current efforts to control human soil-transmitted helminth (STH infections involve the periodic mass treatment of people, particularly children, in all endemic areas, using benzimidazole and imidothiazole drugs. Given the fact that high levels of resistance have developed to these same drugs in roundworms of livestock, there is a need to monitor drug efficacy in human STHs. The faecal egg count reduction test (FECRT, in which faecal egg output is measured pre- and post-drug treatment, is presently under examination by WHO as a means of detecting the emergence of resistance. We have examined the potential impact of density dependent fecundity on FECRT data. Recent evidence with the canine hookworm indicates that the density dependent egg production phenomenon shows dynamic properties in response to drug treatment. This will impact on measurements of drug efficacy, and hence drug resistance. It is likely that the female worms that survive a FECRT drug treatment in some human cases will respond to the relaxation of density dependent constraints on egg production by increasing their egg output significantly compared to their pre-treatment levels. These cases will therefore underestimate drug efficacy in the FECRT. The degree of underestimation will depend on the ability of the worms within particular hosts to increase their egg output, which will in turn depend on the extent to which their egg output is constrained prior to the drug treatment. As worms within different human cases will likely be present at quite different densities prior to a proposed FECRT, there is potential for the effects of this phenomenon on drug efficacy measurements to vary considerably within any group of potential FECRT candidates. Measurement of relative drug efficacy may be improved by attempting to ensure a consistent degree of underestimation in groups of people involved in separate FECRTs. This may be partly achieved by omission of cases with the heaviest infections

  2. Impact of the FDA warning of potential ceftriaxone and calcium interactions on drug use policy in clinical practice.

    Science.gov (United States)

    Esterly, John S; Steadman, Emily; Scheetz, Marc H

    2011-06-01

    In September 2007, the FDA issued an alert recommending that ceftriaxone and calcium-containing solutions should not be administered to any patient within 48 h of each other. Due to the widespread use of ceftriaxone, significant concern was expressed by the greater healthcare community about the warning, which the FDA eventually retracted in April of 2009. We sought to quantify the impact of the warning on healthcare institutions. A survey was administered to the membership of the Society of Infectious Diseases Pharmacists to quantify perceived changes in ceftriaxone use among healthcare institutions across the United States. A survey of Infectious Diseases experts was conducted. Participants were queried for hospital policies/drug use statistics during two times: immediately after the FDA warning and approximately 13 months post warning (preceding the FDA retraction). Related changes in formulary, drug-use policy, and the number of employee hours that were devoted to addressing the FDA warning were assessed. Ninety-four surveys representing 94 hospital systems were included in the analysis. Approximately half (n = 49, 52%) of respondent institutions enacted at least one drug-use policy change based on the warning; one institution removed ceftriaxone from a clinical protocol. Institutions' final interpretations of the warning differed slightly from initial understanding of the warning, and there was an overall minor decrease in the perceived use of ceftriaxone. The majority of those surveyed (n = 70, 74%) estimated that their respective institutions devoted between 1 and 49 employee hours to address the warning. Hospitals with ID pharmacists had minimal changes to ceftriaxone use after the 2007 FDA warning. Specialized pharmacists may be uniquely situated to help hospitals interpret global recommendations locally.

  3. The Impact of Social Structures on Deviant Behaviors: The Study of 402 High Risk Street Drug Users in Iran

    Directory of Open Access Journals (Sweden)

    Maryam Mehrabi

    2016-01-01

    Full Text Available This study is a sociological analysis of the three dimensions of social structure including institutional, relational, and embodied structures that have an impact on the individuals’ deviant behaviors in the society. The authors used a mix method to analyze the qualitative and quantitative data of 402 high risk abandoned substance users in 2008 in Tehran, capital city of Iran. The leading reasons of substance use were categorized into four fundamental themes as follows: stress, deviant social networks, and low social capital and weak social support sources. In addition, the epidemiology model of regression analysis provides a brief explanation to assess the association between the demographical and etiological variables, and the drug users’ deviant behaviors. In sum, substance use is discussed as a deviant behavior pattern which stems from a comorbidity of weak social structures.

  4. Predicted Impact of the Food and Drug Administration's Menu-Labeling Regulations on Restaurants in 4 New Jersey Cities.

