WorldWideScience

Sample records for estimating drug effects

  1. The effect of qualifying language on perceptions of drug appeal, drug experience, and estimates of side-effect incidence in DTC advertising.

    Science.gov (United States)

    Davis, Joel

    2007-01-01

    This study examined how the use of qualifying language in direct-to-consumer (DTC) pharmaceutical advertising affects consumers' perceptions of drug appeal, anticipated pleasantness of drug usage, and the expected incidence of side-effect occurrence. A sample of 669 individuals participated in a 2 x 8 complete factorial design. The design manipulated the number of side effects associated with drug use and the type of qualifying language used to describe the side effects. The eight experimental qualifying language cells represented one control condition (no qualifying language), three cells where each of three types of qualifying language were presented individually, and four cells where qualifying language was combined. The results indicate that qualifying language has a profound effect on drug perceptions, especially when used in combination. Drug appeal and the anticipated drug-using experience almost always were more positive in the presence of qualifying language. Qualifying language appears to exert its influence by causing individuals to reduce their estimate of the likelihood of experiencing individual side effects. Policy implications of the research, particularly for evaluation of "fair balance" and the reporting of side effects, are presented.

  2. Estimating the Effect of Health Insurance on Personal Prescription Drug Importation.

    Science.gov (United States)

    Zullo, Andrew R; Howe, Chanelle J; Galárraga, Omar

    2017-04-01

    Personal prescription drug importation occurs in the United States because of the high cost of U.S. medicines and lower cost of foreign equivalents. Importation carries a risk of exposure to counterfeit (i.e., falsified, fraudulent), adulterated, and substandard drugs. Inadequate health insurance may increase the risk of importation. We use inverse probability weighted marginal structural models and data on 87,494 individuals from the 2011-2013 National Health Interview Survey to estimate the marginal association between no health insurance and importation within U.S. subpopulations. The marginal prevalence difference [95% confidence limits] for those without (prevalence = 0.031) versus those with health insurance was 0.016 [0.011, 0.021]. The prevalence difference was higher among persons who were Hispanic, born in Latin America, Russia, or Europe, traveled to developing countries, and did not use the Internet to fill prescriptions or to find health information. Health insurance coverage may effectively reduce importation, especially among particular subpopulations.

  3. Therapeutic Drug Monitoring of Second-Generation Antipsychotics for the Estimation of Early Drug Effect in First-Episode Psychosis: A Cross-sectional Assessment.

    Science.gov (United States)

    Bustillo, Mariana; Zabala, Arantzazu; Querejeta, Imanol; Carton, Jaione I; Mentxaka, Oiane; González-Pinto, Ana; García, Sainza; Meana, J Javier; Eguiluz, J Ignacio; Segarra, Rafael

    2018-04-01

    Studies on therapeutic drug monitoring (TDM) of second-generation antipsychotics (SGAs) have provided conflicting results regarding the association between dose, plasma concentrations, and drug effect and have focused rather on analyzing how individual drugs work. No study has attempted to process data from different SGAs globally to offer a panoramic view of the utility of TDM in clinical practice, and data on patients with first-episode psychosis (FEP) are lacking. This study aimed to assess the relationship between dose, plasma concentrations, and drug effect in a sample of patients with FEP, regardless of the SGA prescribed. Data from 64 compliant patients treated with the same SGA during a 2-month follow-up were recorded. Clinical symptoms were assessed using the Positive and Negative Symptoms Scale and the Montgomery-Åsberg Depression Rating Scale. Adverse effects were rated using the Udvalg für Kliniske Undersogelser scale. SGA doses were standardized to chlorpromazine equivalents, and patients were classified into 3 different ranges according to their plasma concentrations (subtherapeutic, therapeutic, and supratherapeutic). Plasma concentration ranges were proportionally related to dose. Patients with supratherapeutic plasma concentrations were treated with doses significantly higher than those with subtherapeutic concentrations. Dose and plasma concentrations were not associated with early drug effect. TDM seems unable to accurately estimate the early effects of SGAs in FEP. Ours is the first study to categorize plasma concentrations of SGAs into ranges for joint processing of data from a larger number of patients.

  4. Estimating the effect of current, previous and never use of drugs in studies based on prescription registries

    DEFF Research Database (Denmark)

    Nielsen, Lars Hougaard; Løkkegaard, Ellen; Andreasen, Anne Helms

    2009-01-01

    PURPOSE: Many studies which investigate the effect of drugs categorize the exposure variable into never, current, and previous use of the study drug. When prescription registries are used to make this categorization, the exposure variable possibly gets misclassified since the registries do not ca...

  5. The association between albuminuria and long-term renal risk : How to improve the precision of drug effect estimates

    NARCIS (Netherlands)

    Kröpelin, Tobias Felix

    2016-01-01

    The worldwide increase in the number of patients with diabetic kidney disease needs to be tackled due to the consequences of the disease. Improving the quality of life and survival of this growing number of patients requires timely access to novel and effective treatments. Timely access to novel

  6. Anticancer drugs in Portuguese surface waters - Estimation of concentrations and identification of potentially priority drugs.

    Science.gov (United States)

    Santos, Mónica S F; Franquet-Griell, Helena; Lacorte, Silvia; Madeira, Luis M; Alves, Arminda

    2017-10-01

    Anticancer drugs, used in chemotherapy, have emerged as new water contaminants due to their increasing consumption trends and poor elimination efficiency in conventional water treatment processes. As a result, anticancer drugs have been reported in surface and even drinking waters, posing the environment and human health at risk. However, the occurrence and distribution of anticancer drugs depend on the area studied and the hydrological dynamics, which determine the risk towards the environment. The main objective of the present study was to evaluate the risk of anticancer drugs in Portugal. This work includes an extensive analysis of the consumption trends of 171 anticancer drugs, sold or dispensed in Portugal between 2007 and 2015. The consumption data was processed aiming at the estimation of predicted environmental loads of anticancer drugs and 11 compounds were identified as potentially priority drugs based on an exposure-based approach (PEC b > 10 ng L -1 and/or PEC c > 1 ng L -1 ). In a national perspective, mycophenolic acid and mycophenolate mofetil are suspected to pose high risk to aquatic biota. Moderate and low risk was also associated to cyclophosphamide and bicalutamide exposition, respectively. Although no evidences of risk exist yet for the other anticancer drugs, concerns may be associated with long term effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Estimation of morbidity effects

    International Nuclear Information System (INIS)

    Ostro, B.

    1994-01-01

    Many researchers have related exposure to ambient air pollution to respiratory morbidity. To be included in this review and analysis, however, several criteria had to be met. First, a careful study design and a methodology that generated quantitative dose-response estimates were required. Therefore, there was a focus on time-series regression analyses relating daily incidence of morbidity to air pollution in a single city or metropolitan area. Studies that used weekly or monthly average concentrations or that involved particulate measurements in poorly characterized metropolitan areas (e.g., one monitor representing a large region) were not included in this review. Second, studies that minimized confounding ad omitted variables were included. For example, research that compared two cities or regions and characterized them as 'high' and 'low' pollution area were not included because of potential confounding by other factors in the respective areas. Third, concern for the effects of seasonality and weather had to be demonstrated. This could be accomplished by either stratifying and analyzing the data by season, by examining the independent effects of temperature and humidity, and/or by correcting the model for possible autocorrelation. A fourth criterion for study inclusion was that the study had to include a reasonably complete analysis of the data. Such analysis would include an careful exploration of the primary hypothesis as well as possible examination of te robustness and sensitivity of the results to alternative functional forms, specifications, and influential data points. When studies reported the results of these alternative analyses, the quantitative estimates that were judged as most representative of the overall findings were those that were summarized in this paper. Finally, for inclusion in the review of particulate matter, the study had to provide a measure of particle concentration that could be converted into PM10, particulate matter below 10

  8. Estimation of the cost-effectiveness of HIV prevention portfolios for people who inject drugs in the United States: A model-based analysis.

    Directory of Open Access Journals (Sweden)

    Cora L Bernard

    2017-05-01

    Full Text Available The risks of HIV transmission associated with the opioid epidemic make cost-effective programs for people who inject drugs (PWID a public health priority. Some of these programs have benefits beyond prevention of HIV-a critical consideration given that injection drug use is increasing across most United States demographic groups. To identify high-value HIV prevention program portfolios for US PWID, we consider combinations of four interventions with demonstrated efficacy: opioid agonist therapy (OAT, needle and syringe programs (NSPs, HIV testing and treatment (Test & Treat, and oral HIV pre-exposure prophylaxis (PrEP.We adapted an empirically calibrated dynamic compartmental model and used it to assess the discounted costs (in 2015 US dollars, health outcomes (HIV infections averted, change in HIV prevalence, and discounted quality-adjusted life years [QALYs], and incremental cost-effectiveness ratios (ICERs of the four prevention programs, considered singly and in combination over a 20-y time horizon. We obtained epidemiologic, economic, and health utility parameter estimates from the literature, previously published models, and expert opinion. We estimate that expansions of OAT, NSPs, and Test & Treat implemented singly up to 50% coverage levels can be cost-effective relative to the next highest coverage level (low, medium, and high at 40%, 45%, and 50%, respectively and that OAT, which we assume to have immediate and direct health benefits for the individual, has the potential to be the highest value investment, even under scenarios where it prevents fewer infections than other programs. Although a model-based analysis can provide only estimates of health outcomes, we project that, over 20 y, 50% coverage with OAT could avert up to 22,000 (95% CI: 5,200, 46,000 infections and cost US$18,000 (95% CI: US$14,000, US$24,000 per QALY gained, 50% NSP coverage could avert up to 35,000 (95% CI: 8,900, 43,000 infections and cost US$25,000 (95% CI: US

  9. Estimation of the cost-effectiveness of HIV prevention portfolios for people who inject drugs in the United States: A model-based analysis

    Science.gov (United States)

    Owens, Douglas K.; Goldhaber-Fiebert, Jeremy D.; Brandeau, Margaret L.

    2017-01-01

    Background The risks of HIV transmission associated with the opioid epidemic make cost-effective programs for people who inject drugs (PWID) a public health priority. Some of these programs have benefits beyond prevention of HIV—a critical consideration given that injection drug use is increasing across most United States demographic groups. To identify high-value HIV prevention program portfolios for US PWID, we consider combinations of four interventions with demonstrated efficacy: opioid agonist therapy (OAT), needle and syringe programs (NSPs), HIV testing and treatment (Test & Treat), and oral HIV pre-exposure prophylaxis (PrEP). Methods and findings We adapted an empirically calibrated dynamic compartmental model and used it to assess the discounted costs (in 2015 US dollars), health outcomes (HIV infections averted, change in HIV prevalence, and discounted quality-adjusted life years [QALYs]), and incremental cost-effectiveness ratios (ICERs) of the four prevention programs, considered singly and in combination over a 20-y time horizon. We obtained epidemiologic, economic, and health utility parameter estimates from the literature, previously published models, and expert opinion. We estimate that expansions of OAT, NSPs, and Test & Treat implemented singly up to 50% coverage levels can be cost-effective relative to the next highest coverage level (low, medium, and high at 40%, 45%, and 50%, respectively) and that OAT, which we assume to have immediate and direct health benefits for the individual, has the potential to be the highest value investment, even under scenarios where it prevents fewer infections than other programs. Although a model-based analysis can provide only estimates of health outcomes, we project that, over 20 y, 50% coverage with OAT could avert up to 22,000 (95% CI: 5,200, 46,000) infections and cost US$18,000 (95% CI: US$14,000, US$24,000) per QALY gained, 50% NSP coverage could avert up to 35,000 (95% CI: 8,900, 43,000) infections and

  10. Estimation of the cost-effectiveness of HIV prevention portfolios for people who inject drugs in the United States: A model-based analysis.

    Science.gov (United States)

    Bernard, Cora L; Owens, Douglas K; Goldhaber-Fiebert, Jeremy D; Brandeau, Margaret L

    2017-05-01

    The risks of HIV transmission associated with the opioid epidemic make cost-effective programs for people who inject drugs (PWID) a public health priority. Some of these programs have benefits beyond prevention of HIV-a critical consideration given that injection drug use is increasing across most United States demographic groups. To identify high-value HIV prevention program portfolios for US PWID, we consider combinations of four interventions with demonstrated efficacy: opioid agonist therapy (OAT), needle and syringe programs (NSPs), HIV testing and treatment (Test & Treat), and oral HIV pre-exposure prophylaxis (PrEP). We adapted an empirically calibrated dynamic compartmental model and used it to assess the discounted costs (in 2015 US dollars), health outcomes (HIV infections averted, change in HIV prevalence, and discounted quality-adjusted life years [QALYs]), and incremental cost-effectiveness ratios (ICERs) of the four prevention programs, considered singly and in combination over a 20-y time horizon. We obtained epidemiologic, economic, and health utility parameter estimates from the literature, previously published models, and expert opinion. We estimate that expansions of OAT, NSPs, and Test & Treat implemented singly up to 50% coverage levels can be cost-effective relative to the next highest coverage level (low, medium, and high at 40%, 45%, and 50%, respectively) and that OAT, which we assume to have immediate and direct health benefits for the individual, has the potential to be the highest value investment, even under scenarios where it prevents fewer infections than other programs. Although a model-based analysis can provide only estimates of health outcomes, we project that, over 20 y, 50% coverage with OAT could avert up to 22,000 (95% CI: 5,200, 46,000) infections and cost US$18,000 (95% CI: US$14,000, US$24,000) per QALY gained, 50% NSP coverage could avert up to 35,000 (95% CI: 8,900, 43,000) infections and cost US$25,000 (95% CI: US$7

  11. Illicit and pharmaceutical drug consumption estimated via wastewater analysis. Part A: chemical analysis and drug use estimates.

    Science.gov (United States)

    Baker, David R; Barron, Leon; Kasprzyk-Hordern, Barbara

    2014-07-15

    This paper presents, for the first time, community-wide estimation of drug and pharmaceuticals consumption in England using wastewater analysis and a large number of compounds. Among groups of compounds studied were: stimulants, hallucinogens and their metabolites, opioids, morphine derivatives, benzodiazepines, antidepressants and others. Obtained results showed the usefulness of wastewater analysis in order to provide estimates of local community drug consumption. It is noticeable that where target compounds could be compared to NHS prescription statistics, good comparisons were apparent between the two sets of data. These compounds include oxycodone, dihydrocodeine, methadone, tramadol, temazepam and diazepam. Whereas, discrepancies were observed for propoxyphene, codeine, dosulepin and venlafaxine (over-estimations in each case except codeine). Potential reasons for discrepancies include: sales of drugs sold without prescription and not included within NHS data, abuse of a drug with the compound trafficked through illegal sources, different consumption patterns in different areas, direct disposal leading to over estimations when using parent compound as the drug target residue and excretion factors not being representative of the local community. It is noticeable that using a metabolite (and not a parent drug) as a biomarker leads to higher certainty of obtained estimates. With regard to illicit drugs, consistent and logical results were reported. Monitoring of these compounds over a one week period highlighted the expected recreational use of many of these drugs (e.g. cocaine and MDMA) and the more consistent use of others (e.g. methadone). Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Illicit and pharmaceutical drug consumption estimated via wastewater analysis. Part A:chemical analysis and drug use estimates

    OpenAIRE

    Baker, David R.; Barron, Leon; Kasprzyk-Hordern, Barbara

    2014-01-01

    This paper presents, for the first time, community-wide estimation of drug and pharmaceuticals consumption in England using wastewater analysis and a large number of compounds. Among groups of compounds studied were: stimulants, hallucinogens and their metabolites, opioids, morphine derivatives, benzodiazepines, antidepressants and others. Obtained results showed the usefulness of wastewater analysis in order to provide estimates of local community drug consumption. It is noticeable that wher...

  13. Influence of drug colour on perceived drug effects and efficacy.

    Science.gov (United States)

    Tao, Da; Wang, Tieyan; Wang, Tieshan; Qu, Xingda

    2018-02-01

    A drug's physical characteristics, such as colour, could be factors influencing its therapeutic effects. It is not well understood whether people's expectations on drug effects and efficacy are affected by colour, especially among Chinese population. This study was conducted to examine people's expectations on drug effects and efficacy on the basis of drug colour, and to reveal possible gender differences in colour-related drug expectations. Participants (n = 224) were asked to classify seven single-coloured and six two-coloured capsules into one of four categories of drug effects, and to indicate the strength of drug efficacy. It is found that all the coloured capsules yielded non-chance distributions in classifications of drug effects, with six single-coloured and four two-coloured capsules associated with specific drug effects. Colour also conveyed differential strengths of drug efficacy in general and in relation to specific drug effects. There were gender differences in drug expectations for some colours and colour combinations. Practitioner Summary: Drug colour was found to have impacts on perceived drug effects and efficacy. The findings from the present study can be used by ergonomics practitioners to design appropriate drug colours in support of drug differentiation, therapeutic effects and medication adherence.

  14. Revisiting the circulation time of Plasmodium falciparum gametocytes: molecular detection methods to estimate the duration of gametocyte carriage and the effect of gametocytocidal drugs

    Directory of Open Access Journals (Sweden)

    Sawa Patrick

    2010-05-01

    Full Text Available Abstract Background There is renewed acknowledgement that targeting gametocytes is essential for malaria control and elimination efforts. Simple mathematical models were fitted to data from clinical trials in order to determine the mean gametocyte circulation time and duration of gametocyte carriage in treated malaria patients. Methods Data were used from clinical trials from East Africa. The first trial compared non-artemisinin combination therapy (non-ACT: sulphadoxine-pyrimethamine (SP plus amodiaquine and artemisinin-based combination therapy (ACT: SP plus artesunate (AS or artemether-lumefantrine. The second trial compared ACT (SP+AS with ACT in combination with a single dose of primaquine (ACT-PQ: SP+AS+PQ. Mature gametocytes were quantified in peripheral blood samples by nucleic acid sequence based amplification. A simple deterministic compartmental model was fitted to gametocyte densities to estimate the circulation time per gametocyte; a similar model was fitted to gametocyte prevalences to estimate the duration of gametocyte carriage after efficacious treatment. Results The mean circulation time of gametocytes was 4.6-6.5 days. After non-ACT treatment, patients were estimated to carry gametocytes for an average of 55 days (95% CI 28.7 - 107.7. ACT reduced the duration of gametocyte carriage fourfold to 13.4 days (95% CI 10.2-17.5. Addition of PQ to ACT resulted in a further fourfold reduction of the duration of gametocyte carriage. Conclusions These findings confirm previous estimates of the circulation time of gametocytes, but indicate a much longer duration of (low density gametocyte carriage after apparently successful clearance of asexual parasites. ACT shortened the period of gametocyte carriage considerably, and had the most pronounced effect on mature gametocytes when combined with PQ.

  15. Illicit drugs in Canadian municipal wastewater and estimates of community drug use

    Energy Technology Data Exchange (ETDEWEB)

    Metcalfe, Chris, E-mail: cmetcalfe@trentu.c [Worsfold Water Quality Centre, Trent University, 1600 West Bank Drive Peterborough, ON, K9J 7B8 (Canada); Tindale, Kathryn [Worsfold Water Quality Centre, Trent University, 1600 West Bank Drive Peterborough, ON, K9J 7B8 (Canada); Li, Hongxia, E-mail: lihongxia@trentu.c [Worsfold Water Quality Centre, Trent University, 1600 West Bank Drive Peterborough, ON, K9J 7B8 (Canada); Rodayan, Angela [Department of Chemical Engineering, McGill University, 3610 University St., Montreal, QC, H3A 2B2 (Canada); Yargeau, Viviane, E-mail: viviane.yargeau@mcgill.c [Department of Chemical Engineering, McGill University, 3610 University St., Montreal, QC, H3A 2B2 (Canada)

    2010-10-15

    In this study of wastewater treatment plants in three Canadian cities, selected illicit drugs, including cocaine and its major metabolite, benzoylecgonine (BE), amphetamine, methamphetamine and ecstasy (i.e. MDMA) were detected in untreated wastewater. Cocaine was the most widely used illicit drug at a median level for the 3 cities of 15.7 doses per day per 1000 people. For the other drugs, the median doses per day per 1000 people were 1.8 for amphetamine, 4.5 for methamphetamine and 0.4 for ecstasy. Methamphetamine use was highest in the largest city and cocaine use was lowest in the smallest city. Removal of the illicit drugs by wastewater treatment was generally >50%, except in a WWTP that uses primary treatment. The community consumption estimate for ecstasy in the present study is far below published estimates of the prevalence of ecstasy use among the Canadian population, which may be due to only occasional use of ecstasy. - Cocaine and amphetamines were detected in untreated and treated sewage in the wastewater treatment plants of three Canadian cities, and community consumption patterns estimated from the concentrations of the drugs in untreated wastewater were consistent with estimates of the use of illicit drugs in Canada.

  16. Illicit drugs in Canadian municipal wastewater and estimates of community drug use

    International Nuclear Information System (INIS)

    Metcalfe, Chris; Tindale, Kathryn; Li, Hongxia; Rodayan, Angela; Yargeau, Viviane

    2010-01-01

    In this study of wastewater treatment plants in three Canadian cities, selected illicit drugs, including cocaine and its major metabolite, benzoylecgonine (BE), amphetamine, methamphetamine and ecstasy (i.e. MDMA) were detected in untreated wastewater. Cocaine was the most widely used illicit drug at a median level for the 3 cities of 15.7 doses per day per 1000 people. For the other drugs, the median doses per day per 1000 people were 1.8 for amphetamine, 4.5 for methamphetamine and 0.4 for ecstasy. Methamphetamine use was highest in the largest city and cocaine use was lowest in the smallest city. Removal of the illicit drugs by wastewater treatment was generally >50%, except in a WWTP that uses primary treatment. The community consumption estimate for ecstasy in the present study is far below published estimates of the prevalence of ecstasy use among the Canadian population, which may be due to only occasional use of ecstasy. - Cocaine and amphetamines were detected in untreated and treated sewage in the wastewater treatment plants of three Canadian cities, and community consumption patterns estimated from the concentrations of the drugs in untreated wastewater were consistent with estimates of the use of illicit drugs in Canada.

  17. Systematic review of guidelines in estimating social costs on drugs.

    Science.gov (United States)

    Alberto Vella, Vincenzo; García-Altes, Anna; Segura García, Lidia; Ibáñez Martínez, Nuria; Colom Farran, Joan

    2017-12-16

    To systematically review guidance documents for the estimation of the social cost of illegal drugs, and to define standards for this estimation. A systematic literature search was conducted between April and May 2015 and updated in November 2015. Pubmed, Scopus, and Google Scholar were searched. Studies were included only if they provided indications of analytical methods for calculating the social cost of illegal drugs consumption. A total of 21 papers were selected for a final review. Four main areas of discussion were identified: a) alternative theories for the framework design; b) basic concepts definition; c) theoretical issues in the application of the framework and; d) definition of the cost matrix and its elements. The review exercise enabled the definition of two analytical approaches, which are proposed as references for estimation in the field. although social cost is a well-established method in the literature, there is a lack of agreement on the most appropriate approaches in the area of estimation of the social cost of illegal drugs consumption. Moreover, the two analytical approaches proposed are aimed at promoting more research focused at sophisticating the methodology in the field. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Drug effects on melanoma

    NARCIS (Netherlands)

    Koomen, Elsje Rosalie

    2010-01-01

    Cutaneous melanoma is the most aggressive form of skin cancer and its incidence among Caucasian populations has increased whereas mortality rates are stabilizing or decreasing. The total burden of melanoma is expected to be increasing. As effective treatment options for advanced melanoma are

  19. Comparing Methods for Estimating Direct Costs of Adverse Drug Events.

    Science.gov (United States)

    Gyllensten, Hanna; Jönsson, Anna K; Hakkarainen, Katja M; Svensson, Staffan; Hägg, Staffan; Rehnberg, Clas

    2017-12-01

    To estimate how direct health care costs resulting from adverse drug events (ADEs) and cost distribution are affected by methodological decisions regarding identification of ADEs, assigning relevant resource use to ADEs, and estimating costs for the assigned resources. ADEs were identified from medical records and diagnostic codes for a random sample of 4970 Swedish adults during a 3-month study period in 2008 and were assessed for causality. Results were compared for five cost evaluation methods, including different methods for identifying ADEs, assigning resource use to ADEs, and for estimating costs for the assigned resources (resource use method, proportion of registered cost method, unit cost method, diagnostic code method, and main diagnosis method). Different levels of causality for ADEs and ADEs' contribution to health care resource use were considered. Using the five methods, the maximum estimated overall direct health care costs resulting from ADEs ranged from Sk10,000 (Sk = Swedish krona; ~€1,500 in 2016 values) using the diagnostic code method to more than Sk3,000,000 (~€414,000) using the unit cost method in our study population. The most conservative definitions for ADEs' contribution to health care resource use and the causality of ADEs resulted in average costs per patient ranging from Sk0 using the diagnostic code method to Sk4066 (~€500) using the unit cost method. The estimated costs resulting from ADEs varied considerably depending on the methodological choices. The results indicate that costs for ADEs need to be identified through medical record review and by using detailed unit cost data. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  20. Estimating incidence of problem drug use using the Horwitz-Thompson estimator - A new approach applied to people who inject drugs in Oslo 1985-2008.

    Science.gov (United States)

    Amundsen, Ellen J; Bretteville-Jensen, Anne L; Kraus, Ludwig

    2016-01-01

    The trend in the number of new problem drug users per year (incidence) is the most important measure for studying the diffusion of problem drug use. Due to sparse data sources and complicated statistical models, estimation of incidence of problem drug use is challenging. The aim of this study is to widen the palette of available methods and data types for estimating incidence of problem drug use over time, and for identifying the trends. This study presents a new method of incidence estimation, applied to people who inject drugs (PWID) in Oslo. The method took into account the transition between different phases of drug use progression - active use, temporary cessation, and permanent cessation. The Horwitz-Thompson estimator was applied. Data included 16 cross-sectional samples of problem drug users who reported their onset of injecting drug use. We explored variation in results for selected probable scenarios of parameter variation for disease progression, as well as the stability of the results based on fewer years of cross-sectional samples. The method yielded incidence estimates of problem drug use, over time. When applied to people in Oslo who inject drugs, we found a significant reduction of incidence of 63% from 1985 to 2008. This downward trend was also present when the estimates were based on fewer surveys (five) and in the results of sensitivity analysis for likely scenarios of disease progression. This new method, which incorporates temporarily inactive problem drug users, may become a useful tool for estimating the incidence of problem drug use over time. The method may be less data intensive than other methods based on first entry to treatment and may be generalized to other groups of substance users. Further studies on drug use progression would improve the validity of the results. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Drug use and AIDS: estimating injection prevalence in a rural state.

    Science.gov (United States)

    Leukefeld, Carl G; Logan, T K; Farabee, David; Clayton, Richard

    2002-01-01

    This paper presents approaches used in one rural U.S. state to describe the level of injecting drug use and to estimate the number of injectors not receiving drug-user treatment. The focus is on two broad areas of estimation that were used to present the prevalence of injecting drug use in Kentucky. The first estimation approach uses available data from secondary data sources. The second approach involves three small community studies.

  2. Estimating maternal genetic effects in livestock

    NARCIS (Netherlands)

    Bijma, P.

    2006-01-01

    This study investigates the estimation of direct and maternal genetic (co)variances, accounting for environmental covariances between direct and maternal effects. Estimated genetic correlations between direct and maternal effects presented in the literature have often been strongly negative, and

  3. Interaction Effects of Students, Drugs and Alienation

    Science.gov (United States)

    Jones, Woodrow, Jr.

    1977-01-01

    This study examined the interaction effect of students, drugs, and alienation in a large university, i.e., the linkages of both social and political alienation with drug behavior. The interaction terms which composed these forms of alienation were evaluated as to their comparative ability to produce drug behavior. (Author)

  4. Radiopharmaceuticals: introduction to drug evaluation and dose estimation

    National Research Council Canada - National Science Library

    Williams, Lawrence E

    2011-01-01

    ...), absorbed dose method for imaging agents, vivo methods for obtaining activity data, errors of activity estimation techniques, phantom-based and patient-based dose estimates and their associated...

  5. EFFECTIVE TOOL WEAR ESTIMATION THROUGH ...

    African Journals Online (AJOL)

    Though a number of researchers have used MLP for fusing the information and estimating the tool status, enough literatures are not available to state the influence of neural network parameters which may affect the accurate estimation of the tool status. This point also has been emphasized in [4], where the authors stated ...

  6. Anticipating drug side effects by comparative pharmacology.

    Science.gov (United States)

    Garcia-Serna, Ricard; Mestres, Jordi

    2010-10-01

    Anticipating the likely side effect profile of drugs is an aspect of key importance in current drug discovery, development and marketing. It was recently shown that drug pairs having similar side effect profiles had also affinity for a common target. Acknowledging that most drugs have a rich polypharmacology, we provide proof that drugs related by side effect similarity have in fact affinities for multiple common targets beyond their primary targets and set the basis for the use of comparative pharmacology to anticipate drug side effects. Nomenclature issues to be able to identify and properly store drugs, targets and side effects from multiple public sources; the construction of drug networks from side effect similarity and the inference of common targets among them; polypharmacology and data completeness; methods for in silico target profiling; and comparative pharmacology and inference of common side effects. The reader is provided with a detailed step-by-step analysis of the entire process from predicting the target profile of a compound to anticipating its side effect profile, and a discussion on the particular needs and limitations found at each stage of the process through illustrative examples. Comparing preclinical pharmacology data obtained in vitro but also predicted in silico using modern virtual screening methods represents an attractive strategy to anticipate clinical drug side effects.

  7. Estimation of the prevalence of adverse drug reactions from social media.

    Science.gov (United States)

    Nguyen, Thin; Larsen, Mark E; O'Dea, Bridianne; Phung, Dinh; Venkatesh, Svetha; Christensen, Helen

    2017-06-01

    This work aims to estimate the degree of adverse drug reactions (ADR) for psychiatric medications from social media, including Twitter, Reddit, and LiveJournal. Advances in lightning-fast cluster computing was employed to process large scale data, consisting of 6.4 terabytes of data containing 3.8 billion records from all the media. Rates of ADR were quantified using the SIDER database of drugs and side-effects, and an estimated ADR rate was based on the prevalence of discussion in the social media corpora. Agreement between these measures for a sample of ten popular psychiatric drugs was evaluated using the Pearson correlation coefficient, r, with values between 0.08 and 0.50. Word2vec, a novel neural learning framework, was utilized to improve the coverage of variants of ADR terms in the unstructured text by identifying syntactically or semantically similar terms. Improved correlation coefficients, between 0.29 and 0.59, demonstrates the capability of advanced techniques in machine learning to aid in the discovery of meaningful patterns from medical data, and social media data, at scale. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Estimation of Intravenous Drug Users' Population in Kermanshah City, West of Iran in 2016 using Capture-recapture Method.

    Science.gov (United States)

    Azhdar, Forod; Esmaeilnasab, Nader; Moradi, Ghobad; Roshani, Daem; Ghaderi, Ebrahim; Nori, Bijan

    2017-08-07

    Drug abuse, particularly intravenous drug use, is one of the most common challenges in human communities so that its negative impact on economic and cultural conditions of society and physical as well as mental health of individuals is evident. We aimed to estimate the IDUs' population in Kermanshah City, West of Iran using Capture-recapture method. A Cross-sectional study. The data in this study were collected from three different sources: Drop in Centers (DICs), Out Reach Teams (ORTs) and Methadone Maintenance Treatment centers (MMTs) in Kermanshah City from Mar 2015 until Mar 2016, and then indirect Capture-recapture was used to estimate the IDUs' population. The number of IDUs registered in DICs, ORTs, and MMTs were 694, 731, and 156 cases, respectively. Having determined the commonalities and removing duplicates, the number of drug users registered were 1,375 cases, after analysis of data, the number of drug users not registered in any center was estimated as 2,042 (95% CI: 1708, 2444). By counting 1,375 cases recorded in these sources, the total number of injection drug users in the Kermanshah City was about 3,417 people, (95% CI: (3083, 3819). The prevalence of IDUs in Kermanshah City is high, which could cause severe economic and social problems in the society. To reduce the negative effects of drug use, awareness and measuring of the drug users population, seem to be necessary overtime.

  9. The lung effects of illicit drugs

    OpenAIRE

    Crista Laslo; Beatrice G. Ioan; Ovidiu G. Bratu; Bogdan Socea; Camelia Diaconu

    2018-01-01

    Illicit drugs use is a real public health issue, especially among young people. The totality of the drugs harmful effects on the body is difficult to quantify, especially because of poor epidemiological data and ethical concerns about the inclusion of consumers in clinical trials. However, health professionals need to be alert to identify, report and fight drug-related pathology. This article aims to draw attention to the lung pathology induced by the consumption of some of the most commonly ...

  10. Sexual side effects induced by psychotropic drugs

    DEFF Research Database (Denmark)

    Kristensen, Ellids

    2002-01-01

    The majority of psychotropic drugs entail sexual side effects. The sexual side effects may reduce quality of life and may give rise to non-compliance. For example, 30-60 per cent of patients treated with antidepressants are known to develop a sexual dysfunction. However, some psychotropic drugs...... with no or very few sexual side effects have begun to emerge. The treatment of sexual side effects induced by psychotropic drugs may consist of: modified sexual habits, reduction in dosage, switching to another medication, possibly in combination with different psychotropic agents, other varieties...

  11. The lung effects of illicit drugs

    Directory of Open Access Journals (Sweden)

    Crista Laslo

    2018-04-01

    Full Text Available Illicit drugs use is a real public health issue, especially among young people. The totality of the drugs harmful effects on the body is difficult to quantify, especially because of poor epidemiological data and ethical concerns about the inclusion of consumers in clinical trials. However, health professionals need to be alert to identify, report and fight drug-related pathology. This article aims to draw attention to the lung pathology induced by the consumption of some of the most commonly used illicit drugs: cocaine, heroin and cannabis.

  12. Analysis of drug prohibition and estimation of budgetary implications of marijuana legalization

    OpenAIRE

    Flegr, Jan

    2009-01-01

    This paper examines the impact of drug prohibition on society. It analyzes starting-points and aims of prohibition and shows, how prohibition attempts to achieve its goals. Furthermore, it explores social costs of prohibition, mainly the impact on potencial health risks of drug use and property and violent crimes. Then it presents main reasons of failure to achieve its goals. Furthemore, this paper estimates probable budgetary implications of marijuana legalization. This estimate is based on ...

  13. Unifying Theories of Psychedelic Drug Effects

    Science.gov (United States)

    Swanson, Link R.

    2018-01-01

    How do psychedelic drugs produce their characteristic range of acute effects in perception, emotion, cognition, and sense of self? How do these effects relate to the clinical efficacy of psychedelic-assisted therapies? Efforts to understand psychedelic phenomena date back more than a century in Western science. In this article I review theories of psychedelic drug effects and highlight key concepts which have endured over the last 125 years of psychedelic science. First, I describe the subjective phenomenology of acute psychedelic effects using the best available data. Next, I review late 19th-century and early 20th-century theories—model psychoses theory, filtration theory, and psychoanalytic theory—and highlight their shared features. I then briefly review recent findings on the neuropharmacology and neurophysiology of psychedelic drugs in humans. Finally, I describe recent theories of psychedelic drug effects which leverage 21st-century cognitive neuroscience frameworks—entropic brain theory, integrated information theory, and predictive processing—and point out key shared features that link back to earlier theories. I identify an abstract principle which cuts across many theories past and present: psychedelic drugs perturb universal brain processes that normally serve to constrain neural systems central to perception, emotion, cognition, and sense of self. I conclude that making an explicit effort to investigate the principles and mechanisms of psychedelic drug effects is a uniquely powerful way to iteratively develop and test unifying theories of brain function. PMID:29568270

  14. Illicit drugs in wastewater of the city of Zagreb (Croatia) - Estimation of drug abuse in a transition country

    International Nuclear Information System (INIS)

    Terzic, Senka; Senta, Ivan; Ahel, Marijan

    2010-01-01

    A comprehensive study of various psychoactive substances and their metabolites was performed in the wastewater treatment plant of the city of Zagreb (780 000 inhabitants) using liquid chromatography/tandem mass spectrometry (LC-MS-MS). The estimation of drug abuse for five different illicit drugs, including heroin, cocaine, marijuana, amphetamine and ecstasy, was made on the basis of their representative excretion rates, which were determined over a period of 8 months. Marijuana (1000 kg/year), heroin (75 kg/year) and cocaine (47 kg/year) were found to be the most frequently consumed illicit drugs, while the consumption of amphetamine-type drugs was much lower (1-3 kg/year). A comparison with other reports indicated that drug abuse profiles in transition countries might be different from those reported for Western Europe, in particular with respect to the comparatively increased consumption of heroin. Enhanced consumption of stimulating drugs (cocaine and ectasy) was systematically detected during weekends. - Wastewater analysis is a promising complementary tool to assess drug abuse patterns.

  15. Illicit drugs in wastewater of the city of Zagreb (Croatia) - Estimation of drug abuse in a transition country

    Energy Technology Data Exchange (ETDEWEB)

    Terzic, Senka, E-mail: terzic@irb.h [Division for Marine and Environmental Research, Rudjer Boskovic Institute, Bijenicka 54, 10000 Zagreb (Croatia); Senta, Ivan; Ahel, Marijan [Division for Marine and Environmental Research, Rudjer Boskovic Institute, Bijenicka 54, 10000 Zagreb (Croatia)

    2010-08-15

    A comprehensive study of various psychoactive substances and their metabolites was performed in the wastewater treatment plant of the city of Zagreb (780 000 inhabitants) using liquid chromatography/tandem mass spectrometry (LC-MS-MS). The estimation of drug abuse for five different illicit drugs, including heroin, cocaine, marijuana, amphetamine and ecstasy, was made on the basis of their representative excretion rates, which were determined over a period of 8 months. Marijuana (1000 kg/year), heroin (75 kg/year) and cocaine (47 kg/year) were found to be the most frequently consumed illicit drugs, while the consumption of amphetamine-type drugs was much lower (1-3 kg/year). A comparison with other reports indicated that drug abuse profiles in transition countries might be different from those reported for Western Europe, in particular with respect to the comparatively increased consumption of heroin. Enhanced consumption of stimulating drugs (cocaine and ectasy) was systematically detected during weekends. - Wastewater analysis is a promising complementary tool to assess drug abuse patterns.

  16. A statistical analysis of the deterrence effects of the Military Services' Drug testing policies

    OpenAIRE

    Martinez, Antonio.

    1998-01-01

    This thesis examines themagnitude of the deterrence effect associated with the militaryservices' drug testing policies. Using data from the 1995Department of Defense Survey of Health Related Behaviors Among Military Personnel and the 1995 National Household Survey on Drug Abuse, illicit drug use rates are modeled as a function of pertinent demographic characteristics. The naturalvariation in drug testing policies is exploited to estimate the deterrence effects of suchprograms. The first analy...

  17. The undesirable effects of neuromuscular blocking drugs

    DEFF Research Database (Denmark)

    Claudius, C; Garvey, L H; Viby-Mogensen, J

    2009-01-01

    Neuromuscular blocking drugs are designed to bind to the nicotinic receptor at the neuromuscular junction. However, they also interact with other acetylcholine receptors in the body. Binding to these receptors causes adverse effects that vary with the specificity for the cholinergic receptor...... in question. Moreover, all neuromuscular blocking drugs may cause hypersensitivity reactions. Often the symptoms are mild and self-limiting but massive histamine release can cause systematic reactions with circulatory and respiratory symptoms and signs. At the end of anaesthesia, no residual effect...... of a neuromuscular blocking drug should be present. However, the huge variability in response to neuromuscular blocking drugs makes it impossible to predict which patient will suffer postoperative residual curarization. This article discusses the undesirable effects of the currently available neuromuscular blocking...

  18. Estimating the market for tuberculosis drugs in industrialized and developing nations.

    Science.gov (United States)

    Schwalbe, N R; Wells, W A; Geaneotes, A P; Forcellina, A; Lee, M G; Dicola, L; Ignatius, H R; Walker, C L; Raafat, T; Patel, N

    2008-10-01

    The successful introduction of new drugs into low- and middle-income countries requires an understanding of the existing market size and market dynamics for the therapeutic area of interest. The drug markets in these countries are, however, less well understood than those in high-income countries. The global market for tuberculosis (TB) drugs was estimated by studying in detail six high-burden countries and four high-income countries, followed by extrapolation. Data were derived from existing pharmaceutical audit databases and interviews with government officials, medical staff and suppliers. The use of qualitative inputs to inform the collection of quantitative information, notably to identify where the major flows of TB drugs are located, allowed a confident estimate of the global market for first-line TB drugs. Final ranges were US$261-316 million or US$310-418 million, depending on whether case notification rates or incidence were used for extrapolations. An estimation of the global TB drug market is made more reliable by a qualitative understanding of TB drug distribution pathways, which differ greatly among countries. The understanding of this structure in key high-burden countries provides the basis for a simpler update of the market estimate in the future.

  19. Estimating prevalence of accumulated HIV-1 drug resistance in a cohort of patients on antiretroviral therapy

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Cozzi-Lepri, Alessandro; Kjær, Jesper

    2011-01-01

    Estimating the prevalence of accumulated HIV drug resistance in patients receiving antiretroviral therapy (ART) is difficult due to lack of resistance testing at all occasions of virological failure and in patients with undetectable viral load. A method to estimate this for 6498 EuroSIDA patients...

  20. Non-sedating antihistamine drugs and cardiac arrhythmias : biased risk estimates from spontaneous reporting systems?

    NARCIS (Netherlands)

    De Bruin, M L; van Puijenbroek, E P; Egberts, A C G; Hoes, A W; Leufkens, H G M

    AIMS: This study used spontaneous reports of adverse events to estimate the risk for developing cardiac arrhythmias due to the systemic use of non-sedating antihistamine drugs and compared the risk estimate before and after the regulatory action to recall the over-the-counter status of some of these

  1. Drug Dosing and Estimated Renal Function-Any Step Forward from Effersoe?

    DEFF Research Database (Denmark)

    Hornum, Mads; Feldt-Rasmussen, Bo

    2017-01-01

    . Despite serious limitations, there has also been a tendency to use estimated GFR (eGFR) as a "hard" clinical endpoint in clinical studies. This has increased the risk of misinterpretation and has led to conclusions that are not necessarily supported by data. Finally, new methods of testing drug toxicity......Drug dosing in accordance with the renal function is a long-standing challenge to clinicians. For many years it has been evident that in many clinical situations there is no easy way to correctly dose any drug that is mainly cleared by the kidneys. Despite the development of many formulas...... for estimating the glomerular filtration rate, they all have serious shortcomings. Much effort has been put in to develop estimation formulas to evaluate the renal function as an alternative to direct methods with the aim of safely dosing drugs that are mainly cleared by the kidneys. Both creatinine- A nd...

  2. The effect of activated charcoal on drug exposure in healthy volunteers: a meta-analysis

    DEFF Research Database (Denmark)

    Jürgens, G; Hoegberg, L C Groth; Graudal, N A

    2009-01-01

    The objective of the study was to estimate the effect of activated charcoal (AC) administered during the first 6 h after drug intake and the effect of drug properties on drug exposure. Sixty-four controlled studies were integrated in a meta-analysis. AC administered 0-5 min after administration...... of a drug reduced median drug exposure by 88.4% (25-75 percentile: 65.0-96.8) (P drug intake (median reduction in drug exposure 27.4% (range 21.3-31.5%, P = 0.0006). The reduction in drug exposure...... was correlated with the AC/drug ratio (rho = 0.69, P drug ingestion but has statistically significant effects even when given...

  3. Non-sedating antihistamine drugs and cardiac arrhythmias -- biased risk estimates from spontaneous reporting systems?

    DEFF Research Database (Denmark)

    De Bruin, M L; van Puijenbroek, E P; Egberts, A C G

    2002-01-01

    AIMS: This study used spontaneous reports of adverse events to estimate the risk for developing cardiac arrhythmias due to the systemic use of non-sedating antihistamine drugs and compared the risk estimate before and after the regulatory action to recall the over-the-counter status of some...... of these drugs. METHODS: All suspected adverse drug reactions (ADRs) reported until July 1999 to the Netherlands Pharmacovigilance Foundation Lareb were used to calculate the ADR reporting odds ratio, defined as the ratio of exposure odds among reported arrhythmia cases, to the exposure odds of other ADRs (non......-sedating antihistamines. In general non-sedating antihistamines are associated with cardiac arrhythmia to a higher extent in comparison with other drugs (ADR reporting odds ratio 2.05 [95% CI: 1.45, 2.89]). The association between arrhythmias and non-sedating antihistamine drugs calculated before 1998...

  4. A Promising New Method to Estimate Drug-Polymer Solubility at Room Temperature

    DEFF Research Database (Denmark)

    Knopp, Matthias Manne; Gannon, Natasha; Porsch, Ilona

    2016-01-01

    The established methods to predict drug-polymer solubility at room temperature either rely on extrapolation over a long temperature range or are limited by the availability of a liquid analogue of the polymer. To overcome these issues, this work investigated a new methodology where the drug......-polymer solubility is estimated from the solubility of the drug in a solution of the polymer at room temperature using the shake-flask method. Thus, the new polymer in solution method does not rely on temperature extrapolations and only requires the polymer and a solvent, in which the polymer is soluble, that does...... not affect the molecular structure of the drug and polymer relative to that in the solid state. Consequently, as this method has the potential to provide fast and precise estimates of drug-polymer solubility at room temperature, we encourage the scientific community to further investigate this principle both...

  5. A side effect resource to capture phenotypic effects of drugs

    DEFF Research Database (Denmark)

    Kuhn, Michael; Campillos, Monica; Letunic, Ivica

    2010-01-01

    on this topic has been hampered by insufficient accessibility of data. Consequently, we have developed a public, computer-readable side effect resource (SIDER) that connects 888 drugs to 1450 side effect terms. It contains information on frequency in patients for one-third of the drug-side effect pairs. For 199......The molecular understanding of phenotypes caused by drugs in humans is essential for elucidating mechanisms of action and for developing personalized medicines. Side effects of drugs (also known as adverse drug reactions) are an important source of human phenotypic information, but so far research...... drugs, the side effect frequency of placebo administration could also be extracted. We illustrate the potential of SIDER with a number of analyses. The resource is freely available for academic research at http://sideeffects.embl.de....

  6. Climate change trade measures : estimating industry effects

    Science.gov (United States)

    2009-06-01

    Estimating the potential effects of domestic emissions pricing for industries in the United States is complex. If the United States were to regulate greenhouse gas emissions, production costs could rise for certain industries and could cause output, ...

  7. Sexual side effects induced by psychotropic drugs

    DEFF Research Database (Denmark)

    Kristensen, Ellids

    2002-01-01

    The majority of psychotropic drugs entail sexual side effects. The sexual side effects may reduce quality of life and may give rise to non-compliance. For example, 30-60 per cent of patients treated with antidepressants are known to develop a sexual dysfunction. However, some psychotropic drugs...... of pharmacologically active substances or specific products for the treatment of sexual dysfunction such as sildenafil. Above all, it should be acknowledged that relatively few data are available in this field and in particular that there is a lack of controlled studies....... with no or very few sexual side effects have begun to emerge. The treatment of sexual side effects induced by psychotropic drugs may consist of: modified sexual habits, reduction in dosage, switching to another medication, possibly in combination with different psychotropic agents, other varieties...

  8. Rapamycin: One Drug, Many Effects

    OpenAIRE

    Li, Jing; Kim, Sang Gyun; Blenis, John

    2014-01-01

    The mammalian target of rapamycin (mTOR) signaling pathway is a master regulator of cell growth and metabolism. Deregulation of the mTOR pathway has been implicated in a number of human diseases such as cancer, diabetes, obesity, neurological diseases and genetic disorders. Rapamycin, a specific inhibitor of mTOR, has been shown to be useful in the treatment of certain diseases. Here we discuss its mechanism of action and highlight recent findings regarding the effects and limitations of rapa...

  9. Arrhythmogenic effects of illicit drugs in athletes.

    Science.gov (United States)

    Furlanello, Francesco; Bentivegna, Stefano; Cappato, Riccardo; De Ambroggi, Luigi

    2003-12-01

    Cardiac arrhythmias are among the most important causes of non-eligibility to sports activities, and may be due to different causes (cardiomyopathies, myocarditis, coronary abnormalities, valvular diseases, primary electrical disorders, abuse of illicit drugs). The list of illicit drugs banned by the International Olympic Committee and yearly updated by the World Anti-Doping Agency includes the following classes: stimulants, narcotics, anabolic agents (androgenic steroids and others such as beta-2 stimulants), peptide hormones, mimetics and analogues, diuretics, agents with an antiestrogenic activity, masking agents. Almost all illicit drugs may cause, through a direct or indirect arrhythmogenic effect, in the short, medium or long term, a wide range of cardiac arrhythmias (focal or reentry type, supraventricular and/or ventricular), lethal or not, even in healthy subjects with no previous history of cardiac diseases. Therefore, given the widespread abuse of illicit drugs among athletes, in the management of arrhythmic athletes the cardiologist should always take into consideration the possibility that the arrhythmias be due to the assumption of illicit drugs (sometimes more than one type), especially if no signs of cardiac diseases are present. On the other hand, in the presence of latent underlying arrhythmogenic heart disease including some inherited cardiomyopathies at risk of sudden cardiac death, illicit drugs could induce severe cardiac arrhythmic effects.

  10. Nanomaterials potentiating standard chemotherapy drugs' effect

    Science.gov (United States)

    Kazantsev, S. O.; Korovin, M. S.

    2017-09-01

    Application of antitumor chemotherapeutic drugs is hindered by a number of barriers, multidrug resistance that makes effective drug deposition inside cancer cells difficult is among them. Recent research shows that potential efficiency of anticancer drugs can be increased with nanoparticles. This review is devoted to the application of nanoparticles for cancer treatment. Various types of nanoparticles currently used in medicine are reviewed. The nanoparticles that have been used for cancer therapy and targeted drug delivery to damaged sites of organism are described. Also, the possibility of nanoparticles application for cancer diagnosis that could help early detection of tumors is discussed. Our investigations of antitumor activity of low-dimensional nanostructures based on aluminum oxides and hydroxides are briefly reviewed.

  11. Rapamycin: one drug, many effects

    Science.gov (United States)

    Li, Jing; Kim, Sang Gyun; Blenis, John

    2014-01-01

    The mammalian target of rapamycin (mTOR) signaling pathway is a master regulator of cell growth and metabolism. Deregulation of the mTOR pathway has been implicated in a number of human diseases such as cancer, diabetes, obesity, neurological diseases and genetic disorders. Rapamycin, a specific inhibitor of mTOR, has been shown to be useful in the treatment of certain diseases. Here we discuss its mechanism of action and highlight recent findings regarding the effects and limitations of rapamycin monotherapy and the potential utility of combination therapy with rapamycin. PMID:24508508

  12. Effects of Psychostimulant Drugs on Developing Brain

    Directory of Open Access Journals (Sweden)

    Ibrahim Durukan

    2013-08-01

    Full Text Available Although psychostimulants have been used for the treatment of attention deficit hyperactivity disorder for approximately 70 years, little is known about the long term effects of these drugs on developing brain. The observable effects of psychostimulants are influenced by the timing of exposure, the age of examination after drug exposure and sex. Preclinical studies point out that chronic psychostimulant exposure before adolescence cause reverse sensitization or tolerance and this leads to reduction in stimulant effectiveness in adolesecence and adulthood. Preclinical studies show the potential long term effects of psychostimulants. But it is necessary to investigate the relationship between preclinical effects and clinical practice. A developmental approach is needed to understand the impact of pediatric medications on the brain that includes assessment at multiple ages to completely characterize the long term effects of these medications. The aim of this paper is to review the effects of psychostimulants on developing brain.

  13. Drug use in Australian nightlife settings: estimation of prevalence and validity of self-report.

    Science.gov (United States)

    Miller, Peter; Curtis, Ashlee; Jenkinson, Rebecca; Droste, Nicolas; Bowe, Steven J; Pennay, Amy

    2015-11-01

    This study aimed to (1) estimate the prevalence of illicit drug use in night-time entertainment districts across five major cities in Australia; and (2) validate self-reported drug use using biochemical marker oral swabs. Street intercept surveys and oral drug swabs conducted over a 7-month period during 2011-12. The night-time entertainment districts of three metropolitan cities (Sydney, Melbourne and Perth) and two regional cities (Wollongong and Geelong) in Australia, between the hours of 10 p.m. and 5 a.m. A total of 7581 individuals agreed to participate in the survey (93% response rate). More than half (62%) the sample was male, with a median age of 22 years (range 18-73). Patrons were approached in thoroughfares and while entering and leaving licensed venues. Data collected included demographics and current session alcohol and other substance use. Drug swabs (n = 401) were performed with a subsample of participants. Approximately 9% [95% confidence interval (CI) = 7-12%] of participants self-reported consumption of illicit or non-prescribed pharmaceutical drugs prior to interview; of those, 81% identified psychostimulants as the drug used. One in five drug swabs returned a positive result, with psychostimulants the most commonly detected drugs (15%; 95% CI = 12-19%). Kappa statistics indicate agreement between self-report of any illicit drug and a positive drug swab is in the slight range [κ = 0.12 (95% CI = 0.05-0.20) P = 0.000]. Self-report findings suggest drug use in Australian nightlife is common, although still very much a minority past-time. Drug swabs indicate a higher prevalence of use (20%) than self-report (9%), which suggests that self-reported drug use may not be reliable in this context. © 2015 Society for the Study of Addiction.

  14. Automated effective dose estimation in CT.

    Science.gov (United States)

    García, M Sánchez; Cameán, M Pombar; Busto, R Lobato; Vega, V Luna; Sueiro, J Mosquera; Martínez, C Otero; del Río, J R Sendón

    2010-01-01

    European regulations require the dose delivered to patients in CT examinations to be monitored and checked against reference levels. Dose estimation has traditionally been performed manually. This is time consuming and therefore it is typically performed on just a few patients and the results extrapolated to the general case. In this work an automated method to estimate the dose in CT studies is presented. The presented software downloads CT studies from the corporative picture archiving and communication system and uses the information on the DICOM headers to perform the dose calculation. Automation enables dose estimations to be performed on a larger fraction of studies, enabling more significant comparisons with diagnostic reference levels (DRLs). A preliminary analysis involving 5800 studies is presented with details of dose distributions for selected CT protocols in use at a university hospital. Average doses are compared with DRLs. Effective dose estimations are also compared with estimations based on the dose length product.

  15. Estimating haplotype effects for survival data

    DEFF Research Database (Denmark)

    Scheike, Thomas; Martinussen, Torben; Silver, J

    2010-01-01

    Genetic association studies often investigate the effect of haplotypes on an outcome of interest. Haplotypes are not observed directly, and this complicates the inclusion of such effects in survival models. We describe a new estimating equations approach for Cox's regression model to assess haplo...

  16. ESTIMATING THE EFFECTS OF EXCHANGE AND INTEREST ...

    African Journals Online (AJOL)

    Empirical evidence from IPOs of German family-owned firms”, CFS Working Paper. 10. Erdem Cumhur, Arslan C.K.and Erdem, M.S.2005 “Effects of Macroeconomic Variables on Instanbul Stock Exchange Indexes“, Applied Financial Economics 15, pp. 987-. 994. Okoli, M. N.: Estimating the Effects of Exhange and Interest ...

  17. Estimating haplotype effects for survival data.

    Science.gov (United States)

    Scheike, Thomas H; Martinussen, Torben; Silver, Jeremy D

    2010-09-01

    Genetic association studies often investigate the effect of haplotypes on an outcome of interest. Haplotypes are not observed directly, and this complicates the inclusion of such effects in survival models. We describe a new estimating equations approach for Cox's regression model to assess haplotype effects for survival data. These estimating equations are simple to implement and avoid the use of the EM algorithm, which may be slow in the context of the semiparametric Cox model with incomplete covariate information. These estimating equations also lead to easily computable, direct estimators of standard errors, and thus overcome some of the difficulty in obtaining variance estimators based on the EM algorithm in this setting. We also develop an easily implemented goodness-of-fit procedure for Cox's regression model including haplotype effects. Finally, we apply the procedures presented in this article to investigate possible haplotype effects of the PAF-receptor on cardiovascular events in patients with coronary artery disease, and compare our results to those based on the EM algorithm. © 2009, The International Biometric Society.

  18. Synthetic drugs with anti-ageing effects.

    Science.gov (United States)

    Kapoor, Vijay K; Dureja, Janhvi; Chadha, Renu

    2009-09-01

    Although ageing is a natural wear and tear phenomenon, it can at least be postponed or prevented by certain approaches. Some chemicals that are present in the diet or in dietary supplements have been documented to have anti-ageing effects. Recently, a number of synthetic drugs used for other therapeutic indications have been shown to have anti-ageing potential.

  19. Using wastewater-based epidemiology to estimate drug consumption-Statistical analyses and data presentation.

    Science.gov (United States)

    Banta-Green, Caleb J; Brewer, Alex J; Ort, Christoph; Helsel, Dennis R; Williams, Jason R; Field, Jennifer A

    2016-10-15

    Analysis of wastewater samples can be used to assess population drug use, but reporting and statistical issues have limited the utility of the approach for epidemiology due to analytical results that are below the limit of quantification or detection. Unobserved or non-quantifiable-censored-data are common and likely to persist as the methodology is applied to more municipalities and a broader array of substances. We demonstrate the use of censored data techniques and account for measurement errors to explore distributions and annual estimates of the daily mean level of drugs excreted per capita. Daily 24-hour composite wastewater samples for 56days in 2009 were obtained using a random sample stratified by day of week and season for 19 municipalities in the Northwest region of the U.S. Methamphetamine, benzoylecgonine (cocaine metabolite), 3,4 methylenedioxymethamphetamine (MDMA), methadone, oxycodone and hydrocodone were identified and quantified in wastewater samples. Four statistical approaches (reporting censoring, Maximum Likelihood Estimation, Kaplan-Meier estimates, or complete data calculations) were used to estimate an annual average, including confidence bounds where appropriate, dependent upon the amount of censoring in the data. The proportion of days within a year with censored data varied greatly by drug across the 19 municipalities, with MDMA varying the most (4% to 94% of observations censored). The different statistical approaches each needed to be used given the levels of censoring of measured drug concentrations. Figures incorporating confidence bounds allow visualization of the data that facilitates appropriate comparisons across municipalities. Results from wastewater sampling that are below detection or quantification limits contain important information and can be incorporated to create a more complete and valid estimate of drug excretion. Copyright © 2016. Published by Elsevier B.V.

  20. Cardiovascular Effects of Performance-Enhancing Drugs.

    Science.gov (United States)

    La Gerche, André; Brosnan, Maria J

    2017-01-03

    Exercise and competitive sports should be associated with a wide range of health benefits with the potential to inspire a positive community health legacy. However, the reputation of sports is being threatened by an ever-expanding armamentarium of agents with real or perceived benefits in performance enhancement. In addition to the injustice of unfair advantage for dishonest athletes, significant potential health risks are associated with performance-enhancing drugs. Performance-enhancing drugs may have an effect on the cardiovascular system by means of directly altering the myocardium, vasculature, and metabolism. However, less frequently considered is the potential for indirect effects caused through enabling athletes to push beyond normal physiological limits with the potential consequence of exercise-induced arrhythmias. This review will summarize the known health effects of PEDs but will also focus on the potentially greater health threat posed by the covert search for performance-enhancing agents that have yet to be recognized by the World Anti-Doping Agency. History has taught us that athletes are subjected to unmonitored trials with experimental drugs that have little or no established efficacy or safety data. One approach to decrease drug abuse in sports would be to accept that there is a delay from when athletes start experimenting with novel agents to the time when authorities become aware of these drugs. This provides a window of opportunity for athletes to exploit with relative immunity. It could be argued that all off-label use of any agent should be deemed illegal. © 2016 American Heart Association, Inc.

  1. Use of glomerular filtration rate estimating equations for drug dosing in HIV-positive patients

    Science.gov (United States)

    Okparavero, Aghogho A; Tighiouart, Hocine; Krishnasami, Zipporah; Wyatt, Christina M; Graham, Hiba; Hellinger, James; Inker, Lesley A

    2014-01-01

    Background Current HIV treatment guidelines recommend using the Cockcroft-Gault equation for drug dosing adjustments. The use of newer glomerular filtration rate (GFR) estimating equations for drug dosing and the appropriateness of physician antiretroviral dosing based on estimated kidney function have not been studied in an HIV-positive population. Methods We evaluated concordance between measured and estimated GFR for the assignment of kidney function categories designated by the Food and Drug Administration (FDA) Guidance for Industry for pharmacokinetic studies, and appropriateness of physician antiretroviral drug dosing for level of kidney function in 200 HIV-positive patients on stable antiretroviral therapy. Estimated kidney function was determined using the Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study and Cockcroft-Gault equations. Results For assignment of FDA-designated kidney function categories, concordance rates between measured and estimated GFR using the CKD-EPI, MDRD Study and Cockcroft-Gault equations were 79%, 71% and 77%, respectively. This pattern was consistent across most subgroups. When actual prescribed dosages were compared to recommended dosages based on the level of estimated kidney function, 3% to 19% of study participants were prescribed higher than recommended dosages. The largest discordance between prescribed and recommended dosages was observed for the Cockcroft-Gault equation. Conclusions The CKD-EPI equation has the highest concordance with measured GFR for the assignment of FDA-designated kidney function categories. Its use may lead to lower dosing related errors in HIV-infected US adults on stable antiretroviral therapy. More education is required with respect to dose adjustment for level of kidney function. PMID:23963249

  2. Effects of antidepressant drugs on sexual function.

    Science.gov (United States)

    Baldwin, D S; Thomas, S C; Birtwistle, J

    1997-01-01

    Adequate sexual expression is an essential part of human relationships, enhancing quality of life and providing a sense of physical, psychological and social well-being. Unfortunately, depression is associated with impairments of sexual function and satisfaction. These problems can worsen a quality of life that is already reduced by the effects of depressive illness. The existing antidepressant drugs are far from ideal, most having adverse effects on sexual function. Unfortunately, the exact incidence of sexual dysfunction during treatment with many antidepressants is not known. Disturbances of sexual interest and performance will only be detected in a reliable fashion when systematic enquiries are made during the course of the standard clinical interview. Growing awareness of the adverse effects of many antidepressants on sexual function has led to some re-evaluation of the earlier claims for the good tolerability of many of the newer drugs. There is a clear need for further well-designed controlled studies of the effects of antidepressants on sexual function, so that this aspect of the tolerability of differing drugs can be assessed more reliably. (IntJ Psych Clin Pract 1997; 1: 47-58).

  3. Informing patients about drug side effects

    Energy Technology Data Exchange (ETDEWEB)

    Morris, L.A.; Kanouse, D.E.

    1982-09-01

    Two hundred forty-nine newly diagnosed hypertensive patients prescribed thiazide medication were recruited for study. Two-thirds were given a leaflet or patient package insert (PPI) that described the drug and its possible side effects, and one-third were not. At a revisit about 1 month later, patients were asked whether they had experienced any of 17 different health problems. For each problem that they experienced, they were asked whether they thought the problem was related to the medicine they were taking. Ten of the health problems were taken verbatim from the PPI's list of possible drug side effects. Patients who received the PPI reported experiencing about the same number of side effects as the non-PPI subjects. However, those who received the PPI were more likely to attribute experienced reactions to the drug. This was true for both reactions specifically listed in the PPI and for similar reactions not listed. Results support the notion of an attribution-labeling process rather than a suggestion effect.

  4. Quantitative Estimation for the Effectiveness of Automation

    International Nuclear Information System (INIS)

    Lee, Seung Min; Seong, Poong Hyun

    2012-01-01

    In advanced MCR, various automation systems are applied to enhance the human performance and reduce the human errors in industrial fields. It is expected that automation provides greater efficiency, lower workload, and fewer human errors. However, these promises are not always fulfilled. As the new types of events related to application of the imperfect and complex automation are occurred, it is required to analyze the effects of automation system for the performance of human operators. Therefore, we suggest the quantitative estimation method to analyze the effectiveness of the automation systems according to Level of Automation (LOA) classification, which has been developed over 30 years. The estimation of the effectiveness of automation will be achieved by calculating the failure probability of human performance related to the cognitive activities

  5. Membrane potential change effects on cationic and neutral drug ...

    African Journals Online (AJOL)

    Membrane potential change effects on cationic and neutral drug - induced erythrocyte shape change and cellular uptake of drugs. A Nwafor, WT Coakley. Abstract. The effect of membrane potential change of the human erythrocytes on cationic drugs tetracaine and chlorpromazine and neutral drug benzyl alcohol induced ...

  6. Estimating met demand for alcohol and other drug treatment in Australia.

    Science.gov (United States)

    Chalmers, Jenny; Ritter, Alison; Berends, Lynda

    2016-11-01

    To estimate the amount of alcohol and other drug (AOD) treatment provided and number of treatment recipients in Australia in 2011-12, and document an approach for future estimates internationally. We combined multiple data sources to estimate the amount of treatment received: administrative data on AOD treatment funded by the Australian and state/territory governments, survey data from treatment providers and programme evaluation data. The various data sources were reconciled, using published studies of treatment activity, to estimate the unique number of treatment recipients. Treatment funded by the Australian and state/territory governments provided by general practitioners, specialist treatment services, hospitals, community- and hospital-based ambulatory mental health-care services and allied health professionals. People receiving AOD treatment in the above settings. Annual quantum of AOD treatment (encounters, episodes, consultations) and the number of unique treatment recipients. In 2011/12 we estimated 1.6 million episodes of care, consultations or encounters, noting that measures of treatment are not comparable. Based on a range of conversion rates to account for people accessing treatment multiple times in that year, we estimated that the number of Australians in receipt of AOD treatment ranged from 202 168 to 232 419. This is an underestimate and subject to error. Using the upper range of the estimate, on average each treatment recipient made 4.7 visits to a general practitioner (GP) or allied health professional providing mental health services for AOD treatment, and had 1.2 treatment episodes with a specialist AOD treatment provider and/or hospital. Between 202 168 and 232 419 Australians are estimated to have received alcohol and other drug treatment in 2011-12. The comprehensive approach used to calculate this estimate, combining multiple independent data sets across treatment settings and programmes, can be replicated in other countries. © 2016

  7. Psychiatric Adverse Effects of Dermatological Drugs

    Directory of Open Access Journals (Sweden)

    Mine Özmen

    2010-07-01

    Full Text Available Dermatological drugs, mostly corticosteroids and isotretinoin, cause different psychiatric adverse effects. During steroid therapy, a wide range of psychiatric conditions, from minor clinical symptoms like insomnia and anxiety to serious psychiatric syndromes like psychosis and delirium might be seen. In medical literature, a causal connection is usually suggested between “isotretinoin”, which is used for treatment of acne vulgaris and depression and suicide attempts. However, there are no statistically significant double-blind randomized studies that support this connection. Clinicians must know patient’s psychiatric history before using any dermatological treatment known as causing psychiatric adverse effects, and psychiatric consultation should be established whenever necessary.

  8. Analysis of drug effects on neurotransmitter release

    International Nuclear Information System (INIS)

    Rowell, P.; Garner, A.

    1986-01-01

    The release of neurotransmitter is routinely studied in a superfusion system in which serial samples are collected and the effects of drugs or other treatments on the amount of material in the superfusate is determined. With frequent sampling interval, this procedure provides a mechanism for dynamically characterizing the release process itself. Using automated data collection in conjunction with polyexponential computer analysis, the equation which describes the release process in each experiment is determined. Analysis of the data during the nontreated phase of the experiment allows an internal control to be used for accurately assessing any changes in neurotransmitter release which may occur during a subsequent treatment phase. The use of internal controls greatly improves the signal to noise ratio and allows determinations of very low concentrations of drugs on small amounts of tissue to be made. In this presentation, the effects of 10 μM nicotine on 3 H-dopamine release in rat nucleus accumbens is described. The time course, potency and efficacy of the drug treatment is characterized using this system. Determinations of the exponential order of the release as well as the rate constants allow one to study the mechanism of the release process. A description of 3 H-dopamine release in normal as well as Ca ++ -free medium is presented

  9. Effect of drugs on orthodontic tooth movement

    Directory of Open Access Journals (Sweden)

    Siti Sarah Aulia Amrullah

    2016-06-01

    Full Text Available Orthodontic tooth movement is basically a biological response to mechanical forces given to the teeth in orthodontic treatment, which involving the periodontal tissue and alveolar bone, resulting in the release of numerous substances from the dental tissues and surrounding structure. Remodeling changes in periodontal tissues are considered to be essential in effecting orthodontic tooth movement which is the base of orthodontic correction. Molecules produced in various diseased tissues or drugs and nutrients consumed regularly by patients, can influence mechanically stressed periodontal tissue through the circulation and interact with target cell combination of which may be inhibitory, additive or synergize. Medications might have an important influence on the rate of tooth movement, and information on their consumption is essential to adequately discuss treatment planning with patients. Therefore it is imperative to the practitioners being in medical profession, must pay close attention to the drug consumption history of every patient before and during the course of treatment.

  10. Impacts of Hydraulic Residence Time Prediction and Diurnal Loading Pattern on the Estimation of Drug Abuse in Urban Areas

    DEFF Research Database (Denmark)

    Ramin, Pedram; Polesel, Fabio; Andresson, Guðmundur

    The measurement of illicit drugs and their human urinary metabolites in influents of municipal wastewater treatment plants (WWTPs) has been recently used to estimate prohibited drug consumption in catchment communities. In this study, a preliminary estimation of the consumption of cocaine (COC...

  11. Effects of Welfare Reform on Illicit Drug Use Of Adult Women

    Science.gov (United States)

    Corman, Hope; Dave, Dhaval M.; Reichman, Nancy E.; Das, Dhiman

    2014-01-01

    Exploiting changes in welfare policy across states and over time and comparing relevant population subgroups within an econometric difference-in-differences framework, we estimate the effects of welfare reform on adult women's illicit drug use from 1992 to 2002, the period during which welfare reform unfolded in the U.S. The analyses are based on all available and appropriate national datasets, each offering unique strengths and measuring a different drug-related outcome. We investigate self-reported illicit drug use (from the National Household Surveys on Drug Abuse and National Surveys on Drug Use and Health), drug-related prison admissions (from the National Corrections Reporting Program), drug-related arrests (from Federal Bureau of Investigation Uniform Crime Reports), and drug-related emergency department episodes (from the Drug Abuse Warning Network). We find robust evidence that welfare reform led to a 10-21% decline in illicit drug use among women at risk of relying on welfare, as well as associated declines in drug-related arrests (6-7%), drug-related hospital emergency department episodes (7-11%), and possibly drug-related prison admissions (11-19%). The findings indicate that an appropriately designed system with sufficient job opportunities for those are able to work can result in both increases in employment and decreases in drug use. PMID:25067860

  12. Adolescent Drug Use and the Deterrent Effect of School-Imposed Penalties

    Science.gov (United States)

    Waddell, G. R.

    2012-01-01

    Estimates of the effect of school-imposed penalties for drug use on a student's consumption of marijuana are biased if both are determined by unobservable school or individual attributes. Reverse causality is also a potential challenge to retrieving estimates of the causal relationship, as the severity of school sanctions may simply reflect the…

  13. [Echinacea drugs--effects and active ingredients].

    Science.gov (United States)

    Bauer, R

    1996-04-01

    Echinacea-containing drugs have to be classified according to the used plant species (Echinacea purpurea, E. pallida or E. angustifolia), the processed part of the plant (root, upper parts or whole plant), and the mode of processing. Significant pharmacological effects have been found in vitro and in vivo for the expressed juice of the upper parts of E. purpurea and for alcoholic extracts of the roots of E. pallida, E. angustifolia and E. purpurea. The activity is mainly directed towards the nonspecific cellular immune system. Several active constituents are discussed: polysaccharides, glycoproteins, caffeic acid derivatives (cichoric acid) and alkamides.

  14. Methods for the Drug Effectiveness Review Project

    Directory of Open Access Journals (Sweden)

    McDonagh Marian S

    2012-09-01

    Full Text Available Abstract The Drug Effectiveness Review Project was initiated in 2003 in response to dramatic increases in the cost of pharmaceuticals, which lessened the purchasing power of state Medicaid budgets. A collaborative group of state Medicaid agencies and other organizations formed to commission high-quality comparative effectiveness reviews to inform evidence-based decisions about drugs that would be available to Medicaid recipients. The Project is coordinated by the Center for Evidence-based Policy (CEbP at Oregon Health & Science University (OHSU, and the systematic reviews are undertaken by the Evidence-based Practice Centers (EPCs at OHSU and at the University of North Carolina. The reviews adhere to high standards for comparative effectiveness reviews. Because the investigators have direct, regular communication with policy-makers, the reports have direct impact on policy and decision-making, unlike many systematic reviews. The Project was an innovator of methods to involve stakeholders and continues to develop its methods in conducting reviews that are highly relevant to policy-makers. The methods used for selecting topics, developing key questions, searching, determining eligibility of studies, assessing study quality, conducting qualitative and quantitative syntheses, rating the strength of evidence, and summarizing findings are described. In addition, our on-going interactions with the policy-makers that use the reports are described.

  15. A pharmacoeconomic modeling approach to estimate a value-based price for new oncology drugs in Europe.

    Science.gov (United States)

    Dranitsaris, George; Ortega, Ana; Lubbe, Martie S; Truter, Ilse

    2012-03-01

    Several European governments have recently mandated price cuts in drugs to reduce health care spending. However, such measures without supportive evidence may compromise patient care because manufacturers may withdraw current products or not launch new agents. A value-based pricing scheme may be a better approach for determining a fair drug price and may be a medium for negotiations between the key stakeholders. To demonstrate this approach, pharmacoeconomic (PE) modeling was used from the Spanish health care system perspective to estimate a value-based price for bevacizumab, a drug that provides a 1.4-month survival benefit to patients with metastatic colorectal cancer (mCRC). The threshold used for economic value was three times the Spanish per capita GDP, as recommended by the World Health Organization (WHO). A PE model was developed to simulate outcomes in mCRC patients receiving chemotherapy ± bevacizumab. Clinical data were obtained from randomized trials and costs from a Spanish hospital. Utility estimates were determined by interviewing 24 Spanish oncology nurses and pharmacists. A price per dose of bevacizumab was then estimated using a target threshold of € 78,300 per quality-adjusted life year gained, which is three times the Spanish per capita GDP. For a 1.4-month survival benefit, a price of € 342 per dose would be considered cost effective from the Spanish public health care perspective. The price may be increased to € 733 or € 843 per dose if the drug were able to improve patient quality of life or enhance survival from 1.4 to 3 months. This study demonstrated that a value-based pricing approach using PE modeling and the WHO criteria for economic value is feasible and perhaps a better alternative to government mandated price cuts. The former approach would be a good starting point for opening dialog between European government payers and the pharmaceutical industry.

  16. Transporters and drug-drug interactions: important determinants of drug disposition and effects.

    Science.gov (United States)

    König, Jörg; Müller, Fabian; Fromm, Martin F

    2013-07-01

    Uptake and efflux transporters determine plasma and tissue concentrations of a broad variety of drugs. They are localized in organs such as small intestine, liver, and kidney, which are critical for drug absorption and elimination. Moreover, they can be found in important blood-tissue barriers such as the blood-brain barrier. Inhibition or induction of drug transporters by coadministered drugs can alter pharmacokinetics and pharmacodynamics of the victim drugs. This review will summarize in particular clinically observed drug-drug interactions attributable to inhibition or induction of intestinal export transporters [P-glycoprotein (P-gp), breast cancer resistance protein (BCRP)], to inhibition of hepatic uptake transporters [organic anion transporting polypeptides (OATPs)], or to inhibition of transporter-mediated [organic anion transporters (OATs), organic cation transporter 2 (OCT2), multidrug and toxin extrusion proteins (MATEs), P-gp] renal secretion of xenobiotics. Available data on the impact of nutrition on transport processes as well as genotype-dependent, transporter-mediated drug-drug interactions will be discussed. We will also present and discuss data on the variable extent to which information on the impact of transporters on drug disposition is included in summaries of product characteristics of selected countries (SPCs). Further work is required regarding a better understanding of the role of the drug metabolism-drug transport interplay for drug-drug interactions and on the extrapolation of in vitro findings to the in vivo (human) situation.

  17. Drug target identification using side-effect similarity

    DEFF Research Database (Denmark)

    Campillos, Monica; Kuhn, Michael; Gavin, Anne-Claude

    2008-01-01

    Targets for drugs have so far been predicted on the basis of molecular or cellular features, for example, by exploiting similarity in chemical structure or in activity across cell lines. We used phenotypic side-effect similarities to infer whether two drugs share a target. Applied to 746 marketed...... drugs, a network of 1018 side effect-driven drug-drug relations became apparent, 261 of which are formed by chemically dissimilar drugs from different therapeutic indications. We experimentally tested 20 of these unexpected drug-drug relations and validated 13 implied drug-target relations by in vitro...... binding assays, of which 11 reveal inhibition constants equal to less than 10 micromolar. Nine of these were tested and confirmed in cell assays, documenting the feasibility of using phenotypic information to infer molecular interactions and hinting at new uses of marketed drugs....

  18. Estimating antimalarial drugs consumption in Africa before the switch to artemisinin-based combination therapies (ACTs

    Directory of Open Access Journals (Sweden)

    Vreeke Ed

    2007-07-01

    Full Text Available Abstract Background Having reliable forecasts is critical now for producers, malaria-endemic countries and agencies in order to adapt production and procurement of the artemisinin-based combination treatments (ACTs, the new first-line treatments of malaria. There is no ideal method to quantify drug requirements for malaria. Morbidity data give uncertain estimations. This study uses drug consumption to provide elements to help estimate quantities and financial requirements of ACTs. Methods The consumption of chloroquine, sulphadoxine/pyrimethamine and quinine both through the private and public sector was assessed in five sub-Saharan Africa countries with different epidemiological patterns (Senegal, Rwanda, Tanzania, Malawi, Zimbabwe. From these data the number of adult treatments per capita was calculated and the volumes and financial implications derived for the whole of Africa. Results Identifying and obtaining data from the private sector was difficult. The quality of information on drug supply and distribution in countries must be improved. The number of adult treatments per capita and per year in the five countries ranged from 0.18 to 0.50. Current adult treatment prices for ACTs range US$ 1–1.8. Taking the upper range for both volumes and costs, the highest number of adult treatments consumed for Africa was estimated at 314.5 million, corresponding to an overall maximum annual need for financing ACT procurement of US$ 566.1 million. In reality, both the number of cases treated and the cost of treatment are likely to be lower (projections for the lowest consumption estimate with the least expensive ACT would require US $ 113 million per annum. There were substantial variations in the market share between public and private sources among these countries (the public sector share ranging from 98% in Rwanda to 33% in Tanzania. Conclusion Additional studies are required to build a more robust methodology, and to assess current consumptions

  19. Estimated prevalence of dementia based on analysis of drug databases in the Region of Madrid (Spain).

    Science.gov (United States)

    de Hoyos-Alonso, M C; Bonis, J; Tapias-Merino, E; Castell, M V; Otero, A

    2016-01-01

    The progressive rise in dementia prevalence increases the need for rapid methods that complement population-based prevalence studies. To estimate the prevalence of dementia in the population aged 65 and older based on use of cholinesterase inhibitors and memantine. Descriptive study of use and prescription of cholinesterase inhibitors and/or memantine in 2011 according to 2 databases: Farm@drid (pharmacy billing records for the Region of Madrid) and BIFAP (database for pharmacoepidemiology research in primary care, with diagnosis and prescription records). We tested the comparability of drug use results from each database using the chi-square test and prevalence ratios. The prevalence of dementia in Madrid was estimated based on the dose per 100 inhabitants/day, adjusting the result for data obtained from BIFAP on combination treatment in the general population (0.37%) and the percentage of dementia patients undergoing treatment (41.13%). Cholinesterase inhibitors and memantine were taken by 2.08% and 0.72% of Madrid residents aged 65 and older was respectively. Both databases displayed similar results for use of these drugs. The estimated prevalence of dementia in individuals aged 65 and older is 5.91% (95% CI%, 5.85-5.95) (52 287 people), and it is higher in women (7.16%) than in men (4.00%). The estimated prevalence of dementia is similar to that found in population-based studies. Analysing consumption of specific dementia drugs can be a reliable and inexpensive means of updating prevalence data periodically and helping rationalise healthcare resources. Copyright © 2014 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.

  20. A case-control study estimating accident risk for alcohol, medicines and illegal drugs.

    Directory of Open Access Journals (Sweden)

    Kim Paula Colette Kuypers

    Full Text Available The aim of the present study was to assess the risk of having a traffic accident after using alcohol, single drugs, or a combination, and to determine the concentrations at which this risk is significantly increased.A population-based case-control study was carried out, collecting whole blood samples of both cases and controls, in which a number of drugs were detected. The risk of having an accident when under the influence of drugs was estimated using logistic regression adjusting for gender, age and time period of accident (cases/sampling (controls. The main outcome measures were odds ratio (OR for accident risk associated with single and multiple drug use. In total, 337 cases (negative: 176; positive: 161 and 2726 controls (negative: 2425; positive: 301 were included in the study.Main findings were that 1 alcohol in general (all the concentrations together caused an elevated crash risk; 2 cannabis in general also caused an increase in accident risk; at a cut-off of 2 ng/mL THC the risk of having an accident was four times the risk associated with the lowest THC concentrations; 3 when ranking the adjusted OR from lowest to highest risk, alcohol alone or in combination with other drugs was related to a very elevated crash risk, with the highest risk for stimulants combined with sedatives.The study demonstrated a concentration-dependent crash risk for THC positive drivers. Alcohol and alcohol-drug combinations are by far the most prevalent substances in drivers and subsequently pose the largest risk in traffic, both in terms of risk and scope.

  1. A case-control study estimating accident risk for alcohol, medicines and illegal drugs.

    Science.gov (United States)

    Kuypers, Kim Paula Colette; Legrand, Sara-Ann; Ramaekers, Johannes Gerardus; Verstraete, Alain Gaston

    2012-01-01

    The aim of the present study was to assess the risk of having a traffic accident after using alcohol, single drugs, or a combination, and to determine the concentrations at which this risk is significantly increased. A population-based case-control study was carried out, collecting whole blood samples of both cases and controls, in which a number of drugs were detected. The risk of having an accident when under the influence of drugs was estimated using logistic regression adjusting for gender, age and time period of accident (cases)/sampling (controls). The main outcome measures were odds ratio (OR) for accident risk associated with single and multiple drug use. In total, 337 cases (negative: 176; positive: 161) and 2726 controls (negative: 2425; positive: 301) were included in the study. Main findings were that 1) alcohol in general (all the concentrations together) caused an elevated crash risk; 2) cannabis in general also caused an increase in accident risk; at a cut-off of 2 ng/mL THC the risk of having an accident was four times the risk associated with the lowest THC concentrations; 3) when ranking the adjusted OR from lowest to highest risk, alcohol alone or in combination with other drugs was related to a very elevated crash risk, with the highest risk for stimulants combined with sedatives. The study demonstrated a concentration-dependent crash risk for THC positive drivers. Alcohol and alcohol-drug combinations are by far the most prevalent substances in drivers and subsequently pose the largest risk in traffic, both in terms of risk and scope.

  2. Methods for estimating and comparing VA outpatient drug benefits with the private sector.

    Science.gov (United States)

    Render, Marta L; Nowak, John; Hammond, Emmett K; Roselle, Gary

    2003-06-01

    To estimate and compare Veterans Health Administration (VA) expenditures for outpatient pharmaceuticals for veterans at six VA facilities with hypothetical private sector costs. Using the VA Pharmacy Benefits Management Strategic Health Care Group (PBM) database, we extracted data for all dispensed outpatient prescriptions from the six study sites over federal fiscal year 1999. After extensive data validation, we converted prescriptions to the same units and merged relevant VA pricing information by National Drug Code to Redbook listed average wholesale price and the Medicaid maximal allowable charge, where available. We added total VA drug expenditures to personnel cost from the pharmacy portion of that medical center's cost distribution report. Hypothetical private sector payments were $200.8 million compared with an aggregate VA budget of $118.8 million. Using National Drug Code numbers, 97% of all items dispensed from the six facilities were matched to private sector price data. Nonmatched pharmaceuticals were largely generic over-the-counter pain relievers and commodities like alcohol swabs. The most commonly prescribed medications reflect the diseases and complaints of an older male population: pain, cardiovascular problems, diabetes, and depression or other psychiatric disorders. Use of the VA PBM database permits researchers to merge expenditure and prescription data to patient diagnoses and sentinel events. A critical element in its use is creating similar units among the systems. Such data sets permit a deeper view of the variability in drug expenditures, an important sector of health care whose inflation has been disproportionate to that of the economy and even health care.

  3. Drugs with anticholinergic side-effects in primary care | Yayla ...

    African Journals Online (AJOL)

    Background: Anticholinergic drugs in elderly people have been associated with some serious side.effects. Patients in Turkey tend to attend primary care centers to have prescriptions of the drugs they chronically use. However, very little are known about how frequent that these drugs are prescribed and their side-effects in ...

  4. The effects of drugs on nutrition

    African Journals Online (AJOL)

    to the oesophageal mucosa; failing hearing, vision, memory; and impaired mobility, which often leads to poor compliance or incorrect dosing. Drug–nutrient interactions are ... Anticholinergic drugs: atropine, oxybutynin, hyoscine, benztropine. Sedatives: diazepam, temasepam. Antidepressants and antipsychotic drugs.

  5. HIV Model Parameter Estimates from Interruption Trial Data including Drug Efficacy and Reservoir Dynamics

    Science.gov (United States)

    Luo, Rutao; Piovoso, Michael J.; Martinez-Picado, Javier; Zurakowski, Ryan

    2012-01-01

    Mathematical models based on ordinary differential equations (ODE) have had significant impact on understanding HIV disease dynamics and optimizing patient treatment. A model that characterizes the essential disease dynamics can be used for prediction only if the model parameters are identifiable from clinical data. Most previous parameter identification studies for HIV have used sparsely sampled data from the decay phase following the introduction of therapy. In this paper, model parameters are identified from frequently sampled viral-load data taken from ten patients enrolled in the previously published AutoVac HAART interruption study, providing between 69 and 114 viral load measurements from 3–5 phases of viral decay and rebound for each patient. This dataset is considerably larger than those used in previously published parameter estimation studies. Furthermore, the measurements come from two separate experimental conditions, which allows for the direct estimation of drug efficacy and reservoir contribution rates, two parameters that cannot be identified from decay-phase data alone. A Markov-Chain Monte-Carlo method is used to estimate the model parameter values, with initial estimates obtained using nonlinear least-squares methods. The posterior distributions of the parameter estimates are reported and compared for all patients. PMID:22815727

  6. Using data from respondent-driven sampling studies to estimate the number of people who inject drugs: Application to the Kohtla-Järve region of Estonia.

    Directory of Open Access Journals (Sweden)

    Jiacheng Wu

    Full Text Available Estimating the size of key risk populations is essential for determining the resources needed to implement effective public health intervention programs. Several standard methods for population size estimation exist, but the statistical and practical assumptions required for their use may not be met when applied to HIV risk groups. We apply three approaches to estimate the number of people who inject drugs (PWID in the Kohtla-Järve region of Estonia using data from a respondent-driven sampling (RDS study: the standard "multiplier" estimate gives 654 people (95% CI 509-804, the "successive sampling" method gives estimates between 600 and 2500 people, and a network-based estimate that uses the RDS recruitment chain gives between 700 and 2800 people. We critically assess the strengths and weaknesses of these statistical approaches for estimating the size of hidden or hard-to-reach HIV risk groups.

  7. The Effects of Childhood Exposure to Drug Users and Religion on Drug Use in Adolescence and Young Adulthood

    Science.gov (United States)

    Jang, Sung Joon; Johnson, Byron R.

    2011-01-01

    Previous research finds drug-using peers and religiosity to be key predictors of drug use among youth, but the effects of childhood exposure to drug users and religion on later drug use have been understudied. The authors hypothesize a child's exposure to parental drug use and religious upbringing have a causal influence on drug use in youth…

  8. Okadaic acid for radiation dose estimation using drug-induced premature chromosome condensation

    International Nuclear Information System (INIS)

    Wang Chunyan; Zhang Wei; Su Xu

    2005-01-01

    Objective: To establish simple biological method for high irradiation dose estimation using drug-induced prematurely condensed chromosomes (PCC) aberrations. Methods: Peripheral blood was taken from healthy adults and irradiated by 0, 1, 2, 5, 10, 15, 20 and 25 Gy 60 Co γ-rays. Then the blood samples were cultured for 48 hrs. One hr before the end of culture , okadaic acid was added into culture medium to induce PCC rings, which were counted for each dose point. Results: The yield of PCC rings was increased with the dose of radiation until 20 Gy. Within the range of 1 to 20 Gy, there was a good dose-response relationship between the yield of PCC rings and radiation dose. Conclusion: Compared with the analysis of frequency of dicentrics, the yield of PCC rings could be a good biodosimetry indicator for estimation of high dose irradiation. (authors)

  9. Illicit Drug Users in the Tanzanian Hinterland: Population Size Estimation Through Key Informant-Driven Hot Spot Mapping.

    Science.gov (United States)

    Ndayongeje, Joel; Msami, Amani; Laurent, Yovin Ivo; Mwankemwa, Syangu; Makumbuli, Moza; Ngonyani, Alois M; Tiberio, Jenny; Welty, Susie; Said, Christen; Morris, Meghan D; McFarland, Willi

    2018-02-12

    We mapped hot spots and estimated the numbers of people who use drugs (PWUD) and who inject drugs (PWID) in 12 regions of Tanzania. Primary (ie, current and past PWUD) and secondary (eg, police, service providers) key informants identified potential hot spots, which we visited to verify and count the number of PWUD and PWID present. Adjustments to counts and extrapolation to regional estimates were done by local experts through iterative rounds of discussion. Drug use, specifically cocaine and heroin, occurred in all regions. Tanga had the largest numbers of PWUD and PWID (5190 and 540, respectively), followed by Mwanza (3300 and 300, respectively). Findings highlight the need to strengthen awareness of drug use and develop prevention and harm reduction programs with broader reach in Tanzania. This exercise provides a foundation for understanding the extent and locations of drug use, a baseline for future size estimations, and a sampling frame for future research.

  10. Incidence and cost estimate of treating pediatric adverse drug reactions in Lagos, Nigeria

    Directory of Open Access Journals (Sweden)

    Kazeem Adeola Oshikoya

    Full Text Available CONTEXT AND OBJECTIVES: Adverse drug reactions (ADRs may cause prolonged hospital admissions with high treatment costs. The burden of ADRs in children has never been evaluated in Nigeria. The incidence of pediatric ADRs and the estimated cost of treatment over an 18-month period were determined in this study. DESIGN AND SETTING: Prospective observational study on children admitted to the pediatric wards of the Lagos State University Teaching Hospital (LASUTH in Nigeria, between July 2006 and December 2007. METHODS: Each patient was assessed for ADRs throughout admission. Medical and non-medical costs to the hospital and patient were estimated for each ADR by reviewing the medical and pharmacy bills, medical charts and diagnostic request forms and by interviewing the parents. Cost estimates were performed in 2007 naira (Nigeria currency from the perspectives of the hospital (government, service users (patients and society (bearers of the total costs attributable to treating ADRs. The total estimated cost was expressed in 2007 United States dollars (USD. RESULTS: Two thousand and four children were admitted during the study; 12 (0.6% were admitted because of ADRs and 23 (1.2% developed ADR(s during admission. Forty ADRs were suspected in these 35 patients and involved 53 medicines. Antibiotics (50% were the most suspected medicines. Approximately 1.83 million naira (USD 15,466.60 was expended to manage all the patients admitted due to ADRs. CONCLUSIONS: Treating pediatric ADRs was very expensive. Pediatric drug use policies in Nigeria need to be reviewed so as to discourage self-medication, polypharmacy prescription and sales of prescription medicines without prescription.

  11. Systematic identification of proteins that elicit drug side effects

    DEFF Research Database (Denmark)

    Kuhn, Michael; Al Banchaabouchi, Mumna; Campillos, Monica

    2013-01-01

    Side effect similarities of drugs have recently been employed to predict new drug targets, and networks of side effects and targets have been used to better understand the mechanism of action of drugs. Here, we report a large-scale analysis to systematically predict and characterize proteins...... that cause drug side effects. We integrated phenotypic data obtained during clinical trials with known drug-target relations to identify overrepresented protein-side effect combinations. Using independent data, we confirm that most of these overrepresentations point to proteins which, when perturbed, cause......) is responsible for hyperesthesia in mice, which, in turn, can be prevented by a drug that selectively inhibits HTR7. Taken together, we show that a large fraction of complex drug side effects are mediated by individual proteins and create a reference for such relations....

  12. Estimation of working memory in macaques for studying drugs for the treatment of cognitive disorders.

    Science.gov (United States)

    Buccafusco, Jerry J

    2008-12-01

    Non-human primates have served as subjects for studies of the cognition-enhancing potential of novel pharmacological agents for over 25 years. Only recently has a greater appreciation of the translational applicability of this model been realized. Though most Old-World monkeys do not appear to acquire an Alzheimer's-like syndrome in old age, their value resides in the brain physiology they have in common with humans. Paradigms like the delayed matching-to-sample task engender behavior that models aspects of working memory that are substrates for the actions of cognition-enhancing drugs. Our studies have provided information relevant to factors that limit the effectiveness of clinical trial design for compounds that potentially improve cognition. For example, cognition-enhancing compounds from different pharmacological classes, when administered to monkeys, can exhibit remarkable pharmacodynamic effects that outlast the presence of the drug in the body. Studies with non-human primates also can provide information regarding dose ranges and individual subject sensitivity experienced in the clinic. Components of working memory are differentially sensitive to drug effects and may be characterized by different dose ranges for certain compounds, even within the same task. Examples are provided that underscore the possible idiosyncrasies of drug action in the pharmacology of cognition--which could be of critical importance in the design of clinical trials.

  13. Monitoring the size and protagonists of the drug market: combining supply and demand data sources and estimates.

    Science.gov (United States)

    Rossi, Carla

    2013-06-01

    The size of the illicit drug market is an important indicator to assess the impact on society of an important part of the illegal economy and to evaluate drug policy and law enforcement interventions. The extent of illicit drug use and of the drug market can essentially only be estimated by indirect methods based on indirect measures and on data from various sources, as administrative data sets and surveys. The combined use of several methodologies and data sets allows to reduce biases and inaccuracies of estimates obtained on the basis of each of them separately. This approach has been applied to Italian data. The estimation methods applied are capture-recapture methods with latent heterogeneity and multiplier methods. Several data sets have been used, both administrative and survey data sets. First, the retail dealer prevalence has been estimated on the basis of administrative data, then the user prevalence by multiplier methods. Using information about behaviour of dealers and consumers from survey data, the average amount of a substance used or sold and the average unit cost have been estimated and allow estimating the size of the drug market. The estimates have been obtained using a supply-side approach and a demand-side approach and have been compared. These results are in turn used for estimating the interception rate for the different substances in term of the value of the substance seized with respect to the total value of the substance to be sold at retail prices.

  14. Graphic Mining of High-Order Drug Interactions and Their Directional Effects on Myopathy Using Electronic Medical Records.

    Science.gov (United States)

    Du, L; Chakraborty, A; Chiang, C-W; Cheng, L; Quinney, S K; Wu, H; Zhang, P; Li, L; Shen, L

    2015-08-01

    We propose to study a novel pharmacovigilance problem for mining directional effects of high-order drug interactions on an adverse drug event (ADE). Our goal is to estimate each individual risk of adding a new drug to an existing drug combination. In this proof-of-concept study, we analyzed a large electronic medical records database and extracted myopathy-relevant case control drug co-occurrence data. We applied frequent itemset mining to discover frequent drug combinations within the extracted data, evaluated directional drug interactions related to these combinations, and identified directional drug interactions with large effect sizes. Furthermore, we developed a novel visualization method to organize multiple directional drug interaction effects depicted as a tree, to generate an intuitive graphical and visual representation of our data-mining results. This translational bioinformatics approach yields promising results, adds valuable and complementary information to the existing pharmacovigilance literature, and has the potential to impact clinical practice.

  15. Target Essentiality and Centrality Characterize Drug Side Effects

    OpenAIRE

    Wang, Xiujuan; Thijssen, Bram; Yu, Haiyuan

    2013-01-01

    Author Summary The ultimate goal of medical research is to develop effective treatments for disease with minimal side effects. Currently, about 20% of drug candidates failed at clinical trial phases II and III due to safety issues. Therefore, understanding the determining factors of drug side effects is of paramount importance to human health and the pharmaceutical industry. Here, we present the first systematic study to uncover key factors leading to drug side effects within the framework of...

  16. Violence and Drug Use in Rural Teens: National Prevalence Estimates from the 2003 Youth Risk Behavior Survey

    Science.gov (United States)

    Johnson, Andrew O.; Mink, Michael D.; Harun, Nusrat; Moore, Charity G.; Martin, Amy B.; Bennett, Kevin J.

    2008-01-01

    Objectives: The purpose of this study was to compare national estimates of drug use and exposure to violence between rural and urban teens. Methods: Twenty-eight dependent variables from the 2003 Youth Risk Behavior Survey were used to compare violent activities, victimization, suicidal behavior, tobacco use, alcohol use, and illegal drug use…

  17. Effect of Contemporary Social Environment, Drug Abuse and ...

    African Journals Online (AJOL)

    marijuana, cannabis) or others in the cult group take drugs to keep them going covering their inferiority complex. Such drugs most often than not are unprescribed drugs, which always have some negative effects on the student's health. in some cases ...

  18. Drug-drug interaction may explain failed antibiotic effectiveness - an ...

    African Journals Online (AJOL)

    The in vivo effect of co-administration of the NSAIDs (acetyl salicylic acid (ASA), piroxicam, indomethacin and paracetamol) with ciprofloxacin against Staphylococcus aureus in Swiss mice, rendered neutropenic by pre-treatment with cyclophosphamide, was evaluated using animal model. Using the murine thigh model, ...

  19. Estimation of effective dose during hysterosalpingography procedures

    International Nuclear Information System (INIS)

    Alzimamil, K.; Babikir, E.; Alkhorayef, M.; Sulieman, A.; Alsafi, K.; Omer, H.

    2014-08-01

    Hysterosalpingography (HSG) is the most frequently used diagnostic tool to evaluate the endometrial cavity and fallopian tube by using conventional x-ray or fluoroscopy. Determination of the patient radiation doses values from x-ray examinations provides useful guidance on where best to concentrate efforts on patient dose reduction in order to optimize the protection of the patients. The aims of this study were to measure the patients entrance surface air kerma doses (ESA K), effective doses and to compare practices between different hospitals in Sudan. ESA K were measured for patient using calibrated thermo luminance dosimeters (TLDs, Gr-200A). Effective doses were estimated using National Radiological Protection Board (NRPB) software. This study was conducted in five radiological departments: Two Teaching Hospitals (A and D), two private hospitals (B and C) and one University Hospital (E). The mean ESD was 20.1 mGy, 28.9 mGy, 13.6 mGy, 58.65 mGy, 35.7, 22.4 and 19.6 mGy for hospitals A,B,C,D, and E), respectively. The mean effective dose was 2.4 mSv, 3.5 mSv, 1.6 mSv, 7.1 mSv and 4.3 mSv in the same order. The study showed wide variations in the ESDs with three of the hospitals having values above the internationally reported values. Number of x-ray images, fluoroscopy time, operator skills x-ray machine type and clinical complexity of the procedures were shown to be major contributors to the variations reported. Results demonstrated the need for standardization of technique throughout the hospital. The results also suggest that there is a need to optimize the procedures. Local DRLs were proposed for the entire procedures. (author)

  20. Effectiveness of adverse effects search filters: drugs versus medical devices

    Directory of Open Access Journals (Sweden)

    Kelly Farrah, MLIS, AHIP

    2016-09-01

    Full Text Available Objective: The study tested the performance of adverse effects search filters when searching for safety information on medical devices, procedures, and diagnostic tests in MEDLINE and Embase. Methods: The sensitivity of 3 filters was determined using a sample of 631 references from 131 rapid reviews related to the safety of health technologies. The references were divided into 2 sets by type of intervention: drugs and nondrug health technologies. Keyword and indexing analysis were performed on references from the nondrug testing set that 1 or more of the filters did not retrieve. Results: For all 3 filters, sensitivity was lower for nondrug health technologies (ranging from 53%– 87% than for drugs (88%–93% in both databases. When tested on the nondrug health technologies set, sensitivity was lower in Embase (ranging from 53%–81% than in MEDLINE (67%–87% for all filters. Of the nondrug records that 1 or more of the filters missed, 39% of the missed MEDLINE records and 18% of the missed Embase records did not contain any indexing terms related to adverse events. Analyzing the titles and abstracts of nondrug records that were missed by any 1 filter, the most commonly used keywords related to adverse effects were: risk, complications, mortality, contamination, hemorrhage, and failure. Conclusions: In this study, adverse effects filters were less effective at finding information about the safety of medical devices, procedures, and tests compared to information about the safety of drugs.

  1. Parametric modeling and optimal experimental designs for estimating isobolograms for drug interactions in toxicology.

    Science.gov (United States)

    Holland-Letz, Tim; Gunkel, Nikolas; Amtmann, Eberhard; Kopp-Schneider, Annette

    2017-11-27

    In toxicology and related areas, interaction effects between two substances are commonly expressed through a combination index [Formula: see text] evaluated separately at different effect levels and mixture ratios. Often, these indices are combined into a graphical representation, the isobologram. Instead of estimating the combination indices at the experimental mixture ratios only, we propose a simple parametric model for estimating the underlying interaction function. We integrate this approach into a joint model where both the parameters of the dose-response functions of the singular substances and the interaction parameters can be estimated simultaneously. As an additional benefit, this concept allows to determine optimal statistical designs for combination studies optimizing the estimation of the interaction function as a whole. From an optimal design perspective, finding the interaction parameters generally corresponds to a [Formula: see text]-optimality resp. [Formula: see text]-optimality design problem, while estimation of all underlying dose response parameters corresponds to a [Formula: see text]-optimality design problem. We show how optimal designs can be obtained in either case as well as how combination designs providing reasonable performance in regard to both criteria can be determined by putting a constraint on the efficiency in regard to one of the criteria and optimizing for the other. As all designs require prior information about model parameter values, which may be unreliable in practice, the effect of misspecifications is investigated as well.

  2. The Effect of Workforce Mobility on Intervention Effectiveness Estimates.

    Science.gov (United States)

    Manjourides, Justin; Sparer, Emily H; Okechukwu, Cassandra A; Dennerlein, Jack T

    2018-03-12

    Little is known about how mobile populations of workers may influence the ability to implement, measure, and evaluate health and safety interventions delivered at worksites. A simulation study is used to objectively measure both precision and relative bias of six different analytic methods as a function of the amount of mobility observed in the workforce. Those six methods are then used to reanalyze a previously conducted cluster-randomized control trial involving a highly mobile workforce in the construction industry. As workforce mobility increases, relative bias in treatment effects derived from standard models to analyze cluster-randomized trials also increases. Controlling for amount of time exposed to the intervention can greatly reduce this bias. Analyzing only subsets of workers who exhibit the least amount of mobility can result in decreased precision of treatment effect estimates. We demonstrate a 59% increase in the treatment effect size from the reanalysis of the previously conducted trial. When evaluating organizational interventions implemented at specific worksites by measuring perceptions and outcomes of workers present at those sites, researchers should consider the effects that the mobility of the workforce may have on the estimated treatment effects. The choice of analytic method can greatly affect both precision and accuracy of estimates.

  3. Effects of drugs on platelet function.

    Science.gov (United States)

    Morse, E E

    1977-01-01

    Numerous drugs and chemicals affect the function of human blood platelets. The mechanism of action of some medications is partly understood. Aspirin is the most frequently involved drug. It appears to interfere with the platelet release reaction by acetylation of a platelet membrane protein which may be involved in the synthesis of prostaglandins. Other anti-inflammatory drugs, including indomethacin, phenylbutazone, ibuprophen (Motrin) and clonixin, also interfere with the release reaction but have a shorter acting course than aspirin. Some drugs stimulate adenylcyclase (gliclazide) or block phosphodiesterase, (dipyridamole, caffeine) both of which actions lead to an increase in adenosine cyclic 3':5' monophosphate (cAMP) and decrease aggregation by adenosine diphosphate (ADP). These interactions should be known to clinical scientists since patients using these medicaments may manifest abnormal platelet function tests in the laboratory and mild hemorrhagic syndromes in the clinic.

  4. Changing effects of direct-to-consumer broadcast drug advertising information sources on prescription drug requests.

    Science.gov (United States)

    Lee, Annisa Lai

    2009-06-01

    This study tracks the changes of the effects of 4 information sources for direct-to-consumer drug advertising on patients' requests for prescription drugs from physicians since the inception of the "Guidance for Industry about Consumer-directed Broadcast Advertisements." The Guidance advises pharmaceuticals to use four information sources for consumers to seek further information to supplement broadcast drug advertisements: small-print information, the Internet, a toll-free number, and health-care providers (nurses, doctors, and pharmacists). Logistic models were created by using survey data collected by the Food and Drug Administration in 1999 and 2002. Results show that throughout the years, health-care providers remain the most used and strongest means associated with patients' direct requests for nonspecific and specific prescription drugs from doctors. The small-print information source gains power and changes from an indirect means associated with patients' discussing drugs with health-care providers to a direct means associated with patients' asking about nonspecific and specific drugs from their doctors. The Internet is not directly related to drug requests, but the effect of its association with patients seeking information from health-care providers grew 11-fold over the course of the study. The toll-free number lost its power altogether for both direct request for a prescription drug and further discussion with health-care providers. Patient demographics will be considered for specific policy implications.

  5. Drug effects on functional structures in isolated perfused pig heart

    Science.gov (United States)

    Trinks, Tobias; Rauh, Robert; Hiller, Michael; Kessler, Manfred D.

    2002-06-01

    Until today monitoring of immediate drug tissue interaction in living organs is an unsolved problem. However, for the development of new drugs and the improvement of medical therapy outcome it would be helpful to get new tools to visualize drug effects on tissue directly. With the EMPHO II SSK and a 3D-scanning device we detected changes of functional structures in an isolated perfused pig heart model after adding commonly used drugs like verapamil, nitroglycerin and salviae miltiorrhizae (Chinese herbal drug). In the paper the results are presented.

  6. The anti-hepatitis drug use effect and inventory management optimization from the perspective of hospital drug supply chain.

    Science.gov (United States)

    Liu, Zhanyu

    2017-09-01

    By analyzing the current hospital anti hepatitis drug use, dosage, indications and drug resistance, this article studied the drug inventory management and cost optimization. The author used drug utilization evaluation method, analyzed the amount and kind distribution of anti hepatitis drugs and made dynamic monitoring of inventory. At the same time, the author puts forward an effective scheme of drug classification management, uses the ABC classification method to classify the drugs according to the average daily dose of drugs, and implements the automatic replenishment plan. The design of pharmaceutical services supply chain includes drug procurement platform, warehouse management system and connect to the hospital system through data exchange. Through the statistical analysis of drug inventory, we put forward the countermeasures of drug logistics optimization. The results showed that drug replenishment plan can effectively improve drugs inventory efficiency.

  7. Quantitative prediction of drug side effects based on drug-related features.

    Science.gov (United States)

    Niu, Yanqing; Zhang, Wen

    2017-09-01

    Unexpected side effects of drugs are great concern in the drug development, and the identification of side effects is an important task. Recently, machine learning methods are proposed to predict the presence or absence of interested side effects for drugs, but it is difficult to make the accurate prediction for all of them. In this paper, we transform side effect profiles of drugs as their quantitative scores, by summing up their side effects with weights. The quantitative scores may measure the dangers of drugs, and thus help to compare the risk of different drugs. Here, we attempt to predict quantitative scores of drugs, namely the quantitative prediction. Specifically, we explore a variety of drug-related features and evaluate their discriminative powers for the quantitative prediction. Then, we consider several feature combination strategies (direct combination, average scoring ensemble combination) to integrate three informative features: chemical substructures, targets, and treatment indications. Finally, the average scoring ensemble model which produces the better performances is used as the final quantitative prediction model. Since weights for side effects are empirical values, we randomly generate different weights in the simulation experiments. The experimental results show that the quantitative method is robust to different weights, and produces satisfying results. Although other state-of-the-art methods cannot make the quantitative prediction directly, the prediction results can be transformed as the quantitative scores. By indirect comparison, the proposed method produces much better results than benchmark methods in the quantitative prediction. In conclusion, the proposed method is promising for the quantitative prediction of side effects, which may work cooperatively with existing state-of-the-art methods to reveal dangers of drugs.

  8. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  9. Effects of pathological conditions on ocular pharmacokinetics of antimicrobial drugs.