    Science.gov (United States)

    Gruner, Jessie; DeWeese, Robin S; Lorts, Cori; Yedidia, Michael J; Ohri-Vachaspati, Punam

    2018-02-01

    To determine the proportion of restaurants that will be required to post calorie information under the Food and Drug Administration's menu-labeling regulations in 4 New Jersey cities. We classified geocoded 2014 data on 1753 restaurant outlets in accordance with the Food and Drug Administration's guidelines, which will require restaurants with 20 or more locations nationwide to post calorie information. We used multivariate logistic regression analyses to assess the association between menu-labeling requirements and census tract characteristics. Only 17.6% of restaurants will be affected by menu labeling; restaurants in higher-income tracts have higher odds than do restaurants in lower-income tracts (odds ratio [OR] = 1.55; P = .02). Restaurants in non-Hispanic Black (OR = 1.62; P = .02) and mixed race/ethnicity (OR = 1.44; P = .05) tracts have higher odds than do restaurants in non-Hispanic White tracts of being affected. Additional strategies are needed to help consumers make healthy choices at restaurants not affected by the menu-labeling law. These findings have implications for designing implementation strategies for the law and for evaluating its impact.

  5. Pharmacokinetics and pharmacodynamics of qinghaosu derivatives: how do they impact on the choice of drug and the dosage regimens?

    Science.gov (United States)

    Kyle, D E; Teja-Isavadharm, P; Li, Q; Leo, K

    1998-01-01

    The critical decisions of which artemisinin derivative(s) to use and by which route(s) of administration for falciparum malaria are complex scientifically and politically. Despite the need for additional pharmacokinetic, pharmacodynamic and toxicokinetic data, these drugs are too important to delay concise, rational recommendations any longer. These types of decisions must be made now, implemented on a multinational level with WHO leadership, and revised as new findings emerge. For acute, uncomplicated disease, per os dosing of artesunate or artemether for three days is recommended, but only in combination with other antimalarial drugs like mefloquine. For severe falciparum malaria, intravenous administration is the preferred route, yet current formulations for intravenous dosing are not optimal and should be an area for future development emphasis. Clearly intramuscular administration of artemether has proven effective for severe disease, yet dosing regimens shouldn't be designed with ultimate parasitological cure as the aim and the problem of bioavailability of the sesame oil formulations must be examined further. Once the life-saving reduction in parasitemia and pathophysiological sequelae have been achieved, the patient can be given oral medication to affect radical cure. Much more data will be required to define the role of per rectum dosing for the treatment of severe malaria, yet this approach holds great promise as a life-saving intervention in rural areas where this disease has it most dramatic impact.

  6. The impact of renal protection clinics on prescription of and adherence to cardioprotective drug therapy in chronic kidney disease patients.

    Science.gov (United States)

    Lepeytre, Fanny; Cardinal, Héloise; Fradette, Lorraine; Verhave, Jacobien; Dorais, Marc; LeLorier, Jacques; Pichette, Vincent; Madore, François

    2017-06-01

    Background: The aim of this study was to assess the impact of follow-up in renal protection clinics on the prescription of and adherence to cardioprotective drugs in patients with chronic kidney disease (CKD). Methods: We studied stage 4 and 5 CKD patients who initiated follow-up in three renal protection clinics. The prescription pattern of antihypertensive agents (AHA) and lipid-lowering agents (LLAs) was measured as the percentage of patients who are prescribed the agents of interest at a given time. Adherence to drug therapy was defined as the percentage of days, during a pre-defined observation period, in which patients have an on-hand supply of their prescribed medications. Results: A total of 259 CKD patients were enrolled and followed for up to 1 year after referral to renal protection clinics. There was a significant increase in the prescription of angiotensin-converting enzyme inhibitors (34-39%), angiotensin II receptor blockers (11-14%), beta-blockers (40-51%), calcium channel blockers (62-74%), diuretics (66-78%) and LLAs (39-47%) during follow-up in the renal protection clinic compared with baseline (P-values protection clinics. Conclusion: Our results suggest that referral and follow-up in a renal protection clinic may increase the prescription of cardioprotective agents in CKD patients, but does not appear to improve adherence to these medications.