    Science.gov (United States)

    Ueda, Kayoko; Ohtori, Akira; Tojo, Kakuji

    2010-10-01

    A diffusion model of ocular pharmacokinetics was used to estimate the effects of pathological conditions on ocular pharmacokinetics. In vivo rabbit data after topical instillation of ciprofloxacin and ofloxacin were compared with the simulated concentrations in the aqueous and vitreous humors. The barrier capacity of the surrounding membranes such as the retina/choroid/sclera (RCS) membrane and the cornea was characterized by dimensionless Sherwood number derived by the pseudo-steady state approach (PSSA). We assumed the barrier capacity decreased by inflammation; when the barrier capacity of the RCS membrane and the cornea was assumed to be one-tenth for the RCS membrane and a half for the cornea respectively, the in vivo data agreed with the simulated profile without contradiction. The drug concentration gradient simulated in the vitreous body near the RCS membrane was more significant in the inflamed eyes than in the normal eyes, suggesting that the elimination of the drugs from the RCS membrane was enhanced by inflammation. The present diffusion model can better describe the ocular pharmacokinetics in both normal and diseased conditions.

  10. The SIDER database of drugs and side effects

    DEFF Research Database (Denmark)

    Kuhn, Michael; Letunic, Ivica; Jensen, Lars Juhl

    2016-01-01

    , targets and side effects into a more complete picture of the therapeutic mechanism of actions of drugs and the ways in which they cause adverse reactions. To this end, we have created the SIDER ('Side Effect Resource', http://sideeffects.embl.de) database of drugs and ADRs. The current release, SIDER 4...

  11. The Effects of High and Low Fear Messages about Drugs

    Science.gov (United States)

    Smart, Reginald G.; Fejer, Dianne

    1974-01-01

    Reports two studies of effects of high and low fear messages about drugs. In the first study three levels of threat appeal about marijuana were used. The second study concerned attitudes toward a non-existent drug-MOT. The effects of fear level for MOT were very large and indicate that high fear appeals are superior. (Author)

  12. Nutritional conditioning : The effect of fasting on drug metabolism

    NARCIS (Netherlands)

    Lammers, L.A.

    2018-01-01

    The studies described in this thesis focus on the effect of fasting, as nutritional modulator, on drug metabolism. Drug metabolism varies considerably between and within patients, which may result in treatment failure or, conversely, in untoward side effects. Many factors contribute to the

  13. Antipsychotic Drug Side Effects for Persons with Intellectual Disability

    Science.gov (United States)

    Matson, Johnny L.; Mahan, Sara

    2010-01-01

    Antipsychotic drugs are the most frequently prescribed of the psychotropic drugs among the intellectually disabled (ID) population. Given their widespread use, efforts to systematically assess and report side effects are warranted. Specific scaling methods such as the "Matson Evaluation of Side Effects" ("MEDS"), the "Abnormal Inventory Movement…

  14. Exploring Spanish health social media for detecting drug effects.

    Science.gov (United States)

    Segura-Bedmar, Isabel; Martínez, Paloma; Revert, Ricardo; Moreno-Schneider, Julián

    2015-01-01

    Adverse Drug reactions (ADR) cause a high number of deaths among hospitalized patients in developed countries. Major drug agencies have devoted a great interest in the early detection of ADRs due to their high incidence and increasing health care costs. Reporting systems are available in order for both healthcare professionals and patients to alert about possible ADRs. However, several studies have shown that these adverse events are underestimated. Our hypothesis is that health social networks could be a significant information source for the early detection of ADRs as well as of new drug indications. In this work we present a system for detecting drug effects (which include both adverse drug reactions as well as drug indications) from user posts extracted from a Spanish health forum. Texts were processed using MeaningCloud, a multilingual text analysis engine, to identify drugs and effects. In addition, we developed the first Spanish database storing drugs as well as their effects automatically built from drug package inserts gathered from online websites. We then applied a distant-supervision method using the database on a collection of 84,000 messages in order to extract the relations between drugs and their effects. To classify the relation instances, we used a kernel method based only on shallow linguistic information of the sentences. Regarding Relation Extraction of drugs and their effects, the distant supervision approach achieved a recall of 0.59 and a precision of 0.48. The task of extracting relations between drugs and their effects from social media is a complex challenge due to the characteristics of social media texts. These texts, typically posts or tweets, usually contain many grammatical errors and spelling mistakes. Moreover, patients use lay terminology to refer to diseases, symptoms and indications that is not usually included in lexical resources in languages other than English.

  15. Developing an Agent-Based Drug Model to Investigate the Synergistic Effects of Drug Combinations.

    Science.gov (United States)

    Gao, Hongjie; Yin, Zuojing; Cao, Zhiwei; Zhang, Le

    2017-12-14

    The growth and survival of cancer cells are greatly related to their surrounding microenvironment. To understand the regulation under the impact of anti-cancer drugs and their synergistic effects, we have developed a multiscale agent-based model that can investigate the synergistic effects of drug combinations with three innovations. First, it explores the synergistic effects of drug combinations in a huge dose combinational space at the cell line level. Second, it can simulate the interaction between cells and their microenvironment. Third, it employs both local and global optimization algorithms to train the key parameters and validate the predictive power of the model by using experimental data. The research results indicate that our multicellular system can not only describe the interactions between the microenvironment and cells in detail, but also predict the synergistic effects of drug combinations.

  16. VirtualToxLab — A platform for estimating the toxic potential of drugs, chemicals and natural products

    International Nuclear Information System (INIS)

    Vedani, Angelo; Dobler, Max; Smieško, Martin

    2012-01-01

    The VirtualToxLab is an in silico technology for estimating the toxic potential (endocrine and metabolic disruption, some aspects of carcinogenicity and cardiotoxicity) of drugs, chemicals and natural products. The technology is based on an automated protocol that simulates and quantifies the binding of small molecules towards a series of proteins, known or suspected to trigger adverse effects. The toxic potential, a non-linear function ranging from 0.0 (none) to 1.0 (extreme), is derived from the individual binding affinities of a compound towards currently 16 target proteins: 10 nuclear receptors (androgen, estrogen α, estrogen β, glucocorticoid, liver X, mineralocorticoid, peroxisome proliferator-activated receptor γ, progesterone, thyroid α, and thyroid β), four members of the cytochrome P450 enzyme family (1A2, 2C9, 2D6, and 3A4), a cytosolic transcription factor (aryl hydrocarbon receptor) and a potassium ion channel (hERG). The interface to the technology allows building and uploading molecular structures, viewing and downloading results and, most importantly, rationalizing any prediction at the atomic level by interactively analyzing the binding mode of a compound with its target protein(s) in real-time 3D. The VirtualToxLab has been used to predict the toxic potential for over 2500 compounds: the results are posted on (http://www.virtualtoxlab.org). The free platform — the OpenVirtualToxLab — is accessible (in client–server mode) over the Internet. It is free of charge for universities, governmental agencies, regulatory bodies and non-profit organizations. -- Highlights: ► In silico technology for estimating the toxic potential of drugs and chemicals. ► Simulation of binding towards 16 proteins suspected to trigger adverse effects. ► Mechanistic interpretation and real-time 3D visualization. ► Accessible over the Internet. ► Free of charge for universities, governmental agencies, regulatory bodies and NPOs.

  17. VirtualToxLab — A platform for estimating the toxic potential of drugs, chemicals and natural products

    Energy Technology Data Exchange (ETDEWEB)

    Vedani, Angelo, E-mail: angelo.vedani@unibas.ch [Biographics Laboratory 3R, Klingelbergstrasse 50, 4056 Basel (Switzerland); Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel (Switzerland); Dobler, Max [Biographics Laboratory 3R, Klingelbergstrasse 50, 4056 Basel (Switzerland); Smieško, Martin [Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, 4056 Basel (Switzerland)

    2012-06-01

    The VirtualToxLab is an in silico technology for estimating the toxic potential (endocrine and metabolic disruption, some aspects of carcinogenicity and cardiotoxicity) of drugs, chemicals and natural products. The technology is based on an automated protocol that simulates and quantifies the binding of small molecules towards a series of proteins, known or suspected to trigger adverse effects. The toxic potential, a non-linear function ranging from 0.0 (none) to 1.0 (extreme), is derived from the individual binding affinities of a compound towards currently 16 target proteins: 10 nuclear receptors (androgen, estrogen α, estrogen β, glucocorticoid, liver X, mineralocorticoid, peroxisome proliferator-activated receptor γ, progesterone, thyroid α, and thyroid β), four members of the cytochrome P450 enzyme family (1A2, 2C9, 2D6, and 3A4), a cytosolic transcription factor (aryl hydrocarbon receptor) and a potassium ion channel (hERG). The interface to the technology allows building and uploading molecular structures, viewing and downloading results and, most importantly, rationalizing any prediction at the atomic level by interactively analyzing the binding mode of a compound with its target protein(s) in real-time 3D. The VirtualToxLab has been used to predict the toxic potential for over 2500 compounds: the results are posted on (http://www.virtualtoxlab.org). The free platform — the OpenVirtualToxLab — is accessible (in client–server mode) over the Internet. It is free of charge for universities, governmental agencies, regulatory bodies and non-profit organizations. -- Highlights: ► In silico technology for estimating the toxic potential of drugs and chemicals. ► Simulation of binding towards 16 proteins suspected to trigger adverse effects. ► Mechanistic interpretation and real-time 3D visualization. ► Accessible over the Internet. ► Free of charge for universities, governmental agencies, regulatory bodies and NPOs.

  18. Background Suppression Effects on Signal Estimation

    Energy Technology Data Exchange (ETDEWEB)

    Burr, Tom [Los Alamos National Laboratory

    2008-01-01

    Gamma detectors at border crossings are intended to detect illicit nuclear material. One performance challenge involves the fact that vehicles suppress the natural background, thus potentially reducing detection probability for threat items. Methods to adjust for background suppression have been considered in related but different settings. Here, methods to adjust for background suppression are tested in the context of signal estimation. Adjustment methods include several clustering options. We find that for the small-to-moderate suppression magnitudes exhibited in the analyzed data, suppression adjustment is only moderatel helpful in locating the signal peak, and in estimating its width or magnitude.

  19. 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.

  20. 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

  1. Adoption of pharmaceutical innovation and the growth of drug expenditure in Taiwan: is it cost effective?

    Science.gov (United States)

    Hsieh, Chee-Ruey; Sloan, Frank A

    2008-01-01

    To investigate the impact of adopting pharmaceutical innovations on the growth of pharmaceutical expenditures, focusing specifically on Taiwan's experience. We first provide a descriptive analysis of cost impacts of introducing new drugs into Taiwan's national formulary using data from Taiwan. We then use a statistical method to decompose the growth of pharmaceutical expenditures during 1997-2001 into three components: 1) treatment expansion; 2) treatment substitution; and 3) price effect. By incorporating the estimated benefit from prior studies, we calculate the incremental cost-effectiveness ratio for new drugs as a whole. We find that from 1997 to 2001 public expenditures on pharmaceuticals grew 57%. The primary drivers of this expenditure growth were treatment expansion and treatment substitution. Prices declined by 18%. Cost per life-year gained resulting from introduction of new drugs was US$1053 (in 2003 dollars) from the perspective of the public payer and US$1824 from the perspective of society as a whole. Overall, our analysis provides evidence with previous studies that the drug reimbursement price is not the primary driver of increased spending. Rather the introduction of new drugs into the formulary leading to expansion of treatment, expansion and substitution of the new drugs for existing drugs may increase spending. Although the adoption of pharmaceutical innovation is costly, the estimated benefit of adopting pharmaceutical innovation generally far exceeds the cost, indicating that the adoption of pharmaceutical innovation is on the whole worthwhile.

  2. Some remarks on the effects of drugs, lack of sleep and loud noise on human performance.

    NARCIS (Netherlands)

    Sanders, A.F. & A.A. Bunt.

    1971-01-01

    Some literature is reviewed on the effect of some drugs, (amphetamine, hypnotics, alcohol), loud noise and sleep loss in test of time estimation, decision making, long term performance and short term memory. Results are most clear with respect to amphetamine, hypnotics and lack of sleep, in that

  3. Australian governments' spending on preventing and responding to drug abuse should target the main sources of drug-related harm and the most cost-effective interventions.

    Science.gov (United States)

    McDonald, David

    2011-01-01

    A notable feature of Australian drug policy is the limited public and professional attention given to the financial costs of drug abuse and to the levels and patterns of government expenditures incurred in preventing and responding to this. Since 1991, Collins and Lapsley have published scholarly reports documenting the social costs of drug abuse in Australia and their reports also contain estimates of governments' drug budgets: revenue and expenditures. They show that, in 2004-2005, Australian governments expended at least $5288 million on drug abuse, with 50% of the expenditure directed to preventing and dealing with alcohol-related problems, 45% to illicit drugs and just 5% to tobacco. Some 60% of the expenditure was directed at drug crime and 37% at health interventions. This pattern of resource allocation does not adequately reflect an evidence-informed policy orientation in that it largely fails to focus on the drug types that are the sources of the most harm (tobacco and alcohol rather than illicit drugs), and the sectors for which we have the strongest evidence of the cost-effectiveness of the available interventions (treatment and harm reduction rather than legislation and law enforcement). The 2010-2014 phase of Australia's National Drug Strategy should include incremental changes to the resource allocation mix, and not simply maintain the historical resource allocation formulae. © 2010 Australasian Professional Society on Alcohol and other Drugs.

  4. The Economics of the Drug War: Effective Federal Policy of Missed Opportunity?

    National Research Council Canada - National Science Library

    McGuire, Marvin

    2002-01-01

    .... Using the 1999 illegal quantities and prices, the derived legal prices, and the estimated demand elasticities for four illegal drugs, we calculated the estimated quantity demanded for these drugs in legal markets...

  5. Assessing bias in community-based prevalence estimates: towards an unduplicated count of problem drinkers and drug users.

    Science.gov (United States)

    Weisner, C; Schmidt, L; Tam, T

    1995-03-01

    General population survey estimates of the overall prevalence of problem drinking and drug use in a community are biased by the exclusion of non-household populations. Estimates based on compiling prevalences in community institutions may also be biased due to over-counting of users of more than one institution. This paper examines prevalence estimates derived from probability samples of problem drinkers in the general population and within alcohol treatment, drug treatment, mental health, criminal justice and welfare agencies in a single US county. Data sets are merged and weighted to reflect a community sample of institutions, and a 17% subset of cases is identified within the institutional samples that are not living in housing units typically included in general population sampling frames. The difference in prevalences of problem drinking in the household and non-household populations is found to be large: 11% and 48%, respectively. Even greater differences are found between estimates of unprescribed weekly drug use (6% and 47%, respectively) and combined problem drinking and weekly drug use (2% and 27%, respectively). This suggests that confining samples to the household population can systematically under-represent the prevalence of problem drinking and drug use. A second source of bias in prevalence is characteristic of studies using records from multiple institutions. When duplication of service use in the five agency samples is considered, it becomes apparent that prevalence may be biased upward due to over-counting of multiple service users.

  6. Heat effects on drug delivery across human skin

    Science.gov (United States)

    Hao, Jinsong; Ghosh, Priyanka; Li, S. Kevin; Newman, Bryan; Kasting, Gerald B.; Raney, Sam G.

    2016-01-01

    Introduction Exposure to heat can impact the clinical efficacy and/or safety of transdermal and topical drug products. Understanding these heat effects and designing meaningful in vitro and in vivo methods to study them are of significant value to the development and evaluation of drug products dosed to the skin. Areas covered This review provides an overview of the underlying mechanisms and the observed effects of heat on the skin and on transdermal/topical drug delivery, thermoregulation and heat tolerability. The designs of several in vitro and in vivo heat effect studies and their results are reviewed. Expert opinion There is substantial evidence that elevated temperature can increase transdermal/topical drug delivery. However, in vitro and in vivo methods reported in the literature to study heat effects of transdermal/topical drug products have utilized inconsistent study conditions, and in vitro models require better characterization. Appropriate study designs and controls remain to be identified, and further research is warranted to evaluate in vitro-in vivo correlations and the ability of in vitro models to predict in vivo effects. The physicochemical and pharmacological properties of the drug(s) and the drug product, as well as dermal clearance and heat gradients may require careful consideration. PMID:26808472

  7. The effect of globalization of drug manufacturing, production, and sourcing and challenges for American drug safety.

    Science.gov (United States)

    Woo, J; Wolfgang, S; Batista, H

    2008-03-01

    Americans benefit from one of the safest drug supplies and one of the highest standards of consumer protection in the world. Over the past decade, though, a general trend toward globalization of the supply chains for finished pharmaceutical products and active pharmaceutical ingredients has created new challenges for the Food and Drug Administration (FDA) in ensuring the safety and quality of the drug supply. Explosive growth in pharmaceutical manufacturing for the US market is particularly evident in the developing regions of Asia. Manufacturing sites in China and India now comprise approximately 40% of all FDA-registered foreign sites, having increased from 30% in 2002. (In 2001, when legislation first went into effect requiring registration of all foreign drug manufacturing sites, 140 registered sites in China listed 797 drug items for potential importation; as of 1 October 2007, that number had grown to 815 registered sites and well over 3,000 listed items.) In total in 2006, the United States received >145,000 line entries of imported drug products from >160 countries, up from only 1,300 line entries in 2000. FDA regulatory oversight resources (e.g., those allocated to inspection and testing of imports) are being challenged to keep up with the explosive growth of imported drugs. (In 2006, the FDA performed inspections at 212 foreign drug firms. This number has remained relatively consistent over the past 6 years, starting at 249 in 2001 and ranging from 190 to 260 on an annual basis.)

  8. Comparing fixed effects and covariance structure estimators for panel data

    DEFF Research Database (Denmark)

    Ejrnæs, Mette; Holm, Anders

    2006-01-01

    In this article, the authors compare the traditional econometric fixed effect estimator with the maximum likelihood estimator implied by covariance structure models for panel data. Their findings are that the maximum like lipoid estimator is remarkably robust to certain types of misspecifications...

  9. Effects of Multidimensional Family Therapy (MDFT) on Nonopioid Drug Abuse:

    DEFF Research Database (Denmark)

    Filges, Trine; Andersen, Ditte; Jørgensen, Anne-Marie Klint

    2015-01-01

    Purpose: This review evaluates the evidence of the effects of multidimensional family therapy (MDFT) on drug use reduction in young people for the treatment of nonopioid drug use.  Method: We followed Campbell Collaboration guidelines to conduct a systematic review of randomized and nonrandomized...... trials. Meta-analytic methods were used to quantitatively synthesize study results.  Results: The search yielded five studies that met inclusion criteria. MDFT was found to be more effective than other treatments on drug abuse problem severity and drug use frequency in the short run but not in the long...... run and demonstrated positive effects on treatment retention compared to control conditions.  Discussion: While additional research is needed, the review offers support for MDFT as a treatment to young nonopioid drug abusers. The number of studies included in this review was limited, however...

  10. Nutritional regulation of homocysteine: effects of drugs.

    Science.gov (United States)

    Varela-Moreiras, G

    2001-10-01

    Homocysteine plays a critical regulation role at the intersection of two metabolic pathways: remethylation and transsulfuration. Both are nutritionally regulated per se, and this issue constitutes the main goal of the present short review. In addition, several factors (i.e., drugs) may change the nutritional modulation, altering the normal functioning of the methionine/methylation cycle. The metabolism of a substrate is closely linked to that of it cofactors: in the case of homocysteine, there are three vitamins acting as cofactors or coenzymes: B6, B12 and folate. Vitamin B6 is involved in the formation of cystathionine from homocysteine (transsulfuration pathway). It is also critical for the formation of 5,10-methylentetrahydrofolate from tetrahydrofolate (folic acid derivatives), and therefore is closely related to the metabolism of folate. The latter is in conjunction with vitamin B12 involved in the remethylation of homocysteine to methionine. This reaction is B12-dependent. Different animal and human studies have proved the existence of a relation between vitamin status and homocysteine. Other dietary components as methionine content, riboflavin, alcohol or coffee consumption are being investigated in relation to homocysteine concentration. Drugs may interfere with the utilization of nutrients. This fact may be of special importance for vitamins (i.e., folate). Administration of drugs in populations with adequate vitamin intake is not usually a problem, but the existence of risk groups (the elderly, adolescents, smokers, dieters, etc.) may lead to specific vitamin deficiencies which may lead to elevated homocysteine. The case of folate is analysed since this vitamin shows the most reported number of interactions with drugs.

  11. Estimating the coverage of a targeted mobile tuberculosis screening programme among illicit drug users and homeless persons with truncated models.

    Science.gov (United States)

    van Hest, N A H; De Vries, G; Smit, F; Grant, A D; Richardus, J H

    2008-05-01

    Truncated models are indirect methods to estimate the size of a hidden population which, in contrast to the capture-recapture method, can be used on a single information source. We estimated the coverage of a tuberculosis screening programme among illicit drug users and homeless persons with a mobile digital X-ray unit between 1 January 2003 and 31 December 2005 in Rotterdam, The Netherlands, using truncated models. The screening programme reached about two-third of the estimated target population at least once annually. The intended coverage (at least two chest X-rays per person per year) was about 23%. We conclude that simple truncated models can be used relatively easily on available single-source routine data to estimate the size of a population of illicit drug users and homeless persons. We assumed that the most likely overall bias in this study would be overestimation and therefore the coverage of the targeted mobile tuberculosis screening programme would be higher.

  12. Effect of gamma irradiation on drugs

    International Nuclear Information System (INIS)

    Crucq, A.S.; Deridder, V.; Engalytcheff, A.; Slegers, C.; Tilquin, P.

    2005-01-01

    Several drugs (ceftazidime, vancomycin, glucagon, erythromycin and dobutamine) were studied in order to determine their radiostability. The methods used to measure the degradation of the drug were the potency and the colour change after irradiation. Electron spin resonance (ESR) is currently being used to detect irradiated foodstuffs and may be a promising technique to detect irradiated drugs. Trapped radicals in cefazolin sodium were studied and quantified by ESR for this purpose. It is proposed that the trapped radicals play an important role in the formation of the final radiolytic compounds. The potency of ceftazidime was not significantly modified after an irradiation of 25 kGy, whereas the potency of erythromycin and dobutamine decreased slightly. Glucagon was revealed to be radiosensitive with a significant decrease in its potency after irradiation. The visible spectra of glucagon and dobutamine did not change significantly after irradiation. The absorbance of erythromycin and vancomycin increased after irradiation. According to European Pharmacopoeia standards, the colour change of ceftazidime is unacceptable. The ESR spectra reveal that the trapped radicals in cefazolin sodium are characteristic of an irradiation. The radical concentration is dependent on the irradiation dose and decays over time. Radical concentration in cefazolin sodium was reduced by 99% after 100 days of storage. These radicals are responsible for about 13% of the measured final radiolytic product. Ionic reactions could also lead to final radiolytic products. (author)

  13. The effect of membrane diffusion potential change on anionic drugs ...

    African Journals Online (AJOL)

    The effect of membrane potential change on anionic drugs Indomethacin and barbitone induced human erythrocyte shape change and red cell uptake of drug has been studied using microscopy and spectrophotometry techniques respectively. The membrane potential was changed by reducing the extracellular chloride ...

  14. Measuring Effects of a Skills Training Intervention for Drug Abusers.

    Science.gov (United States)

    Hawkins, J. David; And Others

    1986-01-01

    A test was conducted of a supplemental skills training and social-network-development aftercare program with 130 drug abusers from four residential therapeutic communities. The intervention produced positive effects on subjects' performance at the conclusion of treatment. Performance improved in situations involving avoidance of drug use, coping…

  15. Pro-cognitive drug effects modulate functional brain network organization

    Directory of Open Access Journals (Sweden)

    Carsten eGiessing

    2012-08-01

    Full Text Available Previous studies document that cholinergic and noradrenergic drugs improve attention, memory and cognitive control in healthy subjects and patients with neuropsychiatric disorders. In humans neural mechanisms of cholinergic and noradrenergic modulation have mainly been analyzed by investigating drug-induced changes of task-related neural activity measured with fMRI. Endogenous neural activity has often been neglected. Further, although drugs affect the coupling between neurons, only a few human studies have explicitly addressed how drugs modulate the functional connectome, i.e. the functional neural interactions within the brain. These studies have mainly focused on synchronization or correlation of brain activations. Recently, there are some drug studies using graph theory and other new mathematical approaches to model the brain as a complex network of interconnected processing nodes. Using such measures it is possible to detect not only focal, but also subtle, widely distributed drug effects on functional network topology. Most important, graph theoretical measures also quantify whether drug-induced changes in topology or network organization facilitate or hinder information processing. Several studies could show that functional brain integration is highly correlated with behavioral performance suggesting that cholinergic and noradrenergic drugs which improve measures of cognitive performance should increase functional network integration. The purpose of this paper is to show that graph theory provides a mathematical tool to develop theory-driven biomarkers of pro-cognitive drug effects, and also to discuss how these approaches can contribute to the understanding of the role of cholinergic and noradrenergic modulation in the human brain. Finally we discuss the global workspace theory as a theoretical framework of pro-cognitive drug effects and argue that pro-cognitive effects of cholinergic and noradrenergic drugs might be related to higher

  16. Pro-cognitive drug effects modulate functional brain network organization

    Science.gov (United States)

    Giessing, Carsten; Thiel, Christiane M.

    2012-01-01

    Previous studies document that cholinergic and noradrenergic drugs improve attention, memory and cognitive control in healthy subjects and patients with neuropsychiatric disorders. In humans neural mechanisms of cholinergic and noradrenergic modulation have mainly been analyzed by investigating drug-induced changes of task-related neural activity measured with functional magnetic resonance imaging (fMRI). Endogenous neural activity has often been neglected. Further, although drugs affect the coupling between neurons, only a few human studies have explicitly addressed how drugs modulate the functional connectome, i.e., the functional neural interactions within the brain. These studies have mainly focused on synchronization or correlation of brain activations. Recently, there are some drug studies using graph theory and other new mathematical approaches to model the brain as a complex network of interconnected processing nodes. Using such measures it is possible to detect not only focal, but also subtle, widely distributed drug effects on functional network topology. Most important, graph theoretical measures also quantify whether drug-induced changes in topology or network organization facilitate or hinder information processing. Several studies could show that functional brain integration is highly correlated with behavioral performance suggesting that cholinergic and noradrenergic drugs which improve measures of cognitive performance should increase functional network integration. The purpose of this paper is to show that graph theory provides a mathematical tool to develop theory-driven biomarkers of pro-cognitive drug effects, and also to discuss how these approaches can contribute to the understanding of the role of cholinergic and noradrenergic modulation in the human brain. Finally we discuss the “global workspace” theory as a theoretical framework of pro-cognitive drug effects and argue that pro-cognitive effects of cholinergic and noradrenergic drugs

  17. Empirical estimation of under-reporting in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

    Science.gov (United States)

    Alatawi, Yasser M; Hansen, Richard A

    2017-07-01

    To examine how closely reporting rates in the FDA Adverse Event Reporting System (FAERS) reflect expected rates of known adverse drug events (ADEs). We selected three groups of drugs to reflect hypothesized variation in sensitivity to reporting, including statins, biologics, and narrow therapeutics index drugs (NTI). The numbers of ADEs in FAERS were divided by utilization estimates from ambulatory health care data (NAMCS/NHAMCS) to calculate a reported proportion. One sample z-test for proportions compared the proportion of ADEs reported to an expected ADE proportion derived from drug labels, reference databases, and peer-reviewed papers. The majority of drug-ADE pairs showed significant under-reporting. For example, roughly 0.01% to 44% of statin events were reported (z-test p 100%) and NTI (20% to >100%) drugs had relatively higher reporting rates. Roughly 20% to 33% of the minimum number of expected serious events were reported with biologics and NTI drugs. This study supports previous evidence of under-reporting of ADEs in spontaneous reporting data. But, under-reporting varies considerably by the type of drug and the type of ADEs, and this variability in under-reporting should be considered when interpreting safety signals.

  18. [Variability and trends in dementia drug consumption in Castile-La Mancha (Spain). Estimated prevalence of Alzheimer's disease].

    Science.gov (United States)

    Criado-Alvarez, J J; Romo Barrientos, C

    2010-05-01

    Alzheimer disease (AD) is one of the most prevalent degenerative disorders in the population over 65 years. We believe that the prevalence in Spain is between 4-11% for the population over 65 years-old. Drugs are currently available to treat this disease in its different phases. We estimated the prevalence of AD by calculating the defined daily doses per 100 inhabitants over 65 years old and days of dementia drugs (therapeutic group N06DA and N06DX) for the years 2004-2008 for each of the provinces of Castile-La Mancha (Spain). We have provided the data requirements specified by the Regional Health Service of Castile-La Mancha. The prevalence of AD is than 2.98 per 100-days for the whole region, there is variation in drug use and consumption, with a predominance of donepezil in all provinces except Guadalajara. On the whole, the consumption of these drugs has increased by 8% annually. The consumption of dementia drugs is used to estimate the distribution of AD in Castile-La Mancha (Spain). These figures do not yet accurately estimate the prevalence of the disease, despite the increase in consumption. We can establish the variability in medical practice for this disease.

  19. Estimating and Testing Mediation Effects with Censored Data

    Science.gov (United States)

    Wang, Lijuan; Zhang, Zhiyong

    2011-01-01

    This study investigated influences of censored data on mediation analysis. Mediation effect estimates can be biased and inefficient with censoring on any one of the input, mediation, and output variables. A Bayesian Tobit approach was introduced to estimate and test mediation effects with censored data. Simulation results showed that the Bayesian…

  20. Assessment of Albendazole (an antiparasitic drug) effects on the ...

    African Journals Online (AJOL)

    Assessment of Albendazole (an antiparasitic drug) effects on the physiological activities of the cardiac, smooth and skeletal muscles of some experimental animals. Mohamed AA El-Rahman, Mohamed AA Omran, Ismail M Abdel-Nabi, Moustafa F Mohamed ...

  1. Estimating the power of Mars’ greenhouse effect

    Science.gov (United States)

    Haberle, Robert M.

    2013-03-01

    Extensive modeling of Mars in conjunction with in situ observations suggests that the annual average global mean surface temperature is Tsbar∼202 K. Yet its effective temperature, i.e., the temperature at which a blackbody radiates away the energy it absorbs, is Te ∼ 208 K. How can a planet with a CO2 atmosphere have a mean annual surface temperature that is actually less than its effective temperature? We use the Ames General Circulation Model explain why this is the case and point out that the correct comparison of the effective temperature is with the effective surface temperature Tse, which is the fourth root of the annual and globally averaged value of Ts4. This may seem obvious, but the distinction is often not recognized in the literature.

  2. The effects of heroin administration and drug cues on impulsivity.

    Science.gov (United States)

    Jones, Jermaine D; Vadhan, Nehal P; Luba, Rachel R; Comer, Sandra D

    2016-08-01

    Drug addiction is a chronic relapsing disorder characterized by compulsive drug seeking and continued use despite negative consequences. Behavioral impulsivity is a strong predictor of the initiation and maintenance of drug addiction. Preclinical data suggest that heroin may exacerbate impulsive characteristics in an individual but this has yet to be assessed in clinical samples. The current secondary data analysis sought to investigate the effects of heroin on impulsivity along with the effects of exposure to drug cues. Using the current data set, we also tentatively assessed the etiological relationship between impulsivity and heroin abuse. Sixteen heroin-dependent participants were recruited to complete Immediate Memory Task/Delayed Memory Task (IMT/DMT) and GoStop tasks following repeated heroin administration, following acute heroin administration, and following a drug cue exposure session. Four preceding days of active heroin availability, compared to four preceding days of placebo drug availability, increased impulsivity assessed using the IMT and DMT. Presentation of drug cues similarly acted to increase impulsivity assessments on all three tasks. It also appears that heavier users were more susceptible to the influence of drug cues on impulsivity. The present study represents a step toward a more comprehensive understanding of the interaction between opioid abuse and impulsivity. A better understanding of these factors could provide critical insight into the maintenance of heroin use and relapse.

  3. Extravasational side effects of cytotoxic drugs: A preventable catastrophe

    OpenAIRE

    Thakur, Jagdeep S.; Chauhan, C. G. S.; Diwana, Vijay K.; Chauhan, Dayal C.; Thakur, Anamika

    2008-01-01

    In addition to their therapeutic effects on malignant cells, cytotoxic agents have the potential of causing destruction of healthy, normal cells. Extravasation of the drug can produce extensive necrosis of the skin and subcutaneous tissue. Management of these extravasational effects differs from one centre to another and prevention is usually strongly emphasized. We analyzed our management of 12 patients referred to us over five years with extravasation of cytotoxic drugs and reviewed the lit...

  4. Abnormal Involuntary Movements: Side-Effect of Neuroleptic Drugs

    OpenAIRE

    Oyewumi, L. K.

    1982-01-01

    Neuroleptics are antipsychotic drugs. In addition to their antipsychotic properties, many physicians use them as anti-anxiety or antiemetics. Indeed, most patients referred to psychiatrists would have been given one, or a combination, of these drugs. Physicians should therefore be aware of their side-effects. Abnormal involuntary movements, now recognized as side-effects of neuroleptics, are broadly classified as acute early occurring movement disorders and late appearing movement disorders. ...

  5. Poly-drug trafficking: Estimating the scale, trends and harms at the Australian border.

    Science.gov (United States)

    Hughes, Caitlin Elizabeth; Chalmers, Jenny; Bright, David Anthony; McFadden, Michael

    2016-05-01

    International drug law enforcement agencies have identified an apparent rise in high level drug traffickers choosing to deal in multiple different drugs. It is hypothesised that this may be a "deliberate modus operandi" and that the formation of "portfolios of trades" may make such traffickers more profitable, harmful and resilient to changes in drug supply and policing. In this paper we provide the first exploration of the extent, nature and harms of poly-drug trafficking at Australian borders. Two different methods were used. First, we used Australian Federal Police (AFP) data on all commercial level seizures at the Australian border from 1999 to 2012 to identify the proportion of seizures that were poly-drug and trends over time. Second, we used unit-record data on a sub-set of 20 drug trafficking cases and linked-cases (defined as the original drug trafficking case and all other criminal cases that were connected via common offenders and/or suspects) to compare the profiles of poly-drug and mono-drug traffickers, including: the total weight and type of drug seized, the value of assets seized, and the level of involvement in other crime (such as money laundering and corruption). Between 5% and 35% of commercial importations at the Australian border involved poly-drug trafficking. Poly-drug trafficking occurred in almost every year of analysis (1999-2012), but it increased only slightly over time. Compared to mono-drug traffickers poly-drug traffickers were characterised by: larger quantities of drugs seized, larger networks, longer criminal histories and more involvement in other types of serious crime. Some fears about poly-drug traffickers may have been overstated particularly about the inherent escalation of this form of trafficking. Nevertheless, this suggests poly-drug traffickers are likely to pose added risks to governments and law enforcement than mono-drug traffickers. They may necessitate different types of policy responses. Copyright © 2016 Elsevier

  6. Can genetic estimators provide robust estimates of the effective number of breeders in small populations?

    Directory of Open Access Journals (Sweden)

    Marion Hoehn

    Full Text Available The effective population size (N(e is proportional to the loss of genetic diversity and the rate of inbreeding, and its accurate estimation is crucial for the monitoring of small populations. Here, we integrate temporal studies of the gecko Oedura reticulata, to compare genetic and demographic estimators of N(e. Because geckos have overlapping generations, our goal was to demographically estimate N(bI, the inbreeding effective number of breeders and to calculate the N(bI/N(a ratio (N(a =number of adults for four populations. Demographically estimated N(bI ranged from 1 to 65 individuals. The mean reduction in the effective number of breeders relative to census size (N(bI/N(a was 0.1 to 1.1. We identified the variance in reproductive success as the most important variable contributing to reduction of this ratio. We used four methods to estimate the genetic based inbreeding effective number of breeders N(bI(gen and the variance effective populations size N(eV(gen estimates from the genotype data. Two of these methods - a temporal moment-based (MBT and a likelihood-based approach (TM3 require at least two samples in time, while the other two were single-sample estimators - the linkage disequilibrium method with bias correction LDNe and the program ONeSAMP. The genetic based estimates were fairly similar across methods and also similar to the demographic estimates excluding those estimates, in which upper confidence interval boundaries were uninformative. For example, LDNe and ONeSAMP estimates ranged from 14-55 and 24-48 individuals, respectively. However, temporal methods suffered from a large variation in confidence intervals and concerns about the prior information. We conclude that the single-sample estimators are an acceptable short-cut to estimate N(bI for species such as geckos and will be of great importance for the monitoring of species in fragmented landscapes.

  7. Effect of renal function on antihypertensive drug safety and efficacy in children.

    Science.gov (United States)

    Watt, Kevin M; Avant, Debbie; Sherwin, Jennifer; Benjamin, Daniel K; Hornik, Christoph; Benjamin, Daniel K; Li, Jennifer S; Smith, P Brian

    2018-01-01

    Hypertension and chronic kidney disease (CKD) are common comorbidities. Guidelines recommend treating hypertension in children with CKD because it is a modifiable risk factor for subsequent cardiovascular disease. Children with CKD are frequently excluded from antihypertensive drug trials. Consequently, safety and efficacy data for antihypertensive drugs are lacking in children with CKD. We determined the incidence of adverse events in 10 pediatric antihypertensive trials to determine the effect of renal function on antihypertensive safety and efficacy in children. These trials were submitted to the US Food and Drug Administration from 1998 to 2005. We determined the number and type of adverse events reported during the trials and compared these numbers in participants with normal renal function and those with decreased function (defined as an estimated glomerular filtration rate [eGFR] children in the 10 studies, 315 had decreased renal function. We observed no difference between the two cohorts in the incidence of adverse events or adverse drug reactions related to study drug. Only 5 participants, all with decreased renal function, experienced a serious adverse event; none was recorded by investigators to be study drug-related. Among treated participants, children with decreased renal function who received a high dose of study drug had a significantly larger drop in diastolic blood pressure compared with children with normal renal function. These data show that antihypertensive treatment in children with renal dysfunction can be safe and efficacious, and consideration should be given to their inclusion in selected drug development programs.

  8. Estimation of Biological Effects of Tritium.

    Science.gov (United States)

    Umata, Toshiyuki

    2017-01-01

    Nuclear fusion technology is expected to create new energy in the future. However, nuclear fusion requires a large amount of tritium as a fuel, leading to concern about the exposure of radiation workers to tritium beta radiation. Furthermore, countermeasures for tritium-polluted water produced in decommissioning of the reactor at Fukushima Daiichi Nuclear Power Station may potentially cause health problems in radiation workers. Although, internal exposure to tritium at a low dose/low dose rate can be assumed, biological effect of tritium exposure is not negligible, because tritiated water (HTO) intake to the body via the mouth/inhalation/skin would lead to homogeneous distribution throughout the whole body. Furthermore, organically-bound tritium (OBT) stays in the body as parts of the molecules that comprise living organisms resulting in long-term exposure, and the chemical form of tritium should be considered. To evaluate the biological effect of tritium, the effect should be compared with that of other radiation types. Many studies have examined the relative biological effectiveness (RBE) of tritium. Hence, we report the RBE, which was obtained with radiation carcinogenesis classified as a stochastic effect, and serves as a reference for cancer risk. We also introduce the outline of the tritium experiment and the principle of a recently developed animal experimental system using transgenic mouse to detect the biological influence of radiation exposure at a low dose/low dose rate.

  9. Medicare Part D and Its Effect on the Use of Prescription Drugs and Use of Other Health Care Services of the Elderly

    Science.gov (United States)

    Kaestner, Robert; Nasreen Khan,

    2012-01-01

    We examine the effect of gaining prescription drug insurance, as a result of Medicare Part D, on use of prescription drugs and other medical services for a nationally representative sample of Medicare beneficiaries. Given the heightened importance of prescription drugs for those with chronic illness, we provide separate estimates for elderly in…

  10. Simulation of Metabolic Drug-Drug Interactions Perpetrated by Fluvoxamine Using Hybridized Two-Compartment Hepatic Drug-Pool-Based Tube Modeling and Estimation of In Vivo Inhibition Constants.

    Science.gov (United States)

    Iga, Katsumi

    2015-10-01

    Co-administration of fluvoxamine (FLV) (perpetrator) and ramelteon (victim, high-clearance CYP1A2 substrate) reportedly showed a 130-fold increase in the area under blood-ramelteon-levels curve (AUCR), which is unpredictable by any method assuming the traditional well-stirred hepatic extraction (Eh ) model. Thus, in order to predict this drug interaction (DDI), a mathematical method that allows simulation of dynamic changes in blood victim levels in response to metabolic inhibition by a perpetrator, without the use of any specialized tools, was derived using hybridized two-compartment hepatic drug-pool-based tube modeling. Using this method, the ramelteon-victimized DDI could be simulated in comparison with other victim DDIs, assuming a consistent FLV dosing regimen. Despite large differences in AUCRs, CYP1A2 or CYP2C19 substrate-victimized DDIs resulted in equivalent inhibition constants (Ki , around 3 nM) and net enzymatic inhibitory activities calculated by eliminating hepatic availability increases for victims. Thus, the unusually large ramelteon DDI could be attributed to the Eh of ramelteon itself. This DDI risk could also be accurately predicted from Ki s estimated in the other CYP1A2 or CYP2C19-substrate interactions. Meanwhile, dynamic changes in blood perpetrator levels were demonstrated to have a small effect on DDI, thus suggesting the usefulness of a tube-based static method for DDI prediction. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  11. The Potential Return on Public Investment in Detecting Adverse Drug Effects.

    Science.gov (United States)

    Huybrechts, Krista F; Desai, Rishi J; Park, Moa; Gagne, Joshua J; Najafzadeh, Mehdi; Avorn, Jerry

    2017-06-01

    Many countries lack fully functional pharmacovigilance programs, and public budgets allocated to pharmacovigilance in industrialized countries remain low due to resource constraints and competing priorities. Using 3 case examples, we sought to estimate the public health and economic benefits resulting from public investment in active pharmacovigilance programs to detect adverse drug effects. We assessed 3 examples in which early signals of safety hazards were not adequately recognized, resulting in continued exposure of a large number of patients to these drugs when safer and effective alternative treatments were available. The drug examples studied were rofecoxib, cerivastatin, and troglitazone. Using an individual patient simulation model and the health care system perspective, we estimated the potential costs that could have been averted by early systematic detection of safety hazards through the implementation of active surveillance programs. We found that earlier drug withdrawal made possible by active safety surveillance would most likely have resulted in savings in direct medical costs of $773-$884 million for rofecoxib, $3-$10 million for cerivastatin, and $38-$63 million for troglitazone in the United States through the prevention of adverse events. By contrast, the yearly public investment in Food and Drug Administration initiated population-based pharmacovigilance activities in the United States is about $42.5 million at present. These examples illustrate a critical and economically justifiable role for active adverse effect surveillance in protecting the health of the public.

  12. Estimating Equilibrium Effects of Job Search Assistance

    DEFF Research Database (Denmark)

    Gautier, Pieter; Muller, Paul; van der Klaauw, Bas

    Randomized experiments provide policy relevant treatment effects if there are no spillovers between participants and nonparticipants. We show that this assumption is violated for a Danish activation program for unemployed workers. Using a difference-in-difference model e show that the nonparticip...

  13. Estimating police effectiveness with individual victimisation data

    NARCIS (Netherlands)

    Vollaard, B.; Koning, P.

    2005-01-01

    In this paper, we present evidence on the effect of greater numbers of police personnel on victimisation of crime and experience of nuisance. We make use of individual data from a Dutch victimisation survey unique in its size, duration and scope. By using individual victimisation data we provide

  14. Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study.

    Science.gov (United States)

    Sharma, Aditya; Hill, Andrew; Kurbatova, Ekaterina; van der Walt, Martie; Kvasnovsky, Charlotte; Tupasi, Thelma E; Caoili, Janice C; Gler, Maria Tarcela; Volchenkov, Grigory V; Kazennyy, Boris Y; Demikhova, Olga V; Bayona, Jaime; Contreras, Carmen; Yagui, Martin; Leimane, Vaira; Cho, Sang Nae; Kim, Hee Jin; Kliiman, Kai; Akksilp, Somsak; Jou, Ruwen; Ershova, Julia; Dalton, Tracy; Cegielski, Peter

    2017-07-01

    Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa. We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa. The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12·4% (95% prediction interval 9·4-16·2) in India, 8·9% (4·5-11·7) in the Philippines, 32·5% (27·0-35·8) in Russia, and 5·7% (3·0-7·6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8·9% (95% prediction interval 5·1-12·9) in India, 9·0% (4·0-14·7) in the Philippines, 9·0% (4·8-14·2) in Russia, and 8·5% (2·5-14·7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040. MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR

  15. Effects of hospital generic drug substitution on diabetes therapy

    Directory of Open Access Journals (Sweden)

    Chen HY

    2014-01-01

    Full Text Available Hui-Yin Chen,1 Hui-Ru Chang,2 Hui-Chu Lang3 1Department of Auditing, Mackay Memorial Hospital, Taipei, Taiwan; 2Department of Social Insurance, Ministry of Health and Welfare, Taipei, Taiwan; 3Institute of Hospital and Health Care Administration, National Yang-Ming University, Taipei, Taiwan Objectives: To evaluate the effects on physicians’ prescribing behavior and on the therapeutic outcome of non-insulin-dependent diabetes patients of substituting different generic brands of metformin. Methods: We adopt a retrospective cohort study involving 280 type-2 diabetes patients who regularly used the outpatient services of one medical center and who had changed metformin brands five times between 2003 and 2008. The aim was to examine the effects of switching brands. The generalized estimating equation was used to determine whether drug brand switching affected patient glycated hemoglobin A1c (HbA1c levels, their prescribed daily dose, or their adherence to medication with metformin. Results: HbA1c levels increased from 7.91 to 8.34 throughout the study period, although it was found that brand switching did not adversely affect HbA1c levels after controlling for patient characteristics and the time course of the study. Furthermore, the prescribed daily dose of metformin was stable throughout the study period, and was approximately 0.8 of the defined daily dose. Finally, although adherence was significantly higher with the original metformin than with the four generic brands, patients still maintained high levels of adherence of >0.8. Conclusion: Although switching between different brands of metformin slightly affected the prescribing behavior of the physicians, there was no unfavorable effect on patient HbA1c levels. Thus, the policy of substituting between different generic brands of metformin is a good cost-effective approach that does not adversely affect the quality of diabetes patient care. Keywords: metformin, generic substitution, glycemic

  16. [Effect of anticholinergic drugs on cognitive impairment in the elderly].

    Science.gov (United States)

    López-Álvarez, Jorge; Zea Sevilla, María Ascensión; Agüera Ortiz, Luis; Fernández Blázquez, Miguel Ángel; Valentí Soler, Meritxell; Martínez-Martín, Pablo

    2015-01-01

    The use of anticholinergic drugs is common in the elderly, even in people with cognitive impairment. A systematic search was conducted in PubMed (anticholinergic effects, anticholinergic and dementia) to define the effects of anticholinergic drugs in the elderly. We emphasized the search in patterns of use, the combined use with AChEIs, the measurement of the Serum Anticholinergic Activity, and the short-term and long-term cognitive effects. The conclusions are that the use of anticholinergic drugs is common in the elderly, even more so than the medical prescription of AChEIs in Alzheimer's disease. The use of anticholinergic drugs may result in cognitive impairment. In long-term use it may generate a worsening of cognitive functions. It can lead to a wrong diagnosis of mild cognitive impairment or dementia, and they can also initiate signs of dementia. Greater cognitive effects appear when there is a previous deficit, but cognitive effects from anticholinergic drugs disappear in severe dementia. The presence of ApoEɛ4 increases the vulnerability for cognitive impairment when these drugs are employed. Copyright © 2013 SEP y SEPB. Published by Elsevier España. All rights reserved.

  17. Estimation of drug abuse in 9 Polish cities by wastewater analysis.

    Science.gov (United States)

    Klupczynska, Agnieszka; Dereziński, Paweł; Krysztofiak, Janusz; Kokot, Zenon J

    2016-03-01

    The aim of this work was to measure illicit drug residues in raw sewage samples collected from nine Polish cities in order to determine trends in illicit drug use in these urban populations. This is the first study involving an analysis of samples from several sewage treatment plants in Poland and covering such a large population. Concentration of illicit drugs was determined using a high performance liquid chromatography-tandem mass spectrometry method. The samples were subjected to a multistep preparation procedure with a solid phase extraction as a main pre-treatment step. Among the selected drugs investigated in the study, amphetamine was found in the greatest amounts in all sewage samples and consequently was the most prevalent drug of abuse. Higher loads of illicit drug residues were found during weekends compared to the weekdays, especially for 3,4-methylenedioxymethamphetamine (ecstasy) and benzoylecgonine, main metabolite of cocaine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. 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....

  19. ADVERPred-Web Service for Prediction of Adverse Effects of Drugs.

    Science.gov (United States)

    Ivanov, Sergey M; Lagunin, Alexey A; Rudik, Anastasia V; Filimonov, Dmitry A; Poroikov, Vladimir V

    2018-01-22

    Application of structure-activity relationships (SARs) for the prediction of adverse effects of drugs (ADEs) has been reported in many published studies. Training sets for the creation of SAR models are usually based on drug label information which allows for the generation of data sets for many hundreds of drugs. Since many ADEs may not be related to drug consumption, one of the main problems in such studies is the quality of data on drug-ADE pairs obtained from labels. The information on ADEs may be included in three sections of the drug labels: "Boxed warning," "Warnings and Precautions," and "Adverse reactions." The first two sections, especially Boxed warning, usually contain the most frequent and severe ADEs that have either known or probable relationships to drug consumption. Using this information, we have created manually curated data sets for the five most frequent and severe ADEs: myocardial infarction, arrhythmia, cardiac failure, severe hepatotoxicity, and nephrotoxicity, with more than 850 drugs on average for each effect. The corresponding SARs were built with PASS (Prediction of Activity Spectra for Substances) software and had balanced accuracy values of 0.74, 0.7, 0.77, 0.67, and 0.75, respectively. They were implemented in a freely available ADVERPred web service ( http://www.way2drug.com/adverpred/ ), which enables a user to predict five ADEs based on the structural formula of compound. This web service can be applied for estimation of the corresponding ADEs for hits and lead compounds at the early stages of drug discovery.

  20. Stabilizing Agents for Drug Nanocrystals: Effect on Bioavailability

    Directory of Open Access Journals (Sweden)

    Annika Tuomela

    2016-05-01

    Full Text Available Drug nanocrystals are a versatile option for drug delivery purposes, and while the number of poorly soluble drug materials is all the time increasing, more research in this area is performed. Drug nanocrystals have a simple structure—a solid drug core is surrounded by a layer of stabilizing agent. However, despite the considerably simple structure, the selection of an appropriate stabilizer for a certain drug can be challenging. Mostly, the stabilizer selection is based purely on the requirement of physical stability, e.g., maintaining the nanosized particle size as long as possible after the formation of drug nanocrystals. However, it is also worth taking into account that stabilizer can affect the bioavailability in the final formulation via interactions with cells and cell layers. In addition, formation of nanocrystals is only one process step, and for the final formulation, more excipients are often added to the composition. The role of the stabilizers in the final formulation can be more than only stabilizing the nanocrystal particle size. A good example is the stabilizer’s role as cryoprotectant during freeze drying. In this review, the stabilizing effect, role of stabilizers in final nanocrystalline formulations, challenges in reaching in vitro–in vivo correlation with nanocrystalline products, and stabilizers’ effect on higher bioavailability are discussed.

  1. Treatment Effect Estimation Using Nonlinear Two-Stage Instrumental Variable Estimators: Another Cautionary Note.

    Science.gov (United States)

    Chapman, Cole G; Brooks, John M

    2016-12-01

    To examine the settings of simulation evidence supporting use of nonlinear two-stage residual inclusion (2SRI) instrumental variable (IV) methods for estimating average treatment effects (ATE) using observational data and investigate potential bias of 2SRI across alternative scenarios of essential heterogeneity and uniqueness of marginal patients. Potential bias of linear and nonlinear IV methods for ATE and local average treatment effects (LATE) is assessed using simulation models with a binary outcome and binary endogenous treatment across settings varying by the relationship between treatment effectiveness and treatment choice. Results show that nonlinear 2SRI models produce estimates of ATE and LATE that are substantially biased when the relationships between treatment and outcome for marginal patients are unique from relationships for the full population. Bias of linear IV estimates for LATE was low across all scenarios. Researchers are increasingly opting for nonlinear 2SRI to estimate treatment effects in models with binary and otherwise inherently nonlinear dependent variables, believing that it produces generally unbiased and consistent estimates. This research shows that positive properties of nonlinear 2SRI rely on assumptions about the relationships between treatment effect heterogeneity and choice. © Health Research and Educational Trust.

  2. May disordered protein cause serious drug side effect?

    Science.gov (United States)

    Tou, Weng Ieong; Chen, Calvin Yu-Chian

    2014-04-01

    Insomnia is a self-reported disease where patients lose their ability to initiate and maintain sleep, leading to daytime performance impairment. Several drug targets to ameliorate insomnia symptoms have been discovered; however, these drug targets lead to serious side effects. Thus, we characterize the structural properties of these sleep-related receptors and the clock complex and discuss a possible drug design that will reduce side effects. Computational prediction shows that disordered property is shared. Over 30% of the structure of CLOCK, PER1/2/3, BMAL-1, muscarinic acetylcholine receptor-M1, melatonin receptor and casein kinase I are structurally disordered (the remaining proteins represent insomnia drugs might be closely related to the protein architecture. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Bias effects on magnitude and ratio estimation power function exponents.

    Science.gov (United States)

    Fagot, R F; Pokorny, R

    1989-03-01

    A bias model of relative judgment was used to derive a ratio estimation (RE) power function, and its effectiveness in providing estimates of exponents free of the effects of standards was evaluated. The RE bias model was compared with the simple RE power function that ignores bias. Results showed that when bias was not taken into account, estimates of exponents exhibited the usual effects of standards observed in previous research. However, the introduction of bias parameters into the RE power function virtually eliminated these effects. Exponents calculated from "equal-range segments" (e.g., low stimulus range vs. high stimulus range) judged by magnitude estimation (ME) were examined: the effects of equal-range segments on exponents were much stronger for ME than standards were for RE, using the bias model.

  4. The problematic estimation of "imitation effects" in multilevel models

    Directory of Open Access Journals (Sweden)

    2003-09-01

    Full Text Available It seems plausible that a person's demographic behaviour may be influenced by that among other people in the community, for example because of an inclination to imitate. When estimating multilevel models from clustered individual data, some investigators might perhaps feel tempted to try to capture this effect by simply including on the right-hand side the average of the dependent variable, constructed by aggregation within the clusters. However, such modelling must be avoided. According to simulation experiments based on real fertility data from India, the estimated effect of this obviously endogenous variable can be very different from the true effect. Also the other community effect estimates can be strongly biased. An "imitation effect" can only be estimated under very special assumptions that in practice will be hard to defend.

  5. Effects of Trypanocidal Drugs on the Function of Trypanosomes.

    Science.gov (United States)

    1980-09-01

    W A 31 073 EFFECTS OF TRYPANOCIDAL DRUGS ON THE FUNCTION 0F1/ TRYPANOSOMES(J) COLONO STATE UNIV FORT COLLNS DEPT OF PATHOLOGY G C HILL SEP 8U DUMO 7...NAME ANO AGORESS 10. PROGRAM ELE.*J-NT, PROJEC., TL’ AREA A WORK UNIT NUMBERS Colorado State University 62770A Department of Pathology ...against all stages of the infection in both Gambian and Rhodesian sleeping sickness. It should also be incapable of inducing drug resistauice and active

  6. Estimation of Site Effects in Beijing City

    Science.gov (United States)

    Ding, Z.; Chen, Y. T.; Panza, G. F.

    For the realistic modeling of the seismic ground motion in lateral heterogeneous anelastic media, the database of 3-D geophysical structures for Beijing City has been built up to model the seismic ground motion in the City, caused by the 1976 Tangshan and the 1998 Zhangbei earthquakes. The hybrid method, which combines the modal summation and the finite-difference algorithms, is used in the simulation. The modeling of the seismic ground motion, for both the Tangshan and the Zhangbei earthquakes, shows that the thick Quaternary sedimentary cover amplifies the peak values and increases the duration of the seismic ground motion in the northwestern part of the City. Therefore the thickness of the Quaternary sediments in Beijing City is the key factor controling the local ground effects. Four zones are defined on the base of the different thickness of the Quaternary sediments. The response spectra for each zone are computed, indicating that peak spectral values as high as 0.1 g are compatible with past seismicity and can be well exceeded if an event similar to the 1697 Sanhe-Pinggu occurs.

  7. Estimation of site effects in Beijing City

    International Nuclear Information System (INIS)

    Ding, Z.; Chen, Y.T.; Panza, G.F.

    2002-01-01

    For the realistic modeling of the seismic ground motion in lateral heterogeneous anelastic media, the database of 3-D geophysical structures for Beijing City has been built up to model the seismic ground motion in the City, caused by the 1976 Tangshan and the 1998 Zhangbei earthquakes. The hybrid method, that combines the modal summation and the finite difference algorithms, is used in the simulation. The modeling of the seismic ground motion for both the Tangshan and the Zhangbei earthquakes shows that the thick Quaternary sedimentary cover amplifies the peak values and increases the duration of the seismic ground motion in the northwest part of the City. Therefore the thickness of the Quaternary sediments in Beijing City is the key factor that controls the local ground effects, and four zones are defined on the base of the different thickness of the Quaternary sediments. The response spectra for each zone are computed, indicating that peak spectral values as high as 0.1g are compatible with past seismicity and can be well exceeded if an event similar to the 1697 Sanhe-Pinggu occurs. (author)

  8. Effect and Safety of Shihogyejitang for Drug Resistant Childhood Epilepsy

    Directory of Open Access Journals (Sweden)

    Jinsoo Lee

    2016-01-01

    Full Text Available Objective. Herbal medicine has been widely used to treat drug resistant epilepsy. Shihogyejitang (SGT has been commonly used to treat epilepsy. We investigated the effect and safety of SGT in children with drug resistant epilepsy. Design. We reviewed medical records of 54 patients with epilepsy, who failed to respond to at least two antiepileptic drugs and have been treated with SGT between April 2006 and June 2014 at the Department of Pediatric Neurology, I-Tomato Hospital, Korea. Effect was measured by the response rate, seizure-free rate, and retention rate at six months. We also checked adverse events, change in antiepileptic drugs use, and the variables related to the outcome. Results. Intent-to-treat analysis showed that, after six months, 44.4% showed a >50% seizure reduction, 24.1% including seizure-free, respectively, and 53.7% remained on SGT. Two adverse events were reported, mild skin rash and fever. Focal seizure type presented significantly more positive responses when compared with other seizure types at six months (p=0.0284, Fisher’s exact test. Conclusion. SGT is an effective treatment with excellent tolerability for drug resistant epilepsy patients. Our data provide evidence that SGT may be used as alternative treatment option when antiepileptic drug does not work in epilepsy children.

  9. National population size estimation of illicit drug users through the network scale-up method in 2013 in Iran.

    Science.gov (United States)

    Nikfarjam, Ali; Shokoohi, Mostafa; Shahesmaeili, Armita; Haghdoost, Ali Akbar; Baneshi, Mohammad Reza; Haji-Maghsoudi, Saiedeh; Rastegari, Azam; Nasehi, Abbas Ali; Memaryan, Nadereh; Tarjoman, Termeh

    2016-05-01

    For a better understanding of the current situation of drug use in Iran, we utilized the network scale-up approach to estimate the prevalence of illicit drug use in the entire country. We implemented a self-administered, street-based questionnaire to 7535 passersby from the general public over 18 years of age by street based random walk quota sampling (based on gender, age and socio-economic status) from 31 provinces in Iran. The sample size in each province was approximately 400, ranging from 200 to 1000. In each province 75% of sample was recruited from the capital and the remaining 25% was recruited from one of the large cities of that province through stratified sampling. The questionnaire comprised questions on demographic information as well as questions to measure the total network size of participants as well as the network size in each of seven drug use groups including Opium, Shire (combination of Opium residue and pure opium), Crystal Methamphetamine, heroin/crack (which in Iranian context is a cocaine-free drug that mostly contains heroin, codeine, morphine and caffeine with or without other drugs), Hashish, Methamphetamine/LSD/ecstasy, and injecting drugs. The estimated size for each group was adjusted for transmission and barrier ratios. The most common type of illicit drug used was opium with the prevalence of 1500 per 100,000 population followed by shire (660), crystal methamphetamine (590), hashish (470), heroin/crack (350), methamphetamine, LSD and ecstasy (300) and injecting drugs (280). All types of substances were more common among men than women. The use of opium, shire and injecting drugs was more common in individuals over 30 whereas the use of stimulants and hashish was largest among individuals between 18 and 30 years of age. It seems that younger individuals and women are more desired to use new synthetic drugs such as crystal methamphetamine. Extending the preventive programs especially in youth as like as scaling up harm reduction

  10. Academic achievement and adolescent drug use: an examination of reciprocal effects and correlated growth trajectories.

    Science.gov (United States)

    Henry, Kimberly L

    2010-01-01

    The primary aim was to examine correlated growth trajectories and reciprocal effects between academic achievement and drug use over the course of junior high school. One hundred and three male and 98 female students from 3 rural junior high schools were surveyed 4 times over the course of 3 years. Dual trajectory latent growth models were estimated. Growth trajectories of school achievement and drug use over the course of junior high were highly correlated. Students who demonstrated deteriorating achievement during the course of junior high school showed an increase in drug use during this same time frame. Cross-process regressions indicated that students who demonstrated superior academic achievement in sixth grade exhibited a shallower rate of increase in drug use (ie, their drug use escalated to a lesser extent). The processes of academic disengagement (as marked by deteriorating grades) and drug use during adolescence appear to be related to one another. Prevention initiatives aimed at keeping adolescents academically engaged in school may have protective benefits against escalation of drug use.

  11. Estimating population effects of vaccination using large, routinely collected data.

    Science.gov (United States)

    Halloran, M Elizabeth; Hudgens, Michael G

    2018-01-30

    Vaccination in populations can have several kinds of effects. Establishing that vaccination produces population-level effects beyond the direct effects in the vaccinated individuals can have important consequences for public health policy. Formal methods have been developed for study designs and analysis that can estimate the different effects of vaccination. However, implementing field studies to evaluate the different effects of vaccination can be expensive, of limited generalizability, or unethical. It would be advantageous to use routinely collected data to estimate the different effects of vaccination. We consider how different types of data are needed to estimate different effects of vaccination. The examples include rotavirus vaccination of young children, influenza vaccination of elderly adults, and a targeted influenza vaccination campaign in schools. Directions for future research are discussed. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  12. [Evaluation of educational effects on drug dependence abstinence for convicts].

    Science.gov (United States)

    Sakurai, Tomoko; Nishikawa, Kyoko; Tanaka, Takanori

    2011-06-01

    The object of this study is to evaluate the educational effects of group work sessions on drug dependence abstinence for convicts in Fukui Prison. Questionnaire surveys were conducted among participants on the first and last session. The results of surveys were analyzed quantitatively. The average ages of 50 respondents were 39 years. 95.9% of them used methamphetamine among drugs and the majority has used drugs for the past 5 years. 93.9% of respondents had no medical treatment histories and 95.8% of them have not used any formal consultations. The survey result before the sessions showed that 75.5% of respondents showed positive stances towards participations on educational group work sessions. The survey after the sessions showed 67.4% of respondents were able to talk their drug problems in group meetings and 87.0% responded that group work sessions were helpful for solving drug problems. Also, 80.0% responded that they can stop using drugs and the percentage dropped by 11.0% from the first session. In terms of the participation in self-help groups after releases from the prison, the majority responded negatively, although 78.0% showed positive responses to using consultation services. The outcomes by means of evaluation scale also showed a significant improvement on denial and no relevant change on interpersonal trusts. This study revealed that it was possible to confirm the effectiveness of drug abstinence education through group work. It is important to consider three points in further studies; 1) cooperation between judicial and medical institutions for introducing consultation and medical treatments among convicts; 2) follow-up programs for reinforcing education on drug abstinence; 3) social welfare services in cooperation with educational effects to prevent repeated offences.

  13. Numerical estimation of the effects of climatic variations on human ...

    African Journals Online (AJOL)

    temperature, humidity, solar radiation and wind speed) are used to develop a numerical model for estimating the effect of climatic changes on human thermal comfort in Botswana. Numerical values of energy load for four different comfort classes were ...

  14. Drug Facts

    Medline Plus

    Full Text Available ... Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, ... Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug Use and Kids ...

  15. Estimated percentages and characteristics of men who have sex with men and use injection drugs--United States, 1999-2011.

    Science.gov (United States)

    2013-09-20

    Male-to-male sex and illicit injection drug use are important transmission routes for human immunodeficiency virus (HIV) infection. Of all new HIV infections in 2010, 80% were among men, of which 78% were among men who have sex with men (MSM), 6% among male injection drug users (IDU), and 4% among men who have sex with men and inject drugs (MSM/IDU). MSM/IDU might have different prevention needs from men who are either MSM or IDU, but not both. A combination of effective, scalable, and evidence-based approaches that address male-to-male sex and injection drug use behaviors might reduce HIV infections among MSM/IDU. To refine calculations of disease rates attributed to MSM and IDU by accounting for MSM/IDU, CDC used data from 1999-2008 National Health and Nutrition Examination Survey (NHANES) to estimate the percentage and number of MSM/IDU in the general population. To further describe demographic similarities and differences of MSM/IDU identified by different surveillance systems, CDC also compared data from four HIV surveillance systems: the 2008 and 2009 National HIV Behavioral Surveillance System (NHBS), the 2011 National HIV Surveillance System (NHSS), and the 2007-2009 Medical Monitoring Project (MMP). Of males aged ≥ 18 years, MSM/IDU comprised an estimated 0.35% in NHANES, 7%-20% in NHBS, an estimated 4%-8% in NHSS, and 9% in MMP. Across surveillance systems, MSM/IDU accounted for 4%-12% of MSM and 11%-39% of male IDU. Risk reduction programs and interventions targeted toward male IDU populations might be more effective if they also incorporate messages about male-to-male sex.

  16. The adverse effects of albendazole and praziquantel in mass drug ...

    African Journals Online (AJOL)

    and headache. This shows that more pupils from Mwea, (albendazole and praziquantel) than from Ndia (albendazole alone) experienced minor side effects. These results show that both drugs have temporary, minor side effects, which can be managed by trained schoolteachers by ensuring that the school children do not ...

  17. Does the placebo effect modulate drug bioavailability? Randomized cross-over studies of three drugs.

    Science.gov (United States)

    Hammami, Muhammad M; Yusuf, Ahmed; Shire, Faduma S; Hussein, Rajaa; Al-Swayeh, Reem

    2017-05-23

    Medication effect is the sum of its drug, placebo, and drug*placebo interaction effects. It is conceivable that the interaction effect involves modulating drug bioavailability; it was previously observed that being aware of caffeine ingestion may prolong caffeine plasma half-life. This study was set to evaluate such concept using different drugs. Balanced single-dose, two-period, two-group, cross-over design was used to compare the pharmacokinetics of oral cephalexin, ibuprofen, and paracetamol, each described by its name (overt) or as placebo (covert). Volunteers and study coordinators were deceived as to study aim. Drug concentrations were determined blindly by in-house, high performance liquid chromatography assays. Terminal-elimination half-life (t ½ ) (primary outcome), maximum concentration (C max ), C max first time (T max ), terminal-elimination-rate constant (λ), area-under-the-concentration-time-curve, to last measured concentration (AUC T ), extrapolated to infinity (AUC I ), or to T max of overt drug (AUC Overttmax ), and C max /AUC I were calculated blindly using standard non-compartmental method. Covert-vs-overt effect on drug pharmacokinetics was evaluated by analysis-of-variance (ANOVA, primary analysis), 90% confidence interval (CI) using the 80.00-125.00% bioequivalence range, and percentage of individual pharmacokinetic covert/overt ratios that are outside the +25% range. Fifty, 30, and 50 healthy volunteers (18%, 10%, and 6% females, mean (SD) age 30.8 (6.2), 31.4 (6.6), and 31.2 (5.4) years) participated in 3 studies on cephalexin, ibuprofen, and paracetamol, respectively. Withdrawal rate was 4%, 0%, and 4%, respectively. Eighteen blood samples were obtained over 6, 10, and 14 h in each study period of the three drugs, respectively. ANOVA showed no significant difference in any pharmacokinetic parameter for any of the drugs. The 90% CIs for AUC T , AUC I , C max , AUC Overttmax , and C max /AUC I were within the bioequivalence range, except

  18. Estimation of illicit drug use in the main cities of Colombia by means of urban wastewater analysis.

    Science.gov (United States)

    Bijlsma, Lubertus; Botero-Coy, Ana M; Rincón, Rolando J; Peñuela, Gustavo A; Hernández, Félix

    2016-09-15

    Wastewater-based epidemiology (WBE) relies on the principle that traces of compounds, which a population is exposed to or consume, are excreted unchanged or as metabolites in urine and/or feces, and ultimately end up in the sewer network. Measuring target metabolic residues i.e. biomarkers in raw urban wastewater allows identifying the exposure or use of substances of interest in a community. Up to date, the most popular application of WBE is the estimation of illicit drug use and studies have been made mainly across Europe, which has allowed estimating and comparing drug use in many European cities. However, until now a comprehensive study applying WBE on the most frequently consumed illicit drugs has not been performed in South American countries. In this work, we applied this approach to samples from Colombia, selecting two of the most populated cities: Bogotá and Medellin. Several biomarkers were selected to estimate drug use of cocaine, cannabis, amphetamine, methamphetamine, MDMA (ecstasy), heroin and ketamine. Composite samples (24-h) were collected at the corresponding municipal wastewater treatment plants. Sample treatment was performed at location by applying solid-phase extraction (SPE). Before SPE, the samples were spiked with appropriate isotope labeled internal standards. In parallel, samples (spiked with the analytes under study at two concentration levels) were also processed for quality control. Analysis of influent wastewater was made by liquid chromatography-tandem mass spectrometry, with triple quadrupole analyzer. Data shown in this paper reveal a high use of cocaine by the population of the selected Colombian cities, particularly from Medellin, while the use of other illicit drugs were low. The relevance of using quality control samples, particularly in collaborative studies, as those presented in this work, where research groups from different countries participate and where the samples had to be shipped overseas, is highlighted in this

  19. How to Estimate and Interpret Various Effect Sizes

    Science.gov (United States)

    Vacha-Haase, Tammi; Thompson, Bruce

    2004-01-01

    The present article presents a tutorial on how to estimate and interpret various effect sizes. The 5th edition of the Publication Manual of the American Psychological Association (2001) described the failure to report effect sizes as a "defect" (p. 5), and 23 journals have published author guidelines requiring effect size reporting. Although…

  20. [Side effects of drugs on the oral cavity].

    Science.gov (United States)

    Bascones-Martínez, Antonio; Muñoz-Corcuera, Marta; Bascones-Ilundain, Cristina

    2015-02-02

    Although drugs are the most powerful therapeutic tools we have for improving the quality of life of the population, their use is not free of adverse effects. Today there are many polymedicated patients, and it is difficult to find the cause of their adverse effects that increase exponentially when more than 4 drugs are combined. There are a large number of drugs that can result in numerous adverse effects in the oral cavity. The most common are xerostomia, altered taste, gingival enlargement and mucositis caused by cancer treatment. We also review other disorders of the salivary glands, oral mucosal changes, pigmentations, halitosis, osteonecrosis, opportunistic infections and bleeding diathesis. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  1. Trends in reports of driving following illicit drug consumption among regular drug users in Australia, 2007-2013: Has random roadside drug testing had a deterrent effect?

    Science.gov (United States)

    Horyniak, Danielle; Dietze, Paul; Lenton, Simon; Alati, Rosa; Bruno, Raimondo; Matthews, Allison; Breen, Courtney; Burns, Lucy

    2017-07-01

    Driving following illicit drug consumption ('drug-driving') is a potential road safety risk. Roadside drug testing (RDT) is conducted across Australia with the dual aims of prosecuting drivers with drugs in their system and deterring drug-driving. We examined trends over time in self-reported past six-month drug-driving among sentinel samples of regular drug users and assessed the impact of experiences of RDT on drug-driving among these participants. Data from 1913 people who inject drugs (PWID) and 3140 regular psychostimulant users (RPU) who were first-time participants in a series of repeat cross-sectional sentinel studies conducted in Australian capital cities from 2007 to 2013 and reported driving in the past six months were analysed. Trends over time were assessed using the χ 2 test for trend. Multivariable logistic regressions assessed the relationship between experiences of RDT and recent drug-driving, adjusting for survey year, jurisdiction of residence and socio-demographic and drug use characteristics. The percentage of participants reporting recent (past six months) drug-driving decreased significantly over time among both samples (PWID: 83% [2007] vs. 74% [2013], p<0.001; RPU: 72% vs. 56%, p<0.001), but drug-driving remained prevalent. Lifetime experience of RDT increased significantly over time (PWID: 6% [2007] vs. 32% [2013], p<0.001; RPU: 2% vs. 11%, p<0.001). There were no significant associations between experiencing RDT and drug-driving among either PWID or RPU. Although there is some evidence that drug-driving among key risk groups of regular drug users is declining in Australia, possibly reflecting a general deterrent effect of RDT, experiencing RDT appears to have no specific deterrent effect on drug-driving. Further intervention, with a particular focus on changing attitudes towards drug-driving, may be needed to further reduce this practice among these groups. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Drug-Drug Interactions, Effectiveness, and Safety of Hormonal Contraceptives in Women Living with HIV

    Science.gov (United States)

    Scarsi, Kimberly K.; Darin, Kristin M.; Chappell, Catherine A.; Nitz, Stephanie M.; Lamorde, Mohammed

    2016-01-01

    Family planning options, including hormonal contraceptives, are essential for improving reproductive health among the more than 17 million women living with human immunodeficiency virus (HIV) worldwide. For these women, prevention of unintended pregnancy decreases maternal and child mortality, as well as reduces the risk of perinatal HIV transmission. Similarly, treatment of HIV with antiretroviral therapy (ART) is essential for reducing morbidity and mortality among HIV-positive individuals, as well as preventing HIV transmission between sexual partners or from mother to child. Importantly, despite the benefits of hormonal contraceptives, barriers to effective family planning methods exist for HIV-positive women. Specifically, drug-drug interactions can occur between some antiretroviral medications and some hormonal contraceptives, which may influence both contraceptive efficacy and tolerability. In addition, safety concerns have been raised about the impact of hormonal contraceptives on HIV disease progression, tolerability and the risk of female-to-male HIV transmission. This review article summarizes the potential for drug-drug interactions, tolerability, and contraceptive effectiveness when hormonal contraceptives are combined with ART. In addition, the evidence surrounding the influence of hormonal contraceptives on HIV transmission and HIV disease progression in women living with HIV are summarized. PMID:27562873

  3. Effect size estimates: current use, calculations, and interpretation.

    Science.gov (United States)

    Fritz, Catherine O; Morris, Peter E; Richler, Jennifer J

    2012-02-01

    The Publication Manual of the American Psychological Association (American Psychological Association, 2001, American Psychological Association, 2010) calls for the reporting of effect sizes and their confidence intervals. Estimates of effect size are useful for determining the practical or theoretical importance of an effect, the relative contributions of factors, and the power of an analysis. We surveyed articles published in 2009 and 2010 in the Journal of Experimental Psychology: General, noting the statistical analyses reported and the associated reporting of effect size estimates. Effect sizes were reported for fewer than half of the analyses; no article reported a confidence interval for an effect size. The most often reported analysis was analysis of variance, and almost half of these reports were not accompanied by effect sizes. Partial η2 was the most commonly reported effect size estimate for analysis of variance. For t tests, 2/3 of the articles did not report an associated effect size estimate; Cohen's d was the most often reported. We provide a straightforward guide to understanding, selecting, calculating, and interpreting effect sizes for many types of data and to methods for calculating effect size confidence intervals and power analysis.

  4. Extravasational side effects of cytotoxic drugs: A preventable catastrophe

    Directory of Open Access Journals (Sweden)

    Thakur Jagdeep

    2008-01-01

    Full Text Available In addition to their therapeutic effects on malignant cells, cytotoxic agents have the potential of causing destruction of healthy, normal cells. Extravasation of the drug can produce extensive necrosis of the skin and subcutaneous tissue. Management of these extravasational effects differs from one centre to another and prevention is usually strongly emphasized. We analyzed our management of 12 patients referred to us over five years with extravasation of cytotoxic drugs and reviewed the literature for different approaches with regard to prophylaxis and management of extravasational effects. Materials and Methods: This study was done in the department of plastic surgery of a medical college. Five years of retrospective data were studied of patients referred to our department with extravasation of cytotoxic drugs. Results: We managed 12 cases referred to our department with extravasation of cytotoxic drugs. Mitomycin C was used in seven cases (58.33%, vincristine in two cases (16.66%, 5-Florouracil in another two cases while doxorubicin was responsible for extravasational side effects in one case (8.33%. The size of necrosis ranged from 3.75 cm 2 to 25 cm 2 with average size of 9.6 cm 2 . In terms of the area involved, the dorsum of the hand was involved in five cases (41.66%, the wrist in another five cases (41.66%, and the cubital fossa in the remaining two cases (16.66%. All cases were treated with daily debridement of necrotic tissue, saline dressing, and split skin grafting. Conclusion: Extravasation of cytotoxic drugs further increases the suffering of cancer patients. This catastrophe can only be avoided by vigilance and immediate application of antidotes. Once the local toxicity of the drugs takes effect, morbidity is unavoidable

  5. Adult head CT scans: the uncertainties of effective dose estimates

    International Nuclear Information System (INIS)

    Gregory, Kent J.; Bibbo, Giovanni; Pattison, John E.

    2008-01-01

    Full Text: CT scanning is a high dose imaging modality. Effective dose estimates from CT scans can provide important information to patients and medical professionals. For example, medical practitioners can use the dose to estimate the risk to the patient, and judge whether this risk is outweighed by the benefits of the CT examination, while radiographers can gauge the effect of different scanning protocols on the patient effective dose, and take this into consideration when establishing routine scan settings. Dose estimates also form an important part of epidemiological studies examining the health effects of medical radiation exposures on the wider population. Medical physicists have been devoting significant effort towards estimating patient radiation doses from diagnostic CT scans for some years. The question arises: How accurate are these effective dose estimates? The need for a greater understanding and improvement of the uncertainties in CT dose estimates is now gaining recognition as an important issue (BEIR VII 2006). This study is an attempt to analyse and quantify the uncertainty components relating to effective dose estimates from adult head CT examinations that are calculated with four commonly used methods. The dose estimation methods analysed are the Nagel method, the ImpaCT method, the Wellhoefer method and the Dose-Length Product (DLP) method. The analysis of the uncertainties was performed in accordance with the International Standards Organisation's Guide to the Expression of Uncertainty in Measurement as discussed in Gregory et al (Australas. Phys. Eng. Sci. Med., 28: 131-139, 2005). The uncertainty components vary, depending on the method used to derive the effective dose estimate. Uncertainty components in this study include the statistical and other errors from Monte Carlo simulations, uncertainties in the CT settings and positions of patients in the CT gantry, calibration errors from pencil ionization chambers, the variations in the organ

  6. Estimating the coverage of a targeted mobile tuberculosis screening programme among illicit drug users and homeless persons with truncated models

    Science.gov (United States)

    VAN HEST, N. A. H.; De VRIES, G.; SMIT, F.; GRANT, A. D.; RICHARDUS, J. H.

    2008-01-01

    SUMMARY Truncated models are indirect methods to estimate the size of a hidden population which, in contrast to the capture–recapture method, can be used on a single information source. We estimated the coverage of a tuberculosis screening programme among illicit drug users and homeless persons with a mobile digital X-ray unit between 1 January 2003 and 31 December 2005 in Rotterdam, The Netherlands, using truncated models. The screening programme reached about two-third of the estimated target population at least once annually. The intended coverage (at least two chest X-rays per person per year) was about 23%. We conclude that simple truncated models can be used relatively easily on available single-source routine data to estimate the size of a population of illicit drug users and homeless persons. We assumed that the most likely overall bias in this study would be overestimation and therefore the coverage of the targeted mobile tuberculosis screening programme would be higher. PMID:17631692

  7. Recommendations on the effect of antidiabetic drugs in bone.

    Science.gov (United States)

    Rozas-Moreno, Pedro; Reyes-García, Rebeca; Jódar-Gimeno, Esteban; Varsavsky, Mariela; Luque-Fernández, Inés; Cortés-Berdonces, María; Muñoz-Torres, Manuel

    2017-03-01

    To provide recommendations on the effect of antidiabetic drugs on bone fragility to help select the most adequate antidiabetic treatment, especially in diabetic patients with high risk of fracture. Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. The GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) was used to establish both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each antidiabetic drug: AND "osteoporosis", "fractures", "bone mineral density", "bone markers", "calciotropic hormones". Papers in English with publication date before 30 April 2016 were reviewed. Recommendations were jointly discussed by the Working Group. The document summaries the data on the potential effects of antidiabetic drugs on bone metabolism and fracture risk. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Cardiovascular effects of current and future anti-obesity drugs

    DEFF Research Database (Denmark)

    Comerma Steffensen, Simon Gabriel; Grann, Martin; Andersen, Charlotte U

    2014-01-01

    The prevalence of obesity increases and is associated with increases in co-morbidities e.g. type 2 diabetes, hyperlipidemia, hypertension, obstructive sleep apnea, heart disease, stroke, asthma, several forms of cancer, depression, and may result in reduction of expected remaining lifespan. We have...... reviewed the adverse effects on the cardiovascular system of anti-obesity drugs now retracted from the market as well as the cardiovascular profile of current drugs and potential pathways which are considered for treatment of obesity. Fenfluramine, and sibutramine were withdrawn due to increased...... side effects need to be clarified regarding phentermine and lorcaserin. Drugs approved for type 2 diabetes including glucagon like peptide (GLP-1) analogues and metformin also cause moderate weight losses and have a favourable cardiovascular profile, while the anti-obesity potential of nebivolol...

  9. Colored noise effects on batch attitude accuracy estimates

    Science.gov (United States)

    Bilanow, Stephen

    1991-01-01

    The effects of colored noise on the accuracy of batch least squares parameter estimates with applications to attitude determination cases are investigated. The standard approaches used for estimating the accuracy of a computed attitude commonly assume uncorrelated (white) measurement noise, while in actual flight experience measurement noise often contains significant time correlations and thus is colored. For example, horizon scanner measurements from low Earth orbit were observed to show correlations over many minutes in response to large scale atmospheric phenomena. A general approach to the analysis of the effects of colored noise is investigated, and interpretation of the resulting equations provides insight into the effects of any particular noise color and the worst case noise coloring for any particular parameter estimate. It is shown that for certain cases, the effects of relatively short term correlations can be accommodated by a simple correction factor. The errors in the predicted accuracy assuming white noise and the reduced accuracy due to the suboptimal nature of estimators that do not take into account the noise color characteristics are discussed. The appearance of a variety of sample noise color characteristics are demonstrated through simulation, and their effects are discussed for sample estimation cases. Based on the analysis, options for dealing with the effects of colored noise are discussed.

  10. Illicit drugs and pharmaceuticals in the environment - Forensic applications of environmental data. Part 1: Estimation of the usage of drugs in local communities

    Energy Technology Data Exchange (ETDEWEB)

    Kasprzyk-Hordern, Barbara, E-mail: b.kasprzyk-hordern@hud.ac.u [University of Huddersfield, Department of Chemical and Biological Sciences, Queensgate, Huddersfield HD1 3DH (United Kingdom); University of Glamorgan, Sustainable Environment Research Centre, Faculty of Health, Sport and Science, Pontypridd CF37 1DL (United Kingdom); Dinsdale, Richard M.; Guwy, Alan J. [University of Glamorgan, Sustainable Environment Research Centre, Faculty of Health, Sport and Science, Pontypridd CF37 1DL (United Kingdom)

    2009-06-15

    Pharmaceuticals and recently also illicit drugs have been recognised as emerging environmental contaminants due to their potential environmental impact: frequent occurrence, persistence and risk to aquatic life and humans. This manuscript is part one of the two-part study aiming to provide a better understanding and application of environmental data not only for environmental aims but also to meet forensic objectives. An attempt to use wastewater data is made in order to verify patterns of the usage of drugs (in particular illicit) in local communities. The average usage of cocaine in South Wales was estimated at 0.9 g day{sup -1} 1000 people{sup -1}, which equals 1 tonne of this drug used or disposed of to sewage annually in Wales. The calculated usage of amphetamine denoted 2.5 g day{sup -1} 1000 people{sup -1} and is suspected to be an overestimate. Because no analysis of enantiomers of amphetamine was undertaken, no distinction between amphetamine's legal and illicit usage could be made. - Wastewater as an indicative source of information can be used in forensic applications.

  11. The Mirror Illusion’s Effects on Body State Estimation

    Science.gov (United States)

    Soliman, Tamer M.; Buxbaum, Laurel J.; Jax, Steven A.

    2016-01-01

    The mirror illusion uses a standard mirror to create a compelling illusion in which movements of one limb seem to be made by the other hidden limb. In this paper we adapt a motor control framework to examine which estimates of the body’s configuration are affected by the illusion. We propose that the illusion primarily alters estimates related to upcoming states of the body (the desired state and the predicted state), with smaller effects on the estimate of the body state prior to movement initiation. Support for this proposal is provided both by behavioral effects of the illusion as well as neuroimaging evidence from one neural region, V6A, that is critically involved in the mirror illusion and limb state estimation more generally. PMID:27390062

  12. Estimation of Nonlinear Dynamic Panel Data Models with Individual Effects

    Directory of Open Access Journals (Sweden)

    Yi Hu

    2014-01-01

    Full Text Available This paper suggests a generalized method of moments (GMM based estimation for dynamic panel data models with individual specific fixed effects and threshold effects simultaneously. We extend Hansen’s (Hansen, 1999 original setup to models including endogenous regressors, specifically, lagged dependent variables. To address the problem of endogeneity of these nonlinear dynamic panel data models, we prove that the orthogonality conditions proposed by Arellano and Bond (1991 are valid. The threshold and slope parameters are estimated by GMM, and asymptotic distribution of the slope parameters is derived. Finite sample performance of the estimation is investigated through Monte Carlo simulations. It shows that the threshold and slope parameter can be estimated accurately and also the finite sample distribution of slope parameters is well approximated by the asymptotic distribution.

  13. Estimating trends in the proportion of transmitted and acquired HIV drug resistance in a long term observational cohort in Germany.

    Directory of Open Access Journals (Sweden)

    Daniel Schmidt

    Full Text Available OBJECTIVE: We assessed trends in the proportion of transmitted (TDR and acquired (ADR HIV drug resistance and associated mutations between 2001 and 2011 in the German ClinSurv-HIV Drug Resistance Study. METHOD: The German ClinSurv-HIV Drug Resistance Study is a subset of the German ClinSurv-HIV Cohort. For the ClinSurv-HIV Drug Resistance Study all available sequences isolated from patients in five study centres of the long term observational ClinSurv-HIV Cohort were included. TDR was estimated using the first viral sequence of antiretroviral treatment (ART naïve patients. One HIV sequence/patient/year of ART experienced patients was considered to estimate the proportion of ADR. Trends in the proportion of HIV drug resistance were calculated by logistic regression. RESULTS: 9,528 patients were included into the analysis. HIV-sequences of antiretroviral naïve and treatment experienced patients were available from 34% (3,267/9,528 of patients. The proportion of TDR over time was stable at 10.4% (95% CI 9.1-11.8; p for trend = 0.6; 2001-2011. The proportion of ADR among all treated patients was 16%, whereas it was high among those with available HIV genotypic resistance test (64%; 1,310/2,049 sequences; 95% CI 62-66 but declined significantly over time (OR 0.8; 95% CI 0.77-0.83; p for trend<0.001; 2001-2011. Viral load monitoring subsequent to resistance testing was performed in the majority of treated patients (96% and most of them (67% were treated successfully. CONCLUSIONS: The proportion of TDR was stable in this study population. ADR declined significantly over time. This decline might have been influenced by broader resistance testing, resistance test guided therapy and the availability of more therapeutic options and not by a decline in the proportion of TDR within the study population.

  14. Using human genetics to predict the effects and side-effects of drugs

    DEFF Research Database (Denmark)

    Stender, Stefan; Tybjærg-Hansen, Anne

    2016-01-01

    PURPOSE OF REVIEW: 'Genetic proxies' are increasingly being used to predict the effects of drugs. We present an up-to-date overview of the use of human genetics to predict effects and adverse effects of lipid-targeting drugs. RECENT FINDINGS: LDL cholesterol lowering variants in HMG-Coenzyme A re...

  15. Effect of drugs on chemoreceptor responsiveness in fetal sheep

    NARCIS (Netherlands)

    Boekkooi, P. F.; Baan, J.; Teitel, D. F.; Rudolph, A. M.

    1995-01-01

    This study was designed to examine the effects of the drugs ketamine, morphine, pentobarbital, and propranolol on fetal chemoreceptor responsiveness. Eleven fetal lambs (gestational age 125-133 d) were chronically instrumented with a catheter in a hindlimb artery and vein and a forelimb artery; a

  16. Book Review: The Drug Effect | Kriegler | South African Crime ...

    African Journals Online (AJOL)

    Title: The Drug Effect: Health, Crime and Society Editors: Suzanne Fraser and David Moore Publisher: Cambridge University Press Price: R500.00 (incl. VAT and postage) Pages: 260. Availability: Published. Available through all academic bookstores. ISBN: 978-0-521-15605-9 ...

  17. Adolescent Initiation of Drug Use: Effects of Prenatal Cocaine Exposure

    Science.gov (United States)

    Richardson, Gale A.; Larkby, Cynthia; Goldschmidt, Lidush; Day, Nancy L.

    2013-01-01

    Objective: To investigate the direct effects of prenatal cocaine exposure (PCE) on adolescent drug use, while controlling for other predictors of adolescent use. Method: Data are from a longitudinal study of PCE in which women and their offspring were assessed throughout childhood. Adolescents were interviewed at 15 years about their age at…

  18. Dissolution enhancement of drugs. part i: technologies and effect of ...

    African Journals Online (AJOL)

    and steam aided granulation. In these techniques carrier plays an important role in improving solubility and dissolution rate. Polymers, superdisintegrants, surfactants are extensively studied in recent years for dissolution enhancement in drugs. This part of this review discusses technological overview and effect of polymers,

  19. Side effects of drugs used in directly observed treatment short ...

    African Journals Online (AJOL)

    Aim: The study assessed the side effects of drugs used in directly observed treatment short course in a newly diagnosed pulmonary tuberculosis patients at the chest unit of University of Nigeria Teaching Hospital in Enugu State, Nigeria. Methods: A retrospective study, involving a 3-year review of case files of TB patients ...

  20. Estimating the size of the HIV epidemic among injecting drug users in Amsterdam

    NARCIS (Netherlands)

    van Haastrecht, H. J.; Bindels, P. J.; van den Hoek, A. A.; Coutinho, R. A.

    1997-01-01

    Aim of this study was to assess the cumulative incidence of HIV-infection, AIDS and pre-AIDS death in the population of injecting drug users (IDU) in Amsterdam. By assuming equivalence, between a cohort of IDU and the IDU population, of the ratios of incidences of AIDS and pre-AIDS death to the

  1. Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Kirk, Ole; Reiss, Peter

    2010-01-01

    OBJECTIVES:: Chronic kidney disease (CKD) in HIV-positive persons might be caused by both HIV and traditional or non-HIV-related factors. Our objective was to investigate long-term exposure to specific antiretroviral drugs and CKD. DESIGN:: A cohort study including 6843 HIV-positive persons...

  2. Is immunotherapy an opportunity for effective treatment of drug addiction?

    Science.gov (United States)

    Zalewska-Kaszubska, Jadwiga

    2015-11-27

    Immunotherapy has a great potential of becoming a new therapeutic strategy in the treatment of addiction to psychoactive drugs. It may be used to treat addiction but also to prevent neurotoxic complications of drug overdose. In preclinical studies two immunological methods have been tested; active immunization, which relies on the administration of vaccines and passive immunization, which relies on the administration of monoclonal antibodies. Until now researchers have succeeded in developing vaccines and/or antibodies against addiction to heroin, cocaine, methamphetamine, nicotine and phencyclidine. Their effectiveness has been confirmed in preclinical studies. At present, clinical studies are being conducted for vaccines against nicotine and cocaine and also anti-methamphetamine monoclonal antibody. These preclinical and clinical studies suggest that immunotherapy may be useful in the treatment of addiction and drug overdose. However, there are a few problems to be solved. One of them is controlling the level of antibodies due to variability between subjects. But even obtaining a suitable antibody titer does not guarantee the effectiveness of the vaccine. Additionally, there is a risk of intentional or unintentional overdose. As vaccines prevent passing of drugs through the blood/brain barrier and thereby prevent their positive reinforcement, some addicted patients may erroneously seek higher doses of psychoactive substances to get "high". Consequently, vaccination should be targeted at persons who have a strong motivation to free themselves from drug dependency. It seems that immunotherapy may be an opportunity for effective treatment of drug addiction if directed to adequate candidates for treatment. For other addicts, immunotherapy may be a very important element supporting psycho- and pharmacotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Estimation of illicit drug use in the main cities of Colombia by means of urban wastewater analysis

    Energy Technology Data Exchange (ETDEWEB)

    Bijlsma, Lubertus; Botero-Coy, Ana M. [Research Institute for Pesticides and Water (IUPA), University Jaume I, Castellón (Spain); Rincón, Rolando J. [Chemistry Department, Faculty of Sciences, University Antonio Nariño (Colombia); Peñuela, Gustavo A. [Grupo GDCON, Facultad de Ingeniería, Universidad de Antioquia, 70 # 52-21, Medellin (Colombia); Hernández, Félix, E-mail: felix.hernandez@uji.es [Research Institute for Pesticides and Water (IUPA), University Jaume I, Castellón (Spain)

    2016-09-15

    Wastewater-based epidemiology (WBE) relies on the principle that traces of compounds, which a population is exposed to or consume, are excreted unchanged or as metabolites in urine and/or feces, and ultimately end up in the sewer network. Measuring target metabolic residues i.e. biomarkers in raw urban wastewater allows identifying the exposure or use of substances of interest in a community. Up to date, the most popular application of WBE is the estimation of illicit drug use and studies have been made mainly across Europe, which has allowed estimating and comparing drug use in many European cities. However, until now a comprehensive study applying WBE on the most frequently consumed illicit drugs has not been performed in South American countries. In this work, we applied this approach to samples from Colombia, selecting two of the most populated cities: Bogotá and Medellin. Several biomarkers were selected to estimate drug use of cocaine, cannabis, amphetamine, methamphetamine, MDMA (ecstasy), heroin and ketamine. Composite samples (24-h) were collected at the corresponding municipal wastewater treatment plants. Sample treatment was performed at location by applying solid-phase extraction (SPE). Before SPE, the samples were spiked with appropriate isotope labeled internal standards. In parallel, samples (spiked with the analytes under study at two concentration levels) were also processed for quality control. Analysis of influent wastewater was made by liquid chromatography-tandem mass spectrometry, with triple quadrupole analyzer. Data shown in this paper reveal a high use of cocaine by the population of the selected Colombian cities, particularly from Medellin, while the use of other illicit drugs were low. The relevance of using quality control samples, particularly in collaborative studies, as those presented in this work, where research groups from different countries participate and where the samples had to be shipped overseas, is highlighted in this

  4. Estimation of illicit drug use in the main cities of Colombia by means of urban wastewater analysis

    International Nuclear Information System (INIS)

    Bijlsma, Lubertus; Botero-Coy, Ana M.; Rincón, Rolando J.; Peñuela, Gustavo A.; Hernández, Félix

    2016-01-01

    Wastewater-based epidemiology (WBE) relies on the principle that traces of compounds, which a population is exposed to or consume, are excreted unchanged or as metabolites in urine and/or feces, and ultimately end up in the sewer network. Measuring target metabolic residues i.e. biomarkers in raw urban wastewater allows identifying the exposure or use of substances of interest in a community. Up to date, the most popular application of WBE is the estimation of illicit drug use and studies have been made mainly across Europe, which has allowed estimating and comparing drug use in many European cities. However, until now a comprehensive study applying WBE on the most frequently consumed illicit drugs has not been performed in South American countries. In this work, we applied this approach to samples from Colombia, selecting two of the most populated cities: Bogotá and Medellin. Several biomarkers were selected to estimate drug use of cocaine, cannabis, amphetamine, methamphetamine, MDMA (ecstasy), heroin and ketamine. Composite samples (24-h) were collected at the corresponding municipal wastewater treatment plants. Sample treatment was performed at location by applying solid-phase extraction (SPE). Before SPE, the samples were spiked with appropriate isotope labeled internal standards. In parallel, samples (spiked with the analytes under study at two concentration levels) were also processed for quality control. Analysis of influent wastewater was made by liquid chromatography-tandem mass spectrometry, with triple quadrupole analyzer. Data shown in this paper reveal a high use of cocaine by the population of the selected Colombian cities, particularly from Medellin, while the use of other illicit drugs were low. The relevance of using quality control samples, particularly in collaborative studies, as those presented in this work, where research groups from different countries participate and where the samples had to be shipped overseas, is highlighted in this

  5. The effect of newer anti-rheumatic drugs on osteogenic cell proliferation: an in-vitro study

    Directory of Open Access Journals (Sweden)

    Laing Patrick

    2009-05-01

    Full Text Available Abstract Background Disease modifying anti-rheumatic drugs (DMARDs may interfere with bone healing. Previous studies give conflicting advice regarding discontinuation of these drugs in the peri-operative setting. No consensus exists in current practice especially with the newer DMARDs such as Leflunomide, Etanercept, and Infliximab. The aim of this study was to assess the in-vitro effect of these drugs alone and in relevant clinical combinations on Osteoblast activity. Methods Osteoblasts were cultured from femoral heads obtained from five young otherwise healthy patients undergoing total hip replacement. The cells were cultured using techniques that have been previously described. A full factorial design was used to set up the experiment on samples obtained from the five donors. Normal therapeutic concentrations of the various DMARDs were added alone and in combination to the media. The cell proliferation was estimated after two weeks using spectrophotometric technique using Roche Cell proliferation Kit. Multilevel regression analysis was used to estimate which drugs or combination of drugs significantly affected cell proliferation. Results Infliximab and Leflunomide had an overall significant inhibitory effect (p Conclusion Our study indicates that in-vitro osteoblast proliferation can be inhibited by the presence of certain DMARDs. Combinations of drugs had an influence and could negate the action of a drug on osteoblast proliferation. The response to drugs may be donor-dependent.

  6. The effectiveness of compulsory drug treatment: A systematic review.

    Science.gov (United States)

    Werb, D; Kamarulzaman, A; Meacham, M C; Rafful, C; Fischer, B; Strathdee, S A; Wood, E

    2016-02-01

    Despite widespread implementation of compulsory treatment modalities for drug dependence, there has been no systematic evaluation of the scientific evidence on the effectiveness of compulsory drug treatment. We conducted a systematic review of studies assessing the outcomes of compulsory treatment. We conducted a search in duplicate of all relevant peer-reviewed scientific literature evaluating compulsory treatment modalities. The following academic databases were searched: PubMed, PAIS International, Proquest, PsycINFO, Web of Science, Soc Abstracts, JSTOR, EBSCO/Academic Search Complete, REDALYC, SciELO Brazil. We also searched the Internet, and article reference lists, from database inception to July 15th, 2015. Eligibility criteria are as follows: peer-reviewed scientific studies presenting original data. Primary outcome of interest was post-treatment drug use. Secondary outcome of interest was post-treatment criminal recidivism. Of an initial 430 potential studies identified, nine quantitative studies met the inclusion criteria. Studies evaluated compulsory treatment options including drug detention facilities, short (i.e., 21-day) and long-term (i.e., 6 months) inpatient treatment, community-based treatment, group-based outpatient treatment, and prison-based treatment. Three studies (33%) reported no significant impacts of compulsory treatment compared with control interventions. Two studies (22%) found equivocal results but did not compare against a control condition. Two studies (22%) observed negative impacts of compulsory treatment on criminal recidivism. Two studies (22%) observed positive impacts of compulsory inpatient treatment on criminal recidivism and drug use. There is limited scientific literature evaluating compulsory drug treatment. Evidence does not, on the whole, suggest improved outcomes related to compulsory treatment approaches, with some studies suggesting potential harms. Given the potential for human rights abuses within compulsory

  7. Oral fluid drug tests: effects of adulterants and foodstuffs.

    Science.gov (United States)

    Wong, Raphael C; Tran, Minhchau; Tung, James K

    2005-06-10

    An on-site oral fluid drug screen, Oratect, was used to investigate the effects of adulterants and foodstuffs on oral fluid test results. Common foods, beverages, food ingredients, cosmetics and hygienic products were demonstrated not to cause false positive results when tested 30 min after their consumption. Evaluations of two commercial oral fluid adulterants, "Clear Choice Fizzy Flush" and "Test'in Spit n Kleen Mouthwash" suggest their mechanism of action is the clearing of residual drugs of abuse compounds through rinsing of the oral cavity. They do not directly destroy the drug compounds or change the pH of the oral fluid. It is also suggested that a common mouthwash would perform similar action.

  8. [Effects of penetration enhancers on curcumin transdermal drug delivery].

    Science.gov (United States)

    Gao, Zhen-Shen; Wang, Lan; Zhang, Mei

    2012-01-01

    To study the effects of penetration enhancers and their combinations on the curcumine transdermal drug delivery (CUR-TDDS). The penetration rate of curcumin through rat skin in vitro was measured using Valia-Chien diffusion cells, and orthogonal design method was set up for experimental design. The optimum penetration enhancers were: 3% hydroxypropyl beta cyclodextrins (HP-beta-CD), 9% borneol and 3% peppermint oil. The HP-beta-CD has the most potent enhancing effect.

  9. Alcohol and Student Performance: Estimating the Effect of Legal Access

    OpenAIRE

    Jason M. Lindo; Isaac D. Swensen; Glen R. Waddell

    2011-01-01

    We consider the effect of legal access to alcohol, which is known to increase drinking behavior, on academic performance. We first estimate the effect using an RD design but argue that this approach is not well-suited to the research question in our setting. Our preferred approach instead exploits the longitudinal nature of the data, essentially identifying the effect by comparing a student's academic performance before and after turning 21. We find that students' grades fall below their expe...

  10. Effect of the anticarcinogenic drug 6-mercaptopurine on mineral metabolism

    International Nuclear Information System (INIS)

    Amemiya, K.

    1987-01-01

    The effect of 6-mercaptopurine (6-MP) on mineral metabolism was investigated using rats and mice. A single 6-mercaptopurine injection in pregnant rats on day 11 of gestation proved to be highly teratogenic. At term, fetuses from 6-MP injected dams had lower livers zinc concentrations than non-injected or vehicle injected controls while dams showed no differences in liver zinc. Fetuses from dams injected with 6-MP and fed supplemental levels of zinc had a lower frequency of malformations and had higher hepatic zinc concentrations than fetuses from dams fed less zinc with drug injection. Non-pregnant mice injected with 6-MP had higher zinc concentrations compared to controls. In addition, iron, copper and calcium concentrations were higher in the livers of 6-MP injected mice than in controls, indicating that the drug affected several elements. Hepatic concentrations of metallothionein (MT) were also elevated in 6-MP injected mice, suggesting that the change in zinc concentrations associated with drug administration was the result of a drug induction of MT. Dams injected with 6-MP on day 13 of pregnancy had livers which retained more of an absorbed dose of 65 zinc than non-injected dams. Plasma from these drug injected dams also retained less of the absorbed dose than control dams. In contrast, day 14 from dams injected with 6-MP, retained less of an absorbed dose than control embryos

  11. [Prevalence estimates of problem drug users in the Czech Republic in 2006 and 2007 using the capture-recapture method].

    Science.gov (United States)

    Mravčík, Viktor; Sopko, Bruno

    2013-07-01

    An estimate of problem drug use prevalence is a substantial part of the monitoring of the epidemiological situation in drug use and its consequences and an important indicator for drug policy implementation. The capture-recapture method (CRM) is one of the most commonly used standard methods for this purpose worldwide. The CRM was used to estimate the numbers of problem drug users (PDU) and problem users of opiates/opioids (PUO) in the Czech Republic in 2006 and 2007. The following data sources were used: the General Health Insurance Company records of payments to out- and in-patient psychiatric care providers, records of admissions to psychiatric hospitals, replacement therapy register, and reports of newly diagnosed cases of viral hepatitis. Cases were defined as diagnoses F11, F15, and F19 according to the International Classification of Diseases, Tenth Revision (ICD-10) from the health insurance and admission records, the replacement therapy register covers PUO by definition, and injecting drug users were selected from reported cases of viral hepatitis. Log-linear analysis in Rcapture (R) was performed and the Akaike information criterion was used for model selection. Altogether 12,882 and 13,505 individuals entered into analysis of PDUs and 5146 and 5409 individuals entered into analysis of PUO in 2006 and 2007, respectively. The estimates of PDUs were 23,900 (95% CI: 20,700-28,500) in 2006 and 31,000 (25,500-39,400) in 2007. The estimates of PUO were 6,864 (6,641-7,113) in 2006 and 7,096 (6,871-7,346) in 2007. The male/female ratio was 2.2/1. In PDU estimates, 83% were in the age range 15-34 and 17% were aged above 34; in PUO estimates, the respective rates were 80% and 20%. The prevalence rates of PDU in the age range 15-64 were 2.28 and 2.95 per 1,000 population in 2006 and 2007, respectively. The prevalence rates of PUO in the age range 15-64 were 0.65 and 0.67 per 1,000 in 2006 and 2007, respectively. The highest prevalence of both PDUs and PUO was

  12. Radiotherapy and "new" drugs-new side effects?

    Science.gov (United States)

    2011-01-01

    Background and purpose Targeted drugs have augmented the cancer treatment armamentarium. Based on the molecular specificity, it was initially believed that these drugs had significantly less side effects. However, currently it is accepted that all of these agents have their specific side effects. Based on the given multimodal approach, special emphasis has to be placed on putative interactions of conventional cytostatic drugs, targeted agents and other modalities. The interaction of targeted drugs with radiation harbours special risks, since the awareness for interactions and even synergistic toxicities is lacking. At present, only limited is data available regarding combinations of targeted drugs and radiotherapy. This review gives an overview on the current knowledge on such combined treatments. Materials and methods Using the following MESH headings and combinations of these terms pubmed database was searched: Radiotherapy AND cetuximab/trastuzumab/panitumumab/nimotuzumab, bevacizumab, sunitinib/sorafenib/lapatinib/gefitinib/erlotinib/sirolimus, thalidomide/lenalidomide as well as erythropoietin. For citation crosscheck the ISI web of science database was used employing the same search terms. Results Several classes of targeted substances may be distinguished: Small molecules including kinase inhibitors and specific inhibitors, antibodies, and anti-angiogenic agents. Combination of these agents with radiotherapy may lead to specific toxicities or negatively influence the efficacy of RT. Though there is only little information on the interaction of molecular targeted radiation and radiotherapy in clinical settings, several critical incidents are reported. Conclusions The addition of molecular targeted drugs to conventional radiotherapy outside of approved regimens or clinical trials warrants a careful consideration especially when used in conjunction in hypo-fractionated regimens. Clinical trials are urgently needed in order to address the open question in regard

  13. Radiotherapy and "new" drugs-new side effects?

    Directory of Open Access Journals (Sweden)

    Niyazi Maximilian

    2011-12-01

    Full Text Available Abstract Background and purpose Targeted drugs have augmented the cancer treatment armamentarium. Based on the molecular specificity, it was initially believed that these drugs had significantly less side effects. However, currently it is accepted that all of these agents have their specific side effects. Based on the given multimodal approach, special emphasis has to be placed on putative interactions of conventional cytostatic drugs, targeted agents and other modalities. The interaction of targeted drugs with radiation harbours special risks, since the awareness for interactions and even synergistic toxicities is lacking. At present, only limited is data available regarding combinations of targeted drugs and radiotherapy. This review gives an overview on the current knowledge on such combined treatments. Materials and methods Using the following MESH headings and combinations of these terms pubmed database was searched: Radiotherapy AND cetuximab/trastuzumab/panitumumab/nimotuzumab, bevacizumab, sunitinib/sorafenib/lapatinib/gefitinib/erlotinib/sirolimus, thalidomide/lenalidomide as well as erythropoietin. For citation crosscheck the ISI web of science database was used employing the same search terms. Results Several classes of targeted substances may be distinguished: Small molecules including kinase inhibitors and specific inhibitors, antibodies, and anti-angiogenic agents. Combination of these agents with radiotherapy may lead to specific toxicities or negatively influence the efficacy of RT. Though there is only little information on the interaction of molecular targeted radiation and radiotherapy in clinical settings, several critical incidents are reported. Conclusions The addition of molecular targeted drugs to conventional radiotherapy outside of approved regimens or clinical trials warrants a careful consideration especially when used in conjunction in hypo-fractionated regimens. Clinical trials are urgently needed in order to

  14. Phase noise effects on turbulent weather radar spectrum parameter estimation

    Science.gov (United States)

    Lee, Jonggil; Baxa, Ernest G., Jr.

    1990-01-01

    Accurate weather spectrum moment estimation is important in the use of weather radar for hazardous windshear detection. The effect of the stable local oscillator (STALO) instability (jitter) on the spectrum moment estimation algorithm is investigated. Uncertainty in the stable local oscillator will affect both the transmitted signal and the received signal since the STALO provides transmitted and reference carriers. The proposed approach models STALO phase jitter as it affects the complex autocorrelation of the radar return. The results can therefore by interpreted in terms of any source of system phase jitter for which the model is appropriate and, in particular, may be considered as a cumulative effect of all radar system sources.