  7. Crosslinked electrospun PVA nanofibrous membranes: elucidation of their physicochemical, physicomechanical and molecular disposition

    International Nuclear Information System (INIS)

    Shaikh, Rubina P; Kumar, Pradeep; Choonara, Yahya E; Du Toit, Lisa C; Pillay, Viness

    2012-01-01

    The effects of modifying electrospun poly(vinyl alcohol) (PVA) nanofibers through crosslinking using glutaraldehyde (GA) are explored in this paper. Various concentrations of PVA solutions containing model drugs rifampicin (RIF) and isoniazid (INH) were electrospun and thereafter crosslinked using GA vapors. PVA nanofibers demonstrated high drug entrapment efficiency of 98.77% ± 1.384% and 95.07% ± 1.988% for the INH- and RIF-loaded PVA nanofibers, respectively. The surface morphology, molecular vibrational transitions, tensile attributes and in vitro drug release were characterized and supported by in silico molecular mechanics simulations. Results indicated that crosslinking caused a significant reduction in the rate of drug release where 81.11% ± 2.35% of INH and 59.31% ± 2.57% of RIF were released after 12 h. Tensile properties such as the ultimate strength and Young's modulus increased after crosslinking, caused by crosslinks forming between PVA nanofibers as was revealed through scanning electron microscopy analysis. Fourier Transform infrared analysis was conducted to further support the mode of crosslinking. Additionally, image processing analysis was carried out to quantify the effect of formulation variables on the morphology of nanofibers. Furthermore, the effect of GA-induced crosslinking and addition of drugs on the performance of electrospun fibers was further elucidated and conceptualized using a molecular mechanics assisted model building and energy refinement approach via molecular mechanics energy relationships by exploring the spatial disposition of energy-minimized molecular structures of the polymer, crosslinker and the drugs. (paper)

  8. Descriptive Analysis on the Impacts of Universal Zero-Markup Drug Policy on a Chinese Urban Tertiary Hospital.

    Directory of Open Access Journals (Sweden)

    Wei Tian

    Full Text Available Universal Zero-Markup Drug Policy (UZMDP mandates no price mark-ups on any drug dispensed by a healthcare institution, and covers the medicines not included in the China's National Essential Medicine System. Five tertiary hospitals in Beijing, China implemented UZMDP in 2012. Its impacts on these hospitals are unknown. We described the effects of UZMDP on a participating hospital, Jishuitan Hospital, Beijing, China (JST.This retrospective longitudinal study examined the hospital-level data of JST and city-level data of tertiary hospitals of Beijing, China (BJT 2009-2015. Rank-sum tests and join-point regression analyses were used to assess absolute changes and differences in trends, respectively.In absolute terms, after the UZDMP implementation, there were increased annual patient-visits and decreased ratios of medicine-to-healthcare-charges (RMOH in JST outpatient and inpatient services; however, in outpatient service, physician work-days decreased and physician-workload and inflation-adjusted per-visit healthcare charges increased, while the inpatient physician work-days increased and inpatient mortality-rate reduced. Interestingly, the decreasing trend in inpatient mortality-rate was neutralized after UZDMP implementation. Compared with BJT and under influence of UZDMP, JST outpatient and inpatient services both had increasing trends in annual patient-visits (annual percentage changes[APC] = 8.1% and 6.5%, respectively and decreasing trends in RMOH (APC = -4.3% and -5.4%, respectively, while JST outpatient services had increasing trend in inflation-adjusted per-visit healthcare charges (APC = 3.4% and JST inpatient service had decreasing trend in inflation-adjusted per-visit medicine-charges (APC = -5.2%.Implementation of UZMDP seems to increase annual patient-visits, reduce RMOH and have different impacts on outpatient and inpatient services in a Chinese urban tertiary hospital.