  15. Computer-aided estimation of the hERG-mediated cardiotoxicity risk of potential drug components.

    Science.gov (United States)

    Radchenko, E V; Rulev, Yu A; Safanyaev, A Ya; Palyulin, V A; Zefirov, N S

    2017-03-01

    The hERG potassium channel is one of the most important anti-targets determining cardiotoxicity of potential drugs. Using fragmental descriptors and artificial neural networks, the predictive models of the relationship between the structure of organic compounds and their activity with respect to hERG were built, and the structural factors affecting it were analyzed. By their predictive ability and applicability domain, these models (N = 1000, Q 2 = 0.77, RMSE cv = 0.45 for affinity and N = 2886, Q 2 = 0.60, RMSE cv = 0.55 for channel inhibition) are superior to the previously published models and can be used to minimize the risk of cardiotoxicity during drug development.

  16. Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: a pilot study.

    Science.gov (United States)

    Hon, Chun-Yip; Chua, Prescillia Ps; Danyluk, Quinn; Astrakianakis, George

    2014-06-01

    Occupational exposure to antineoplastic drugs has been documented to result in various adverse health effects. Despite the implementation of control measures to minimize exposure, detectable levels of drug residual are still found on hospital work surfaces. Cleaning these surfaces is considered as one means to minimize the exposure potential. However, there are no consistent guiding principles related to cleaning of contaminated surfaces resulting in hospitals to adopt varying practices. As such, this pilot study sought to evaluate current cleaning protocols and identify those factors that were most effective in reducing contamination on drug preparation surfaces. Three cleaning variables were examined: (1) type of cleaning agent (CaviCide®, Phenokil II™, bleach and chlorhexidine), (2) application method of cleaning agent (directly onto surface or indirectly onto a wipe) and (3) use of isopropyl alcohol after cleaning agent application. Known concentrations of antineoplastic drugs (either methotrexate or cyclophosphamide) were placed on a stainless steel swatch and then, systematically, each of the three cleaning variables was tested. Surface wipes were collected and quantified using high-performance liquid chromatography-tandem mass spectrometry to determine the percent residual of drug remaining (with 100% being complete elimination of the drug). No one single cleaning agent proved to be effective in completely eliminating all drug contamination. The method of application had minimal effect on the amount of drug residual. In general, application of isopropyl alcohol after the use of cleaning agent further reduced the level of drug contamination although measureable levels of drug were still found in some cases.

  17. Bayesian approach to estimate AUC, partition coefficient and drug targeting index for studies with serial sacrifice design.

    Science.gov (United States)

    Wang, Tianli; Baron, Kyle; Zhong, Wei; Brundage, Richard; Elmquist, William

    2014-03-01

    The current study presents a Bayesian approach to non-compartmental analysis (NCA), which provides the accurate and precise estimate of AUC 0 (∞) and any AUC 0 (∞) -based NCA parameter or derivation. In order to assess the performance of the proposed method, 1,000 simulated datasets were generated in different scenarios. A Bayesian method was used to estimate the tissue and plasma AUC 0 (∞) s and the tissue-to-plasma AUC 0 (∞) ratio. The posterior medians and the coverage of 95% credible intervals for the true parameter values were examined. The method was applied to laboratory data from a mice brain distribution study with serial sacrifice design for illustration. Bayesian NCA approach is accurate and precise in point estimation of the AUC 0 (∞) and the partition coefficient under a serial sacrifice design. It also provides a consistently good variance estimate, even considering the variability of the data and the physiological structure of the pharmacokinetic model. The application in the case study obtained a physiologically reasonable posterior distribution of AUC, with a posterior median close to the value estimated by classic Bailer-type methods. This Bayesian NCA approach for sparse data analysis provides statistical inference on the variability of AUC 0 (∞) -based parameters such as partition coefficient and drug targeting index, so that the comparison of these parameters following destructive sampling becomes statistically feasible.

  18. Synergistic effects of plasma-activated medium and chemotherapeutic drugs in cancer treatment

    Science.gov (United States)

    Chen, Chao-Yu; Cheng, Yun-Chien; Cheng, Yi-Jing

    2018-04-01

    Chemotherapy is an important treatment method for metastatic cancer, but the drug-uptake efficiency of cancer cells needs to be enhanced in order to diminish the side effects of chemotherapeutic drugs and improve survival. The use of a nonequilibrium low-temperature atmospheric-pressure plasma jet (APPJ) has been demonstrated to exert selective effects in cancer therapy and to be able to enhance the uptake of molecules by cells, which makes an APPJ a good candidate adjuvant in combination chemotherapy. This study estimated the effects of direct helium-based APPJ (He-APPJ) exposure (DE) and He-APPJ-activated RPMI medium (PAM) on cell viability and migration. Both of these treatments decreased cell viability and inhibited cell migration, but to different degrees in different cell types. The use of PAM as a culture medium resulted in the dialkylcarbocyanine (DiI) fluorescent dye entering the cells more efficiently. PAM was combined with the anticancer drug doxorubicin (Doxo) to treat human heptocellular carcinoma HepG2 cells and human adenocarcinomic alveolar basal epithelial A549 cells. The results showed that the synergistic effects of combined PAM and Doxo treatment resulted in stronger lethality in cancer cells than did PAM or Doxo treatment alone. To sum up, PAM has potential as an adjuvant in combination with other drugs to improve curative cancer therapies.

  19. Facing the estimation of effective population size based on molecular markers: comparison of estimators

    DEFF Research Database (Denmark)

    Jimenez Mena, Belen; Verrier, Etienne; Hospital, Frederic

    We performed a simulation study of several estimators of the effective population size (Ne): NeH = estimator based on the rate of decrease in heterozygosity; NeT = estimator based on the temporal method; NeLD = linkage disequilibrium-based method. We first focused on NeH, which presented...... under scenarios of 3 and 20 bi-allelic loci. Increasing the number of loci largely improved the performance of NeT and NeLD. We highlight the value of NeT and NeLD when large numbers of bi-allelic loci are available, which is nowadays the case for SNPs markers....... an increase in the variability of values over time. The distance from the mean and the median to the true Ne increased over time too. This was caused by the fixation of alleles through time due to genetic drift and the changes in the distribution of allele frequencies. We compared the three estimators of Ne...

  20. The effect of direct-to-consumer advertising on prescription drug use by older adults.

    Science.gov (United States)

    Datti, Balaji; Carter, Mary W

    2006-01-01

    Although older adults are frequent consumers of prescription drugs and increasingly the intended audience of direct-to-consumer advertising (DTCA) marketing efforts, little is known about the effect of DTCA on older adults' prescription drug-seeking behaviour. In response, the objective of this study is to examine factors associated with requesting a prescription drug from a physician following exposure to DTCA among older adults, and whether the drug or other medical treatment was prescribed during the encounter. A secondary data analysis of the "Public Health Impact of Direct-to-Consumer Advertising of Prescription Drugs", a data set publicly available through the Inter-university Consortium for Political and Social Research (ICPSR 3687), was conducted. For the purposes of this study, only those respondents who indicated that they had been exposed to DTCA (n = 2601) were included in the study sample. Using a two-step weighted logistic regression approach, separate models were estimated to examine first, whether a request for the advertised drug was made following exposure to DTCA and secondly, the outcomes of any patient-physician encounters that occurred following exposure to DTCA. Descriptive analysis of the outcome variables revealed that, among respondents exposed to DTCA, 31% (n = 801) requested a prescription drug from their physician. Approximately 5% of those who made a request were > or =75 years of age. Among respondents requesting a prescription drug, 69% (n = 556) received a prescription in response to their request, of whom, approximately 5% were > or =75 years of age. Multivariate findings suggest that although adults > or =75 years of age are less likely to request a prescription drug following exposure to DTCA (odds ratio [OR] = 0.58; p = 0.032), when they do approach their physicians, they are more likely to receive recommendations for further treatment, with ORs indicating a 250% (OR = 3.507; p = 0.002) increase in the odds of further referral

  1. Propensity score estimation to address calendar time-specific channeling in comparative effectiveness research of second generation antipsychotics.

    Directory of Open Access Journals (Sweden)

    Stacie B Dusetzina

    Full Text Available Channeling occurs when a medication and its potential comparators are selectively prescribed based on differences in underlying patient characteristics. Drug safety advisories can provide new information regarding the relative safety or effectiveness of a drug product which might increase selective prescribing. In particular, when reported adverse effects vary among drugs within a therapeutic class, clinicians may channel patients toward or away from a drug based on the patient's underlying risk for an adverse outcome. If channeling is not identified and appropriately managed it might lead to confounding in observational comparative effectiveness studies.To demonstrate channeling among new users of second generation antipsychotics following a Food and Drug Administration safety advisory and to evaluate the impact of channeling on cardiovascular risk estimates over time.Florida Medicaid data from 2001-2006.Retrospective cohort of adults initiating second generation antipsychotics. We used propensity scores to match olanzapine initiators with other second generation antipsychotic initiators. To evaluate channeling away from olanzapine following an FDA safety advisory, we estimated calendar time-specific propensity scores. We compare the performance of these calendar time-specific propensity scores with conventionally-estimated propensity scores on estimates of cardiovascular risk.Increased channeling away from olanzapine was evident for some, but not all, cardiovascular risk factors and corresponded with the timing of the FDA advisory. Covariate balance was optimized within period and across all periods when using the calendar time-specific propensity score. Hazard ratio estimates for cardiovascular outcomes did not differ across models (Conventional PS: 0.97, 95%CI: 0.81-3.18 versus calendar time-specific PS: 0.93, 95%CI: 0.77-3.04.Changes in channeling over time was evident for several covariates but had limited impact on cardiovascular risk

  2. [Effects of Xenobiotics on Drug Pharmacokinetics and Safety].

    Science.gov (United States)

    Katoh, Miki

    2015-01-01

    The use of nanotechnology has increased over the past 10 years, and various nanomaterials with a wide range of applications have been developed. Carbon nanotubes (CNTs), which are cylindrical molecules consisting of hexagonally arranged carbon atoms, are nanomaterials with high utility. Recently, applications of single-walled CNT (SWCNT) in the medical field for drug-delivery and as gene-delivery agents have been proposed. Due to its structural characteristics and physicochemical properties, the inhalation of SWCNT could be considered as one route for targeted drug delivery into the lungs. Therefore, it is necessary to investigate the effects of SWCNT on the physiological state and response of the cells upon delivery into the lung. We clarified the different response of two carcinoma cell lines to SWCNT exposure, and determined these differences may be due to different cell functions. Furthermore, SWCNT exposure resulted in a global downregulation of stress-responsive genes in normal human bronchial epithelial cells, thereby indicating that the factors involved in the stress responses were not activated by SWCNT. We then tried to ascertain the possible effect of SWCNT on the fate of drugs delivered with SWCNT. Exposure to SWCNT down-regulated the mRNA expression and enzymatic activity of CYP1A1 and CYP1B1 by preventing the binding of activated aryl hydrocarbon receptors to the enhancer region of these genes. This review provides basic information for the prediction of human responses to SWCNT exposure by inhalation, and in its use as a drug delivery carrier.

  3. Time improvement of photoelectric effect calculation for absorbed dose estimation

    International Nuclear Information System (INIS)

    Massa, J M; Wainschenker, R S; Doorn, J H; Caselli, E E

    2007-01-01

    Ionizing radiation therapy is a very useful tool in cancer treatment. It is very important to determine absorbed dose in human tissue to accomplish an effective treatment. A mathematical model based on affected areas is the most suitable tool to estimate the absorbed dose. Lately, Monte Carlo based techniques have become the most reliable, but they are time expensive. Absorbed dose calculating programs using different strategies have to choose between estimation quality and calculating time. This paper describes an optimized method for the photoelectron polar angle calculation in photoelectric effect, which is significant to estimate deposited energy in human tissue. In the case studies, time cost reduction nearly reached 86%, meaning that the time needed to do the calculation is approximately 1/7 th of the non optimized approach. This has been done keeping precision invariant

  4. Risk estimates for the health effects of alpha radiation

    International Nuclear Information System (INIS)

    Thomas, D.C.; McNeill, K.G.

    1981-09-01

    This report provides risk estimates for various health effects of alpha radiation. Human and animal data have been used to characterize the shapes of dose-response relations and the effects of various modifying factors, but quantitative risk estimates are based solely on human data: for lung cancer, on miners in the Colorado plateau, Czechoslovakia, Sweden, Ontario and Newfoundland; for bone and head cancers, on radium dial painters and radium-injected patients. Slopes of dose-response relations for lung cancer show a tendency to decrease with increasing dose. Linear extrapolation is unlikely to underestimate the excess risk at low doses by more than a factor of l.5. Under the linear cell-killing model, our best estimate

  5. Effectiveness and risks of combining antipsychotic drugs with electroconvulsive treatment.

    Science.gov (United States)

    Sanz-Fuentenebro, Francisco Javier; Vidal Navarro, Ignacio; Ballesteros Sanz, Daniel; Verdura Vizcaíno, Ernesto

    2011-01-01

    The simultaneous application of electroconvulsive therapy (ECT) and psychotropic drugs is based on sparse data. Despite this, and the restrictive approach of the Guidelines and Consensus is widespread in the usual care, it is widely practiced in routine clinical. We reviewed the results of search on the topic in MEDLINE, PsychINFO, EMBASE and Cochrane, and the main guidelines on the subject and analyzed for drug groups. Except some reservation with regard to classical MAOIs, antidepressants are safe and effective enhancers of the TEC. It is desirable to discontinuation of BZD whenever clinically possible before the course of ECT for risk of interference, if not possible will have to use proper technique to ensure effective incentives. It is advisable to stop or reduce the dose of lithium prior to ECT based on a cost-benefit analysis of the risk of relapse, if maintained will be adjusted lower levels and cognitive effects minimizing techniques. The combination with "classic" and "atypical" antipsychotics power positive clinical effects and the risk of combined use is low. The positive data are collected with clozapine and ECT-resistant psychosis, with little presence of effects of the decrease of seizure threshold by clozapine, and important effect of empowerment, but of limited duration. Although it is strictly necessary to identify situations in terms of drugs, patient and ECT technique, and care necessary to develop tests that provide methodologically sound data, the combined use of ECT and psychotropic drugs in general presents an acceptable risk level and efficacy data by encouraging empowerment. Copyright © 2010 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

  6. Relevance of the Updated Food and Drug Administration Alteplase Label for Acute Ischemic Stroke: The Estimated Impact and Current Guidelines.

    Science.gov (United States)

    Shiue, Harn J; Albright, Karen C; Sands, Kara A

    2018-04-01

    In 2015, the Food and Drug Administration updated the contraindications for the use of alteplase in acute ischemic stroke (AIS), potentially creating a greater impact on treatment. A history of intracranial hemorrhage and recent stroke within 3 months were removed as contraindications, increasing the number of patients eligible for alteplase. The aim of this commentary is to call attention to the updates and discuss them relative to current American Heart Association/American Stroke Association guidelines. Additionally, we estimate the clinical impact of the updates by analyzing AIS admissions to a large-volume Comprehensive Stroke Center.

  7. Spatial analysis of drug-related hospital admissions: an auto-Gaussian model to estimate the hospitalization rates in Italy

    Directory of Open Access Journals (Sweden)

    Emanuela Colasante

    2008-12-01

    Full Text Available

    Introduction: The aim of this study is to evaluate, even if partially, how much the drug use phenomenon impacts on the Italian National Heatlh System throughout the estimation at local level (Local Health Unit of the hospitalization rate caused by substance use and abuse such as opiates, barbiturates-sedativeshypnotics, cocaine and cannabis, and keeping in mind the phenomenon distribution in the space and so the fact that what happens in a specific area depends on what is happening in the neighbourhoods close to it (spatial autocorrelation.

    Methods: Data from hospital discharge database were provided by the Ministry of Health and an auto- Gaussian model was fitted. The spatial trend can be a function of other explanatory variables or can simply be modeled as a function of spatial location. Both models were fitted and compared using the number of subjects kept in charge by Drug Addiction Services and the number of beds held by hospitals as covariates.

    Results: Concerning opiates use related hospitalizations, results show areas where the phenomenon was less prominent in 2001 (Lombardy, part of Liguria, Umbria, part of Latium, Campania, Apulia and Sicily. In the following years, the hospitalization rates increased in some areas, such as the north of Apulia, part of Campania and Latium. A dependence of the opiates related hospitalization rates on the rate of subjects kept in charge by the Drug Addiction Services is highlighted. Concerning barbiturates-sedatives-hypnotics consumption, the best model is the one without covariates and estimated hospitalization rates are lower then 3 per thousand. The model with only the covariate “rate of subjects kept in charge by Drug Addiction Services” has been used both for cocaine and cannabis. In these two cases, more than a half of the Local Health Units report hospitalization rates lower than 0.5 per thousand

  8. The past matters: estimating intrinsic hookworm transmission intensity in areas with past mass drug administration to control lymphatic filariasis.

    Science.gov (United States)

    Werkman, Marleen; Truscott, James E; Toor, Jaspreet; Wright, James E; Anderson, Roy M

    2017-05-23

    Current WHO guidelines for soil-transmitted helminth (STH) control focus on mass drug administration (MDA) targeting preschool-aged (pre-SAC) and school-aged children (SAC), with the goal of eliminating STH as a public health problem amongst children. Recently, attention and funding has turned towards the question whether MDA alone can result in the interruption of transmission for STH. The lymphatic filariasis (LF) elimination programme, have been successful in reaching whole communities. There is the possibility of building upon the infrastructure created for these LF-programmes to enhance the control of STH. Using hookworm as an example, we explore what further MDA coverage might be required to induce interruption of transmission for hookworm in the wake of a successful LF programme. Analyses based on the model of STH transmission and MDA impact predict the effects of previous LF control by MDA over five years, on a defined baseline prevalence of STH in an area with a defined transmission intensity (the basic reproductive number R 0 ). If the LF MDA programme achieved a high coverage (70, 70 and 60% for pre-SAC, SAC and adults, respectively) we expect that in communities with a hookworm prevalence of 15%, after 5 years of LF control, the intrinsic R 0 value in that setting is 2.47. By contrast, if lower LF coverages were achieved (40, 40 and 30% for pre-SAC, SAC and adults, respectively), with the same prevalence of 15% at baseline (after 5 years of LF MDA), the intrinsic hookworm R 0 value is predicted to be 1.67. The intrinsic R 0 value has a large effect on the expected successes of follow-up STH programmes post LF MDA. Consequently, the outcomes of identical programmes may differ between these communities. To design the optimal MDA intervention to eliminate STH infections, it is vital to have information on historical MDA programmes and baseline prevalence to estimate the intrinsic transmission intensity for the defined setting (R 0 ). The baseline

  9. Estimating study costs for use in VOI, a study of dutch publicly funded drug related research

    NARCIS (Netherlands)

    Van Asselt, A.D.; Ramaekers, B.L.; Corro Ramos, I.; Joore, M.A.; Al, M.J.; Lesman-Leegte, I.; Postma, M.J.; Vemer, P.; Feenstra, T.F.

    2016-01-01

    Objectives: To perform value of information (VOI) analyses, an estimate of research costs is needed. However, reference values for such costs are not available. This study aimed to analyze empirical data on research budgets and, by means of a cost tool, provide an overview of costs of several types

  10. Sampling strategies for estimating brook trout effective population size

    Science.gov (United States)

    Andrew R. Whiteley; Jason A. Coombs; Mark Hudy; Zachary Robinson; Keith H. Nislow; Benjamin H. Letcher

    2012-01-01

    The influence of sampling strategy on estimates of effective population size (Ne) from single-sample genetic methods has not been rigorously examined, though these methods are increasingly used. For headwater salmonids, spatially close kin association among age-0 individuals suggests that sampling strategy (number of individuals and location from...

  11. Randomised Controlled Trials May Underestimate Drug Effects: Balanced Placebo Trial Design

    Science.gov (United States)

    Lund, Karen; Vase, Lene; Petersen, Gitte L.; Jensen, Troels S.; Finnerup, Nanna B.

    2014-01-01

    Background It is an inherent assumption in randomised controlled trials that the drug effect can be estimated by subtracting the response during placebo from the response during active drug treatment. Objective To test the assumption of additivity. The primary hypothesis was that the total treatment effect is smaller than the sum of the drug effect and the placebo effect. The secondary hypothesis was that non-additivity was most pronounced in participants with large placebo effects. Methods We used a within-subject randomised blinded balanced placebo design and included 48 healthy volunteers (50% males), mean (SD) age 23.4 (6.2) years. Experimental pain was induced by injections of hypertonic saline into the masseter muscle. Participants received four injections with hypertonic saline along with lidocaine or matching placebo in randomised order: A: received hypertonic saline/told hypertonic saline; B: received hypertonic saline+lidocaine/told hypertonic saline; C: received hypertonic saline+placebo/told hypertonic saline+pain killer; D: received hypertonic saline+lidocaine/told hypertonic saline+pain killer. The primary outcome measure was the area under the curve (AUC, mm2) of pain intensity during injections. Results There was a significant difference between the sum of the drug effect and the placebo effect (mean AUC 6279 mm2 (95% CI, 4936–7622)) and the total treatment effect (mean AUC 5455 mm2 (95% CI, 4585–6324)) (P = 0.049). This difference was larger for participants with large versus small placebo effects (P = 0.015), and the difference correlated significantly with the size of the placebo effect (r = 0.65, P = 0.006). Conclusion Although this study examined placebo effects and not the whole placebo response as in randomised controlled trials, it does suggest that the additivity assumption may be incorrect, and that the estimated drug effects in randomised controlled trials may be underestimated, particularly in studies reporting large

  12. REBAMIPIDE: EFFECTIVE DRUG PREVENTION OF NSAID ENTEROPATHY IS POSSIBLE

    Directory of Open Access Journals (Sweden)

    E. V. Moroz

    2016-01-01

    Full Text Available Prevention of gastrointestinal tract (GIT complications is the most important element for the rational use of nonsteroidal anti-inflammatory drugs (NSAIDs and low-dose aspirin (LDA. Proton pump inhibitors (PPIs have long been the only medication to prevent these complications. However, PPIs are only effective in preventing and treating upper GIT diseases (NSAID gastropathy rather than small intestinal injury (NSAID enteropathy. Rebamipide has emerged as a novel agent to protect the gastrointestinal mucosa today. The effect of the drug differs from that of PPIs: it is a typical gastroand enteroprotector that enhances the synthesis of endogenous prostaglandins and possesses a significant anti-inflammatory potential. Rebamipide has long been widely used by doctors inJapan,South Korea, andChinaas an effective and safe agent for the treatment of many diseases of the digestive system. There is a strong evidence base for the efficacy of rebamipide in preventing and treating NSAID gastropathy and NSAID enteropathy (including LDA-induced injuries. Controlled studies have found that the drug is not inferior to the classic gastroprotective agent misoprostol, significantly outperforming the latter in its tolerability. This review describes the mechanism of action of rebamipide and main clinical trials of its therapeutic effect in NSAID gastropathy and NSAID enteropathy. 

  13. Effect of Drug Loading Method and Drug Physicochemical Properties on the Material and Drug Release Properties of Poly (Ethylene Oxide Hydrogels for Transdermal Delivery

    Directory of Open Access Journals (Sweden)

    Rachel Shet Hui Wong

    2017-07-01

    Full Text Available Novel poly (ethylene oxide (PEO hydrogel films were synthesized via UV cross-linking with pentaerythritol tetra-acrylate (PETRA as cross-linking agent. The purpose of this work was to develop a novel hydrogel film suitable for passive transdermal drug delivery via skin application. Hydrogels were loaded with model drugs (lidocaine hydrochloride (LID, diclofenac sodium (DIC and ibuprofen (IBU via post-loading and in situ loading methods. The effect of loading method and drug physicochemical properties on the material and drug release properties of medicated film samples were characterized using scanning electron microscopy (SEM, swelling studies, differential scanning calorimetry (DSC, fourier transform infrared spectroscopy (FT-IR, tensile testing, rheometry, and drug release studies. In situ loaded films showed better drug entrapment within the hydrogel network and also better polymer crystallinity. High drug release was observed from all studied formulations. In situ loaded LID had a plasticizing effect on PEO hydrogel, and films showed excellent mechanical properties and prolonged drug release. The drug release mechanism for the majority of medicated PEO hydrogel formulations was determined as both drug diffusion and polymer chain relaxation, which is highly desirable for controlled release formulations.

  14. Prescription drugs for human use generally recognized as safe and effective and not misbranded: drugs used in research: radioactive drugs for certain research uses; amended reporting requirements

    International Nuclear Information System (INIS)

    Anon.

    1978-01-01

    This amendment revises the reporting requirements for research studies in which radioactive drugs are used. It deletes the requirement for detailed measurements and calculations for each subject in the study; instead, it permits submission of data on a representative subject. The effect will be to decrease the burden in reporting required of the Radioactive Drug Research Committee, but still provide the agency with data to evaluate the risk attributable to radioactive drugs

  15. Cardiovascular effects of current and future anti-obesity drugs.

    Science.gov (United States)

    Comerma-Steffensen, Simon; Grann, Martin; Andersen, Charlotte U; Rungby, Jorgen; Simonsen, Ulf

    2014-05-01

    The prevalence of obesity increases and is associated with increases in co-morbidities e.g. type 2 diabetes, hyperlipidemia, hypertension, obstructive sleep apnea, heart disease, stroke, asthma, several forms of cancer, depression, and may result in reduction of expected remaining lifespan. We have reviewed the adverse effects on the cardiovascular system of anti-obesity drugs now retracted from the market as well as the cardiovascular profile of current drugs and potential pathways which are considered for treatment of obesity. Fenfluramine, and sibutramine were withdrawn due to increased cardiovascular risk, while an inverse agonist at cannabinoid type 1 (CB1) receptors, rimonobant was withdrawn due to serious psychiatric problems. At present there are only few treatments available including orlistat and, phentermine alone or in combination with topiramate and lorcaserin, although cardiovascular side effects need to be clarified regarding phentermine and lorcaserin. Drugs approved for type 2 diabetes including glucagon like peptide (GLP-1) analogues and metformin also cause moderate weight losses and have a favourable cardiovascular profile, while the anti-obesity potential of nebivolol remains unexplored. Pathways with anti-obesity potential include sirtuin activation, blockade of transient receptor potential (TRPV1) channels, acetyl-CoA carboxylase 1 and 2 inhibitors, uncoupling protein activators, bile acids, crotonins, CB1 antagonists, but the cardiovascular profile remains to be investigated. For type 2 diabetes, new drug classes with possible advantageous cardiovascular profiles, e.g. GLP-1 analogues and sodium-glucose co-transport type 2 inhibitors, are associated with weight loss and are currently being evaluated as anti-obesity drugs.

  16. Estimated effects of interfacial vaporization on fission product scrubbing

    International Nuclear Information System (INIS)

    Moody, F.J.; Nagy, S.G.

    1983-01-01

    When bubbles containing non-condensible gas rise through a water pool, interfacial evaporation causes a flow of vapor into the bubbles. The inflow reduces the outward particle motion toward the bubble wall, diminishing the effectiveness of fission product particle removal. This analysis provides an estimate of evaporation on pool scrubbing effectiveness. It is shown that hot gas, which boils water at the bubble wall, reduces the effective scrubbing height by less than five centimeters. Although the evaporative humidification in a rising bubble containing non-condensible gas has a diminishing effect on scrubbing mechanisms, substantial decontamination is still expected even for the limiting case of a saturated pool

  17. An in vivo approach for globally estimating the drug flow between blood and tissue for nafamostat mesilate: the main hydrolysis site determination in human.

    Science.gov (United States)

    Cao, Yan-Guang; Chen, Yuan-Cheng; Hao, Kun; Zhang, Ming; Liu, Xiao-Quan

    2008-11-01

    Nafamostat mesilate, an ester drug with extensive hydrolysis in vivo, exhibits species difference in the relative contribution for its hydrolysis in blood and tissues. For the rat, the main hydrolysis site may be blood and human may be tissue (mainly by liver). The paper gave in vivo evidence that human tissue may give more contribution for its hydrolysis. In the initial phase of drug administration, the drug accumulating level in tissue was low; the efflux fraction from tissue into blood can be ignorable comparing with the drug influx into tissue. Based on urine and plasma metabolite analysis, we concluded that in the initial phase almost all the drug hydrolysis in blood was excreted into urine. Then according to the initial urine metabolite analysis, we can estimate the drug hydrolysis rate in blood. The rate of drug diffusion from blood into tissues can be deduced based on the mass balance analysis of the initial blood drug. With the estimated rate constants, the drug efflux from tissues into blood was calculated according to equation: OFT-B (efflux from tissues) = OFB-U (blood hydrolysis fraction)+OFB-T (influx into tissues)-DB (hydrolysis in blood). The net flow (influent flux minus effluent flux) represented the drug hydrolysis fraction in tissue. As the result indicated, in human about 20% drug administrated was hydrolyzed in blood and nearly 80% in tissues. The relative hydrolysis fraction indicated that the main hydrolysis site in human body may locate in tissue, which was different to rats.

  18. The Effect of Opioids, Alcohol, and Nonsteroidal Anti-inflammatory Drugs on Fracture Union.

    Science.gov (United States)

    Richards, Christopher J; Graf, Kenneth W; Mashru, Rakesh P

    2017-10-01

    The estimated rate of fracture nonunion is between 5% and 10%, adding significant cost to the health care system. The cause of fracture nonunion is multifactorial, including the severity of the injury, patient factors resulting in aberrancies in the biology of fracture, and the side effects of pain control modalities. Minimizing surgeon-controlled factors causing nonunion is important to reduce the cost of health care and improve patient outcomes. Opioids, alcohol, and nonsteroidal anti-inflammatory drugs have been implicated as risk factors for fracture nonunion. Current literature was reviewed to examine the effects of opioids, alcohol, and nonsteroidal anti-inflammatory drugs on fracture union. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Deuterium isotope effects on drug pharmacokinetics. I. System-dependent effects of specific deuteration with aldehyde oxidase cleared drugs.

    Science.gov (United States)

    Sharma, Raman; Strelevitz, Timothy J; Gao, Hongying; Clark, Alan J; Schildknegt, Klaas; Obach, R Scott; Ripp, Sharon L; Spracklin, Douglas K; Tremaine, Larry M; Vaz, Alfin D N

    2012-03-01

    The pharmacokinetic properties of drugs may be altered by kinetic deuterium isotope effects. With specifically deuterated model substrates and drugs metabolized by aldehyde oxidase, we demonstrate how knowledge of the enzyme's reaction mechanism, species differences in the role played by other enzymes in a drug's metabolic clearance, and differences in systemic clearance mechanisms are critically important for the pharmacokinetic application of deuterium isotope effects. Ex vivo methods to project the in vivo outcome using deuterated carbazeran and zoniporide with hepatic systems demonstrate the importance of establishing the extent to which other metabolic enzymes contribute to the metabolic clearance mechanism. Differences in pharmacokinetic outcomes in guinea pig and rat, with the same metabolic clearance mechanism, show how species differences in the systemic clearance mechanism can affect the in vivo outcome. Overall, to gain from the application of deuteration as a strategy to alter drug pharmacokinetics, these studies demonstrate the importance of understanding the systemic clearance mechanism and knowing the identity of the metabolic enzymes involved, the extent to which they contribute to metabolic clearance, and the extent to which metabolism contributes to the systemic clearance.

  20. Effect of drugs used in psychoses on cerebral dopamine metabolism

    Science.gov (United States)

    O'Keeffe, Ruth; Sharman, D. F.; Vogt, Marthe

    1970-01-01

    1. Chlorpromazine 15 mg/kg, given daily to cats for 2 weeks, produced a rise in homovanillic acid (HVA) content of the caudate nucleus, whereas the same dose of thioridazine lacked this effect. Of these two drugs, only chlorpromazine causes a high incidence of drug-induced Parkinsonism in man. 2. In the mouse, chlorpromazine, thioridazine and haloperidol increased striatal concentrations of HVA and accelerated the disappearance of dopamine (DA) after inhibition of catecholamine synthesis with α-methyltyrosine. Low doses of the three compounds increased, whereas high doses reduced, the concentration of DA in the striatum. In their effects on the DA metabolism of the mouse, chlorpromazine and thioridazine had the same potency, but haloperidol was between 10 and 100 times more active than the other two drugs. In producing hypothermia and sedation, the three compounds were equiactive. 3. Oxypertine, another drug apt to produce Parkinsonism in man, caused a severe reduction in striatal DA and hypothalamic noradrenaline (NA). Though the clinical signs produced in the mouse were indistinguishable from those seen after the same dose of chlorpromazine, the biochemical changes in the brain were thus quite different. 4. Though all the drugs used caused temporary motor disabilities in animals, these bore no resemblance to human Parkinsonism, even when treatment was continued for 7 weeks or more as it was in cats and monkeys. The latter were treated with chlorpromazine 7·5 mg/kg daily, a dose chosen to avoid loss of weight and which may have been too small to produce toxic side-effects. It caused no changes in striatal DA turnover. 5. Even at the high dose of 50 mg/kg, phenoxybenzamine did not increase DA turnover in mouse brain, but it sedated the mice as did the tranquillizers. 6. Atropine sulphate, 25 mg/kg, reduced the HVA content of mouse striatum and partially antagonized the rise in HVA produced by phenothiazines. The effect was surmountable. Possible modes of action

  1. [Failure mode and effects analysis on computerized drug prescriptions].

    Science.gov (United States)

    Paredes-Atenciano, J A; Roldán-Aviña, J P; González-García, Mercedes; Blanco-Sánchez, M C; Pinto-Melero, M A; Pérez-Ramírez, C; Calvo Rubio-Burgos, Miguel; Osuna-Navarro, F J; Jurado-Carmona, A M

    2015-01-01

    To identify and analyze errors in drug prescriptions of patients treated in a "high resolution" hospital by applying a Failure mode and effects analysis (FMEA).Material and methods A multidisciplinary group of medical specialties and nursing analyzed medical records where drug prescriptions were held in free text format. An FMEA was developed in which the risk priority index (RPI) was obtained from a cross-sectional observational study using an audit of the medical records, carried out in 2 phases: 1) Pre-intervention testing, and (2) evaluation of improvement actions after the first analysis. An audit sample size of 679 medical records from a total of 2,096 patients was calculated using stratified sampling and random selection of clinical events. Prescription errors decreased by 22.2% in the second phase. FMEA showed a greater RPI in "unspecified route of administration" and "dosage unspecified", with no significant decreases observed in the second phase, although it did detect, "incorrect dosing time", "contraindication due to drug allergy", "wrong patient" or "duplicate prescription", which resulted in the improvement of prescriptions. Drug prescription errors have been identified and analyzed by FMEA methodology, improving the clinical safety of these prescriptions. This tool allows updates of electronic prescribing to be monitored. To avoid such errors would require the mandatory completion of all sections of a prescription. Copyright © 2014 SECA. Published by Elsevier Espana. All rights reserved.

  2. Drug*placebo interaction effect may bias clinical trials interpretation: hybrid balanced placebo and randomized placebo-controlled design.

    Science.gov (United States)

    Hammami, Muhammad M; Hammami, Safa; Al-Swayeh, Reem; Al-Gaai, Eman; Farah, Faduma Abdi; De Padua, Sophia J S

    2016-11-29

    Conventional randomized placebo-controlled study design assumes the absence of drug*placebo interaction. We hypothesized the presence of such an interaction and that conventionally estimated drug effect might be biased. The objectives of the study were to determine the drug*placebo interaction effect (main) and compare conventionally estimated and interaction model-estimated drug effects (secondary). We used a hybrid of balanced placebo and randomized placebo-controlled designs. Four hundred eighty healthy volunteers were randomized to three groups. The first received hydroxyzine (25 mg) described as hydroxyzine or placebo, the second received placebo described as hydroxyzine or placebo, and the third received hydroxyzine and placebo described as unknown; each in a randomized crossover design. Seven participants failed to crossover. Group assignment was concealed from participants and study coordinators. Coordinators were blinded to group and intervention assignment. Participants and coordinators were deceived as to study objectives. Main outcomes were mean area-under-the-curve of drowsiness (therapeutic outcome) and mouth-dryness (adverse outcome), self-reported on 100 mm visual analog scale over 7 h. Drug, placebo, placebo + interaction, and total effects were estimated using analysis of covariance by comparing received hydroxyzine/told placebo to received placebo/told placebo, received placebo/told hydroxyzine to received placebo/told placebo, received hydroxyzine/told hydroxyzine to received hydroxyzine/told placebo, and received hydroxyzine/told hydroxyzine to received placebo/told placebo, respectively. Drug effect was also conventionally estimated in the third group. Mean (SD) age was 31.4 (6.6) years, 65% were males. There was significant difference between placebo + interaction effect and placebo effect for both drowsiness and mouth-dryness with a mean difference (95% confidence interval) of 35.1 (5.6 to 64.6) and 23.8 (2.4 to 45.2) mm

  3. Effect of reduction of antiepileptic drugs in patients with drug-refractory epilepsy.

    Science.gov (United States)

    Dash, Deepa; Aggarwal, Vikas; Joshi, Rupa; Padma, Madakasira Vasantha; Tripathi, Manjari

    2015-04-01

    The present study was conducted with the aim of evaluating the effects of reducing the number of antiepileptic drugs (AEDs) administered to patients with drug-refractory epilepsy (DRE) during their admission and document any change in seizure frequency in subsequent follow up. A total of 962 patients with DRE who were admitted to the neurology wards waiting for connection to video EEG were recruited for this prospective study. After their admission to the neurology ward, modifications in the number and dosage of AEDs were done with a target of a maximum of three AEDs in every patient. Drug tapering was done using a standardized protocol. The primary outcome was the change in seizure frequency in the follow-up period of 6 months. Secondary outcome measures were the adverse event profile (AEP) and the quality of life (QOL). Of the 1134 patients screened, 962 patients gave consent to participate in the study. The mean number of AEDs received by each patient was 4.24. After the tapering following a standardized protocol each patient received a mean of 2.65 AEDs per patient. In 82.70% patients with DRE, there was either a reduction or no change in seizure frequency in the subsequent 6 months follow up. There was a significant reduction in the AEP score after the reduction in the number of AEDs (P = 0. 001). Our study proves that optimization of reduction of the number of AED's in patients with DRE leads to reduction or no change in seizure frequency with a significant decrease in adverse effects. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  4. Effect of reporting bias on meta-analyses of drug trials

    DEFF Research Database (Denmark)

    Hart, Beth; Lundh, Andreas; Bero, Lisa

    2012-01-01

    To investigate the effect of including unpublished trial outcome data obtained from the Food and Drug Administration (FDA) on the results of meta-analyses of drug trials.......To investigate the effect of including unpublished trial outcome data obtained from the Food and Drug Administration (FDA) on the results of meta-analyses of drug trials....

  5. Temperature-Induced Surface Effects on Drug Nanosuspensions.

    Science.gov (United States)

    Aleandri, Simone; Schönenberger, Monica; Niederquell, Andres; Kuentz, Martin

    2018-02-21

    The trial-and-error approach is still predominantly used in pharmaceutical development of nanosuspensions. Physicochemical dispersion stability is a primary focus and therefore, various analytical bulk methods are commonly employed. Clearly less attention is directed to surface changes of nanoparticles even though such interface effects can be of pharmaceutical relevance. Such potential effects in drug nanosuspensions were to be studied for temperatures of 25 and 37°C by using complementary surface analytical methods. Atomic force microscopy, inverse gas chromatography and UV surface dissolution imaging were used together for the first time to assess pharmaceutical nanosuspensions that were obtained by wet milling. Fenofibrate and bezafibrate were selected as model drugs in presence of sodium dodecyl sulfate and hydroxypropyl cellulose as anionic and steric stabilizer, respectively. It was demonstrated that in case of bezafibrate nanosuspension, a surface modification occurred at 37°C compared to 25°C, which notably affected dissolution rate. By contrast, no similar effect was observed in case of fenofibrate nanoparticles. The combined usage of analytical surface methods provides the basis for a better understanding of phenomena that take place on drug surfaces. Such understanding is of importance for pharmaceutical development to achieve desirable quality attributes of nanosuspensions.

  6. Effectiveness of a smartphone app for guiding antidepressant drug selection.

    Science.gov (United States)

    Man, Colin; Nguyen, Cathina; Lin, Steven

    2014-09-01

    Major depression is a prevalent chronic disease in the United States. However, many physicians lack access to decision support tools at point of care to help choose antidepressants in a rational, evidence-based manner. A patient-centered treatment model that uses a symptom-based approach to selecting antidepressants was developed into a smartphone application to provide instant, evidence-based recommendations and drug monographs. The purpose of this study was to assess the impact of this mobile application on the confidence level of family physicians in treating depression. The smartphone application was provided to 14 family medicine residents and attending physicians from the O'Connor Family Medicine Residency Program in San Jose, CA. Participants were asked to use the software as drug reference and clinical decision support during patient care activities. Three surveys were administered over a 12-week period to assess provider characteristics, outcome measures (ie, confidence in managing depression and choosing an initial antidepressant based on patient symptoms, medical comorbidities, potential side effects, and drug interactions), and fund of antidepressant knowledge. The average confidence levels in managing depression, starting an antidepressant on a patient with depression, and choosing an initial antidepressant based on patient symptoms increased significantly within the period of smartphone application usage. The average scores on the antidepressant knowledge tests also improved. The smartphone application was an effective tool for both increasing confidence in depression treatment and educating physicians. Future studies to evaluate the effectiveness and impact of smartphone applications on medical education and postgraduate training are warranted.

  7. Nonparametric Estimation of Distributions in Random Effects Models

    KAUST Repository

    Hart, Jeffrey D.

    2011-01-01

    We propose using minimum distance to obtain nonparametric estimates of the distributions of components in random effects models. A main setting considered is equivalent to having a large number of small datasets whose locations, and perhaps scales, vary randomly, but which otherwise have a common distribution. Interest focuses on estimating the distribution that is common to all datasets, knowledge of which is crucial in multiple testing problems where a location/scale invariant test is applied to every small dataset. A detailed algorithm for computing minimum distance estimates is proposed, and the usefulness of our methodology is illustrated by a simulation study and an analysis of microarray data. Supplemental materials for the article, including R-code and a dataset, are available online. © 2011 American Statistical Association.

  8. Modeling in-sewer transformations at catchment scale - implications on drug consumption estimates in wastewater-based epidemiology.

    Science.gov (United States)

    McCall, Ann-Kathrin; Palmitessa, Rocco; Blumensaat, Frank; Morgenroth, Eberhard; Ort, Christoph

    2017-10-01

    To which extent illicit drugs are transformed during in-sewer transport, depends on a number of factors: i) substance-specific transformation rates, ii) environmental conditions, iii) point of discharge (location of drug user) and iv) sewer network properties, primarily hydraulic residence time (HRT) and the ratio of biofilm contact area to wastewater volume (A/V eq ). Assessing associated uncertainties typically requires numerous simulations. Therefore, we propose a new two-step modeling framework: 1) Quantify hydrodynamic conditions. This computationally demanding step was performed once in SWMM to derive HRT and A/V eq for each potential point of discharge (node) in three catchments of different size. 2) Estimate biomarker loss. In this step, Monte Carlo simulations were performed for defined scenarios. Depending on assumptions about drug user distribution and prevalence, a number of nodes was sampled. For each node an empirical first-order transformation model was applied with flow-path-corresponding HRT and A/V eq from step 1. Biotic and abiotic transformation rates were sampled from distributions combining variability of different biofilms. In our modeling study, median losses were >30% for amphetamine, 6-monoacetylmorphine and 6-acetylcodeine in all three catchments with high uncertainty (5%-100% loss), which would imply a systematic underestimation of consumption when neglecting in-sewer processes. Median losses for 21 other investigated biomarkers were model input objectively. Our approach allows efficient testing and, furthermore, can be expanded for many other human biomarkers. Accounting for biomarker stability during in-sewer transport will avoid biased estimates and further improve wastewater-based epidemiology. Copyright © 2017. Published by Elsevier Ltd.

  9. Effect of drug law enforcement on drug market violence: a systematic review.

    Science.gov (United States)

    Werb, Dan; Rowell, Greg; Guyatt, Gordon; Kerr, Thomas; Montaner, Julio; Wood, Evan

    2011-03-01

    Violence is amongst the primary concerns of communities around the world and research has demonstrated links between violence and the illicit drug trade, particularly in urban settings. Given the growing emphasis on evidence-based policy-making, and the ongoing severe drug market violence in Mexico and other settings, we conducted a systematic review to examine the impacts of drug law enforcement on drug market violence. We conducted a systematic review using Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. Specifically, we undertook a search of English language electronic databases (Academic Search Complete, PubMed, PsycINFO, EMBASE, Web of Science, Sociological Abstracts, Social Service Abstracts, PAIS International and Lexis-Nexis), the Internet (Google, Google Scholar), and article reference lists, from database inception to January 24, 2011. Overall, 15 studies were identified that evaluated the impact of drug law enforcement on drug market violence, including 11 (73%) longitudinal analyses using linear regression, 2 (13%) mathematical drug market models, and 2 (13%) qualitative studies. Fourteen (93%) studies reported an adverse impact of drug law enforcement on levels of violence. Ten of the 11 (91%) studies employing longitudinal qualitative analyses found a significant association between drug law enforcement and drug market violence. Our findings suggest that increasing drug law enforcement is unlikely to reduce drug market violence. Instead, the existing evidence base suggests that gun violence and high homicide rates may be an inevitable consequence of drug prohibition and that disrupting drug markets can paradoxically increase violence. In this context, and since drug prohibition has not meaningfully reduced drug supply, alternative regulatory models will be required if drug supply and drug market violence are to be meaningfully reduced. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Using pharmacokinetic modeling to determine the effect of drug and food on gastrointestinal transit in dogs.

    Science.gov (United States)

    Sjödin, Linnea; Visser, Sandra; Al-Saffar, Ahmad

    2011-01-01

    The gastrointestinal (GI) tract is one of the target organs of adverse drug effects in different phases of drug development. This study aimed to investigate the feasibility of population pharmacokinetic modeling to quantify the rate of gastric emptying (GE) and small intestinal transit time (SITT) in response to drugs that affect GI motility in fed and fasted dogs. Paracetamol and sulfapyridine (sulfasalazine metabolite) pharmacokinetics were used as markers for GE and SITT, respectively. In two separate studies, under fed and fasted conditions, six male beagle dogs received a 15min intravenous infusion of vehicle, atropine (0.06mg/kg) or erythromycin (1mg/kg) followed by an intragastric administration of a mixture of paracetamol (24mg/kg) and sulfasalazine (20mg/kg). Food was given just before or at 6h after drug administration in the fed and fasted study, respectively. Blood samples were collected for analysis of paracetamol and sulfapyridine in plasma. Population pharmacokinetic analysis of paracetamol and sulfapyridine in plasma was used to determine the rate of GE and SITT. The quantitative parameter estimates demonstrated a detailed and significant influence of atropine, erythromycin and food on GE and SITT. Compared to fasted conditions food intake delayed GE in pharmacologically treated dogs and SITT was shortened after treatment with vehicle or erythromycin. Atropine substantially delayed GE in fed and fasted conditions but the effect on SITT was evident only under fed condition. Erythromycin, in contrast, increased GE only in fasted conditions, and generally delayed SITT. Population pharmacokinetic modeling of paracetamol and sulfapyridine provides a suitable preclinical non-invasive experimental method for quantification of drug- and food-induced changes in the rate of GE and SITT in conscious beagle dogs for use in safety evaluations to predict changes in GI transit and/or to explain the pharmacokinetic profile of drugs under development. Copyright

  11. Liver Effects of Clinical Drugs Differentiated in Human Liver Slices

    Directory of Open Access Journals (Sweden)

    Alison E. M. Vickers

    2017-03-01

    Full Text Available Drugs with clinical adverse effects are compared in an ex vivo 3-dimensional multi-cellular human liver slice model. Functional markers of oxidative stress and mitochondrial function, glutathione GSH and ATP levels, were affected by acetaminophen (APAP, 1 mM, diclofenac (DCF, 1 mM and etomoxir (ETM, 100 μM. Drugs targeting mitochondria more than GSH were dantrolene (DTL, 10 μM and cyclosporin A (CSA, 10 μM, while GSH was affected more than ATP by methimazole (MMI, 500 μM, terbinafine (TBF, 100 μM, and carbamazepine (CBZ 100 μM. Oxidative stress genes were affected by TBF (18%, CBZ, APAP, and ETM (12%–11%, and mitochondrial genes were altered by CBZ, APAP, MMI, and ETM (8%–6%. Apoptosis genes were affected by DCF (14%, while apoptosis plus necrosis were altered by APAP and ETM (15%. Activation of oxidative stress, mitochondrial energy, heat shock, ER stress, apoptosis, necrosis, DNA damage, immune and inflammation genes ranked CSA (75%, ETM (66%, DCF, TBF, MMI (61%–60%, APAP, CBZ (57%–56%, and DTL (48%. Gene changes in fatty acid metabolism, cholestasis, immune and inflammation were affected by DTL (51%, CBZ and ETM (44%–43%, APAP and DCF (40%–38%, MMI, TBF and CSA (37%–35%. This model advances multiple dosing in a human ex vivo model, plus functional markers and gene profile markers of drug induced human liver side-effects.

  12. Examining the Effects of School-Based Drug Prevention Programs on Drug Use in Rural Settings: Methodology and Initial Findings

    Science.gov (United States)

    Brown, C. Hendricks; Guo, Jing; Singer, L. Terri; Downes, Katheryne; Brinales, Joseph M.

    2007-01-01

    Context: Although there have been substantial advances in knowledge about drug prevention over the last decade, the majority of school-based drug prevention studies have been conducted in urban settings. There is little knowledge about the effectiveness of such programs when they are implemented in rural populations. Purpose: To examine the…

  13. Measures to reduce car-fleet consumption - Estimation of effects

    International Nuclear Information System (INIS)

    Iten, R.; Hammer, S.; Keller, M.; Schmidt, N.; Sammer, K.; Wuestenhagen, R.

    2005-09-01

    This comprehensive report for the Swiss Federal Office of Energy (SFOE) takes a look at the results of a study that estimated the effects of measures that were to be taken in order to reduce the fuel consumption of fleets of vehicles as part of the SwissEnergy programme. The research reported on aimed to estimate the effects of the Energy Label on energy consumption and research concerning the results to be expected from the introduction of a bonus-malus system. Questions reviewed include the effect of fuel consumption data on making decisions concerning which vehicle to purchase, the effects of the Energy Label on consumption, the awareness of other appropriate information sources, the possible effects of a bonus-malus system and how the effectiveness of the Energy Label could be improved. The answers and results obtained are reviewed and commented on. Finally, an overall appraisal of the situation is presented and recommendations for increasing the effectiveness of the Energy Label are made

  14. Effect of irradiation of drugs and aiding substances

    International Nuclear Information System (INIS)

    Schnell, R.; Boegl, W.

    1982-01-01

    In this bibliographic study (Part I - VI), the results of more than 300 radiation tested pharmaceuticals are discussed and evaluated. The substances were treated with ionizing radiation in their pure form (solid substance or liquid), as aqueous or alcohol solution, as emulsion or in compound form, almost exclusively with gamma radiation from cobaldt-60 sources. The radiation doses applied amounted from some krd to about 100 Mrd. The results of the original papers analyzed in this Part VI are not summarized separately since the final Part VII of the study on the effects of irradiation of drugs and drug additives will contain a survey for all essential data discussed in Parts I to VI. (orig./MG) [de

  15. ESTIMATION OF AGING EFFECTS OF PILES IN MALAYSIAN OFFSHORE LOCATIONS

    Directory of Open Access Journals (Sweden)

    JERIN M. GEORGE

    2017-04-01

    Full Text Available An increasing demand for extending life and subsequently higher loading requirements of offshore jacket platforms are among the key problems faced by the offshore industry. The Aging effect has been proved to increase the axial capacity of piles, but proper methods to estimate and quantify these effects have not been developed. Borehole data from ten different Malaysian offshore locations have been analysed and they were employed to estimate the setup factor for different locations using AAU method. The setup factors found were used in the Skov and Denver equation to calculate capacity ratios of the offshore piles. The study showed that there will be an average improvement in the axial capacity of offshore piles by 42.2% and 34.9% for clayey and mixed soils respectively after a time equal to the normal design life (25 years of a jacket platform.

  16. Estimating the herd immunity effect of rotavirus vaccine.

    Science.gov (United States)

    Pollard, Suzanne L; Malpica-Llanos, Tanya; Friberg, Ingrid K; Fischer-Walker, Christa; Ashraf, Sania; Walker, Neff

    2015-07-31

    Diarrhea is one of the leading causes of death in children under 5, and an estimated 39% of these deaths are attributable to rotavirus. Currently two live, oral rotavirus vaccines have been introduced on the market; however, the herd immunity effect associated with rotavirus vaccine has not yet been quantified. The purpose of this meta-analysis was to estimate the herd immunity effects associated with rotavirus vaccines. We performed a systematic literature review of articles published between 2008 and 2014 that measured the impact of rotavirus vaccine on severe gastroenteritis (GE) morbidity or mortality. We assessed the quality of published studies using a standard protocol and conducted meta-analyses to estimate the herd immunity effect in children less than one year of age across all years presented in the studies. We conducted these analyses separately for studies reporting a rotavirus-specific GE outcome and those reporting an all-cause GE outcome. In studies reporting a rotavirus-specific GE outcome, four of five of which were conducted in the United States, the median herd effect across all study years was 22% [19-25%]. In studies reporting an all-cause GE outcome, all of which were conducted in Latin America, the median herd effect was 24.9% [11-30%]. There is evidence that rotavirus vaccination confers a herd immunity effect in children under one year of age in the United States and Latin American countries. Given the high variability in vaccine efficacy across regions, more studies are needed to better examine herd immunity effects in high mortality regions. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. EFFECTS OF DRUG ABUSE AND DRUG TRAFFICKING AMONG THE YOUTH IN EAST AFRICAN COMMUNITY (EAC)

    OpenAIRE

    UZABAKIRIHO, Abdulkarim

    2018-01-01

    The East AfricanCommunity (EAC) is the regional intergovernmental organization made up ofcountries such as; The Republic of Rwanda, Uganda, Burundi, Kenya and Tanzaniawith its headquarter in Arusha-Tanzania. Drug abuse is the habitual taking ofaddictives or illegal drugs. The use of drugs has increased among the youth inEAC and this region now operates as a potential source of drug consumption,supply and transit route especially from Middle East Countries of Asia toAfrica. Alcohol, Tabacco, C...

  18. Estimating Effective Subsidy Rates of Student Aid Programs

    OpenAIRE

    Stacey H. CHEN

    2008-01-01

    Every year millions of high school students and their parents in the US are asked to fill out complicated financial aid application forms. However, few studies have estimated the responsiveness of government financial aid schemes to changes in financial needs of the students. This paper identifies the effective subsidy rate (ESR) of student aid, as defined by the coefficient of financial needs in the regression of financial aid. The ESR measures the proportion of subsidy of student aid under ...

  19. Estimation and Inference for Very Large Linear Mixed Effects Models

    OpenAIRE

    Gao, K.; Owen, A. B.

    2016-01-01

    Linear mixed models with large imbalanced crossed random effects structures pose severe computational problems for maximum likelihood estimation and for Bayesian analysis. The costs can grow as fast as $N^{3/2}$ when there are N observations. Such problems arise in any setting where the underlying factors satisfy a many to many relationship (instead of a nested one) and in electronic commerce applications, the N can be quite large. Methods that do not account for the correlation structure can...

  20. Evaluation of Rock Stress Estimation by the Kaiser effect

    International Nuclear Information System (INIS)

    Lehtonen, A.

    2005-11-01

    The knowledge of in situ stress is the key input parameter in many rock mechanics analyses. Information on stress allows the definition of boundary conditions for various modelling and engineering tasks. Presently, the estimation of stresses in bedrock is one of the most difficult, time-consuming and high-priced rock mechanical investigations. In addition, the methods used today have not evolved significantly in many years. This brings out a demand for novel, more economical and practical methods for stress estimation. In this study, one such method, Kaiser effect based on acoustic emission of core samples, has been evaluated. It can be described as a 'memory' in rock that is indicated by a change in acoustic emission emitted during uniaxial loading test. The most tempting feature of this method is the ability to estimate the in situ stress state from core specimens in laboratory conditions. This yields considerable cost savings compared to laborious borehole measurements. Kaiser effect has been studied in order to determine in situ stresses for decades without any major success. However, recent studies in Australia and China have been promising and made the estimation of stress tensor possible from differently oriented core samples. The aim of this work has been to develop a similar estimation method in Finland (including both equipment and data reduction), and to test it on samples obtained from Olkiluoto, Eurajoki. The developed measuring system proved to work well. The quality of obtained data varied, but they were still interpretable. The results obtained from these tests were compared with results of previous overcoring measurements, and they showed quite good correlation. Thus, the results were promising, but the method still needs further development and more testing before the final decision on its feasibility can be made. (orig.)

  1. Ex vivo analysis identifies effective HIV-1 latency–reversing drug combinations

    Science.gov (United States)

    Laird, Gregory M.; Bullen, C. Korin; Rosenbloom, Daniel I.S.; Martin, Alyssa R.; Hill, Alison L.; Durand, Christine M.; Siliciano, Janet D.; Siliciano, Robert F.

    2015-01-01

    Reversal of HIV-1 latency by small molecules is a potential cure strategy. This approach will likely require effective drug combinations to achieve high levels of latency reversal. Using resting CD4+ T cells (rCD4s) from infected individuals, we developed an experimental and theoretical framework to identify effective latency-reversing agent (LRA) combinations. Utilizing ex vivo assays for intracellular HIV-1 mRNA and virion production, we compared 2-drug combinations of leading candidate LRAs and identified multiple combinations that effectively reverse latency. We showed that protein kinase C agonists in combination with bromodomain inhibitor JQ1 or histone deacetylase inhibitors robustly induce HIV-1 transcription and virus production when directly compared with maximum reactivation by T cell activation. Using the Bliss independence model to quantitate combined drug effects, we demonstrated that these combinations synergize to induce HIV-1 transcription. This robust latency reversal occurred without release of proinflammatory cytokines by rCD4s. To extend the clinical utility of our findings, we applied a mathematical model that estimates in vivo changes in plasma HIV-1 RNA from ex vivo measurements of virus production. Our study reconciles diverse findings from previous studies, establishes a quantitative experimental approach to evaluate combinatorial LRA efficacy, and presents a model to predict in vivo responses to LRAs. PMID:25822022

  2. Data error effects on net radiation and evapotranspiration estimation

    International Nuclear Information System (INIS)

    Llasat, M.C.; Snyder, R.L.

    1998-01-01

    The objective of this paper is to evaluate the potential error in estimating the net radiation and reference evapotranspiration resulting from errors in the measurement or estimation of weather parameters. A methodology for estimating the net radiation using hourly weather variables measured at a typical agrometeorological station (e.g., solar radiation, temperature and relative humidity) is presented. Then the error propagation analysis is made for net radiation and for reference evapotranspiration. Data from the Raimat weather station, which is located in the Catalonia region of Spain, are used to illustrate the error relationships. The results show that temperature, relative humidity and cloud cover errors have little effect on the net radiation or reference evapotranspiration. A 5°C error in estimating surface temperature leads to errors as big as 30 W m −2 at high temperature. A 4% solar radiation (R s ) error can cause a net radiation error as big as 26 W m −2 when R s ≈ 1000 W m −2 . However, the error is less when cloud cover is calculated as a function of the solar radiation. The absolute error in reference evapotranspiration (ET o ) equals the product of the net radiation error and the radiation term weighting factor [W = Δ(Δ1+γ)] in the ET o equation. Therefore, the ET o error varies between 65 and 85% of the R n error as air temperature increases from about 20° to 40°C. (author)

  3. Effects of anaesthesia techniques and drugs on pulmonary function

    Directory of Open Access Journals (Sweden)

    Vijay Saraswat

    2015-01-01

    Full Text Available The primary task of the lungs is to maintain oxygenation of the blood and eliminate carbon dioxide through the network of capillaries alongside alveoli. This is maintained by utilising ventilatory reserve capacity and by changes in lung mechanics. Induction of anaesthesia impairs pulmonary functions by the loss of consciousness, depression of reflexes, changes in rib cage and haemodynamics. All drugs used during anaesthesia, including inhalational agents, affect pulmonary functions directly by acting on respiratory system or indirectly through their actions on other systems. Volatile anaesthetic agents have more pronounced effects on pulmonary functions compared to intravenous induction agents, leading to hypercarbia and hypoxia. The posture of the patient also leads to major changes in pulmonary functions. Anticholinergics and neuromuscular blocking agents have little effect. Analgesics and sedatives in combination with volatile anaesthetics and induction agents may exacerbate their effects. Since multiple agents are used during anaesthesia, ultimate effect may be different from when used in isolation. Literature search was done using MeSH key words 'anesthesia', 'pulmonary function', 'respiratory system' and 'anesthesia drugs and lungs' in combination in PubMed, Science Direct and Google Scholar filtered by review and research articles sorted by relevance.

  4. Effects of the great recession on drugs consumption in Spain.

    Science.gov (United States)

    Martin Bassols, Nicolau; Vall Castelló, Judit

    2016-09-01

    This paper presents evidence on how the consumption of legal and illegal drugs has changed in response to the Great Recession in Spain. We use a large scale survey from 2005 to 2011 to analyze the association between changes in local economic conditions and drug consumption among individuals aged 15-64. Although Spain was one of the countries hardest hit by the economic downturn, the crisis was unevenly felt across the country. Therefore, we exploit this difference in unemployment rates across provinces to identify the effects of business cycle variations on the consumption of legal and illegal drugs. To the best of our knowledge, this is the first study to find a relation between the deterioration of local economic conditions and a strong increase in the consumption of marihuana and cocaine. We also report a decrease in alcohol consumption but a significant escalation in abusive smoking behavior (smoking every day). We believe that these findings are important not only for the potential negative implications at the individual level but also for the costs to society as a whole. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. A comparison of estimated and calculated effective porosity

    Science.gov (United States)

    Stephens, Daniel B.; Hsu, Kuo-Chin; Prieksat, Mark A.; Ankeny, Mark D.; Blandford, Neil; Roth, Tracy L.; Kelsey, James A.; Whitworth, Julia R.

    Effective porosity in solute-transport analyses is usually estimated rather than calculated from tracer tests in the field or laboratory. Calculated values of effective porosity in the laboratory on three different textured samples were compared to estimates derived from particle-size distributions and soil-water characteristic curves. The agreement was poor and it seems that no clear relationships exist between effective porosity calculated from laboratory tracer tests and effective porosity estimated from particle-size distributions and soil-water characteristic curves. A field tracer test in a sand-and-gravel aquifer produced a calculated effective porosity of approximately 0.17. By comparison, estimates of effective porosity from textural data, moisture retention, and published values were approximately 50-90% greater than the field calibrated value. Thus, estimation of effective porosity for chemical transport is highly dependent on the chosen transport model and is best obtained by laboratory or field tracer tests. Résumé La porosité effective dans les analyses de transport de soluté est habituellement estimée, plutôt que calculée à partir d'expériences de traçage sur le terrain ou au laboratoire. Les valeurs calculées de la porosité effective au laboratoire sur trois échantillons de textures différentes ont été comparées aux estimations provenant de distributions de taille de particules et de courbes caractéristiques sol-eau. La concordance était plutôt faible et il semble qu'il n'existe aucune relation claire entre la porosité effective calculée à partir des expériences de traçage au laboratoire et la porosité effective estimée à partir des distributions de taille de particules et de courbes caractéristiques sol-eau. Une expérience de traçage de terrain dans un aquifère de sables et de graviers a fourni une porosité effective calculée d'environ 0,17. En comparaison, les estimations de porosité effective de données de

  6. Estimation of Drug Particle Size in Intact Tablets by 2-Dimensional X-Ray Diffractometry.

    Science.gov (United States)

    Thakral, Seema; Thakral, Naveen K; Suryanarayanan, Raj

    2018-01-01

    The average grain size of a crystalline material can be determined from the γ-profile of Debye rings in 2-dimensional X-ray diffraction frames. Our objectives were to: (1) validate the method for organic powders and use it to determine the grain size in intact tablets, and (2) demonstrate the pharmaceutical application of this technique by determining the grain size of the active pharmaceutical ingredient in marketed formulations. Six sieve fractions of sucrose were prepared and the particle size distribution was confirmed by laser diffraction. Their average grain size was determined from the 2-dimensional X-ray diffraction frames by the γ-profile method. For particles size determined by the 3 methods were in good agreement. When these particles were compressed, there was no discernible change in the sucrose grain size in tablets. When the particles were >250 μm, compression resulted in a mixture of large grains and fine powder. The grain size of acetaminophen in 11 marketed tablet formulations was determined to be either ∼35 μm or ∼80 μm. This nondestructive technique can therefore be potentially useful to estimate the grain size of crystalline formulation components in intact tablets. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  7. A unified frame of predicting side effects of drugs by using linear neighborhood similarity.

    Science.gov (United States)

    Zhang, Wen; Yue, Xiang; Liu, Feng; Chen, Yanlin; Tu, Shikui; Zhang, Xining

    2017-12-14

    Drug side effects are one of main concerns in the drug discovery, which gains wide attentions. Investigating drug side effects is of great importance, and the computational prediction can help to guide wet experiments. As far as we known, a great number of computational methods have been proposed for the side effect predictions. The assumption that similar drugs may induce same side effects is usually employed for modeling, and how to calculate the drug-drug similarity is critical in the side effect predictions. In this paper, we present a novel measure of drug-drug similarity named "linear neighborhood similarity", which is calculated in a drug feature space by exploring linear neighborhood relationship. Then, we transfer the similarity from the feature space into the side effect space, and predict drug side effects by propagating known side effect information through a similarity-based graph. Under a unified frame based on the linear neighborhood similarity, we propose method "LNSM" and its extension "LNSM-SMI" to predict side effects of new drugs, and propose the method "LNSM-MSE" to predict unobserved side effect of approved drugs. We evaluate the performances of LNSM and LNSM-SMI in predicting side effects of new drugs, and evaluate the performances of LNSM-MSE in predicting missing side effects of approved drugs. The results demonstrate that the linear neighborhood similarity can improve the performances of side effect prediction, and the linear neighborhood similarity-based methods can outperform existing side effect prediction methods. More importantly, the proposed methods can predict side effects of new drugs as well as unobserved side effects of approved drugs under a unified frame.

  8. Observational Pharmacoepidemiology in the Drug Safety and Effectiveness Evaluation

    Directory of Open Access Journals (Sweden)

    José Cabrita

    2017-04-01

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

  9. Evaluation of the effects of a designated program on illegal drug cessation among adolescents who experiment with drugs.

    Science.gov (United States)

    Chang, Chiu-Ching; Liao, Jung-Yu; Huang, Chiu-Mieh; Hsu, Hsiao-Pei; Chen, Chih-Che; Guo, Jong-Long

    2018-01-16

    Studies indicate that adolescent-onset drug users experience a greater likelihood of dependence that continues into adulthood. The importance of early intervention was evident in treating adolescents before their substance use progressed. We examined the effectiveness of an intervention program that prevents students who experiment with drugs from reusing them. The study was based on 10 out of 18 invited schools that were randomly assigned to either the intervention group (5 schools, n = 43) or the comparison group (5 schools, n = 41). The intervention group received an E-course program that comprised a main intervention course (12 sessions) and a booster course (2 sessions). By reducing the burden of teaching content during the 14 sessions, the in-class counselor had opportunities for face-to-face discussions with students on their ambivalence toward quitting illegal drugs. The comparison group received the conventional didactic drug prevention course (2 sessions). Outcomes in terms of stress management, refusal skills, pros of drug use, cons of drug use, and drug use resistance self-efficacy were measured via structured questionnaires conducted thrice: at baseline, after the main intervention sessions, and after the booster sessions. A linear mixed model (LMM) was employed to investigate the effects of time and groups on the outcome variables with group, time, and group × time as fixed effects. Subjects and schools were selected as random effects in order to consider both within-subject and within-school correlations. There was a significant group × time interaction with regard to stress management, refusal skills, pros of drug use, and drug use resistance self-efficacy, excluding cons of drug use. The intervention group displayed better stress management compared to the comparison group after the booster intervention. Similar between-group differences were identified in that the intervention group displayed better refusal skills and drug use

  10. Alcohol and student performance: estimating the effect of legal access.

    Science.gov (United States)

    Lindo, Jason M; Swensen, Isaac D; Waddell, Glen R

    2013-01-01

    We consider the effect of legal access to alcohol on student achievement. Our preferred approach identifies the effect through changes in one's performance after gaining legal access to alcohol, controlling flexibly for the expected evolution of grades as one makes progress towards their degree. We also report RD-based estimates but argue that an RD design is not well suited to the research question in our setting. We find that students' grades fall below their expected levels upon being able to drink legally, but by less than previously documented. We also show that there are effects on women and that the effects are persistent. Using the 1997 National Longitudinal Survey of Youth, we show that students drink more often after legal access but do not consume more drinks on days on which they drink. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. THE COMPARATIVE EFFECT OF TWO ANTIPARASITIC DRUGS IN SHEEP

    OpenAIRE

    DANIELA MOł

    2008-01-01

    This study was performed in two consecutive years, 2006 and 2007, on 30 łurcana breed, 2-5 years aged sheep from Timis and Caras-Severin districts, with clinical signs of ovine oestrosis. The animals received two antiparasitic drugs, Ivomec and Rafoxanid and after 12 days after treatment they were slaughtered and their heads were been examined in the way of Oestrus ovis larvae discovering. The effect of treatment with Ivomec was superior to those of Rafoxanid, demonstrated by number of larvae...

  12. Health effects estimation code development for accident consequence analysis

    International Nuclear Information System (INIS)

    Togawa, O.; Homma, T.

    1992-01-01

    As part of a computer code system for nuclear reactor accident consequence analysis, two computer codes have been developed for estimating health effects expected to occur following an accident. Health effects models used in the codes are based on the models of NUREG/CR-4214 and are revised for the Japanese population on the basis of the data from the reassessment of the radiation dosimetry and information derived from epidemiological studies on atomic bomb survivors of Hiroshima and Nagasaki. The health effects models include early and continuing effects, late somatic effects and genetic effects. The values of some model parameters are revised for early mortality. The models are modified for predicting late somatic effects such as leukemia and various kinds of cancers. The models for genetic effects are the same as those of NUREG. In order to test the performance of one of these codes, it is applied to the U.S. and Japanese populations. This paper provides descriptions of health effects models used in the two codes and gives comparisons of the mortality risks from each type of cancer for the two populations. (author)

  13. Drug Facts

    Medline Plus

    Full Text Available ... some signs and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely ... So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug ...

  14. Bayesian Estimation of Small Effects in Exercise and Sports Science.

    Science.gov (United States)

    Mengersen, Kerrie L; Drovandi, Christopher C; Robert, Christian P; Pyne, David B; Gore, Christopher J

    2016-01-01

    The aim of this paper is to provide a Bayesian formulation of the so-called magnitude-based inference approach to quantifying and interpreting effects, and in a case study example provide accurate probabilistic statements that correspond to the intended magnitude-based inferences. The model is described in the context of a published small-scale athlete study which employed a magnitude-based inference approach to compare the effect of two altitude training regimens (live high-train low (LHTL), and intermittent hypoxic exposure (IHE)) on running performance and blood measurements of elite triathletes. The posterior distributions, and corresponding point and interval estimates, for the parameters and associated effects and comparisons of interest, were estimated using Markov chain Monte Carlo simulations. The Bayesian analysis was shown to provide more direct probabilistic comparisons of treatments and able to identify small effects of interest. The approach avoided asymptotic assumptions and overcame issues such as multiple testing. Bayesian analysis of unscaled effects showed a probability of 0.96 that LHTL yields a substantially greater increase in hemoglobin mass than IHE, a 0.93 probability of a substantially greater improvement in running economy and a greater than 0.96 probability that both IHE and LHTL yield a substantially greater improvement in maximum blood lactate concentration compared to a Placebo. The conclusions are consistent with those obtained using a 'magnitude-based inference' approach that has been promoted in the field. The paper demonstrates that a fully Bayesian analysis is a simple and effective way of analysing small effects, providing a rich set of results that are straightforward to interpret in terms of probabilistic statements.

  15. Bayesian Estimation of Small Effects in Exercise and Sports Science.

    Directory of Open Access Journals (Sweden)

    Kerrie L Mengersen

    Full Text Available The aim of this paper is to provide a Bayesian formulation of the so-called magnitude-based inference approach to quantifying and interpreting effects, and in a case study example provide accurate probabilistic statements that correspond to the intended magnitude-based inferences. The model is described in the context of a published small-scale athlete study which employed a magnitude-based inference approach to compare the effect of two altitude training regimens (live high-train low (LHTL, and intermittent hypoxic exposure (IHE on running performance and blood measurements of elite triathletes. The posterior distributions, and corresponding point and interval estimates, for the parameters and associated effects and comparisons of interest, were estimated using Markov chain Monte Carlo simulations. The Bayesian analysis was shown to provide more direct probabilistic comparisons of treatments and able to identify small effects of interest. The approach avoided asymptotic assumptions and overcame issues such as multiple testing. Bayesian analysis of unscaled effects showed a probability of 0.96 that LHTL yields a substantially greater increase in hemoglobin mass than IHE, a 0.93 probability of a substantially greater improvement in running economy and a greater than 0.96 probability that both IHE and LHTL yield a substantially greater improvement in maximum blood lactate concentration compared to a Placebo. The conclusions are consistent with those obtained using a 'magnitude-based inference' approach that has been promoted in the field. The paper demonstrates that a fully Bayesian analysis is a simple and effective way of analysing small effects, providing a rich set of results that are straightforward to interpret in terms of probabilistic statements.

  16. In silico prediction of harmful effects triggered by drugs and chemicals

    International Nuclear Information System (INIS)

    Vedani, Angelo; Dobler, Max; Lill, Markus A.

    2005-01-01

    While the computer-assisted discovery and optimization of drug candidates based on the known three-dimensional structure of the macromolecular target (structure-based design) or a binding-site surrogate (receptor modeling) is doubtless one of the more potent approaches in rational drug design, the simulation and quantification of side effects triggered by drugs and chemicals are still in their infancy. Major obstacles include the often not available 3D structure of the molecular target, the low specificity of the involved bioregulators and the identification of the controlling metabolic pathways. In the recent past, our laboratory has explored concepts allowing to simulate receptor-mediated toxic phenomena by developing algorithms, allowing to construct realistic 3D binding-site surrogates of receptors known or assumed triggering adverse effects and validating them against large batches of molecular data. The underlying technology (software Quasar and Raptor, respectively) specifically allows for induced fit, solvation phenomena and entropic effects. It has been applied to various systems both of pharmacological and toxicological interest including the neurokinin-1, chemokine-3, bradykinin B 2 , steroid, 5 HT 2A , aryl hydrocarbon, estrogen and androgen receptor, respectively. In this account, we describe the design of a virtual laboratory allowing for a reliable estimation of harmful effects triggered by drugs, chemicals and their metabolites in silico. In the recent past, the Biographics Laboratory 3R has compiled a 3D database including the surrogates of three major receptor systems known to mediate adverse effects (the aryl hydrocarbon, the estrogen and the androgen receptor, respectively) and validated them against a total of 345 compounds (drugs, chemicals, toxins) using multidimensional QSAR technologies. Within this pilot project, we could demonstrate that our virtual laboratory is able to both recognize toxic compounds substantially different from those

  17. Examining the Feasibility and Utility of Estimating Partial Expected Value of Perfect Information (via a Nonparametric Approach) as Part of the Reimbursement Decision-Making Process in Ireland: Application to Drugs for Cancer.

    Science.gov (United States)

    McCullagh, Laura; Schmitz, Susanne; Barry, Michael; Walsh, Cathal

    2017-11-01

    In Ireland, all new drugs for which reimbursement by the healthcare payer is sought undergo a health technology assessment by the National Centre for Pharmacoeconomics. The National Centre for Pharmacoeconomics estimate expected value of perfect information but not partial expected value of perfect information (owing to computational expense associated with typical methodologies). The objective of this study was to examine the feasibility and utility of estimating partial expected value of perfect information via a computationally efficient, non-parametric regression approach. This was a retrospective analysis of evaluations on drugs for cancer that had been submitted to the National Centre for Pharmacoeconomics (January 2010 to December 2014 inclusive). Drugs were excluded if cost effective at the submitted price. Drugs were excluded if concerns existed regarding the validity of the applicants' submission or if cost-effectiveness model functionality did not allow required modifications to be made. For each included drug (n = 14), value of information was estimated at the final reimbursement price, at a threshold equivalent to the incremental cost-effectiveness ratio at that price. The expected value of perfect information was estimated from probabilistic analysis. Partial expected value of perfect information was estimated via a non-parametric approach. Input parameters with a population value at least €1 million were identified as potential targets for research. All partial estimates were determined within minutes. Thirty parameters (across nine models) each had a value of at least €1 million. These were categorised. Collectively, survival analysis parameters were valued at €19.32 million, health state utility parameters at €15.81 million and parameters associated with the cost of treating adverse effects at €6.64 million. Those associated with drug acquisition costs and with the cost of care were valued at €6.51 million and €5.71

  18. Development of a Predictive Model for the Stabilizer Concentration Estimation in Microreservoir Transdermal Drug Delivery Systems Using Lipophilic Pressure-Sensitive Adhesives as Matrix/Carrier.

    Science.gov (United States)

    Chenevas-Paule, Clémence; Wolff, Hans-Michael; Ashton, Mark; Schubert, Martin; Dodou, Kalliopi

    2017-05-01

    Microreservoir-type transdermal drug delivery systems (MTDDS) can prevent drug crystallization; however, no current predictive model considers the impact of drug load and hydration on their physical stability. We investigated MTDDS films containing polyvinylpyrrolidone (PVP) as polymeric drug stabilizer in lipophilic pressure-sensitive adhesive (silicone). Medicated and unmedicated silicone films with different molar N-vinylpyrrolidone:drug ratios were prepared and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, microscopy, dynamic vapor sorption (DVS), and stability testing for 4 months at different storage conditions. Homogeneously distributed drug-PVP associates were observed when nonaqueous emulsions, containing drug-PVP (inner phase) and silicone adhesive (outer phase), were dried to films. DVS data were essential to predict physical stability at different humidities. A predictive thermodynamic model was developed based on drug-polymer hydrogen-bonding interactions, using the Hoffman equation, to estimate the drug-PVP ratio needed to obtain stable MTDDS and to evaluate the impact of humidity on their physical stability. This new approach considers the impact of polymorphism on drug solubility by using easily accessible experimental data (T m and DVS) and avoids uncertainties associated with the solubility parameter approach. In conclusion, a good fit of predicted and experimental data was observed. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  19. Chest X ray effective doses estimation in computed radiography

    International Nuclear Information System (INIS)

    Abdalla, Esra Abdalrhman Dfaalla

    2013-06-01

    Conventional chest radiography is technically difficult because of wide in tissue attenuations in the chest and limitations of screen-film systems. Computed radiography (CR) offers a different approach utilizing a photostimulable phosphor. photostimulable phosphors overcome some image quality limitations of chest imaging. The objective of this study was to estimate the effective dose in computed radiography at three hospitals in Khartoum. This study has been conducted in radiography departments in three centres Advanced Diagnostic Center, Nilain Diagnostic Center, Modern Diagnostic Center. The entrance surface dose (ESD) measurement was conducted for quality control of x-ray machines and survey of operators experimental techniques. The ESDs were measured by UNFORS dosimeter and mathematical equations to estimate patient doses during chest X rays. A total of 120 patients were examined in three centres, among them 62 were males and 58 were females. The overall mean and range of patient dosed was 0.073±0.037 (0.014-0.16) mGy per procedure while the effective dose was 3.4±01.7 (0.6-7.0) mSv per procedure. This study compared radiation doses to patients radiographic examinations of chest using computed radiology. The radiation dose was measured in three centres in Khartoum- Sudan. The results of the measured effective dose showed that the dose in chest radiography was lower in computed radiography compared to previous studies.(Author)

  20. Estimating Terra MODIS Polarization Effect Using Ocean Data

    Science.gov (United States)

    Wald, Andrew E.; Brinkmann, Jake; Wu, Aisheng; Xiong, Jack

    2016-01-01

    Terra MODIS has been known since pre-launch to have polarization sensitivity, particularly in shortest-wavelength bands 8 and 9. On-orbit reflectance trending of pseudo-invariant sites show a variation in reflectance as a function of band and scan mirror angle of incidence consistent with time-dependent polarization effects from the rotating double-sided scan mirror. The MODIS Characterization Support Team [MCST] estimates the Mueller matrix trending from this variation as observed from a single desert site, but this effect is not included in Collection 6 [C6] calibration. Here we extend the MCSTs current polarization sensitivity monitoring to two ocean sites distributed over latitude to helpestimate the uncertainties in the derived Mueller matrix. The Mueller matrix elements derived for polarization-sensitive Band 8 for a given site are found to be fairly insensitive to surface brdf modeling. The site-to-site variation is a measure of the uncertainty in the Mueller estimation.Results for band 8 show that the polarization correction reduces mirror-side striping by up to 50% and reduces the instrument polarization effect on reflectance time series of an ocean target.

  1. Estimating intervention effects of prevention programs: accounting for noncompliance.

    Science.gov (United States)

    Stuart, Elizabeth A; Perry, Deborah F; Le, Huynh-Nhu; Ialongo, Nicholas S

    2008-12-01

    Individuals not fully complying with their assigned treatments is a common problem encountered in randomized evaluations of behavioral interventions. Treatment group members rarely attend all sessions or do all "required" activities; control group members sometimes find ways to participate in aspects of the intervention. As a result, there is often interest in estimating both the effect of being assigned to participate in the intervention, as well as the impact of actually participating and doing all of the required activities. Methods known broadly as "complier average causal effects" (CACE) or "instrumental variables" (IV) methods have been developed to estimate this latter effect, but they are more commonly applied in medical and treatment research. Since the use of these statistical techniques in prevention trials has been less widespread, many prevention scientists may not be familiar with the underlying assumptions and limitations of CACE and IV approaches. This paper provides an introduction to these methods, described in the context of randomized controlled trials of two preventive interventions: one for perinatal depression among at-risk women and the other for aggressive disruptive behavior in children. Through these case studies, the underlying assumptions and limitations of these methods are highlighted.

  2. Pharmacogenomic and clinical data link non-pharmacokinetic metabolic dysregulation to drug side effect pathogenesis

    DEFF Research Database (Denmark)

    Zielinski, Daniel C.; Filipp, F. V.; Bordbar, A.

    2015-01-01

    Drug side effects cause a significant clinical and economic burden. However, mechanisms of drug action underlying side effect pathogenesis remain largely unknown. Here, we integrate pharmacogenomic and clinical data with a human metabolic network and find that non-pharmacokinetic metabolic pathways...... the relationships between the cellular response to drugs, genetic variation of patients and cell metabolism may help managing side effects by personalizing drug prescriptions and nutritional intervention strategies....

  3. Estimation of effective elastic constants for grid plate

    International Nuclear Information System (INIS)

    Shibanuma, Kiyoshi; Kuriyama, Masaaki; Okumura, Yoshikazu

    1980-07-01

    This article contains a method of estimation for the effective elastic constants of a grid plate, which is a flat perforated plate with pipes for cooling. The elastic constants of the grid plate are formulated for two symmetric axes. In the case of using OFCu(E 0 = 12500 kg/mm 2 , ν 0 = 0.34) as the material of the grid, the results are given as follows. E sub(L) = 3180 kg/mm 2 , E sub(T) = 3860 kg/mm 2 upsilon sub(LT) = 0.12, upsilon sub(TL) = 0.15 (author)

  4. Estimation of Rotor Effective Wind Speed: A Comparison

    DEFF Research Database (Denmark)

    Soltani, Mohsen; Knudsen, Torben; Svenstrup, Mikael

    2013-01-01

    Modern wind turbine controllers use wind speed information to improve power production and reduce loads on the turbine components. The turbine top wind speed measurement is unfortunately imprecise and not a good representative of the rotor effective wind speed. Consequently, many different model......-based algorithms have been proposed that are able to estimate the wind speed using common turbine measurements. In this paper, we present a concise yet comprehensive analysis and comparison of these techniques, reviewing their advantages and drawbacks. We implement these techniques and compare the results on both...

  5. Effects of drug solubility, state and loading on controlled release in bicomponent electrospun fibers

    OpenAIRE

    Natu, Mădălina V.; Sousa, Hermínio C. de; Gil, M. H.

    2010-01-01

    Bicomponent fibers of two semi-crystalline (co)polymers, poly(ɛ-caprolactone), and poly(oxyethylene-b-oxypropylene-b-oxyethylene), were obtained by electrospinning. Acetazolamide and timolol maleate were loaded in the fibers in different concentrations (below and above the drug solubility limit in polymer) in order to determine the effect of drug solubility in polymer, drug state, drug loading and fiber composition on fiber morphology, drug distribution and release kinetics. The high loadings...

  6. Effect of drug solubility and lipid carrier on drug release from lipid nanoparticles for dermal delivery.

    Science.gov (United States)

    Zoubari, Gaith; Staufenbiel, Sven; Volz, Pierre; Alexiev, Ulrike; Bodmeier, Roland

    2017-01-01

    Lipid nanoparticles have gained increased interest in the field of dermal products because of various advantages such as improved drug absorption and controlled drug release. The main objective was to investigate the influence of drug solubility and type of lipid carrier on the in vitro drug release. Drugs of different solubilities in the release medium PBS pH 7.4 (dexamethasone: 0.1mg/ml and diclofenac sodium: 5.0mg/ml) and three different lipids (in which the drugs had the highest solubility), Gelucire® 50/13 (solid lipid, mp: 50°C), Witepsol® S55 (solid lipid, mp: 33.5-35.5°C) and Capryol® 90 (liquid lipid) were chosen. The lipid nanoparticles were prepared by high shear homogenization. All nanosuspensions were in the nanometer range (up to 400nm) and the drug encapsulation efficiency was between 84% and 95%. The drug release was prolonged over 48h without an initial burst release and was dependent on the lipid carrier. Formulations containing a higher amount of solid Gelucire® 50/13 released the drugs slower due to the high affinity of the drugs to this lipid product. Inclusion of the liquid lipid Capryol® 90 resulted in a less organized lipidic structures (softer particles) and therefore a faster drug release. Despite its higher water solubility, diclofenac was released slower than dexamethasone because of its higher solubility in the lipid carriers. DSC studies indicated a partial miscibility between the solid lipids and a good miscibility between the solid and liquid lipids. Primary studies using total internal reflection fluorescence (TIRF) microscopy indicated that it is possible to detect individual fluorescently labeled dexamethasone (DXM-F) molecules dissolved in the liquid lipid Capryol® 90. These studies will allow for the precise determination of the drug distribution within the lipid carrier, and the changes upon drug release. In conclusion, lipid carrier type and drug solubility in the lipid have a large influence on the in vitro drug

  7. The test-negative design for estimating influenza vaccine effectiveness.

    Science.gov (United States)

    Jackson, Michael L; Nelson, Jennifer C

    2013-04-19

    The test-negative design has emerged in recent years as the preferred method for estimating influenza vaccine effectiveness (VE) in observational studies. However, the methodologic basis of this design has not been formally developed. In this paper we develop the rationale and underlying assumptions of the test-negative study. Under the test-negative design for influenza VE, study subjects are all persons who seek care for an acute respiratory illness (ARI). All subjects are tested for influenza infection. Influenza VE is estimated from the ratio of the odds of vaccination among subjects testing positive for influenza to the odds of vaccination among subjects testing negative. With the assumptions that (a) the distribution of non-influenza causes of ARI does not vary by influenza vaccination status, and (b) VE does not vary by health care-seeking behavior, the VE estimate from the sample can generalized to the full source population that gave rise to the study sample. Based on our derivation of this design, we show that test-negative studies of influenza VE can produce biased VE estimates if they include persons seeking care for ARI when influenza is not circulating or do not adjust for calendar time. The test-negative design is less susceptible to bias due to misclassification of infection and to confounding by health care-seeking behavior, relative to traditional case-control or cohort studies. The cost of the test-negative design is the additional, difficult-to-test assumptions that incidence of non-influenza respiratory infections is similar between vaccinated and unvaccinated groups within any stratum of care-seeking behavior, and that influenza VE does not vary across care-seeking strata. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. [Effect of psychotropic drugs on vigilance and motor performances].

    Science.gov (United States)

    Amado-Boccara, I; Galinowski, A; Poirier, M F; Lôo, H

    1992-05-23

    This review paper deals with the impact of psychotropic drugs on vigilance, awakening and motricity. Antidepressants can be divided into 3 categories, depending on the subject's awakening: sedatives with a strong anticholinergic component, compounds devoid of positive or negative impact on cognition and stimulating antidepressants. The principal effect of lithium is to lengthen the reaction time. Taken acutely, neuroleptics produce alterations of fine motor gestures, but when taken chronically they spare the functioning of cognition. Benzodiazepines act on vigilance in various ways, depending on their half-life and on their plasma peak time after oral administration. The effect of anticonvulsants on cognition is more pronounced with phenytoin and barbiturates than with carbamazepine or valproate sodium. The problems of comparative analysis in this field and the trends in current studies are underlined.

  9. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Kids Drug Use and Unborn Children Drug Use and Your Health Other Effects on ... Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids ...

  10. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  12. Drug Safety

    Science.gov (United States)

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  13. Combination Effect of Antituberculosis Drugs and Ethanolic Extract of Selected Medicinal Plants against Multi-Drug Resistant Mycobacterium tuberculosis Isolates

    Science.gov (United States)

    Fauziyah, Prabasiwi Nur; Sukandar, Elin Yulinah; Ayuningtyas, Dhyan Kusuma

    2017-01-01

    Adverse drug reaction and resistance to antituberculosis drugs remain the causes of tuberculosis therapeutic failure. This research aimed to find the combination effect of standard antituberculosis drugs with Hibiscus sabdariffa L., Kaempferia galanga L., and Piper crocatum N.E. Br against multi-drug resistant (MDR) Mycobacterium tuberculosis isolates. Two MDR strains (i.e., isoniazid/ethambutol resistant and rifampicin/streptomycin resistant) of M. tuberculosis were inoculated in Löwenstein–Jensen medium containing a combination of standard antituberculosis drugs and ethanolic extracts of H. sabdariffa calyces, K. galanga rhizomes, and P. crocatum leaves using various concentration combinations of drug and extract. The colony numbers were observed for 8 weeks. The effect of the combination was analyzed using the proportion method which was calculated by the mean percentage of inhibition reduction in a number of colonies on drug–extract containing medium compared to extract-free control medium. The results showed that all three plant extracts achieved good combination effects with rifampicin against the rifampicin/streptomycin resistant strain. Antagonistic effects were, however, observed with streptomycin, ethambutol and isoniazid, therefore calling for caution when using these plants in combination with antituberculosis treatment. PMID:28335544

  14. In vivo evaluation of drug-drug interactions linked to UGT inhibition: the effect of probenecid on dalcetrapib pharmacokinetics.

    Science.gov (United States)

    Aceves Baldó, Pau; Anzures-Cabrera, Judith; Bentley, Darren

    2013-03-01

    To assess the effect of the UGT inhibitor probenecid on the pharmacokinetics of dalcetrapib, an investigational drug whose pharmacologically active thiol form undergoes glucuronidation (fm UGT ≥ 0.25). A two-way crossover study in 20 healthy subjects. Subjects received a single 600 mg dose of dalcetrapib with or without probenecid (500 mg 4 times daily for 6 days). AUC∞ and Cmax of dalcetrapib thiol were increased by 14% and 21%, respectively, by co-administration of probenecid. This case study illustrates the difficulty in predicting clinically relevant drug-drug interactions for UGT substrates based only on the fraction metabolized by glucuronidation.

  15. Expression of Genes for Drug Transporters in the Human Female Genital Tract and Modulatory Effect of Antiretroviral Drugs.

    Directory of Open Access Journals (Sweden)

    Karolin Hijazi

    Full Text Available Anti-retroviral (ARV -based microbicides are one of the strategies pursued to prevent HIV-1 transmission. Delivery of ARV drugs to subepithelial CD4+ T cells at concentrations for protection is likely determined by drug transporters expressed in the cervicovaginal epithelium. To define the role of drug transporters in mucosal disposition of topically applied ARV-based microbicides, these must be tested in epithelial cell line-based biopharmaceutical assays factoring the effect of relevant drug transporters. We have characterised gene expression of influx and efflux drug transporters in a panel of cervicovaginal cell lines and compared this to expression in cervicovaginal tissue. We also investigated the effect of dapivirine, darunavir and tenofovir, currently at advanced stages of microbicides development, on expression of drug transporters in cell lines. Expression of efflux ABC transporters in cervical tissue was best represented in HeLa, Ect1/E6E7 and End1/E6E7 cell lines. Expression of influx OCT and ENT transporters in ectocervix matched expression in Hela while expression of influx SLCO transporters in vagina was best reflected in VK2/E6E7 cell line. Stimulation with darunavir and dapivirine upregulated MRP transporters, including MRP5 involved in transport of tenofovir. Dapivirine also significantly downregulated tenofovir substrate MRP4 in cervical cell lines. Treatment with darunavir and dapivirine showed no significant effect on expression of BCRP, MRP2 and P-glycoprotein implicated in efflux of different ARV drugs. Darunavir strongly induced expression in most cell lines of CNT3 involved in cell uptake of nucleotide/nucleoside analogue reverse transcriptase inhibitors and SLCO drug transporters involved in cell uptake of protease inhibitors. This study provides insight into the suitability of cervicovaginal cell lines for assessment of ARV drugs in transport kinetics studies. The modulatory effect of darunavir and dapivirine on

  16. Estimation of dietary supplements intake in a selected group of women over 50 and the risk assessment of interactions between the ingredients of dietary supplements and drugs

    Science.gov (United States)

    Sadowska, Joanna; Bruszkowska, Magda

    Concurrent use of dietary supplements and drugs may result in complications of pharmacotherapy due to possible interactions between their ingredients. The aim of the survey was to estimate the intake of dietary supplements in a group of women over 50 and to analyse the risk of interactions between the ingredients of dietary supplements and drugs taken by the women. The study was carried out among 146 women over 50 years of age. Questionnaire included detailed questions on the type of prescription drugs, OTC (over-the-counter) drugs, and dietary supplements taken. The risk of interactions was determined on the basis of chemical composition of the drugs and supplements specified by the manufacturer, by comparing the obtained data with literature reports on known interactions. The analysis has shown that 88.4% of respondents constantly took prescription drugs, 44.5% of them took OTC drugs, and 66.4% of respondents took dietary supplements throughout the survey period. It has been found that 71.3% of surveyed women taking prescription drugs, took dietary supplements as well. Among women taking supplements and drugs, 36.9% of respondents were taking them concurrently, 60.9% kept such an interval, but only 21.8% of them waited for at least two hours. It has been found that the drug-supplement interactions might occur in 35.8% women under the survey. The analysis of the obtained results has revealed that taking dietary supplements by the group under survey was frequent, and the risk of interactions between dietary supplements and drugs was significant. It is recommended that doctors ask their patients about taken supplements during regular check-ups, and inform them about possible interactions between dietary supplements and drugs. Moreover, appropriate would be to change the labelling of dietary supplements, so that the packaging provides information on possible interactions between their ingredients and drugs.

  17. 49 CFR 40.207 - What is the effect of a cancelled drug test?

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false What is the effect of a cancelled drug test? 40.207 Section 40.207 Transportation Office of the Secretary of Transportation PROCEDURES FOR TRANSPORTATION WORKPLACE DRUG AND ALCOHOL TESTING PROGRAMS Problems in Drug Tests § 40.207 What is the effect of...

  18. Estimating Effects of Species Interactions on Populations of Endangered Species.

    Science.gov (United States)

    Roth, Tobias; Bühler, Christoph; Amrhein, Valentin

    2016-04-01

    Global change causes community composition to change considerably through time, with ever-new combinations of interacting species. To study the consequences of newly established species interactions, one available source of data could be observational surveys from biodiversity monitoring. However, approaches using observational data would need to account for niche differences between species and for imperfect detection of individuals. To estimate population sizes of interacting species, we extended N-mixture models that were developed to estimate true population sizes in single species. Simulations revealed that our model is able to disentangle direct effects of dominant on subordinate species from indirect effects of dominant species on detection probability of subordinate species. For illustration, we applied our model to data from a Swiss amphibian monitoring program and showed that sizes of expanding water frog populations were negatively related to population sizes of endangered yellow-bellied toads and common midwife toads and partly of natterjack toads. Unlike other studies that analyzed presence and absence of species, our model suggests that the spread of water frogs in Central Europe is one of the reasons for the decline of endangered toad species. Thus, studying population impacts of dominant species on population sizes of endangered species using data from biodiversity monitoring programs should help to inform conservation policy and to decide whether competing species should be subject to population management.

  19. Dopaminergic Drug Effects on Probability Weighting during Risky Decision Making

    Science.gov (United States)

    Timmer, Monique H. M.; ter Huurne, Niels P.

    2018-01-01

    Abstract Dopamine has been associated with risky decision-making, as well as with pathological gambling, a behavioral addiction characterized by excessive risk-taking behavior. However, the specific mechanisms through which dopamine might act to foster risk-taking and pathological gambling remain elusive. Here we test the hypothesis that this might be achieved, in part, via modulation of subjective probability weighting during decision making. Human healthy controls (n = 21) and pathological gamblers (n = 16) played a decision-making task involving choices between sure monetary options and risky gambles both in the gain and loss domains. Each participant played the task twice, either under placebo or the dopamine D2/D3 receptor antagonist sulpiride, in a double-blind counterbalanced design. A prospect theory modelling approach was used to estimate subjective probability weighting and sensitivity to monetary outcomes. Consistent with prospect theory, we found that participants presented a distortion in the subjective weighting of probabilities, i.e., they overweighted low probabilities and underweighted moderate to high probabilities, both in the gain and loss domains. Compared with placebo, sulpiride attenuated this distortion in the gain domain. Across drugs, the groups did not differ in their probability weighting, although gamblers consistently underweighted losing probabilities in the placebo condition. Overall, our results reveal that dopamine D2/D3 receptor antagonism modulates the subjective weighting of probabilities in the gain domain, in the direction of more objective, economically rational decision making. PMID:29632870

  20. Estimation of the effective distribution coefficient from the solubility constant

    International Nuclear Information System (INIS)

    Wang, Yug-Yea; Yu, C.

    1994-01-01

    An updated version of RESRAD has been developed by Argonne National Laboratory for the US Department of Energy to derive site-specific soil guidelines for residual radioactive material. In this updated version, many new features have been added to the, RESRAD code. One of the options is that a user can input a solubility constant to limit the leaching of contaminants. The leaching model used in the code requires the input of an empirical distribution coefficient, K d , which represents the ratio of the solute concentration in soil to that in solution under equilibrium conditions. This paper describes the methodology developed to estimate an effective distribution coefficient, Kd, from the user-input solubility constant and the use of the effective K d for predicting the leaching of contaminants

  1. Estimation of effective dose equivalente from external irradiations

    International Nuclear Information System (INIS)

    Wakabayashi, T.

    1985-07-01

    A methodology for computing effective dose equivalent, derived from the computer code ALGAM: Monte Carlo Estimation of Internal Dose from Gamma-ray Sources in a Phantom Man, developed at Oak Ridge National Laboratory, is presented. The modified code was run for 12 different photon energy levels, from 0,010 Mev to 4.0 Mev, which provides computing the absorved dose, for these energy levels, in each one of the 97 organs of the original code. The code also was run for the principal energy levels used in the calibration of the dosimetric films. The results of the absorved doses per photon obtained for these levels of energy have been transformed in effective dose equivalents. (M.A.C.) [pt

  2. Model Specifications for Estimating Labor Market Returns to Associate Degrees: How Robust Are Fixed Effects Estimates? A CAPSEE Working Paper

    Science.gov (United States)

    Belfield, Clive; Bailey, Thomas

    2017-01-01

    Recently, studies have adopted fixed effects modeling to identify the returns to college. This method has the advantage over ordinary least squares estimates in that unobservable, individual-level characteristics that may bias the estimated returns are differenced out. But the method requires extensive longitudinal data and involves complex…

  3. The Economics of the Drug War: Effective Federal Policy of Missed Opportunity?

    Science.gov (United States)

    2002-06-01

    relevant literature to capture the costs incurred relative to the benefits realized. In doing so, we estimate the costs of the drug war. Moreover...results seem to indicate that past U.S. drug policies have failed to achieve their stated objectives. D. POTENTIAL COSTS . . . POTENTIAL BENEFITS ...FamilyWatch, Efficacy, ReconsiDer Forum of Drug Policy, Multi-Disciplinary Association for Psychedelic Studies, and finally, the National

  4. Can current electronic systems meet drug safety and effectiveness requirements?

    Science.gov (United States)

    Holbrook, Anne; Grootendorst, Paul; Willison, Don; Goldsmith, Charles; Sebaldt, Rolf; Keshavjee, Karim

    2005-01-01

    Every health policy jurisdiction is endeavoring to enhance its ability to evaluate drug effectiveness, safety and cost in the real world (pharmacosurveillance). A nominal group consensus conference of stakeholders finalized data items deemed necessary for pharmacosurveillance. Large administrative datasets (LADs), electronic health records (EHRs) and electronic patient registries (PRs), were investigated as sources of this information and for their vulnerability to methodologic bias. Health data privacy legislation and research guidelines were systematically reviewed for their constraint to linked data resource analyses. More than 129 data items were strongly recommended for routine pharmacosurveillance. LADs had very complete information, but restricted to a small number of required data items. EHRs, especially with e-pharmacy links, offer by far the most complete set of health information domains but data entry completeness is highly variable. Adjustment methods for channeling bias are inadequate to mimic randomized trials. Anonymized, linked data held within a secure academic research environment, poses the least privacy concerns. Notwithstanding major technical, methodologic and privacy challenges, individual-level linkage of health data resources poses the best option for pharmacosurveillance today. In future, drug regulators and reimbursement agencies should consider mandatory post-marketing randomized trials.

  5. Bone composition: relationship to bone fragility and antiosteoporotic drug effects.

    Science.gov (United States)

    Boskey, Adele L

    2013-01-01

    The composition of a bone can be described in terms of the mineral phase, hydroxyapatite, the organic phase, which consists of collagen type I, noncollagenous proteins, other components and water. The relative proportions of these various components vary with age, site, gender, disease and treatment. Any drug therapy could change the composition of a bone. This review, however, will only address those pharmaceuticals used to treat or prevent diseases of bone: fragility fractures in particular, and the way they can alter the composition. As bone is a heterogeneous tissue, its composition must be discussed in terms of the chemical makeup, properties of its chemical constituents and their distributions in the ever-changing bone matrix. Emphasis, in this review, is placed on changes in composition as a function of age and various diseases of bone, particularly osteoporosis. It is suggested that while some of the antiosteoporotic drugs can and do modify composition, their positive effects on bone strength may be balanced by negative ones.

  6. Potentiation of Anticancer Drugs: Effects of Pentoxifylline on Neoplastic Cells

    Directory of Open Access Journals (Sweden)

    Miroslav Barancik

    2011-12-01

    Full Text Available The drug efflux activity of P-glycoprotein (P-gp, a product of the mdr1 gene, ABCB1 member of ABC transporter family represents a mechanism by which tumor cells escape death induced by chemotherapeutics. In this study, we investigated the mechanisms involved in the effects of pentoxifylline (PTX on P-gp-mediated multidrug resistance (MDR in mouse leukemia L1210/VCR cells. Parental sensitive mouse leukemia cells L1210, and multidrug-resistant cells, L1210/VCR, which are characterized by the overexpression of P-gp, were used as experimental models. The cells were exposed to 100 μmol/L PTX in the presence or absence of 1.2 μmol/L vincristine (VCR. Western blot analysis indicated a downregulation of P-gp protein expression when multidrug-resistant L1210/VCR cells were exposed to PTX. The effects of PTX on the sensitization of L1210/VCR cells to VCR correlate with the stimulation of apoptosis detected by Annexin V/propidium iodide apoptosis necrosis kit and proteolytic activation of both caspase-3 and caspase-9 monitored by Western blot analysis. Higher release of matrix metalloproteinases (MMPs, especially MMP-2, which could be attenuated by PTX, was found in L1210/VCR than in L1210 cells by gelatin zymography in electrophoretic gel. Exposure of resistant cells to PTX increased the content of phosphorylated Akt kinase. In contrast, the presence of VCR eliminated the effects of PTX on Akt kinase phosphorylation. Taken together, we conclude that PTX induces the sensitization of multidrug-resistant cells to VCR via downregulation of P-gp, stimulation of apoptosis and reduction of MMPs released from drug-resistant L1210/VCR cells. These facts bring new insights into the mechanisms of PTX action on cancer cells.

  7. Epileptogenic side effects of psychotropic drugs. Practical recommendations.

    Science.gov (United States)

    Itil, T M; Soldatos, C

    1980-09-26

    Patient- and drug-related factors influence the inherent epileptogenic properties of psychotropic drugs. This article suggests measures to deal with these properties prophylactically and therapeutically in epileptic and nonepileptic psychiatric patients. The appropriate use of psychotropic drugs is emphasized in light of their epileptogenic potential.

  8. Drug dosing in patients with renal insufficiency in a hospital setting using electronic prescribing and automated reporting of estimated glomerular filtration rate

    DEFF Research Database (Denmark)

    Nielsen, Anita L; Henriksen, Daniel P; Marinakis, Christianna

    2014-01-01

    the clinical support system Renbase(®) as reference, we investigated the use and dosing of drugs in patients with impaired renal function in a university hospital setting using electronic prescription and automatic reporting of estimated glomerular filtration rate (eGFR). In all, 232 patients with an e......In patients with impaired renal function, drug dose adjustment is often required. Non-adherence to clinical prescribing recommendations may result in severe adverse events. In previous studies, the prevalence rate of non-adherence to recommended dosing has been reported to be 19-67%. Using......GFR in the range of 10-49 ml/min/1.73m(2) were included. We identified 436 episodes with administration of renal risk drugs (prescribed to 183 patients): 410 drugs required dose adjustment according to the eGFR and 26 should be avoided. In total, the use or dosing of 66 (15%) of the 436 renal risk drugs...

  9. Integrative relational machine-learning for understanding drug side-effect profiles.

    Science.gov (United States)

    Bresso, Emmanuel; Grisoni, Renaud; Marchetti, Gino; Karaboga, Arnaud Sinan; Souchet, Michel; Devignes, Marie-Dominique; Smaïl-Tabbone, Malika

    2013-06-26

    Drug side effects represent a common reason for stopping drug development during clinical trials. Improving our ability to understand drug side effects is necessary to reduce attrition rates during drug development as well as the risk of discovering novel side effects in available drugs. Today, most investigations deal with isolated side effects and overlook possible redundancy and their frequent co-occurrence. In this work, drug annotations are collected from SIDER and DrugBank databases. Terms describing individual side effects reported in SIDER are clustered with a semantic similarity measure into term clusters (TCs). Maximal frequent itemsets are extracted from the resulting drug x TC binary table, leading to the identification of what we call side-effect profiles (SEPs). A SEP is defined as the longest combination of TCs which are shared by a significant number of drugs. Frequent SEPs are explored on the basis of integrated drug and target descriptors using two machine learning methods: decision-trees and inductive-logic programming. Although both methods yield explicit models, inductive-logic programming method performs relational learning and is able to exploit not only drug properties but also background knowledge. Learning efficiency is evaluated by cross-validation and direct testing with new molecules. Comparison of the two machine-learning methods shows that the inductive-logic-programming method displays a greater sensitivity than decision trees and successfully exploit background knowledge such as functional annotations and pathways of drug targets, thereby producing rich and expressive rules. All models and theories are available on a dedicated web site. Side effect profiles covering significant number of drugs have been extracted from a drug ×side-effect association table. Integration of background knowledge concerning both chemical and biological spaces has been combined with a relational learning method for discovering rules which explicitly

  10. Effect of cyclosporine on drug transport and pharmacokinetics of nifedipine.

    Science.gov (United States)

    Dorababu, Madhura; Nishimura, Asako; Prabha, Thangavelu; Naruhashi, Kazumasa; Sugioka, Nobuyuki; Takada, Kanji; Shibata, Nobuhito

    2009-11-01

    Nifedipine (NFP) is an anti-hypersensitive drug and a well-known substrate of cytochrome P450 3A4 (CYP3A4), while cyclosporine (CSP) is a potent p-glycoprotein (P-gp) inhibitor. P-gp is a drug transporter, which determines the absorption and bioavailability of many drugs that are substrates for P-gp. Drugs that induce or inhibit P-gp may have a profound effect on the absorption and pharmacokinetics (PK) of drugs transported by P-gp within the body, possibly compromising their bioavailability. But the role of P-gp in the NFP efflux and its impact on PK profile is not known. Hence in our present study we attempted to investigate the effect of CSP on oral absorption and PK of NFP. Rhodamine 123 (Rho 123), a known P-gp substrate was used as a positive control. Male Wistar rats (350-400 g) were used for the study. Rats were divided into 4 groups (n=6 each); one group was treated with vehicle (cremophor) followed by NFP (0.2 mg/kg; i.v. bolus) and the other group with CSP (10 mg/kg; i.v.) followed by NFP. Group 3 and 4 were treated with vehicle (cremophor) followed by Rho 123 (0.2 mg/kg, i.v.) and CSP (10 mg/kg; i.v.) followed by Rho 123 (0.2 mg/kg, i.v.) respectively. The blood samples were collected at 0, 5, 10, 15, 30, 60, 90, 120, 180 and 240 min after NFP administration. NFP concentrations in plasma were analyzed by LC-MS-MS and Rho 123 was analyzed by fluorimetric detector. NFP efflux was significantly decreased in CSP treated rats (49.1% decrease, PNFP concentration in plasma were not changed. However the decrease in NFP efflux did not show any significant changes in NFP PK parameters (T(max); 2.0 vs. 2.5 min, C(max); 0.084 vs. 0.076 microg/ml, T(1/2); 84.0 vs. 91.4 min, AUC(0-t); 4.183 vs. 3.467 microg h/ml, AUC(infinity); 5.915 vs. 4.769 microg h/ml, AUMC(0-t); 224.073 vs. 173.063 microg h/ml, AUMC(infinity); 776.871 vs. 575.038 microg h/ml, MRT(0-t); 53.608 vs. 49.538 microg h/ml, MRT(infinity); 118.194 vs. 115.246 microg h/ml, CL(tot); 0.0375 vs. 0.0433 l

  11. Supersaturating drug delivery systems: effect of hydrophilic cyclodextrins and other excipients on the formation and stabilization of supersaturated drug solutions.