  9. Descriptive Analysis on the Impacts of Universal Zero-Markup Drug Policy on a Chinese Urban Tertiary Hospital.

    Science.gov (United States)

    Tian, Wei; Yuan, Jiangfan; Yang, Dong; Zhang, Lanjing

    2016-01-01

    Universal Zero-Markup Drug Policy (UZMDP) mandates no price mark-ups on any drug dispensed by a healthcare institution, and covers the medicines not included in the China's National Essential Medicine System. Five tertiary hospitals in Beijing, China implemented UZMDP in 2012. Its impacts on these hospitals are unknown. We described the effects of UZMDP on a participating hospital, Jishuitan Hospital, Beijing, China (JST). This retrospective longitudinal study examined the hospital-level data of JST and city-level data of tertiary hospitals of Beijing, China (BJT) 2009-2015. Rank-sum tests and join-point regression analyses were used to assess absolute changes and differences in trends, respectively. In absolute terms, after the UZDMP implementation, there were increased annual patient-visits and decreased ratios of medicine-to-healthcare-charges (RMOH) in JST outpatient and inpatient services; however, in outpatient service, physician work-days decreased and physician-workload and inflation-adjusted per-visit healthcare charges increased, while the inpatient physician work-days increased and inpatient mortality-rate reduced. Interestingly, the decreasing trend in inpatient mortality-rate was neutralized after UZDMP implementation. Compared with BJT and under influence of UZDMP, JST outpatient and inpatient services both had increasing trends in annual patient-visits (annual percentage changes[APC] = 8.1% and 6.5%, respectively) and decreasing trends in RMOH (APC = -4.3% and -5.4%, respectively), while JST outpatient services had increasing trend in inflation-adjusted per-visit healthcare charges (APC = 3.4%) and JST inpatient service had decreasing trend in inflation-adjusted per-visit medicine-charges (APC = -5.2%). Implementation of UZMDP seems to increase annual patient-visits, reduce RMOH and have different impacts on outpatient and inpatient services in a Chinese urban tertiary hospital.

  10. The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment

    Science.gov (United States)

    Greim, Helmut; Kaden, Debra A.; Larson, Richard A.; Palermo, Christine M.; Rice, Jerry M.; Ross, David; Snyder, Robert

    2014-01-01

    Hematopoietic stem cells (HSCs) are a unique population of somatic stem cells that can both self-renew for long-term reconstitution of HSCs and differentiate into hematopoietic progenitor cells, which in turn give rise, in a hierarchical manner, to the entire myeloid and lymphoid lineages. The differentiation and maturation of these lineages occurs in the bone marrow niche, a microenvironment that regulates self-renewal, survival, differentiation, and proliferation, with interactions among signaling pathways in the HSCs and the niche required to establish and maintain homeostasis. The accumulation of genetic mutations and cytogenetic abnormalities within cells of the partially differentiated myeloid lineage, particularly as a result of exposure to benzene or cytotoxic anticancer drugs, can give rise to malignancies like acute myeloid leukemia and myelodysplastic syndrome. Better understanding of the mechanisms driving these malignancies and susceptibility factors, both within hematopoietic progenitor cells and cells within the bone marrow niche, may lead to the development of strategies for prevention of occupational and cancer therapy–induced disease. PMID:24495159

  11. Stabilized helical peptides: overview of the technologies and its impact on drug discovery.

    Science.gov (United States)

    Klein, Mark

    2017-11-01

    Protein-protein interactions are predominant in the workings of all cells. Until now, there have been a few successes in targeting protein-protein interactions with small molecules. Peptides may overcome some of the challenges of small molecules in disrupting protein-protein interactions. However, peptides present a new set of challenges in drug discovery. Thus, the study of the stabilization of helical peptides has been extensive. Areas covered: Several technological approaches to helical peptide stabilization have been studied. In this review, stapled peptides, foldamers, and hydrogen bond surrogates are discussed. Issues regarding design principles are also discussed. Furthermore, this review introduces select computational techniques used to aid peptide design and discusses clinical trials of peptides in a more advanced stage of development. Expert opinion: Stabilized helical peptides hold great promise in a wide array of diseases. However, the field is still relatively new and new design principles are emerging. The possibilities of peptide modification are quite extensive and expanding, so the design of stabilized peptides requires great attention to detail in order to avoid a large number of failed lead peptides. The start of clinical trials with stapled peptides is a promising sign for the future.