    Science.gov (United States)

    Brewster, M E; Vandecruys, R; Verreck, G; Peeters, J

    2008-03-01

    Supersaturating drug delivery systems (SDDS) utilize two important design elements in their preparation including converting the drug of interest into a high energy state or other rapidly dissolving form to facilitate the formation of supersaturated drug solutions and providing a means for stabilizing the formed supersaturated solution such that significant drug absorption is possible from the gastrointestinal tract. This has been referred to as a "spring" and "parachute" approach. The current effort is designed to assess materials which may affect properties in SDDS. To this end, a series of excipients was tested in a co-solvent/solvent quench method to assess their ability to attain and maintain supersaturation for a group of 14 drug development candidates. The approach focussed on hydrophilic cyclodextrins including hydroxypropyl-beta-cyclodextrin (HPbetaCD) and sulfobutyl-beta-cyclodextrin (SBEbetaCD). Various rheological polymers and surfactants were also included in the study. Consistent with previous investigations, the pharmaceutical polymers, as a class, had minimal effects on the extent of supersaturation but tended to be good stabilizers while the surfactants tended to provide for the greatest degree of supersaturation but the formed systems were poorly stable. This study found that hydrophilic cyclodextrins, especially SBEbetaCD, gave superior results in terms of attaining and maintaining supersaturation. A knowledge of the behavior and performance of excipients in this context can be useful in designing solid oral dosage forms for difficult-to-formulate drugs and drug candidates.

  12. Nonlinear mixed-effects modelling of in vitro drug susceptibility and molecular correlates of multidrug resistant Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Julie A Simpson

    Full Text Available The analysis of in vitro anti-malarial drug susceptibility testing is vulnerable to the effects of different statistical approaches and selection biases. These confounding factors were assessed with respect to pfmdr1 gene mutation and amplification in 490 clinical isolates. Two statistical approaches for estimating the drug concentration associated with 50% effect (EC50 were compared: the commonly used standard two-stage (STS method, and nonlinear mixed-effects modelling. The in vitro concentration-effect relationships for, chloroquine, mefloquine, lumefantrine and artesunate, were derived from clinical isolates obtained from patients on the western border of Thailand. All isolates were genotyped for polymorphisms in the pfmdr1 gene. The EC50 estimates were similar for the two statistical approaches but 15-28% of isolates in the STS method had a high coefficient of variation (>15% for individual estimates of EC50 and these isolates had EC50 values that were 32 to 66% higher than isolates derived with more precision. In total 41% (202/490 of isolates had amplification of pfmdr1 and single nucleotide polymorphisms were found in 50 (10%. Pfmdr1 amplification was associated with an increase in EC50 for mefloquine (139% relative increase in EC50 for 2 copies, 188% for 3+ copies, lumefantrine (82% and 75% for 2 and 3+ copies respectively and artesunate (63% and 127% for 2 and 3+ copies respectively. In contrast pfmdr1 mutation at codons 86 or 1042 were associated with an increase in chloroquine EC50 (44-48%. Sample size calculations showed that to demonstrate an EC50 shift of 50% or more with 80% power if the prevalence was 10% would require 430 isolates and 245 isolates if the prevalence was 20%. In conclusion, although nonlinear mixed-effects modelling did not demonstrate any major advantage for determining estimates of anti-malarial drug susceptibility, the method includes all isolates, thereby, potentially improving confirmation of candidate

  13. The effect size, study design, and development experience in commercially sponsored studies for new drug applications in approved drugs.

    Science.gov (United States)

    Fukunaga, Satoshi; Kusama, Makiko; Ono, Shunsuke

    2014-01-01

    Pharmaceutical companies incorporate different features into the trials for new drug applications (NDAs) to render them efficient, making use of their experience. The objective of this analysis was to examine the associations between outcome and features related to study design and clinical development experience in commercially sponsored clinical trials. We collected data of phase 2 and phase 3 trials of all the drugs that obtained approval for depression, schizophrenia, asthma, hypertension, and diabetes in Japan from 1970 to 2011. In total, 145 trials from 90 test drugs were eligible for our study. We calculated the effect size, the standard mean of differences between test drug and comparator therapeutic effects, as the objective variable for use in our analysis. A linear mixed effect model with nested and crossed random effects was used in the analysis including variety of therapeutic area, test drugs and clinical trials. The analysis showed that trial features including sample size, subjective endpoints and active comparator of the same mode of action were negatively associated with effect size. In addition, sponsors' domestic clinical development experience with similar drugs seemed to have a positive association, but prior development experience in foreign countries did not. The accumulation of skills and knowledge within sponsors, and accumulated experience in domestic professionals who implement clinical trials under study contracts with sponsors would be of great importance for yielding clear outcomes. This study provides additional evidence with respect to possible sizes and directions of the influence of study design features that must be considered when planning and implementing trials for new drug applications, and when retrospectively comparing outcomes from trials with different designs and environments.

  14. Evaluating lidar point densities for effective estimation of aboveground biomass

    Science.gov (United States)

    Wu, Zhuoting; Dye, Dennis G.; Stoker, Jason M.; Vogel, John M.; Velasco, Miguel G.; Middleton, Barry R.

    2016-01-01

    The U.S. Geological Survey (USGS) 3D Elevation Program (3DEP) was recently established to provide airborne lidar data coverage on a national scale. As part of a broader research effort of the USGS to develop an effective remote sensing-based methodology for the creation of an operational biomass Essential Climate Variable (Biomass ECV) data product, we evaluated the performance of airborne lidar data at various pulse densities against Landsat 8 satellite imagery in estimating above ground biomass for forests and woodlands in a study area in east-central Arizona, U.S. High point density airborne lidar data, were randomly sampled to produce five lidar datasets with reduced densities ranging from 0.5 to 8 point(s)/m2, corresponding to the point density range of 3DEP to provide national lidar coverage over time. Lidar-derived aboveground biomass estimate errors showed an overall decreasing trend as lidar point density increased from 0.5 to 8 points/m2. Landsat 8-based aboveground biomass estimates produced errors larger than the lowest lidar point density of 0.5 point/m2, and therefore Landsat 8 observations alone were ineffective relative to airborne lidar for generating a Biomass ECV product, at least for the forest and woodland vegetation types of the Southwestern U.S. While a national Biomass ECV product with optimal accuracy could potentially be achieved with 3DEP data at 8 points/m2, our results indicate that even lower density lidar data could be sufficient to provide a national Biomass ECV product with accuracies significantly higher than that from Landsat observations alone.

  15. Impact of relativistic effects on cosmological parameter estimation

    Science.gov (United States)

    Lorenz, Christiane S.; Alonso, David; Ferreira, Pedro G.

    2018-01-01

    Future surveys will access large volumes of space and hence very long wavelength fluctuations of the matter density and gravitational field. It has been argued that the set of secondary effects that affect the galaxy distribution, relativistic in nature, will bring new, complementary cosmological constraints. We study this claim in detail by focusing on a subset of wide-area future surveys: Stage-4 cosmic microwave background experiments and photometric redshift surveys. In particular, we look at the magnification lensing contribution to galaxy clustering and general-relativistic corrections to all observables. We quantify the amount of information encoded in these effects in terms of the tightening of the final cosmological constraints as well as the potential bias in inferred parameters associated with neglecting them. We do so for a wide range of cosmological parameters, covering neutrino masses, standard dark-energy parametrizations and scalar-tensor gravity theories. Our results show that, while the effect of lensing magnification to number counts does not contain a significant amount of information when galaxy clustering is combined with cosmic shear measurements, this contribution does play a significant role in biasing estimates on a host of parameter families if unaccounted for. Since the amplitude of the magnification term is controlled by the slope of the source number counts with apparent magnitude, s (z ), we also estimate the accuracy to which this quantity must be known to avoid systematic parameter biases, finding that future surveys will need to determine s (z ) to the ˜5 %- 10 % level. On the contrary, large-scale general-relativistic corrections are irrelevant both in terms of information content and parameter bias for most cosmological parameters but significant for the level of primordial non-Gaussianity.

  16. Alcohol and adult hippocampal neurogenesis: Promiscuous drug, wanton effects

    Science.gov (United States)

    Geil, Chelsea R.; Hayes, Dayna M.; McClain, Justin A.; Liput, Daniel J.; Marshall, S. Alex; Chen, Kevin Y.; Nixon, Kimberly

    2014-01-01

    Adult neurogenesis is now widely accepted as an important contributor to hippocampal integrity and function but also dysfunction when adult neurogenesis is affected in neuropsychiatric diseases such as alcohol use disorders. Excessive alcohol consumption, the defining characteristic of alcohol use disorders, results in a variety of cognitive and behavioral impairments related wholly or in part to hippocampal structure and function. Recent preclinical work has shown that adult neurogenesis may be one route by which alcohol produces hippocampal neuropathology. Alcohol is a pharmacologically promiscuous drug capable of interfering with adult neurogenesis through multiple mechanisms. This review will discuss the primary mechanisms underlying alcohol-induced changes in adult hippocampal neurogenesis including alcohol's effects on neurotransmitters, CREB and its downstream effectors, and the neurogenic niche. PMID:24842804

  17. THE COMPARATIVE EFFECT OF TWO ANTIPARASITIC DRUGS IN SHEEP

    Directory of Open Access Journals (Sweden)

    DANIELA MOł

    2008-10-01

    Full Text Available This study was performed in two consecutive years, 2006 and 2007, on 30 łurcana breed, 2-5 years aged sheep from Timis and Caras-Severin districts, with clinical signs of ovine oestrosis. The animals received two antiparasitic drugs, Ivomec and Rafoxanid and after 12 days after treatment they were slaughtered and their heads were been examined in the way of Oestrus ovis larvae discovering. The effect of treatment with Ivomec was superior to those of Rafoxanid, demonstrated by number of larvae found in nasal ways and sinuses. It was also observed the higher incidence of ovine oestrosis in 2006 in comparison with 2007, attributed to meteorological conditions.

  18. [Evaluation of effective treatment drugs against Acanthamoeba cyst].

    Science.gov (United States)

    Tahara, K; Asari, S; Shimomura, Y; Endo, T; Yanagihara, T

    1997-10-01

    Cysts of 2 isolates of Acanthamoeba from the cornea of 2 patients with confirmed Acanthamoeba keratitis were tested in vitro for sensitivity to antimycotic agents such as fluconazole, miconazole, amphotericin-B, pimaricin, antiprotozoal agents such as pentamidine isetionate and antiseptics which could be use in the ophthamological region. Pimaricin was the most successful cysticidal agent against the two strains. Sensitivity to pentamidine isetionate showed variation. Fluconazole, miconazole and amphotericin-B were resistant against cysts with concentration of eye drops that have been used in the treatment of Acanthamoeba keratitis. It was supposed that 5% pimaricin eye drops could be use in the treatment of Acanthamoeba keratitis in addition to keratomycosis. Pentamidine isetionate which belong to the diamidine family, is not yet clear as to the side effects to corneal epithelium cell, but we believe that this drug could be expected as a new therapeutic agent for Acanthamoeba keratitis.

  19. Effects of antidepressant drugs on different receptors in the brain

    International Nuclear Information System (INIS)

    Hall, H.; Oegren, S.-O.

    1981-01-01

    Radioligand receptor binding techniques were used to characterize the effects of different structural types of antidepressant drugs on neurotransmitter receptors. The tricyclic antidepressants more or less potently inhibited the binding to rat brain preparations of several different radiolabelled ligands ([ 3 H]WB4101, [ 3 H]QNB, [ 3 H]d-LSD, [ 3 H]mepyramine). The potency of the nontricyclic antidepressants varied greatly. Mianserin, potently displaced [ 3 H]mepyramine, [ 3 H]d-LSD and [ 3 H]WB4101 while it was very weak on [ 3 H]QNB-binding. Nomifensine and the specific 5-HT uptake inhibitors zimelidine and alaproclate had very low affinity for these receptors. All the antidepressants tested were practically devoid of activity on [ 3 H]DHA binding, [ 3 H]spiroperidol binding, [ 3 H]flunitrazepam binding, [ 3 H]muscimol binding and [ 3 H]naloxone binding. The implications of these findings for biogenic amine theories of affective disorders are discussed. (Auth.)

  20. Antiplatelet Drugs for Secondary Prevention of Cardiovascular Diseases : Drug Utilization, Effectiveness, and Safety

    NARCIS (Netherlands)

    Noorsyahdy, A.Y.

    2017-01-01

    Antiplatelet drugs are recommended for secondary prevention of recurrent cardiovascular events in patients who experience diseases in which the pathophysiology is associated with platelet aggregation and atherosclerosis, including acute coronary syndrome, transient ischemic attack, ischemic stroke,

  1. [Estimates of effective population size inPinus silvestris].

    Science.gov (United States)

    Stern, K; Gregorius, H R

    1972-01-01

    The effective population size for inbreeding has been estimated in a 70 years old population of Scotch Pine in three consecutive years to be 0.46, 0.55 and 0.61 respectively of the actual total population. The following formula was developed to determine differences among trees as regards their male or female flowering and their "maleness" and "femaleness":[Formula: see text] wheren e is the total effective population size for inbreeding,n e ' the male effective part,n e ″ the female effective part, andM a measure for monoecy ranging in values between zero (dioecy) and unity (ideal monoecy). The degree of monoecy was 70, 82 and 78 percent respectively in the three years.Correlation between male flowering over the three years was fairly strong; the same was found for female flowering. But correlation between male and female flowering was weak, both within the same year and over the three year period. Correlation of numbers of female strobili and numbers of ripe cones was weak also.The population model on which the above formulae is based is that of a clonal 'Seed Orchard' where seedlings of several clones are randomly distributed on evenly spaced plots.

  2. Effective dose estimation during conventional and CT urography

    Science.gov (United States)

    Alzimami, K.; Sulieman, A.; Omer, E.; Suliman, I. I.; Alsafi, K.

    2014-11-01

    Intravenous urography (IVU) and CT urography (CTU) are efficient radiological examinations for the evaluation of the urinary system disorders. However patients are exposed to a significant radiation dose. The objectives of this study are to: (i) measure and compare patient radiation dose by computed tomography urography (CTU) and conventional intravenous urography (IVU) and (ii) evaluate organ equivalent dose and cancer risks from CTU and IVU imaging procedures. A total of 141 patients were investigated. A calibrated CT machine (Siemens-Somatom Emotion duo) was used for CTU, while a Shimadzu X ray machine was used for IVU. Thermoluminescence dosimeters (TLD-GR200A) were used to measure patients' entrance surface doses (ESD). TLDs were calibrated under reproducible reference conditions. Patients radiation dose values (DLP) for CTU were 172±61 mGy cm, CTDIvol 4.75±2 mGy and effective dose 2.58±1 mSv. Patient cancer probabilities were estimated to be 1.4 per million per CTU examination. Patients ESDs values for IVU were 21.62±5 mGy, effective dose 1.79±1 mSv. CT involves a higher effective dose than IVU. In this study the radiation dose is considered low compared to previous studies. The effective dose from CTU procedures was 30% higher compared to IVU procedures. Wide dose variation between patient doses suggests that optimization is not fulfilled yet.

  3. Estimates of effective dose in adult CT examinations

    International Nuclear Information System (INIS)

    Mohamed, Mustafa Awad Elhaj.

    2015-12-01

    The goal of study was to estimate effective dose (E) in adult CT examinations for Toshiba X64 slice using CT. Exp version 2.5 software in Sudan. Using of CT in medical diagnosis delivers radiation doses to patients that are higher than those from other radiological procedures. lack of optimized protocols could be an additional source of increased dose in developing countries. In order to achieve these objectives, data of CT-scanner has been collected from three hospitals ( ANH, ZSH and MMH). Data collected included equipment information and scan parameters for individual patients, who were used to asses. 300 adult patients underwent head, chest, abdomen-pelvis and peivis CT examinations. The CT1 w , CTD1 v ol, DLP, patient effective dos and organ doses were estimated, using CT exposure parameters and CT Exp version 2.5 software. A large variation of mean effective dose and organ doses among hospitals was observed for similar CT examinations. These variations largely originated from different CT scanning protocols used in different hospitals and scan length. The mean effective dose in this study in the Brain, PNS, Chest, pulmonary, Abdomen-pelvis, Pelvis, KUB and CTU were 3.2 mSv, 2.6 mSv, 18.9 mSv 17.6 mSv 27.1 mSv, 11.2 mSv, 9.6 mSv and 23.7 mSv respectively, and organ equivalent, doses presented in this study in this study for the eye lens (for head), lungs and thymus ( for chest) , liver, kidney and small intest ( for abdomen t-pelvis), bladder, uterus and gonads ( for pelvis), were 62.9 mSv, 39.5 mSv, 34.1 mSv, 53.9 mSv, 52.6 mSv, 58.1 mSv, 37 mSv, and 34.6 mSv, respectively. These values were mostly comparable to and slightly higher than the values of effective doses reported from similar studies the United Kingdom, Tanzania, Australia, Canada and Sudan. It was concluded that patient effective dose and organ doses could be substantially minimized through careful selection of scanning parameters based on clinical indications of study, patient size, and body

  4. Estimating a marriage matching model with spillover effects.

    Science.gov (United States)

    Choo, Eugene; Siow, Aloysius

    2006-08-01

    We use marriage matching functions to study how marital patterns change when population supplies change. Specifically, we use a behavioral marriage matching function with spillover effects to rationalize marriage and cohabitation behavior in contemporary Canada. The model can estimate a couple's systematic gains to marriage and cohabitation relative to remaining single. These gains are invariant to changes in population supplies. Instead, changes in population supplies redistribute these gains between a couple. Although the model is behavioral, it is nonparametric. It can fit any observed cross-sectional marriage matching distribution. We use the estimated model to quantify the impacts of gender differences in mortality rates and the baby boom on observed marital behavior in Canada. The higher mortality rate of men makes men scarcer than women. We show that the scarceness of men modestly reduced the welfare of women and increased the welfare of men in the marriage market. On the other hand, the baby boom increased older men's net gains to entering the marriage market and lowered middle-aged women's net gains.

  5. Identifying Drug Effects via Pathway Alterations using an Integer Linear Programming Optimization Formulation on Phosphoproteomic Data

    Science.gov (United States)

    Mitsos, Alexander; Melas, Ioannis N.; Siminelakis, Paraskeuas; Chairakaki, Aikaterini D.; Saez-Rodriguez, Julio; Alexopoulos, Leonidas G.

    2009-01-01

    Understanding the mechanisms of cell function and drug action is a major endeavor in the pharmaceutical industry. Drug effects are governed by the intrinsic properties of the drug (i.e., selectivity and potency) and the specific signaling transduction network of the host (i.e., normal vs. diseased cells). Here, we describe an unbiased, phosphoproteomic-based approach to identify drug effects by monitoring drug-induced topology alterations. With our proposed method, drug effects are investigated under diverse stimulations of the signaling network. Starting with a generic pathway made of logical gates, we build a cell-type specific map by constraining it to fit 13 key phopshoprotein signals under 55 experimental conditions. Fitting is performed via an Integer Linear Program (ILP) formulation and solution by standard ILP solvers; a procedure that drastically outperforms previous fitting schemes. Then, knowing the cell's topology, we monitor the same key phosphoprotein signals under the presence of drug and we re-optimize the specific map to reveal drug-induced topology alterations. To prove our case, we make a topology for the hepatocytic cell-line HepG2 and we evaluate the effects of 4 drugs: 3 selective inhibitors for the Epidermal Growth Factor Receptor (EGFR) and a non-selective drug. We confirm effects easily predictable from the drugs' main target (i.e., EGFR inhibitors blocks the EGFR pathway) but we also uncover unanticipated effects due to either drug promiscuity or the cell's specific topology. An interesting finding is that the selective EGFR inhibitor Gefitinib inhibits signaling downstream the Interleukin-1alpha (IL1α) pathway; an effect that cannot be extracted from binding affinity-based approaches. Our method represents an unbiased approach to identify drug effects on small to medium size pathways which is scalable to larger topologies with any type of signaling interventions (small molecules, RNAi, etc). The method can reveal drug effects on pathways

  6. Production of drug nanosuspensions: effect of drug physical properties on nanosizing efficiency.

    Science.gov (United States)

    Liu, Tao; Müller, Rainer H; Möschwitzer, Jan P

    2018-02-01

    Drug nanosuspension is one of the established methods to improve the bioavailability of poorly soluble drugs. Drug physical properties aspect (morphology, solid state, starting size et al) is a critical parameter determining the production efficiency. Some drug modification approaches such as spray-drying were proved to improve the millability of drug powders. However, the mechanism behind those improved performances is unclear. This study is to systematically investigate the influence of those physical properties. Five different APIs (active pharmaceutical ingredients) with different millabilities, i.e. resveratrol, hesperetin, glibenclamide, rutin, and quercetin, were processed by standard high pressure homogenization (HPH), wet bead milling (WBM), and a combinative method of spray-drying and HPH. Smaller starting sizes of certain APIs could accelerate the particle size reduction velocity during both HPH and WBM processes. Spherical particles were observed for almost all spray-dried powders (except spray-dried hesperetin) after spray-drying. The crystallinity of some spray-dried samples such as rutin and glibenclamide became much lower than their corresponding unmodified powders. Almost all spray-dried drug powders after HPH processes could lead to smaller nanocrystal particle size than unmodified APIs. The modified microstructure instead of solid state after spray-drying explained the potential reason for improved nanosizing efficiency. In addition, the contribution of starting size on the production efficiency was also critical according to both HPH and WBM results.

  7. Investigating the Effect of Adding Drug (Lidocaine) to a Drug Delivery System Using Small-Angle X-Ray Scattering

    Science.gov (United States)

    Balogh, Joakim; Pedersen, Jan Skov

    The effect on a model drug delivery system when adding a drug, lidocaine, has been studied. Temperature and concentration dependence of a nonionic microemulsion with part of the oil, 1 and %[vol.]10, substituted with drug has been investigated. A nonionic oil-in-water microemulsion consisting of CH3(CH2)11(OCH2CH2)5OH, (C12E5), decane, water and the drug (lidocaine) that has been used to substitute part of the oil was studied. The microscopic differences have been derived from small-angle X-ray scattering (SAXS) data and the results are compared with light scattering data. Using these results together with the macroscopic differences, as observed in the phase diagram (lowering of phase boundaries), between the systems with and without lidocaine can be explained.

  8. Effect of misclassification of antiretroviral treatment status on the prevalence of transmitted HIV-1 drug resistance

    Directory of Open Access Journals (Sweden)

    Castro Hannah

    2012-03-01

    Full Text Available Abstract Background Estimates of the prevalence of transmitted HIV drug resistance (TDR in a population are derived from resistance tests performed on samples from patients thought to be naïve to antiretroviral treatment (ART. Much of the debate over reliability of estimates of the prevalence of TDR has focused on whether the sample population is representative. However estimates of the prevalence of TDR will also be distorted if some ART-experienced patients are misclassified as ART-naïve. Methods The impact of misclassification bias on the rate of TDR was examined. We developed methods to obtain adjusted estimates of the prevalence of TDR for different misclassification rates, and conducted sensitivity analyses of trends in the prevalence of TDR over time using data from the UK HIV Drug Resistance Database. Logistic regression was used to examine trends in the prevalence of TDR over time. Results The observed rate of TDR was higher than true TDR when misclassification was present and increased as the proportion of misclassification increased. As the number of naïve patients with a resistance test relative to the number of experienced patients with a test increased, the difference between true and observed TDR decreased. The observed prevalence of TDR in the UK reached a peak of 11.3% in 2002 (odds of TDR increased by 1.10 (95% CI 1.02, 1.19, p(linear trend = 0.02 per year 1997-2002 before decreasing to 7.0% in 2007 (odds of TDR decreased by 0.90 (95% CI 0.87, 0.94, p(linear trend Conclusion The effect of misclassification of ART on estimates of the prevalence of TDR may be appreciable, and depends on the number of naïve tests relative to the number of experienced tests. Researchers can examine the effect of ART misclassification on their estimates of the prevalence of TDR if such a bias is suspected.

  9. Withanolide D Exhibits Similar Cytostatic Effect in Drug-Resistant and Drug-Sensitive Multiple Myeloma Cells

    Directory of Open Access Journals (Sweden)

    Mark E. Issa

    2017-09-01

    Full Text Available In spite of recent therapeutic advances, multiple myeloma (MM remains a malignancy with very low curability. This has been partly attributed to the existence of a drug-resistant subpopulation known as cancer stem cells (CSCs. MM-CSCs are equipped with the necessary tools that render them highly resistant to virtually all conventional therapies. In this study, the growth inhibitory effects of withanolide D (WND, a steroidal lactone isolated from Withania somnifera, on drug-sensitive tumoral plasma cells and drug-resistant MM cells have been investigated. In MTT/XTT assays, WND exhibited similar cytostatic effects between drug-resistant and drug-sensitive cell lines in the nM range. WND also induced cell death and apoptosis in MM-CSCs and RPMI 8226 cells, as examined by the calcein/ethidium homodimer and annexin V/propidium iodide stainings, respectively. To determine whether P-glycoprotein (P-gp efflux affected the cytostatic activity of WND, P-gp was inhibited with verapamil and results indicated that the WND cytostatic effect in MM-CSCs was independent of P-gp efflux. Furthermore, WND did not increase the accumulation of the fluorescent P-gp substrate rhodamine 123 in MM-CSCs, suggesting that WND may not inhibit P-gp at the tested relevant doses. Therefore, the WND-induced cytostatic effect may be independent of P-gp efflux. These findings warrant further investigation of WND in MM-CSC animal models.

  10. The health and economic effects of counterfeit drugs.

    Science.gov (United States)

    Blackstone, Erwin A; Fuhr, Joseph P; Pociask, Steve

    2014-06-01

    Counterfeit drugs comprise an increasing percentage of the US drug market and even a larger percentage in less developed countries. Counterfeit drugs involve both lifesaving and lifestyle drugs. To review the health and economic consequences of counterfeit drugs on the US public and on the healthcare system as a whole. This comprehensive review of the literature encompassed a search of MEDLINE/PubMed, Google Scholar, and ProQuest using the keywords "counterfeit drugs," "counterfeit medicines," "fake drugs," and "fake medicines." A search of the various FiercePharma daily newsletter series on the healthcare market was also conducted. In addition, the US Food and Drug Administration and the World Health Organization websites were reviewed for additional information. The issue of counterfeit drugs has been growing in importance in the United States, with the supply of these counterfeit drugs coming from all over the world. Innovation is important to economic growth and US competitiveness in the global marketplace, and intellectual property protections provide the ability for society to prosper from innovation. Especially important in terms of innovation in healthcare are the pharmaceutical and biopharmaceutical industries. In addition to taking income from consumers and drug companies, counterfeit drugs also pose health hazards to patients, including death. The case of bevacizumab (Avastin) is presented as one recent example. Internet pharmacies, which are often the source of counterfeit drugs, often falsely portray themselves as Canadian, to enhance their consumer acceptance. Adding to the problems are drug shortages, which facilitate access for counterfeits. A long and convoluted supply chain also facilitates counterfeits. In addition, the wholesale market involving numerous firms is a convenient target for counterfeit drugs. Trafficking in counterfeits can be extremely profitable; detection of counterfeits is difficult, and the penalties are modest. Counterfeit

  11. Solubility of drugs in aqueous polymeric solution: effect of ovalbumin on microencapsulation process.

    Science.gov (United States)

    Aziz, Hesham Abdul; Tan, Yvonne Tze Fung; Peh, Kok Khiang

    2012-03-01

    Microencapsulation of water-soluble drugs using coacervation-phase separation method is very challenging, as these drugs partitioned into the aqueous polymeric solution, resulting in poor drug entrapment. For evaluating the effect of ovalbumin on the microencapsulation of drugs with different solubility, pseudoephedrine HCl, verapamil HCl, propranolol HCl, paracetamol, and curcuminoid were used. In addition, drug mixtures comprising of paracetamol and pseudoephedrine HCl were also studied. The morphology, encapsulation efficiency, particle size, and in vitro release profile were investigated. The results showed that the solubility of the drug determined the ratio of ovalbumin to be used for successful microencapsulation. The optimum ratios of drug, ovalbumin, and gelatin for water-soluble (pseudoephedrine HCl, verapamil HCl, and propranolol HCl), sparingly water-soluble (paracetamol), and water-insoluble (curcuminoid) drugs were found to be 1:1:2, 2:3:5, and 1:3:4. As for the drug mixture, the optimum ratio of drug, ovalbumin, and gelatin was 2:3:5. Encapsulated particles prepared at the optimum ratios showed high yield, drug loading, entrapment efficiency, and sustained release profiles. The solubility of drug affected the particle size of the encapsulated particle. Highly soluble drugs resulted in smaller particle size. In conclusion, addition of ovalbumin circumvented the partitioning effect, leading to the successful microencapsulation of water-soluble drugs.

  12. Development and Validation of a Reversed-Phase HPLC Method for the Estimation of Zolpidem in Bulk Drug and Tablets

    Directory of Open Access Journals (Sweden)

    E. Konoz

    2013-01-01

    Full Text Available In the present study an isocratic reversed-phase high-performance liquid chromatography method was developed for the estimation of zolpidem in bulk drug and pharmaceutical dosage forms. The quantification was carried out on C18 columns. A mixture of acetonitrile-ammonium acetate (pH=8.0, 0.02 M (60 : 40 v/v was used as the mobile phase, at flow rate of 1.0 mL/min and the determination wavelength at 245 nm. The retention time of zolpidem was found to be 3–5 min. The validation of the proposed method was carried out for specificity, linearity, accuracy, precision, limit of detection, limit of quantification, and robustness. The linear dynamic range was from 2.5 to 30 μg mL−1. Regression equation was found to be y=0.1416x+0.0183 with correlation coefficient r=0.9996. The percentage recovery obtained for zolpidem was greater than 96.5%. Limit of quantification and limit of detection were found to be 2.5 μg mL−1 and 0.83 μg mL−1, respectively. The developed method can be used for routine quality control analysis of zolpidem in tablet formulations.

  13. Effectiveness of anti-osteoporotic drugs to prevent secondary fragility fractures: systematic review and meta-analysis.

    Science.gov (United States)

    Saito, T; Sterbenz, J M; Malay, S; Zhong, L; MacEachern, M P; Chung, K C

    2017-12-01

    Patients with osteoporotic fractures have an increased risk for secondary fractures. However, a rigorous study that assesses the effectiveness of individual osteoporotic drugs in preventing subsequent fractures is lacking. The purpose of this review was to analyze the effectiveness of anti-osteoporotic drugs in preventing secondary fractures. We searched for randomized controlled trials that showed the incidence of secondary fractures while using anti-osteoporotic drugs (bisphosphonates, selective estrogen receptor modulators, parathyroid hormone (PTH), or calcitonin) in MEDLINE, Embase.com , and Cochrane Central Register databases. We estimated risk ratios (RR) and numbers needed to treat (NNT) to prevent secondary fractures. Twenty-six studies met our eligibility criteria. There was a significant reduction in RR (0.38-0.77) after the use of anti-osteoporotic drugs for secondary vertebral fractures. Bisphosphonates and PTH significantly reduced the risk of a secondary non-vertebral fracture (RR 0.59 and 0.64). PTH needed the fewest number of patients to be treated to prevent a secondary vertebral fracture (NNT: 56). Our study demonstrated the effectiveness of anti-osteoporotic agents included in our systematic review in preventing secondary vertebral fractures. Bisphosphonates and PTH were most effective in preventing non-vertebral fractures. We suggest that clinicians should prescribe these drugs to prevent secondary vertebral/non-vertebral fractures.

  14. The effects of global warming on fisheries: Simulation estimates

    Directory of Open Access Journals (Sweden)

    Carlos A. Medel

    2016-04-01

    Full Text Available This paper develops two fisheries models in order to estimate the effect of global warming (GW on firm value. GW is defined as an increase in the average temperature of the Earth’s surface as a result of emissions. It is assumed that (i GW exists, and (ii higher temperatures negatively affect biomass. CO2 The literature on biology and GW supporting these two crucial assumptions is reviewed. The main argument presented is that temperature increase has two effects on biomass, both of which have an impact on firm value. First, higher temperatures cause biomass to oscillate. To measure the effect of biomass oscillation on firm value the model in [1] is modified to include water temperature as a variable. The results indicate that a 1 to 20% variation in biomass causes firm value to fall from 6 to 44%, respectively. Second, higher temperatures reduce biomass, and a modification of the model in [2] reveals that an increase in temperature anomaly between +1 and +8°C causes fishing firm value to decrease by 8 to 10%.

  15. Estimated occurrence of tobacco, alcohol, and other drug use among 12- to 18-year-old students in Panama: results of Panama's 1996 National Youth Survey on Alcohol and Drug Use

    Directory of Open Access Journals (Sweden)

    Gonzalo B. González

    1999-01-01

    Full Text Available This report provides the first epidemiological evidence on tobacco, alcohol, and other drug use among school students in Panama, using data from a student survey completed in 1996. Specifically, we examine sex, age, grade level, type of school, and urban-rural variations in the occurrence of tobacco, alcohol, and other drug use. Estimates of lifetime prevalence and past-year use of these products were obtained using data from Panama's 1996 National Youth Survey on Alcohol and Drug Use (n = 6477. To account for the multistage sampling design of the survey, all estimates and respective standard errors are derived by the Taylor series approximation method using Epi Info 6.0 CSAMPLE software. In general, more males, more older students, and more students in higher grades have used licit and illicit drugs, even though male-female differences tend to be small. Public-private school differences and urban-rural trends vary depending on the drug. The findings of this study are discussed in relation to the epidemiology and prevention of drug use in Panama. Based on these data, we seek to provide information to be used by the Government of Panama in its planning for prevention programs directed toward students in Panamanian schools.

  16. A pH-dilution method for estimation of biorelevant drug solubility along the gastrointestinal tract: application to physiologically based pharmacokinetic modeling.

    Science.gov (United States)

    Gao, Yi; Carr, Robert A; Spence, Julie K; Wang, Weili W; Turner, Teresa M; Lipari, John M; Miller, Jonathan M

    2010-10-04

    Physiologically based pharmacokinetic (PBPK) modeling tools have become an integral part of the modern drug discovery-development process. However, accurate PK prediction of enabling formulations of poorly soluble compounds by applying PBPK modeling has been very limited. This is because current PBPK models rely only on thermodynamic drug solubility inputs (e.g., pH-solubility profile) and give little consideration to the dynamic changes in apparent drug solubility (e.g., supersaturation) that occur during gastrointestinal (GI) transit of an enabling formulation of a water insoluble drug. Moreover, biorepresentative and predictive in vitro tools to measure formulation dependent solubility changes during GI transit remain underdeveloped. In this work, we have developed an in vitro dual pH-dilution method based on rat physiology to estimate the apparent drug concentration in solution along the GI tract during release from solubility enabling formulations. This simple dual pH-dilution method was evaluated using various solubility enabling formulations (i.e., cosolvent solution, amorphous solid dispersions) made using a model early development drug candidate with poor aqueous solubility. The in vitro drug concentration-time profiles from the enabling formulations were used as solubility inputs for PBPK modeling using GastroPlus software. This resulted in excellent predictions of the in vivo oral plasma concentration-time profiles, as compared to using the traditional inputs of thermodynamic pH-solubility profiles. In summary, this work describes a novel in vitro method for facile estimation of formulation dependent GI drug concentration-time profiles and demonstrates the utility of PBPK modeling for oral PK prediction of enabling formulations of poorly soluble drugs.

  17. Effect of PEGylation on Drug Entry into Lipid Bilayer

    DEFF Research Database (Denmark)

    Rissanen, S.; Kumorek, M.; Martinez-Seara, H.

    2014-01-01

    Poly(ethylene glycol) (PEG) is a polymer commonly used for functionalization of drug molecules to increase their bloodstream lifetime, hence efficacy. However, the interactions between the PEGylated drugs and biomembranes are not clearly understood. In this study, we employed atomic-scale molecular...... dynamics (MD) simulations to consider the behavior of two drug molecules functionalized with PEG (tetraphenylporphyrin used in cancer phototherapy and biochanin A belonging to the isoflavone family) in the presence of a lipid bilayer. The commonly held view is that functionalization of a drug molecule...... with a polymer acts as an entropic barrier, inhibiting the penetration of the drug molecule through a cell membrane. Our results indicate that in the bloodstream there is an additional source of electrostatic repulsive interactions between the PEGylated drugs and the lipid bilayer. Both the PEG chain and lipids...

  18. Test implementation of a school-oriented drug prevention program "Study without Drugs": pre- and post-testing for effectiveness.

    Science.gov (United States)

    Ishaak, Fariel; de Vries, Nanne Karel; van der Wolf, Kees

    2014-06-11

    In this article, the test implementation of a school-oriented drug prevention program "Study without Drugs" is discussed. The aims of this study were to determine the results of the process evaluation and to determine whether the proposed school-oriented drug prevention program during a pilot project was effective for the participating pupils. Sixty second-grade pupils at a junior high school in Paramaribo, Suriname participated in the test implementation. They were divided into two classes. For the process evaluation the students completed a structured questionnaire focusing on content and teaching method after every lesson. Lessons were qualified with a score from 0-10. The process was also evaluated by the teachers through structured interviews. Attention was paid to reach, dose delivered, dose received, fidelity, connection, achieved effects/observed behaviors, areas for improvement, and lesson strengths. The effect evaluation was conducted by using the General Liniair Model (repeated measure). The research (-design) was a pre-experimental design with pre-and post-test. No class or sex differences were detected among the pupils with regard to the assessment of content, methodology, and qualification of the lessons. Post-testing showed that participating pupils obtained an increased knowledge of drugs, their drug-resisting skills were enhanced, and behavior determinants (attitude, subjective norm, self-efficacy, and intention) became more negative towards drugs. From the results of the test implementation can be cautiously concluded that the program "Study without Drugs" may yield positive results when applied in schools). Thus, this pilot program can be considered a step towards the development and implementation of an evidence-based school-oriented program for pupils in Suriname.

  19. Gender differences in the effects of cardiovascular drugs

    DEFF Research Database (Denmark)

    Tamargo, Juan; Rosano, G.; Thomas, W

    2017-01-01

    . A better understanding of these sex-related differences is fundamental to improve the safety and efficacy of cardiovascular drugs and for developing proper individualized cardiovascular therapeutic strategies both in men and women. This review briefly summarize gender differences in the pharmacokinetics...... and pharmacodynamics of cardiovascular drugs and provides recommendations to close the gaps in our understanding of sex-specific differences in drug efficacy and safety....

  20. Persuader Sex Differences and Peer Pressure Effects on Attitudes Toward Drug Abuse.

    Science.gov (United States)

    Stone, Christopher I.; Shute, Robert E.

    This experiment was performed to assess the effects of the experimental confederates' sex and contrived group peer pressure on the drug attitudes of male college students. Subjects were exposed to all male or all female groups of experimental confederates (persuaders) who expressed either extremely pro-drug or anti-drug sentiments in a guided…

  1. The effects of cyclodextrins on drug release from fatty suppository bases : II. In vivo observations

    NARCIS (Netherlands)

    Frijlink, H.W.; Eissens, Anko; Schoonen, Adelbert; Lerk, C.F.

    The effects of cyclodextrin complexation on the absorption of drugs from fatty suppositories was evaluated in human volunteers. Three model drugs: diazepam, ibuprofen and prednisolone were used. When diazepam was complexed with γ-cyclcodextrin the drug release from the fatty suppositories was

  2. 76 FR 72422 - Draft Guidance for Industry on Evaluating the Effectiveness of Anticoccidial Drugs in Food...

    Science.gov (United States)

    2011-11-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-D-0784] Draft Guidance for Industry on Evaluating the Effectiveness of Anticoccidial Drugs in Food-Producing Animals; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and...

  3. Effect of Drug and Alcohol Education on Attitudes of High School Students.

    Science.gov (United States)

    Lignell, Constance; Davidhizar, Ruth

    1991-01-01

    Examined effects of 3-week alcohol and drug education course on attitudes about alcohol and drugs in ninth grade students (n=180). Results showed mean attitude score changed in desired direction after education indicating negative feelings toward drugs and alcohol use and abuse, polydrug use, dependency, social pressure, and media pressure and…

  4. Cost-effectiveness of rapid susceptibility testing against second-line drugs for tuberculosis

    NARCIS (Netherlands)

    Dowdy, D. W.; van't Hoog, A.; Shah, M.; Cobelens, F.

    2014-01-01

    Drug susceptibility testing (DST) against second-line tuberculosis drugs (SLDs) is essential for improving outcomes among multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) cases. To evaluate the potential cost-effectiveness of rapid DST for SLDs. We constructed a

  5. The Effectiveness of Drug Abuse Treatment: Implications for Controlling AIDS/HIV Infection. Background Paper 3.

    Science.gov (United States)

    Congress of the U.S., Washington, DC. Office of Technology Assessment.

    This background paper examines evidence for the effectiveness of treatment for drug abuse and evaluates the role of drug abuse treatment as a strategy to prevent Human Immunodeficiency Virus (HIV) spread. Because most intravenous (IV) drug users are not in treatment, the study also examines other approaches to HIV prevention. The remainder of the…

  6. The effect of network biology on drug toxicology

    DEFF Research Database (Denmark)

    Gautier, Laurent; Taboureau, Olivier; Audouze, Karine Marie Laure

    2013-01-01

    Introduction: The high failure rate of drug candidates due to toxicity, during clinical trials, is a critical issue in drug discovery. Network biology has become a promising approach, in this regard, using the increasingly large amount of biological and chemical data available and combining...... biology has the opportunity to contribute to a better understanding of a drug's safety profile. The authors believe that considering a drug action and protein's function in a global physiological environment may benefit our understanding of the impact some chemicals have on human health and toxicity...

  7. Salt Effect on the Cloud Point Phenomenon of Amphiphilic Drug-Hydroxypropylmethyl Cellulose System

    Directory of Open Access Journals (Sweden)

    Mohd. Sajid Ali

    2014-01-01

    Full Text Available Effect of two amphiphilic drugs (tricyclic antidepressant, nortriptyline hydrochloride (NORT, and nonsteroidal anti-inflammatory drug, sodium salt of ibuprofen (IBF on the cloud point of biopolymer hydroxypropylmethyl cellulose (HPMC was studied. Effect of NaCl was also seen on the CP of HPMC-drug system. CP of HPMC increases uniformly on increasing the (drug. Both drugs, though one being anionic (IBF and other cationic (NORT, affect the CP in almost the same manner but with different extent implying the role of hydrophobicity in the interaction between drug and polymer. Salt affects the CP of the drug in a dramatic way as low concentration of salt was only able to increase the value of the CP, though not affecting the pattern. However, in presence of high concentration of salts, minimum was observed on CP versus (drug plots. Various thermodynamic parameters were evaluated and discussed on the basis of the observed results.

  8. Effectiveness and cost-effectiveness of potential responses to future high levels of transmitted HIV drug resistance in antiretroviral drug-naive populations beginning treatment

    DEFF Research Database (Denmark)

    Phillips, Andrew N; Cambiano, Valentina; Miners, Alec

    2014-01-01

    BACKGROUND: With continued roll-out of antiretroviral therapy (ART) in resource-limited settings, evidence is emerging of increasing levels of transmitted drug-resistant HIV. We aimed to compare the effectiveness and cost-effectiveness of different potential public health responses to substantial......-effectiveness threshold. Results from our model will help inform WHO recommendations on monitoring of HIV drug resistance in people starting ART. FUNDING: WHO (with funds provided by the Bill & Melinda Gates Foundation), CHAIN (European Commission)....

  9. Estimating acute air pollution health effects from cohort study data.

    Science.gov (United States)

    Szpiro, Adam A; Sheppard, Lianne; Adar, Sara D; Kaufman, Joel D

    2014-03-01

    Traditional studies of short-term air pollution health effects use time series data, while cohort studies generally focus on long-term effects. There is increasing interest in exploiting individual level cohort data to assess short-term health effects in order to understand the mechanisms and time scales of action. We extend semiparametric regression methods used to adjust for unmeasured confounding in time series studies to the cohort setting. Time series methods are not directly applicable since cohort data are typically collected over a prespecified time period and include exposure measurements on days without health observations. Therefore, long-time asymptotics are not appropriate, and it is possible to improve efficiency by exploiting the additional exposure data. We show that flexibility of the semiparametric adjustment model should match the complexity of the trend in the health outcome, in contrast to the time series setting where it suffices to match temporal structure in the exposure. We also demonstrate that pre-adjusting exposures concurrent with the health endpoints using trends in the complete exposure time series results in unbiased health effect estimation and can improve efficiency without additional confounding adjustment. A recently published article found evidence of an association between short-term exposure to ambient fine particulate matter (PM2.5 ) and retinal arteriolar diameter as measured by retinal photography in the Multi-Ethnic Study of Atherosclerosis (MESA). We reanalyze the data from this article in order to compare the methods described here, and we evaluate our methods in a simulation study based on the MESA data. © 2013, The International Biometric Society.

  10. Acanthamoeba: epidimiology, pathogenicity and evaluation of effectiveness of recent drugs

    International Nuclear Information System (INIS)

    Issa, R.M.

    2007-01-01

    To study the epidimiology of Acanthamoeba and to evaluate the effectiveness of some recent drugs against parasite. The study was carried out from March to May 2005 at the ophthalmic clinic of King Fahad Hospital, Saudi Arabia. Samples of rinsing solutions and saline of contact lens, tap water, Swimming pool water and Soil from Hufof city Saudi Arabia were tested. Mice were used to infect them via intranasal inoculation from isolated culture strain for confirming pathogenicity. Rokitamycin, polymixin B, suramin and chloropromazin were used to study their effects on Acanthamoeba growth in vitro. Acanthamoeba were detected in 20% of solution of contact lens, 20% of tap water, 50% of swimming pool samples and 40% of soil samples. All animals died or were sacrificed and had Acanthamoeba isolated from their organs. Higher percentage of growth inhibition of Acanthamoeba cultured was shown by chloropromazine and rokitamycin after 21 days (100%), while Polymyin B and Suramin showed 83% and 64% inhibition respectively. Acanthamoeba isolated in significant percent of environmental sources. Pathogenicity of organism was confirmed in mice. Contact lens wearers should be aware of the risks associated with Acanthamoeba. Rokitamycin and chlorpromazine showed good inhibition in vitro. (author)

  11. Attitudes towards drug legalization among drug users.

    Science.gov (United States)

    Trevino, Roberto A; Richard, Alan J

    2002-01-01

    Research shows that support for legalization of drugs varies significantly among different sociodemographic and political groups. Yet there is little research examining the degree of support for legalization of drugs among drug users. This paper examines how frequency and type of drug use affect the support for legalization of drugs after adjusting for the effects of political affiliation and sociodemographic characteristics. A sample of 188 drug users and non-drug users were asked whether they would support the legalization of marijuana, cocaine, and heroin. Respondents reported their use of marijuana, crack, cocaine, heroin, speedball, and/or methamphetamines during the previous 30 days. Support for legalization of drugs was analyzed by estimating three separate logistic regressions. The results showed that the support for the legalization of drugs depended on the definition of "drug user" and the type of drug. In general, however, the results showed that marijuana users were more likely to support legalizing marijuana, but they were less likely to support the legalization of cocaine and heroin. On the other hand, users of crack, cocaine, heroin, speedball, and/or methamphetamines were more likely to support legalizing all drugs including cocaine and heroin.

  12. Effectiveness and content analysis of interventions to enhance oral antidiabetic drug adherence in adults with type 2 diabetes: systematic review and meta-analysis

    NARCIS (Netherlands)

    Vignon Zomahoun, H.T.; de Bruin, M.; Guillaumie, L.; Moisan, J.; Grégoire, J.P.; Pérez, N.; Vézina-Im, L.A.; Guénette, L.

    2015-01-01

    Objectives To estimate the pooled effect size of oral antidiabetic drug (OAD) adherence-enhancing interventions and to explore which of the behavior change techniques (BCTs) applied in the intervention groups modified this pooled intervention effect size. Methods We searched relevant studies

  13. The smallest worthwhile effect of nonsteroidal anti-inflammatory drugs and physiotherapy for chronic low back pain: a benefit harm trade-off study

    NARCIS (Netherlands)

    Ferreira, M.L.; Herbert, R.D.; Ferreira, P.H.; Latimer, J.; Ostelo, R.W.J.G.; Grotle, M.; Barrett, B.

    2013-01-01

    Objective The aim of this study was to determine the smallest worthwhile effects of two treatments for nonspecific low back pain (LBP). Study Design and Setting The benefit-harm trade-off method was used to estimate the smallest worthwhile effect of nonsteroidal anti-inflammatory drugs (NSAIDs) and

  14. Improved quantum backtracking algorithms using effective resistance estimates

    Science.gov (United States)

    Jarret, Michael; Wan, Kianna

    2018-02-01

    We investigate quantum backtracking algorithms of the type introduced by Montanaro (Montanaro, arXiv:1509.02374). These algorithms explore trees of unknown structure and in certain settings exponentially outperform their classical counterparts. Some of the previous work focused on obtaining a quantum advantage for trees in which a unique marked vertex is promised to exist. We remove this restriction by recharacterizing the problem in terms of the effective resistance of the search space. In this paper, we present a generalization of one of Montanaro's algorithms to trees containing k marked vertices, where k is not necessarily known a priori. Our approach involves using amplitude estimation to determine a near-optimal weighting of a diffusion operator, which can then be applied to prepare a superposition state with support only on marked vertices and ancestors thereof. By repeatedly sampling this state and updating the input vertex, a marked vertex is reached in a logarithmic number of steps. The algorithm thereby achieves the conjectured bound of O ˜(√{T Rmax }) for finding a single marked vertex and O ˜(k √{T Rmax }) for finding all k marked vertices, where T is an upper bound on the tree size and Rmax is the maximum effective resistance encountered by the algorithm. This constitutes a speedup over Montanaro's original procedure in both the case of finding one and the case of finding multiple marked vertices in an arbitrary tree.

  15. Estimation of effective dose from radionuclides contained in misch metal

    International Nuclear Information System (INIS)

    Furuta, Etsuko; Aburai, Tamaru; Nisizawa, Kunihide

    2003-01-01

    Radionuclides contained in three kinds of misch metal products and two kinds of ingots were analyzed using a Ge (Li) semiconductor detector. Lanthanum-138 ( 138 La) and several daughter nuclides derived from thorium and uranium series were detected in all samples. All misch metal products and ingots were determined to be radioactive consumer products (RCP), although they have not been regarded as RCP in Japan. 138 La showed the highest nuclide content rate of all the radionuclides, and the lanthanum metal ingots displayed the highest specific activity at 720 mBq·g -1 . The maximum external effective dose was estimated to be at 3.7 mSv when a metal match was carried for 8,760 hours at 1 mm from the skin. The calculated effective dose under some conditions exceeded 10 μSv per year. This value corresponded to the exemption standard proposed by the UK's National Radiological Protection Board. Individuals working with large amounts of RCP should be appropriately protected. (author)

  16. Leveraging 3D chemical similarity, target and phenotypic data in the identification of drug-protein and drug-adverse effect associations.

    Science.gov (United States)

    Vilar, Santiago; Hripcsak, George

    2016-01-01

    Drug-target identification is crucial to discover novel applications for existing drugs and provide more insights about mechanisms of biological actions, such as adverse drug effects (ADEs). Computational methods along with the integration of current big data sources provide a useful framework for drug-target and drug-adverse effect discovery. In this article, we propose a method based on the integration of 3D chemical similarity, target and adverse effect data to generate a drug-target-adverse effect predictor along with a simple leveraging system to improve identification of drug-targets and drug-adverse effects. In the first step, we generated a system for multiple drug-target identification based on the application of 3D drug similarity into a large target dataset extracted from the ChEMBL. Next, we developed a target-adverse effect predictor combining targets from ChEMBL with phenotypic information provided by SIDER data source. Both modules were linked to generate a final predictor that establishes hypothesis about new drug-target-adverse effect candidates. Additionally, we showed that leveraging drug-target candidates with phenotypic data is very useful to improve the identification of drug-targets. The integration of phenotypic data into drug-target candidates yielded up to twofold precision improvement. In the opposite direction, leveraging drug-phenotype candidates with target data also yielded a significant enhancement in the performance. The modeling described in the current study is simple and efficient and has applications at large scale in drug repurposing and drug safety through the identification of mechanism of action of biological effects.

  17. Effect of ingested lipids on drug dissolution and release with concurrent digestion: a modeling approach

    Science.gov (United States)

    Buyukozturk, Fulden; Di Maio, Selena; Budil, David E.; Carrier, Rebecca L.