  12. The impact of the use of antiepileptic drugs on the growth of children

    Science.gov (United States)

    2013-01-01

    Background This study investigated whether long-term treatment with antiepileptic drugs (AEDs) had negative effects on statural growth and serum calcium levels in children with epilepsy in Taiwan. Methods Children with epilepsy treated with one prescription of AEDs (monotherapy) for at least 1 year were selected. The AEDs included valproic acid (VPA; Deparkin) in 27 children (11 boys and 16 girls) aged 4-18 years, oxcarbazepine (Trileptal) in 30 children (15 boys and 15 girls) aged 5-18 years, topiramate (Topamax) in 19 children (10 boys and 9 girls) aged 6-18 years, and lamotrigine (Lamicta) in eight children (5 boys and 3 girls) aged 5-13 years. Patients with a history of febrile convulsions were selected as the controls. Results One year of VPA treatment significantly impaired the statural growth of pediatric patients with epilepsy (p effect of VPA on the proliferation of growth plate chondrocytes rather than alterations of serum calcium. Conclusions These results raise serious concerns about the growth of pediatric epilepsy patients who use AEDs, and potentially the need to closely monitor growth in children with epilepsy and adolescents under AED treatment, especially VPA. PMID:24354857

  13. Impact of antiepileptic drugs on bone health: Need for monitoring, treatment, and prevention strategies

    Directory of Open Access Journals (Sweden)

    Ekta Arora

    2016-01-01

    Full Text Available Epilepsy is the most common neurological disorder affecting approximately 50 million people worldwide. In India, overall prevalence of epilepsy is reported to be 5.59/1000 population. Antiepileptic drugs (AEDs constitute the main-stay of treatment with a large number of AEDs available in the market. High incidence of adverse effects is a major limitation with AEDs. One of the major concerns is significant metabolic effects on the bone. However, little attention has been paid to this issue because most of the bone effects remain subclinical for a long time and may take years to manifest clinically. The main effects include hypocalcemia, hypophosphatemia, reduced serum levels of Vitamin D, increase in parathormone (PTH levels, and alterations in bone turnover markers. The CYP450 enzyme-inducing AEDs such as phenytoin, phenobarbital, carbamazepine, and primidone are the most common AEDs associated with bone disorders while the data regarding the effect of valproate and newer AEDs such as lamotrigine, gabapentin, vigabatrin, levetiracetam, and topiramate on bone metabolism and bone density are scanty and controversial. Deficiency of Vitamin D is commonly described as a cause for the bone loss in epileptic patients while others being decreased absorption of calcium, increased PTH levels, and inhibition of calcitonin secretion, etc. However, there are no formal practical guidelines for the management of bone disease among those taking AEDs. Evidence-based strategies regarding monitoring, prevention, and treatment of bone diseases in patients on AED therapy are needed.

  14. Candidiasis and the impact of flow cytometry on antifungal drug discovery.

    Science.gov (United States)

    Ku, Tsun Sheng N; Bernardo, Stella; Walraven, Carla J; Lee, Samuel A

    2017-11-01

    Invasive candidiasis continues to be associated with significant morbidity and mortality as well as substantial health care costs nationally and globally. One of the contributing factors is the development of resistance to antifungal agents that are already in clinical use. Moreover, there are known treatment limitations with all of the available antifungal agents. Since traditional techniques in novel drug discovery are time consuming, high-throughput screening using flow cytometry presents as a potential tool to identify new antifungal agents that would be useful in the management of these patients. Areas covered: In this review, the authors discuss the use of automated high-throughput screening assays based upon flow cytometry to identify potential antifungals from a library comprised of a large number of bioactive compounds. They also review studies that employed the use of this research methodology that has identified compounds with antifungal activity. Expert opinion: High-throughput screening using flow cytometry has substantially decreased the processing time necessary for screening thousands of compounds, and has helped enhance our understanding of fungal pathogenesis. Indeed, the authors see this technology as a powerful tool to help scientists identify new antifungal agents that can be added to the clinician's arsenal in their fight against invasive candidiasis.

  15. Impact of amyloid imaging on drug development in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Mathis, Chester A. [Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 (United States)], E-mail: mathisca@upmc.edu; Lopresti, Brian J. [Department of Radiology, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Klunk, William E. [Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213 (United States)

    2007-10-15

    Imaging agents capable of assessing amyloid-beta (A{beta}) content in vivo in the brains of Alzheimer's disease (AD) subjects likely will be important as diagnostic agents to detect A{beta} plaques in the brain as well as to help test the amyloid cascade hypothesis of AD and as an aid to assess the efficacy of anti-amyloid therapeutics currently under development and in clinical trials. Positron emission tomography (PET) imaging studies of amyloid deposition in human subjects with several A{beta} imaging agents are currently underway. We reported the first PET studies of the carbon 11-labeled thioflavin-T derivative Pittsburgh Compound B in 2004, and this work has subsequently been extended to include a variety of subject groups, including AD patients, mild cognitive impairment patients and healthy controls. The ability to quantify regional A{beta} plaque load in the brains of living human subjects has provided a means to begin to apply this technology as a diagnostic agent to detect regional concentrations of A{beta} plaques and as a surrogate marker of therapeutic efficacy in anti-amyloid drug trials.

  16. Potential impact of diet on treatment effect from anti-TNF drugs in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Andersen, Vibeke; Hansen, Axel Kornerup; Heitmann, Berit Lilienthal

    2017-01-01

    We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such invest......We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies...... for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had......% CI: 1.73–4.31, p diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic...

  17. The disposition of weapon grade plutonium: costs and tradeoffs

    International Nuclear Information System (INIS)

    Weida, W.J.

    1996-01-01

    This paper explores some of the economic issues surrounding a major area of expenditures now facing the nuclear powers: the disposition of weapon-grade plutonium either through 'burning' in nuclear reactors for power generation or by other means. Under the current budgeting philosophy in the United States, programs managed by the Department of Energy (DOE) tend to compete with one another for the total funds assigned to that agency. For example, in the FY1995 DOE budget a tradeoff was made between increased funding for nuclear weapons and reduced funding for site cleanup. No matter which disposition alternative is chosen, if disposition funds are controlled by the DOE in the US or by a government agency in any other country, disposition is likely to compete directly or indirectly with other alternatives for energy funding. And if they are subsidized by any government, research into plutonium as reactor fuel or the operations associated with such use are likely to consume funds that might otherwise be available to support sustainable energy alternatives. When all costs are considered, final waste disposal costs will be incurred whatever disposal option is taken. These costs could potentially be offset by doing something profitable with the plutonium prior to final storage, but this paper has shown that finding a profitable use for plutonium is unlikely. Thus, the more probable case is one where the costs of basic waste storage are increased by whatever costs are associated with the disposition option chosen. The factors most likely to significantly increase costs appear to arise from four areas: (1) The level of subsidization in the 'profitable' parts of the disposition program. (2) Those items (such as reprocessing) that increase the volume of waste and thus, the cost of waste disposal. (3) The cost of security and its direct relationship to the number of times plutonium is handled or moved. (4) The cost of research and development of new and unproven methods of

  18. Unallocated Off-Specification Highly Enriched Uranium: Recommendations for Disposition

    Energy Technology Data Exchange (ETDEWEB)

    Bridges, D. N.; Boeke, S. G.; Tousley, D. R.; Bickford, W.; Goergen, C.; Williams, W.; Hassler, M.; Nelson, T.; Keck, R.; Arbital, J.

    2002-02-27

    The U.S. Department of Energy (DOE) has made significant progress with regard to disposition planning for 174 metric tons (MTU) of surplus Highly Enriched Uranium (HEU). Approximately 55 MTU of this 174 MTU are ''offspec'' HEU. (''Off-spec'' signifies that the isotopic or chemical content of the material does not meet the American Society for Testing and Materials standards for commercial nuclear reactor fuel.) Approximately 33 of the 55 MTU have been allocated to off-spec commercial reactor fuel per an Interagency Agreement between DOE and the Tennessee Valley Authority (1). To determine disposition plans for the remaining {approx}22 MTU, the DOE National Nuclear Security Administration (NNSA) Office of Fissile Materials Disposition (OFMD) and the DOE Office of Environmental Management (EM) co-sponsored this technical study. This paper represents a synopsis of the formal technical report (NNSA/NN-0014). The {approx} 22 MTU of off-spec HEU inventory in this study were divided into two main groupings: one grouping with plutonium (Pu) contamination and one grouping without plutonium. This study identified and evaluated 26 potential paths for the disposition of this HEU using proven decision analysis tools. This selection process resulted in recommended and alternative disposition paths for each group of HEU. The evaluation and selection of these paths considered criteria such as technical maturity, programmatic issues, cost, schedule, and environment, safety and health compliance. The primary recommendations from the analysis are comprised of 7 different disposition paths. The study recommendations will serve as a technical basis for subsequent programmatic decisions as disposition of this HEU moves into the implementation phase.

  19. Dispositional contempt: A first look at the contemptuous person.

    Science.gov (United States)

    Schriber, Roberta A; Chung, Joanne M; Sorensen, Katherine S; Robins, Richard W

    2017-08-01

    Contempt is a powerful emotion. Marriages fail (Gottman, 1994), coworkers are shamed (Melwani & Barsade, 2011), terrorism is tended toward (Tausch et al., 2011). Despite its importance, contempt has not been investigated at the level of personality. The present research examines how our contemptuous reactions can be conceptualized and measured as a stable individual-difference variable with a range of theoretically predicted correlates. First, we introduce a measure of dispositional contempt , the tendency to look down on, distance, and derogate others who violate our standards. We then unpack the dynamics of dispositional contempt. Across 6 studies using self-report and emotion elicitation in student and MTurk samples (Ns = 165 to 1,368), we examined its (a) nomological network, (b) personality and behavioral correlates, and (c) implications for relationship functioning. Dispositional contempt was distinguished from tendencies toward related emotions and was most associated with dispositional envy, anger, and hubristic pride. Somewhat paradoxically, dispositional contempt was related to being cold and "superior," with associations found with narcissism, other-oriented perfectionism, and various antisocial tendencies (e.g., Disagreeableness, Machiavellianism, racism), but it was also related to being self-deprecating and emotionally fragile, with associations found with low self-esteem, insecure attachment, and feeling that others impose perfectionistic standards on oneself. Dispositional contempt predicted contemptuous reactions to eliciting film clips, particularly when targets showed low competence/power. Finally, perceiving one's romantic partner as dispositionally contemptuous was associated with lower commitment and satisfaction. Taken together, results give a first look at the contemptuous person and provide a new organizing framework for understanding contempt. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. SLIGHTLY IRRADIATED FUEL (SIF) INTERIM DISPOSITION PROJECT

    International Nuclear Information System (INIS)

    Norton, S.H.

    2010-01-01

    CH2M HILL Plateau Remediation Company (CH2M HILL PRC) is proud to submit the Slightly Irradiated Fuel (SIF) Interim Disposition Project for consideration by the Project Management Institute as Project of the Year for 2010. The SIF Project was a set of six interrelated sub-projects that delivered unique stand-alone outcomes, which, when integrated, provided a comprehensive and compliant system for storing high risk special nuclear materials. The scope of the six sub-projects included the design, construction, testing, and turnover of the facilities and equipment, which would provide safe, secure, and compliant Special Nuclear Material (SNM) storage capabilities for the SIF material. The project encompassed a broad range of activities, including the following: Five buildings/structures removed, relocated, or built; Two buildings renovated; Structural barriers, fencing, and heavy gates installed; New roadways and parking lots built; Multiple detection and assessment systems installed; New and expanded communication systems developed; Multimedia recording devices added; and A new control room to monitor all materials and systems built. Project challenges were numerous and included the following: An aggressive 17-month schedule to support the high-profile Plutonium Finishing Plant (PFP) decommissioning; Company/contractor changeovers that affected each and every project team member; Project requirements that continually evolved during design and construction due to the performance- and outcome-based nature ofthe security objectives; and Restrictions imposed on all communications due to the sensitive nature of the projects In spite of the significant challenges, the project was delivered on schedule and $2 million under budget, which became a special source of pride that bonded the team. For years, the SIF had been stored at the central Hanford PFP. Because of the weapons-grade piutonium produced and stored there, the PFP had some of the tightest security on the Hanford