    2014-01-01

    Purpose To mechanistically study and model the effect of lipids, either from food or self-emulsifying drug delivery systems (SEDDS), on drug transport in the intestinal lumen. Methods Simultaneous lipid digestion, dissolution/release, and drug partitioning were experimentally studied and modeled for two dosing scenarios: solid drug with a food-associated lipid (soybean oil) and drug solubilized in a model SEDDS (soybean oil and Tween 80 at 1:1 ratio). Rate constants for digestion, permeability of emulsion droplets, and partition coefficients in micellar and oil phases were measured, and used to numerically solve the developed model. Results Strong influence of lipid digestion on drug release from SEDDS and solid drug dissolution into food-associated lipid emulsion were observed and predicted by the developed model. 90 minutes after introduction of SEDDS, there was 9% and 70% drug release in the absence and presence of digestion, respectively. However, overall drug dissolution in the presence of food-associated lipids occurred over a longer period than without digestion. Conclusion A systems-based mechanistic model incorporating simultaneous dynamic processes occurring upon dosing of drug with lipids enabled prediction of aqueous drug concentration profile. This model, once incorporated with a pharmacokinetic model considering processes of drug absorption and drug lymphatic transport in the presence of lipids, could be highly useful for quantitative prediction of impact of lipids on bioavailability of drugs. PMID:24234918

  18. Effect on drug utilization and expenditures of a cost-share change from copayment to coinsurance.

    Science.gov (United States)

    Klepser, Donald G; Huether, Jeffrey R; Handke, Lee J; Williams, Clint E

    2007-01-01

    While increases in prescription drug spending have moderated in recent years, drug spending is still a concern among managed care organizations and health plan administrators. In order to minimize cost increases from year to year, many health care plans have shifted more of the cost of medications to the member-consumer. Coinsurance, a benefit design in which the patient pays a percentage of the cost of the medication, is garnering more attention as a type of cost-sharing that differs from the traditional copayment model. To estimate the impact on medication expenditures and utilization of a pharmacy benefit design change from 3-tier copayment to coinsurance. Drug expenditures and utilization of beneficiaries aged >or =18 years and continuously enrolled in 2 privately insured groups were compared before and after a benefit design change in 1 of the groups. For the 12 months before the benefit design change, both groups had a 3-tier, fixed-dollar copayment structure with identical cost-sharing per 30-day supply: $10 tier-1 copayment for generic drugs, $25 tier-2 copayment for preferred brand drugs, and $40 tier-3 copayment for non-preferred brand drugs. On September 1, 2005, a 4-tier coinsurance benefit design (25% for all tiers except tier-3 [non-preferred] drugs at 50%, with minimum and maximum patient out-of-pocket [OOP] cost applied to each tier) was implemented in the intervention group (N = 46,311). The 3-tier copayment design was maintained in the comparison group (N = 7,916). A difference-in-difference analysis was used to estimate the effect of the benefit design change on expenditures and utilization, overall (for all prescription drugs), and for 3 classes of essential medications: antihypertensives, antidepressants, and statins. Analyses measured changes in outcomes from 6 months pre-change (October 1, 2004, through March 31, 2005) through 6 months post-change (October 1, 2005, through March 31, 2006). In the overall (all drug) analyses, per member per

  19. The Effectiveness of Mandatory-Random Student Drug Testing

    Science.gov (United States)

    James-Burdumy, Susanne; Goesling, Brian; Deke, John; Einspruch, Eric

    2011-01-01

    One approach some U.S. schools now use to combat high rates of adolescent substance use is school-based mandatory-random student drug testing (MRSDT). Under MRSDT, students and their parents sign consent forms agreeing to the students' participation in random drug testing as a condition of participating in athletics and other school-sponsored…

  20. Dissolution Enhancement of Drugs. Part II: Effect of Carriers ...

    African Journals Online (AJOL)

    Recent high throughput screening and combinatorial and parallel synthesis are increasing the number of drug molecules which are highly lipophilic. The oral route is the most preferred route of drug administration due to its convenience, good patient compliance and low medicine production costs. The challenges to ...

  1. The Effective Business Practices of Mexican Drug Trafficking Organizations (DTOs)

    Science.gov (United States)

    2013-06-01

    Zetas employ thousands of people that range in age from young kids playing in the street to older citizens, whose jobs vary from white collar ...favor legitimately buying vehicles or renting houses instead of stealing or committing crimes that would cause bystanders to call the police.208...drugs from the supply chain, little significance of that 4 United Nations Office on Drugs and Crime

  2. [Detoxification effects of two drugs in thallium -poisoned mice].

    Science.gov (United States)

    Wang, Ying; He, Yue-zhong; Zhang, Xi-gang

    2012-06-01

    To observe the thallium eliminating effect of prussian blue, pentetate zinc trisodium (Zn-DTPA), and their combined use in the treatment of acute thallium poisoning in mice. Thallium poisoned mice were reproduced by oral administration of 0.2 ml thallous nitrate (3 mg/ml). They were assigned randomly to four groups according to the random number table method, namely, model group, prussian blue group, Zn-DTPA group and the combination therapy group, with 10 mice in each group. Prussian blue was administered orally [4.52 g×kg(-1)×d(-1), total four times], and Zn-DTPA was injected intraperitoneally [500 mg×kg(-1)×d(-1), one time]4 hours after giving thallium. The dosage of both drugs in combination treatment was as the same as described above. After treatment for 5 days, all the animals were sacrificed. Brain, intestine, kidney and liver of 1 mouse from each group were collected for pathological examination to observe the necrosis. Thallium contents of blood, brain, urine and feces from the other mice were determined. Pathological examination showed that the damage to intestine, kidney and liver was less obvious in treatment group compared with those of the model group. The effect was most obvious in the combination treatment group. However, brain damage was slightly improved. Thallium content in blood (mg/ml) of prussian blue group and the combination treatment group decreased obviously compared with the model group, and the decrease was more obvious in the combination treatment group (0.05 ± 0.01 vs. 0.18 ± 0.02). Thallium content in urine (mg/ml) and feces (mg/kg) was significantly increased after treatment, and the thallium elimination was most significant in the combined treatment group (urine: 11.34 ± 0.81 vs. 0.02 ± 0.01, feces: 13.11 ± 1.84 vs. 0.21 ± 0.07, both P Thallium content in brain was similar among all the groups. The single and combined use of prussian blue and Zn-DTPA could reduce the damage in intestine, kidney and liver. Combined use of

  3. Cost-Effectiveness Analysis of Infrapopliteal Drug-Eluting Stents

    Energy Technology Data Exchange (ETDEWEB)

    Katsanos, Konstantinos, E-mail: katsanos@med.upatras.gr; Karnabatidis, Dimitris; Diamantopoulos, Athanasios; Spiliopoulos, Stavros; Siablis, Dimitris [Patras University Hospital, Department of Interventional Radiology, School of Medicine (Greece)

    2013-02-15

    IntroductionThere are no cost-utility data about below-the-knee placement of drug-eluting stents. The authors determined the cost-effectiveness of infrapopliteal drug-eluting stents for critical limb ischemia (CLI) treatment. The event-free individual survival outcomes defined by the absence of any major events, including death, major amputation, and target limb repeat procedures, were reconstructed on the basis of two published infrapopliteal series. The first included spot Bail-out use of Sirolimus-eluting stents versus bare metal stents after suboptimal balloon angioplasty (Bail-out SES).The second was full-lesion Primary Everolimus-eluting stenting versus plain balloon angioplasty and bail-out bare metal stenting as necessary (primary EES). The number-needed-to-treat (NNT) to avoid one major event and incremental cost-effectiveness ratios (ICERs) were calculated for a 3-year postprocedural period for both strategies. Overall event-free survival was significantly improved in both strategies (hazard ratio (HR) [confidence interval (CI)]: 0.68 [0.41-1.12] in Bail-out SES and HR [CI]: 0.53 [0.29-0.99] in Primary EES). Event-free survival gain per patient was 0.89 (range, 0.11-3.0) years in Bail-out SES with an NNT of 4.6 (CI: 2.5-25.6) and a corresponding ICER of 6,518 Euro-Sign (range 1,685-10,112 Euro-Sign ). Survival gain was 0.91 (range 0.25-3.0) years in Primary EES with an NNT of 2.7 (CI: 1.7-5.8) and an ICER of 11,581 Euro-Sign (range, 4,945-21,428 Euro-Sign ) per event-free life-year gained. Two-way sensitivity analysis showed that stented lesion length >10 cm and/or DES list price >1000 Euro-Sign were associated with the least economically favorable scenario in both strategies. Both strategies of bail-out SES and primary EES placement in the infrapopliteal arteries for CLI treatment exhibit single-digit NNT and relatively low corresponding ICERs.

  4. Estimating the price elasticity of expenditure for prescription drugs in the presence of non-linear price schedules: an illustration from Quebec, Canada.

    Science.gov (United States)

    Contoyannis, Paul; Hurley, Jeremiah; Grootendorst, Paul; Jeon, Sung-Hee; Tamblyn, Robyn

    2005-09-01

    The price elasticity of demand for prescription drugs is a crucial parameter of interest in designing pharmaceutical benefit plans. Estimating the elasticity using micro-data, however, is challenging because insurance coverage that includes deductibles, co-insurance provisions and maximum expenditure limits create a non-linear price schedule, making price endogenous (a function of drug consumption). In this paper we exploit an exogenous change in cost-sharing within the Quebec (Canada) public Pharmacare program to estimate the price elasticity of expenditure for drugs using IV methods. This approach corrects for the endogeneity of price and incorporates the concept of a 'rational' consumer who factors into consumption decisions the price they expect to face at the margin given their expected needs. The IV method is adapted from an approach developed in the public finance literature used to estimate income responses to changes in tax schedules. The instrument is based on the price an individual would face under the new cost-sharing policy if their consumption remained at the pre-policy level. Our preferred specification leads to expenditure elasticities that are in the low range of previous estimates (between -0.12 and -0.16). Naïve OLS estimates are between 1 and 4 times these magnitudes. (c) 2005 John Wiley & Sons, Ltd.

  5. Effect of radioimmunoassay procedures on therapeutic drug monitoring

    International Nuclear Information System (INIS)

    Kampa, I.S.

    1985-01-01

    Methods for the measurement of therapeutic drugs have covered every aspect of analysis from extraction to derivatization. In general, published methods were modified to shorten drug extractions and overall analysis time. The use of different standards, as well as the frequent omission of internal standards, often produced large and clinically unacceptable analytical variations. As a result, physicians would adjust drug dosages according to the physiological response to a standard dose. The introduction of radioimmunoassay techniques for the quantitation of therapeutic drugs have made a significant impact on the clinical chemistry laboratory. The similarities of the various assay methods and the technologists' familiarity with the assay protocols have produced clinically relevant results. Clinical laboratories are now able to frequently analyze a large number of samples with acceptable accuracy and precision. The esoteric test once performed infrequently is today a routine analytical assay often performed STAT. Therapeutic drug monitoring has become a major activity in many clinical laboratories

  6. Inferring Saving in Training Time From Effect Size Estimates

    National Research Council Canada - National Science Library

    Burright, Burke

    2000-01-01

    .... Students' time saving represents a major potential benefit of using them. This paper fills a methodology gap in estimating the students' timesaving benefit of asynchronous training technologies...

  7. [Methodology for Estimating the Risk of Adverse Drug Reactions in Pregnant Women: Analysis of the Japanese Adverse Drug Event Report Database].

    Science.gov (United States)

    Sakai, Takamasa; Ohtsu, Fumiko; Sekiya, Yasuaki; Mori, Chiyo; Sakata, Hiroshi; Goto, Nobuyuki

    2016-01-01

    Safety information regarding drug use during pregnancy is insufficient. The present study aimed to establish an optimal signal detection method to identify adverse drug reactions in pregnant women and to evaluate information in the Japanese Adverse Drug Event Report (JADER) database between April 2004 and November 2014. We identified reports on pregnant women using the Standardised MedDRA Queries. We calculated the proportional reporting ratio (PRR) and reporting odds ratio (ROR) of the risk factors for the two known risks of antithyroid drugs and methimazole (MMI) embryopathy, and ritodrine and fetal/infant cardiovascular events. The PRR and ROR values differed between all reports in the JADER database and those on pregnant women, affecting whether signal detection criteria were met. Therefore we considered that reports on pregnant women should be used when risks associated with pregnancy were determined using signal detection. Analyses of MMI embryopathy revealed MMI signals [PRR, 159.7; ROR, 669.9; 95% confidence interval (CI), 282.4-1588.7] but no propylthiouracil signals (PRR, 1.98; ROR, 2.0; 95%CI, 0.3-15.4). These findings were consistent with those of reported risks. Analyses of fetal/infant cardiovascular events revealed ritodrine signals (PRR, 2.1; ROR, 2.1; 95%CI, 1.4-3.3). These findings were also consistent with reported risks. Mining the JADER database was helpful for analyzing adverse drug reactions in pregnant women.

  8. Understanding peer effects - On the nature, estimation and channels of peer effects

    NARCIS (Netherlands)

    Feld, J.F.; Zölitz, U.N.

    2016-01-01

    This paper estimates peer effects in a university context where students are randomly assigned to sections. While students benefit from better peers on average, low-achieving students are harmed by high-achieving peers. Analyzing students’ course evaluations suggests that peer effects are driven by

  9. Understanding peer effects : on the nature, estimation and channels of peer effects

    NARCIS (Netherlands)

    Feld, J.F.; Zölitz, U.N.

    2016-01-01

    This paper estimates peer effects in a university context where students are randomly assigned to sections. While students benefit from better peers on average, lowachieving students are harmed by high-achieving peers. Analyzing students’ course evaluations suggests that peer effects are driven by

  10. Estimating the cost-effectiveness of detecting cases of chronic hepatitis C infection on reception into prison

    Directory of Open Access Journals (Sweden)

    Edmunds W John

    2006-06-01

    Full Text Available Abstract Background In England and Wales where less than 1% of the population are Injecting drug users (IDUs, 97% of HCV reports are attributed to injecting drug use. As over 60% of the IDU population will have been imprisoned by the age of 30 years, prison may provide a good location in which to offer HCV screening and treatment. The aim of this work is to examine the cost effectiveness of a number of alternative HCV case-finding strategies on prison reception Methods A decision analysis model embedded in a model of the flow of IDUs through prison was used to estimate the cost effectiveness of a number of alternative case-finding strategies. The model estimates the average cost of identifying a new case of HCV from the perspective of the health care provider and how these estimates may evolve over time. Results The results suggest that administering verbal screening for a past positive HCV test and for ever having engaged in illicit drug use prior to the administering of ELISA and PCR tests can have a significant impact on the cost effectiveness of HCV case-finding strategies on prison reception; the discounted cost in 2017 being £2,102 per new HCV case detected compared to £3,107 when no verbal screening is employed. Conclusion The work here demonstrates the importance of targeting those individuals that have ever engaged in illicit drug use for HCV testing in prisons, these individuals can then be targeted for future intervention measures such as treatment or monitored to prevent future transmission.

  11. Effect of Na2SO3 concentration to drug loading and drug release of ascorbic acid in chitosan edible film as drug delivery system membrane

    Directory of Open Access Journals (Sweden)

    Kistriyani Lilis

    2018-01-01

    Full Text Available Chitosan is a type of carbohydrate compounds produced from waste marine products, in particular the class of shrimp, crabs and clams. Chitosan is often process into edible films and utilized for food packaging also has potential as a membrane for drug delivery system. Drug loading and drug release can be controlled by improve the characteristics of the membrane by adding crosslinker. The purpose of this research is to study the effect of addition of crosslinker to the rate of loading and release of ascorbic acid in the chitosan edible film. Na2SO3 was used as crosslinker. Two grams of chitosan was dissolved into 100 ml of distilled water. Acetic acid and plasticizer were added in the solution then heated at 50°C. Na2SO3 solution with mass various of Na2SO3 dissolved, 01026 0.3; and 0.5 grams were added about 30 mL to make edible film. The analysis include of drug loading, drug release and tensile strength. The result showed that the loading of edible film with crosslinker 0.15 g; 0.3 g; and 0.5 g respectively were 60.98 ppm; 52.53 ppm; and 40.88 ppm, meanwhile for the release with crosslinker 0.15 g; 0.3 g; and 0.5 g respectively were 3.78 ppm; 5.72 ppm; and 5.97 ppm.

  12. IMPROVING THE METHODS OF ESTIMATION OF THE UNIT TRAIN EFFECTIVENESS

    Directory of Open Access Journals (Sweden)

    Dmytro KOZACHENKO

    2016-09-01

    Full Text Available The article presents the results of studies of freight transportation by unit trains. The article is aimed at developing the methods of the efficiency evaluation of unit train dispatch on the basis of full-scale experiments. Duration of the car turnover is a random variable when dispatching the single cars and group cars, as well as when dispatching them as a part of a unit train. The existing methodologies for evaluating the efficiency of unit trains’ make-up are based on the use of calculation methodologies and their results can give significant errors. The work presents a methodology that makes it possible to evaluate the efficiency of unit train shipments based on the processing of results of experimental travels using the methods of mathematical statistics. This approach provides probabilistic estimates of the rolling stock use efficiency for different approaches to the organization of car traffic volumes, as well as establishes the effect for each of the participants in the transportation process.

  13. Psychophysical estimation of speed discrimination. II. Aging effects

    Science.gov (United States)

    Raghuram, Aparna; Lakshminarayanan, Vasudevan; Khanna, Ritu

    2005-10-01

    We studied the effects of aging on a speed discrimination task using a pair of first-order drifting luminance gratings. Two reference speeds of 2 and 8 deg/s were presented at stimulus durations of 500 ms and 1000 ms. The choice of stimulus parameters, etc., was determined in preliminary experiments and described in Part I. Thresholds were estimated using a two-alternative-forced-choice staircase methodology. Data were collected from 16 younger subjects (mean age 24 years) and 17 older subjects (mean age 71 years). Results showed that thresholds for speed discrimination were higher for the older age group. This was especially true at stimulus duration of 500 ms for both slower and faster speeds. This could be attributed to differences in temporal integration of speed with age. Visual acuity and contrast sensitivity were not statistically observed to mediate age differences in the speed discrimination thresholds. Gender differences were observed in the older age group, with older women having higher thresholds.

  14. Effect of radiation decontamination on drug-resistant bacteria

    International Nuclear Information System (INIS)

    Ito, Hitoshi

    2006-01-01

    More than 80% of food poisoning bacteria such as Salmonella are reported as antibiotic-resistant to at least one type antibiotic, and more than 50% as resistant to two or more. For the decontamination of food poisoning bacteria in foods, radiation resistibility on drug-resistant bacteria were investigated compared with drug-sensitive bacteria. Possibility on induction of drug-resistant mutation by radiation treatment was also investigated. For these studies, type strains of Escherichia coli S2, Salmonella enteritidis YK-2 and Staphylococcus aureus H12 were used to induce drug-resistant strains with penicillin G. From the study of radiation sensitivity on the drug-resistant strain induced from E. coli S2, D 10 value was obtained to be 0.20 kGy compared with 0.25 kGy at parent strain. On S. enteritidis YK-2, D 10 value was obtained to be 0.14 kGy at drug-resistant strain compared with 0.16 kGy at parent strain. D 10 value was also obtained to be 0.15 kGy at drug-resistant strain compared with 0.21 kGy at parent strain of St. aureus H12. Many isolates of E. coli 157:H7 or other type of E. coli from meats such as beef were resistant to penicillin G, and looked to be no relationship on radiation resistivities between drug-resistant strains and sensitive strains. On the study of radiation sensitivity on E. coli S2 at plate agars containing antibiotics, higher survival fractions were obtained at higher doses compared with normal plate agar. The reason of higher survival fractions at higher doses on plate agar containing antibiotics should be recovery of high rate of injured cells by the relay of cell division, and drug-resistant strains by mutation are hardly induced by irradiation. (author)

  15. Estimating Fitness by Competition Assays between Drug Susceptible and Resistant Mycobacterium tuberculosis of Predominant Lineages in Mumbai, India

    Science.gov (United States)

    Bhatter, Purva; Chatterjee, Anirvan; D'souza, Desiree; Tolani, Monica; Mistry, Nerges

    2012-01-01

    Background Multi Drug Resistant Tuberculosis (MDR TB) is a threat to global tuberculosis control. A significant fitness cost has been associated with DR strains from specific lineages. Evaluation of the influence of the competing drug susceptible strains on fitness of drug resistant strains may have an important bearing on understanding the spread of MDR TB. The aim of this study was to evaluate the fitness of MDR TB strains, from a TB endemic region of western India: Mumbai, belonging to 3 predominant lineages namely CAS, Beijing and MANU in the presence of drug susceptible strains from the same lineages. Methodology Drug susceptible strains from a single lineage were mixed with drug resistant strain, bearing particular non synonymous mutation (rpoB D516V; inhA, A16G; katG, S315T1/T2) from the same or different lineages. Fitness of M.tuberculosis (M.tb) strains was evaluated using the difference in growth rates obtained by using the CFU assay system. Conclusion/Significance While MANU were most fit amongst the drug susceptible strains of the 3 lineages, only Beijing MDR strains were found to grow in the presence of any of the competing drug susceptible strains. A disproportionate increase in Beijing MDR could be an alarm for an impending epidemic in this locale. In addition to particular non synonymous substitutions, the competing strains in an environment may impact the fitness of circulating drug resistant strains. PMID:22479407

  16. A qualitative examination of the effects of international counter-drug interdictions.

    Science.gov (United States)

    Toth, Alexander G; Mitchell, Ojmarrh

    2018-03-07

    The purpose of this study is to utilize unique qualitative data to determine the effects of sporadic international drug interdictions on drug trafficking, and to assess whether the responses of drug traffickers align with rational choice theory. Qualitative data obtained from 23 high-level United States Drug Enforcement Administration (DEA) informants, who are embedded in international drug trafficking groups, are examined to identify common responses to drug interdiction operations. The findings indicate that sporadic counter-drug interdictions do not a have permanent deterrent effect on transnational drug smuggling operations. However, these types of law enforcement operations produce temporary alterations in drug trafficking, as traffickers adopted a variety of methods to thwart the efforts of law enforcement-often by relying on information acquired from corrupt local law enforcement. The results also indicate that while interdiction operations displaced trafficking activities (temporally, spatially, and methodological), there is little evidence that drug traffickers responded to such operations by moving into new areas (i.e., malign spatial displacement). Sporadic international drug interdiction programs do little to deter drug trafficking organizations (DTOs) from engaging in their illicit trade. Instead, DTOs adjust in a calculating manner to these operations to ensure that their illegal products reach consumer marketplaces, which is congruent with the rational choice theoretical perspective. Copyright © 2018 Elsevier B.V. All rights reserved.

  17. Estimation of soil moisture and its effect on soil thermal ...

    Indian Academy of Sciences (India)

    Soil moisture is an important parameter of the earth's climate system. Regression model for estimation of soil moisture at various depths has been developed using the amount of moisture near the surface layer. The estimated values of soil moisture are tested with the measured moisture values and it is found that the ...

  18. [Effect of the GCP Directive on academic drug trials

    DEFF Research Database (Denmark)

    Berendt, L.; Hakansson, C.; Bach, K.F.

    2008-01-01

    was observed over the entire period. Presumably, the introduction of GCP did not entail a decline because of the presence of GCP units at university hospitals. Thus, researchers can conduct clinical drug trials under the same regulations as drug companies Udgivelsesdato: 2008/8/11......Since 2004, adherence to Good Clinical Practice has been mandatory for all clinical drug trials. This was new to the investigator-initiated trials. Our study showed no association between the implementation of the Directive and investigator or industry-initiated trials. However, a steady decline...

  19. Lack of effect of spinal anesthesia on drug metabolism

    International Nuclear Information System (INIS)

    Whelan, E.; Wood, A.J.; Shay, S.; Wood, M.

    1989-01-01

    The effect of spinal anesthesia on drug disposition was determined in six dogs with chronically implanted vascular catheters using propranolol as a model compound. On the first study day, 40 mg of unlabeled propranolol and 200 microCi of [3H]propranolol were injected into the portal and femoral veins respectively. Arterial blood samples were taken for 4 hr for measurement of plasma concentrations of labeled and unlabeled propranolol by high-pressure liquid chromatography (HPLC) and of [3H]propranolol by liquid scintillation counting of the HPLC eluant corresponding to each propranolol peak. Twenty-four hr later, spinal anesthesia was induced with tetracaine (mean dose 20.7 +/- 0.6 mg) with low sacral to midthoracic levels and the propranolol infusions and sampling were then repeated. Spinal anesthesia had no significant effect on either the intrinsic clearance of propranolol (2.01 +/- 0.75 L/min before and 1.9 +/- 0.7 L/min during spinal anesthesia), or on mean hepatic plasma flow (2.01 +/- 0.5 L/min before and 1.93 +/- 0.5 L/min during spinal anesthesia). The systemic clearance and elimination half-life of propranolol were also unchanged by spinal anesthesia (0.9 +/- 0.23 L/min on the first day, 0.7 +/- 0.1 L/min during spinal anesthesia; and 101 +/- 21 min on the first day, 115 +/- 16 min during spinal anesthesia, respectively). The volume of distribution (Vd) of propranolol was similarly unaffected by spinal anesthesia

  20. Cellular Effects of the Antiepileptic Drug Valproic Acid in Glioblastoma

    Directory of Open Access Journals (Sweden)

    Marita Eckert

    2017-12-01

    Full Text Available Background/Aims: Valproic acid (VPA, an anticonvulsant and mood-stabilizing drug is used to treat epileptic seizure of glioblastoma patients. Besides its antiepileptic activity, VPA has been attributed further functions that improve the clinical outcome of glioblastoma patients. Those comprise the inhibition of some histone deacetylase (HDAC isoforms which reportedly may result in radiosensitization. Retrospective analysis of patient data, however, could not unequivocally confirm a prolonged survival of glioblastoma patients receiving VPA. The present study aimed to identify potential VPA targets at the cellular level. Methods: To this end, the effect of VPA on metabolism, Ca2+-, biochemical and electro-signaling, cell-cycling, clonogenic survival and transfilter migration was analyzed in three human glioblastoma lines (T98G, U-87MG, U251 by MTT assay, Ca2+ imaging, immunoblotting, patch-clamp recording, flow cytometry, delayed plating colony formation and modified Boyden chamber assays, respectively. In addition, the effect of VPA on clonogenic survival of primary glioblastoma spheroid cultures treated with temozolomide and fractionated radiation was assessed by limited dilution assay. Results: In 2 of 3 glioblastoma lines, clinical relevant concentrations of VPA slightly slowed down cell cycle progression and decreased clonogenic survival. Furthermore, VPA induced Ca2+ signaling which was accompanied by pronounced K+ channel activity and transfilter cell migration. VPA did not affect metabolic NAD(PH formation or radioresistance of the glioblastoma lines. Finally, VPA did not impair clonogenic survival or radioresistance of temozolomide-treated primary spheroid cultures. Conclusions: Combined, our in vitro data do not propose a general use of VPA as a radiosensitizer in anti-glioblastoma therapy.

  1. The Effect on Treatment Adherence of Administering Drugs as Fixed-Dose Combinations versus as Separate Pills: Systematic Review and Meta-Analysis

    Science.gov (United States)

    van Galen, Katy A.; Nellen, Jeannine F.; Nieuwkerk, Pythia T.

    2014-01-01

    Administering drugs as fixed-dose combinations (FDCs) versus the same active drugs administered as separate pills is assumed to enhance treatment adherence. We synthesized evidence from randomized controlled trials (RCTs) about the effect of FDCs versus separate pills on adherence. We searched PubMed for RCTs comparing a FDC with the same active drugs administered as separate pills, including a quantitative estimate of treatment adherence, without restriction to medical condition. The odds ratio (OR) of optimal adherence with FDCs versus separate pills was used as common effect size and aggregated into a pooled effect estimate using a random effect model with inverse variance weights. Out of 1258 articles screened, only six studies fulfilled inclusion criteria. Across medical conditions, administering drugs as FDC significantly increased the likelihood of optimal adherence (OR 1.33 (95% CI, 1.03–1.71)). Within subgroups of specific medical conditions, the favourable effect of FDCs on adherence was of borderline statistical significance for HIV infection only (OR 1.46 (95% CI, 1.00–2.13)). We observed a remarkable paucity of RCTs comparing the effect on adherence of administering drugs as FDC versus as separate pills. Administering drugs as FDC improved medication adherence. However, this conclusion is based on a limited number of RCTs only. PMID:25276422

  2. Contrasting effects of cord injury on intravenous and oral pharmacokinetics of diclofenac: a drug with intermediate hepatic extraction.

    Science.gov (United States)

    Cruz-Antonio, L; Arauz, J; Franco-Bourland, R E; Guízar-Sahagún, G; Castañeda-Hernández, G

    2012-08-01

    Laboratory investigation in rats submitted to experimental spinal cord injury (SCI). To determine the effect of acute SCI on the pharmacokinetics of diclofenac, a marker drug of intermediate hepatic extraction, administered by the intravenous and the oral routes. Female Wistar rats were submitted to complete section of the spinal cord at the T8 level. SCI and sham-injured rats received 3.2 mg kg(-1) of diclofenac sodium either intravenously or orally, diclofenac concentration was measured in whole blood samples and pharmacokinetic parameters were estimated. Diclofenac was not selected as test drug because of its therapeutic properties, but because to its biopharmaceutical properties, that is, intermediate hepatic extraction. Diclofenac bioavailability after intravenous administration was increased in injured rats compared with controls due to a reduced clearance. In contrast, oral diclofenac bioavailability was diminished in SCI animals due to a reduction in drug absorption, which overrides the effect on clearance. Acute SCI induces significant pharmacokinetic changes for diclofenac, a marker drug with intermediate hepatic extraction. SCI-induced pharmacokinetic changes are not only determined by injury characteristics, but also by the route of administration and the biopharmaceutical properties of the studied drug.

  3. The effect of chronic renal failure on hepatic drug metabolism and drug disposition.

    Science.gov (United States)

    Dreisbach, Albert W; Lertora, Juan J L

    2003-01-01

    There is abundant evidence that chronic renal failure (CRF) and end-stage renal disease (ESRD) alter drug disposition by affecting protein and tissue binding and reducing systemic clearance of renally cleared drugs. What is not fully appreciated is that CRF can significantly reduce nonrenal clearance and alter the bioavailability of drugs predominantly metabolized by the liver. Animal studies in CRF have shown a major down-regulation (40-85%) of hepatic cytochrome P-450 metabolism involving specific isozymes. Phase II reactions such as acetylation and glucuronidation are also involved, with some isozymes showing induction and others inhibition. Hepatic enzymes exhibiting genetic polymorphisms such as N-acetyl-transferase-2 (NAT-2), which is responsible for the rapid and slow acetylator phenotypes, have been shown to be inhibited by ESRD and reversed by transplantation. There is some evidence pointing to the possibility of inhibitory factors circulating in the serum in ESRD patients which may be dialyzable. This review includes all significant animal and clinical studies using the search terms "chronic renal failure,"cytochrome P-450," and "liver metabolism" over the past 10 years obtained from the National Library of Medicine MEDLINE database, including relevant articles back to 1969.

  4. Nonsteroidal anti-inflammatory drugs: adverse effects and their prevention.

    NARCIS (Netherlands)

    Vonkeman, Harald Erwin; van de Laar, Mart A F J

    2010-01-01

    Objectives: To discuss nonsteroidal anti-inflammatory drugs (NSAIDs), their history, development, mode of action, toxicities, strategies for the prevention of toxicity, and future developments. - Methods: Medline search for articles published up to 2007, using the keywords acetylsalicylic acid,

  5. Adverse effects of sympathomimetic drugs in a group of adolescents

    OpenAIRE

    Jerí, F. Raúl; Departamento de Medicina, Sección de Neurología, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú; Carbajal, Carlos; Departamento de Medicina, Sección de Neurología, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú; Sánchez M., César; Departamento de Medicina, Sección de Neurología, Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú

    2014-01-01

    Clinical observations of 35 youths who used hallucinogenic drugs for two to four years are mostly present . The proportion of males was three times compared to women , almost all households were from well integrated and belonged to a higher socio- economic level or medium . The drugs used were marijuana , LSD , barbiturates , mescaline , afetamina , methaqualone and alcohol, in various combinations . All of these young people showed signs of psychological disturbance , personality disorders g...

  6. Effect of Smart Meter Measurements Data On Distribution State Estimation

    DEFF Research Database (Denmark)

    Pokhrel, Basanta Raj; Nainar, Karthikeyan; Bak-Jensen, Birgitte

    2018-01-01

    Smart distribution grids with renewable energy based generators and demand response resources (DRR) requires accurate state estimators for real time control. Distribution grid state estimators are normally based on accumulated smart meter measurements. However, increase of measurements...... in the physical grid can enforce significant stress not only on the communication infrastructure but also in the control algorithms. This paper aims to propose a methodology to analyze needed real time smart meter data from low voltage distribution grids and their applicability in distribution state estimation...

  7. Effect of solcoseryl on antitumour action and acute toxicity of some antineoplastic drugs.

    Science.gov (United States)

    Danysz, A; Sołtysiak-Pawluczuk, D; Czyzewska-Szafran, H; Jedrych, A; Jastrzebski, Z

    1991-01-01

    The in vivo effect of Solcoseryl on the antitumour activity and acute toxicity of some antineoplastic drugs was examined. It was found that Solcoseryl does not inhibit the antineoplastic effectiveness of the drugs against transplantable P 388 leukaemia in mice. Studies of the effect of Solcoseryl on acute toxicity of selected antineoplastic drugs in mice revealed that the biostimulator could exert a modifying influence. The prior administration of Solcoseryl significantly decreases the acute toxicity of methotrexate but has no effect on acute toxicity of 5-fluorouracil, increases the acute toxicity of bleomycin and vinblastine and has no effect on acute toxicity of methotrexate and mitoxantron. On the other hand, Solcoseryl administered simultaneously with the antineoplastic drugs increases acute toxicity of 5-fluorouracil, bleomycin and mitoxantron. The protective effect of the biostimulator noted exclusively against acute toxicity of 5-fluorouracil was also observed after multiple administration of this anticancer drug.

  8. Psychiatric side effects and antiepileptic drugs: Observations from prospective audits.

    Science.gov (United States)

    Stephen, Linda J; Wishart, Abbie; Brodie, Martin J

    2017-06-01

    Psychiatric comorbidities are common in people with epilepsy. A retrospective study of characteristics associated with withdrawal due to psychiatric side effects was undertaken in patients with treated epilepsy participating in prospective audits with new antiepileptic drugs (AEDs). A total of 1058 treated patients with uncontrolled seizures (942 focal-onset seizures, 116 generalized genetic epilepsies [GGEs]) participated in eight prospective, observational audits from 1996 to 2014. These patients were prescribed adjunctive topiramate (n=170), levetiracetam (n=220), pregabalin (n=135), zonisamide (n=203), lacosamide (n=160), eslicarbazepine acetate (n=52), retigabine (n=64), or perampanel (n=54). Doses were titrated according to efficacy and tolerability to optimize zeizure outcomes and reduce side effects. Psychiatric comorbidities were recorded prior to and after the addition of each AED. At baseline, patients with focal-onset seizures (189 of 942; 20.1%) were statistically more likely to have psychiatric diagnoses compared to patients with GGEs (14 of 116, 12.1%; p=0.039). Following adjunctive AED treatment, neuropsychiatric adverse effects led to AED withdrawal in 1.9-16.7% of patients. Patients with a pre-treatment psychiatric history (22 of 209; 10.5%) were statistically more likely to discontinue their new AED due to psychiatric issues compared to patients with no previous psychiatric diagnosis (50 of 849; 5.9%; p=0.017). Patients receiving sodium channel blocking AEDs (4 of 212, 1.9%) were statistically less likely to develop intolerable psychiatric problems, compared to those on AEDs possessing other mechanisms of action (68 of 846, 8.0%; p=0.012). Depression was the commonest problem, leading to discontinuation of AEDs in 2.8% (n=30) patients. Aggression was statistically more common in men (11 of 527, 2.1%) compared to women (1 of 531, 0.2%; p=0.004). Patients with learning disability (12 of 122, 9.8%; p=0.0015) were statistically less likely to have

  9. Drug Facts

    Medline Plus

    Full Text Available ... Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen ... to prescription drugs. The addiction slowly took over his life. I need different people around me. To ...

  10. Estimating the Effects of Parental Divorce and Death With Fixed Effects Models.

    Science.gov (United States)

    Amato, Paul R; Anthony, Christopher J

    2014-04-01

    The authors used child fixed effects models to estimate the effects of parental divorce and death on a variety of outcomes using 2 large national data sets: (a) the Early Childhood Longitudinal Study, Kindergarten Cohort (kindergarten through the 5th grade) and (b) the National Educational Longitudinal Study (8th grade to the senior year of high school). In both data sets, divorce and death were associated with multiple negative outcomes among children. Although evidence for a causal effect of divorce on children was reasonably strong, effect sizes were small in magnitude. A second analysis revealed a substantial degree of variability in children's outcomes following parental divorce, with some children declining, others improving, and most not changing at all. The estimated effects of divorce appeared to be strongest among children with the highest propensity to experience parental divorce.

  11. Estimating the Effects of Parental Divorce and Death With Fixed Effects Models

    Science.gov (United States)

    Amato, Paul R.; Anthony, Christopher J.

    2014-01-01

    The authors used child fixed effects models to estimate the effects of parental divorce and death on a variety of outcomes using 2 large national data sets: (a) the Early Childhood Longitudinal Study, Kindergarten Cohort (kindergarten through the 5th grade) and (b) the National Educational Longitudinal Study (8th grade to the senior year of high school). In both data sets, divorce and death were associated with multiple negative outcomes among children. Although evidence for a causal effect of divorce on children was reasonably strong, effect sizes were small in magnitude. A second analysis revealed a substantial degree of variability in children’s outcomes following parental divorce, with some children declining, others improving, and most not changing at all. The estimated effects of divorce appeared to be strongest among children with the highest propensity to experience parental divorce. PMID:24659827

  12. Venous return curve and its application to assessment of the effect of cardiovascular drugs

    Energy Technology Data Exchange (ETDEWEB)

    Nagashima, Kenshi; Gotoh, Kohshi; Yagi, Yasuo (Gifu Univ. (Japan). Faculty of Medicine) (and others)

    1990-01-01

    In an effort to obtain a venous return curve, occlusion plethysmography with radionuclide was performed in the forearm of 24 patients with various heart diseases. Radionuclide angiocardiography was performed and during the equilibrium phase the region of interest was created over the forearm for repeated venous occlusions. Specific compliance in the vein of the forearm was obtained by drawing the radionuclide count-venous pressure curve from changes in venous pressure and radioactivity of the forearm. Compliance of human systemic veins was then obtained based on some hypotheses. Mean systemic pressure (Pms) was estimated. In addition, right auricular pressure and cardiac output were obtained for drawing part of the venous return curve. In a study of the effect of cardiovascular drugs on the venous return curve, Pms was found to be significantly decreased by the administration of nitroglycerin. Furthermore, systemic venous return curve moved to the leftward. In contrast, nifedipine did not have any influence on Pms in Class I of cardiovascular function; and systemic venous return curve moved clockwise by the administration of the drug. In the case of Class II or III, nifedipine caused the systemic venous return curve to move clockwise with decreasing Pms. (N.K.).

  13. The Effects of Students' Perception of a Speaker's Role on Their Recall of Drug Facts and Their Opinions and Attitudes About Drugs

    Science.gov (United States)

    McCleaf, James E.; Colby, Margaret A.

    1975-01-01

    The ascribed social role of a speaker and his ascribed experience with drugs contributed to significant differences in student recall of drug information. Sex of the respondent was found to have a significant effect on students' scores on the Drug Opinion and Attitudes Test. (RC)

  14. Flow-Field Simulations and Hemolysis Estimates for the Food and Drug Administration Critical Path Initiative Centrifugal Blood Pump.

    Science.gov (United States)

    Heck, Margaret L; Yen, Allen; Snyder, Trevor A; O'Rear, Edgar A; Papavassiliou, Dimitrios V

    2017-10-01

    The design of blood pumps for use in ventricular assist devices, which provide life-saving circulatory support in patients with heart failure, require remarkable precision and attention to detail to replicate the functionality of the native heart. The United States Food and Drug Administration (FDA) initiated a Critical Path Initiative to standardize and facilitate the use of computational fluid dynamics in the study and development of these devices. As a part of the study, a simplified centrifugal blood pump model generated by computer-aided design was released to universities and laboratories nationwide. The effects of changes in fluid rheology due to temperature, hematocrit, and turbulent flow on key metrics of the FDA pump were examined in depth using results from a finite volume-based commercial computational fluid dynamics code. Differences in blood damage indices obtained using Eulerian and Lagrangian formulations were considered. These results are presented and discussed awaiting future validation using experimental results, which will be released by the FDA at a future date. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  15. Modelled in vivo HIV fitness under drug selective pressure and estimated genetic barrier towards resistance are predictive for virological response

    DEFF Research Database (Denmark)

    Deforche, Koen; Cozzi-Lepri, Alessandro; Theys, Kristof

    2008-01-01

    BACKGROUND: A method has been developed to estimate a fitness landscape experienced by HIV-1 under treatment selective pressure as a function of the genotypic sequence thereby also estimating the genetic barrier to resistance. METHODS: We evaluated the performance of two estimated fitness landsca...

  16. 78 FR 76443 - Safety and Effectiveness of Consumer Antiseptics; Topical Antimicrobial Drug Products for Over...

    Science.gov (United States)

    2013-12-17

    ... and Drug Administration 21 CFR Parts 310 and 333 Safety and Effectiveness of Consumer Antiseptics... Docket No. 1975N-0183H) RIN 0910-AF69 Safety and Effectiveness of Consumer Antiseptics; Topical... monograph or proposed rule (the 1994 TFM) for over-the-counter (OTC) antiseptic drug products. In this...

  17. Developing and Negotiating Effective School-Based Drug Abuse Prevention Programs.

    Science.gov (United States)

    Zavela, Kathleen J.

    2002-01-01

    Investigated effective drug prevention strategies for school-aged populations from drug prevention programs funded by the Department of Health and Human Services Center for Substance Abuse Prevention. Interviews with model programs' directors and staff highlighted 15 strategies essential for developing effective programs. Strategies focused on…

  18. Drug-drug interaction and doping, part 1: an in vitro study on the effect of non-prohibited drugs on the phase I metabolic profile of toremifene.

    Science.gov (United States)

    Mazzarino, Monica; de la Torre, Xavier; Fiacco, Ilaria; Palermo, Amelia; Botrè, Francesco

    2014-05-01

    The present study was designed to provide preliminary information on the potential impact of metabolic drug-drug interaction on the effectiveness of doping control strategies currently followed by the anti-doping laboratories to detect the intake of banned agents. In vitro assays based on the use of human liver microsomes and recombinant CYP isoforms were designed and performed to characterize the phase I metabolic profile of the prohibited agent toremifene, selected as a prototype drug of the class of selective oestrogen receptor modulators, both in the absence and in the presence of medicaments (fluconazole, ketoconazole, itraconazole, miconazole, cimetidine, ranitidine, fluoxetine, paroxetine, nefazodone) not included in the World Anti-Doping Agency list of prohibited substances and methods and frequently administered to athletes. The results show that the in vitro model developed in this study was adequate to simulate the in vivo metabolism of toremifene, confirming the results obtained in previous studies. Furthermore, our data also show that ketoconazole, itraconazole, miconazole and nefazodone cause a marked modification in the production of the metabolic products (i.e. hydroxylated and carboxylated metabolites) normally selected by the anti-doping laboratories as target analytes to detect toremifene intake; moderate variations were registered in the presence of fluconazole, paroxetine and fluoxetine; while no significant modifications were measured in the presence of ranitidine and cimetidine. This evidence imposes that the potential effect of drug-drug interactions is duly taken into account in anti-doping analysis, also for a broader significance of the analytical results. Copyright © 2014 John Wiley & Sons, Ltd.

  19. Effect of clinical response to active drugs and placebo on antipsychotics and mood stabilizers relative efficacy for bipolar depression and mania: A meta-regression analysis.

    Science.gov (United States)

    Bartoli, Francesco; Clerici, Massimo; Di Brita, Carmen; Riboldi, Ilaria; Crocamo, Cristina; Carrà, Giuseppe

    2018-01-01

    Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania. We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy ('active drugs') for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy. Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs ( p=0.002), but not to placebo ( p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo ( p=0.047), but not to active drugs ( p=0.98). Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression.

  20. Transdermal enhancement effect and mechanism of iontophoresis for non-steroidal anti-inflammatory drugs.

    Science.gov (United States)

    Zuo, Jing; Du, Lina; Li, Miao; Liu, Boming; Zhu, Weinan; Jin, Yiguang

    2014-05-15

    Iontophoresis is an important approach to improve transdermal drug delivery. However, The transdermal enhancement mechanism of iontophoresis was not well known. The relationship between the physicochemical properties of drugs and the transdermal enhancement effect of iontophoresis was revealed in this study. Non-steroidal anti-inflammatory drugs (NSAIDs) were used as the models, including aspirin, ibuprofen and indomethacin. Their oil-water partition coefficients were measured. The carbomer-based hydrogels of them were prepared. Iontophoresis significantly enhanced in vitro transdermal delivery across the rat skins. Strong lipophilicity could lead to high permeation of drugs. However, the dissociation extent (indicated as pKa) of drugs was the key factor to determine the transdermal enhancement effect of iontophoresis. The more dissociation the drugs were, the higher the transdermal enhancement effect of iontophoresis. The drug-loaded hydrogels combined with iontophoresis improved the treatment of rat raw's inflammatory syndrome. Iontophoresis significantly improved the drugs penetrating into the hypodermis, dermis and epidermis, more deeply than the application of drugs alone according to the experimental result of 5-carboxylfluorescein hydrogels. Iontophoresis led to the unordered arrangement of skin intercellular lipids, the significantly increased flowability and loose stratum corneum structure. Iontophoresis is a promising approach to improve transdermal drug delivery with safety and high efficiency. Copyright © 2014. Published by Elsevier B.V.

  1. Technological strategies to estimate and control diffusive passage times through the mucus barrier in mucosal drug delivery.

    Science.gov (United States)

    Newby, Jay M; Seim, Ian; Lysy, Martin; Ling, Yun; Huckaby, Justin; Lai, Samuel K; Forest, M Gregory

    2018-01-15

    In mucosal drug delivery, two design goals are desirable: 1) insure drug passage through the mucosal barrier to the epithelium prior to drug removal from the respective organ via mucus clearance; and 2) design carrier particles to achieve a prescribed arrival time and drug uptake schedule at the epithelium. Both goals are achievable if one can control "one-sided" diffusive passage times of drug carrier particles: from deposition at the mucus interface, through the mucosal barrier, to the epithelium. The passage time distribution must be, with high confidence, shorter than the timescales of mucus clearance to maximize drug uptake. For 100nm and smaller drug-loaded nanoparticulates, as well as pure drug powders or drug solutions, diffusion is normal (i.e., Brownian) and rapid, easily passing through the mucosal barrier prior to clearance. Major challenges in quantitative control over mucosal drug delivery lie with larger drug-loaded nanoparticulates that are comparable to or larger than the pores within the mucus gel network, for which diffusion is not simple Brownian motion and typically much less rapid; in these scenarios, a timescale competition ensues between particle passage through the mucus barrier and mucus clearance from the organ. In the lung, as a primary example, coordinated cilia and air drag continuously transport mucus toward the trachea, where mucus and trapped cargo are swallowed into the digestive tract. Mucus clearance times in lung airways range from minutes to hours or significantly longer depending on deposition in the upper, middle, lower airways and on lung health, giving a wide time window for drug-loaded particle design to achieve controlled delivery to the epithelium. We review the physical and chemical factors (of both particles and mucus) that dictate particle diffusion in mucus, and the technological strategies (theoretical and experimental) required to achieve the design goals. First we describe an idealized scenario - a homogeneous

  2. Effectiveness of HIV prevention social marketing with injecting drug users.

    Science.gov (United States)

    Gibson, David R; Zhang, Guili; Cassady, Diana; Pappas, Les; Mitchell, Joyce; Kegeles, Susan M

    2010-10-01

    Social marketing involves applying marketing principles to promote social goods. In the context of health behavior, it has been used successfully to reduce alcohol-related car crashes, smoking among youths, and malaria transmission, among other goals. Features of social marketing, such as audience segmentation and repeated exposure to prevention messages, distinguish it from traditional health promotion programs. A recent review found 8 of 10 rigorously evaluated social marketing interventions responsible for changes in HIV-related behavior or behavioral intentions. We studied 479 injection drug users to evaluate a community-based social marketing campaign to reduce injection risk behavior among drug users in Sacramento, California. Injecting drugs is associated with HIV infection in more than 130 countries worldwide.

  3. Ontology-based systematical representation and drug class effect analysis of package insert-reported adverse events associated with cardiovascular drugs used in China.

    Science.gov (United States)

    Wang, Liwei; Li, Mei; Xie, Jiangan; Cao, Yuying; Liu, Hongfang; He, Yongqun

    2017-10-23

    With increased usage of cardiovascular drugs (CVDs) for treating cardiovascular diseases, it is important to analyze CVD-associated adverse events (AEs). In this study, we systematically collected package insert-reported AEs associated with CVDs used in China, and developed and analyzed an Ontology of Cardiovascular Drug AEs (OCVDAE). Extending the Ontology of AEs (OAE) and NDF-RT, OCVDAE includes 194 CVDs, CVD ingredients, mechanisms of actions (MoAs), and CVD-associated 736 AEs. An AE-specific drug class effect is defined to exist when all the drugs (drug chemical ingredients or drug products) in a drug class are associated with an AE, which is formulated as a new proportional class level ratio ("PCR") = 1. Our PCR-based heatmap analysis identified many class level drug effects on different AE classes such as behavioral and neurological AE and digestive system AE. Additional drug-AE correlation tests (i.e., class-level PRR, Chi-squared, and minimal case reports) were also modified and applied to further detect statistically significant drug class effects. Two drug ingredient classes and three CVD MoA classes were found to have statistically significant class effects on 13 AEs. For example, the CVD Active Transporter Interactions class (including reserpine, indapamide, digoxin, and deslanoside) has statistically significant class effect on anorexia and diarrhea AEs.

  4. Pharmacodynamics of immediate and delayed effects of paclitaxel: role of slow apoptosis and intracellular drug retention.

    Science.gov (United States)

    Au, J L; Li, D; Gan, Y; Gao, X; Johnson, A L; Johnston, J; Millenbaugh, N J; Jang, S H; Kuh, H J; Chen, C T; Wientjes, M G

    1998-05-15

    The kinetics of the time-dependent antitumor effects of paclitaxel are not fully understood; some literature reports indicate a higher activity by prolonging treatment durations, whereas other reports indicate no enhancement under in vitro conditions. The present study was designed to address this controversy and to determine the mechanism of the higher cytotoxicity associated with longer treatment durations. Six human epithelial cancer cell lines (bladder RT4, breast MCF7, pharynx FaDu, ovarian SKOV3, and prostate PC3 and DU145) were used. To determine whether the higher activity observed for the longer treatment durations is due to a delayed exhibition of drug effects and/or a reflection of cumulative effects that required a continuous drug exposure, cells were treated with paclitaxel for 3-96 h and then either: (a) immediately processed for drug effect measurement; or (b) washed, incubated in drug-free medium, and processed for drug effect measurement at 96 h. The overall drug effect (i.e., combination of cytostatic and apoptotic effects) was determined by the sulforhodamine B assay, which measures the cellular protein. In addition, to determine whether apoptosis occurs with a time delay, apoptosis was measured in cells that were collected immediately after drug treatment for various durations or in cells that were treated with drugs for 3 h but collected at later time points. Apoptosis was determined using agarose gel electrophoresis and by measuring the cytoplasmic DNA-histone complex using ELISA. The contribution of the intracellularly retained drug to the delayed drug effect was studied by characterizing the kinetics of cellular drug uptake and efflux and by examining the effect of removal of the intracellularly retained drug. All six cell lines showed similar results, as follows: (a) paclitaxel produced cytotoxicity that was exhibited immediately after treatment (immediate effect) and after treatment was terminated (delayed effect); (b) the immediate and

  5. Classification-by-Analogy: Using Vector Representations of Implicit Relationships to Identify Plausibly Causal Drug/Side-effect Relationships.

    Science.gov (United States)

    Mower, Justin; Subramanian, Devika; Shang, Ning; Cohen, Trevor

    2016-01-01

    An important aspect of post-marketing drug surveillance involves identifying potential side-effects utilizing adverse drug event (ADE) reporting systems and/or Electronic Health Records. These data are noisy, necessitating identified drug/ADE associations be manually reviewed - a human-intensive process that scales poorly with large numbers of possibly dangerous associations and rapid growth of biomedical literature. Recent work has employed Literature Based Discovery methods that exploit implicit relationships between biomedical entities within the literature to estimate the plausibility of drug/ADE connections. We extend this work by evaluating machine learning classifiers applied to high-dimensional vector representations of relationships extracted from the literature as a means to identify substantiated drug/ADE connections. Using a curated reference standard, we show applying classifiers to such representations improves performance (+≈37%AUC) over previous approaches. These trained systems reproduce outcomes of the manual literature review process used to create the reference standard, but further research is required to establish their generalizability.

  6. Estimates of the Economic Effects of Sea Level Rise

    International Nuclear Information System (INIS)

    Darwin, R.F.; Tol, R.S.J.

    2001-01-01

    Regional estimates of direct cost (DC) are commonly used to measure the economic damages of sea level rise. Such estimates suffer from three limitations: (1) values of threatened endowments are not well known, (2) loss of endowments does not affect consumer prices, and (3) international trade is disregarded. Results in this paper indicate that these limitations can significantly affect economic assessments of sea level rise. Current uncertainty regarding endowment values (as reflected in two alternative data sets), for example, leads to a 17 percent difference in coastal protection, a 36 percent difference in the amount of land protected, and a 36 percent difference in DC globally. Also, global losses in equivalent variation (EV), a welfare measure that accounts for price changes, are 13 percent higher than DC estimates. Regional EV losses may be up to 10 percent lower than regional DC, however, because international trade tends to redistribute losses from regions with relatively high damages to regions with relatively low damages. 43 refs

  7. Greenhouse effect: A first estimation of the emissions in Italy

    International Nuclear Information System (INIS)

    Gaudioso, D.; Onufrio, G.

    1991-03-01

    The estimate of the anthropogenic emissions of greenhouse gases and the selection of the relevant emission factors represents a preliminary condition to define policies aiming at curbing these emissions. In the first part of this paper there is an analysis of C0 2 emission factors, referred to the various fuels and energy technologies. The values at issue take into account the physico-chemical composition of the different fossil fuels, as well as the overall efficiency of energy production cycles and end uses patterns. As concerns the other greenhouse gases, the available information is summarized at a much more integrate level. The second part presents some estimates of carbon dioxide emissions in Italy, by sector and by fuel; some characteristic levels of specific emissions are also identified. A comparative estimate for CH 4 , N 2 O, CO and CFC's is also made, in order to set up a first reference table of the emissions of greenhouse gases in our country. (author)

  8. Uncertainty and validation. Effect of user interpretation on uncertainty estimates

    Energy Technology Data Exchange (ETDEWEB)

    Kirchner, G. [Univ. of Bremen (Germany); Peterson, R. [AECL, Chalk River, ON (Canada)] [and others

    1996-11-01

    Uncertainty in predictions of environmental transfer models arises from, among other sources, the adequacy of the conceptual model, the approximations made in coding the conceptual model, the quality of the input data, the uncertainty in parameter values, and the assumptions made by the user. In recent years efforts to quantify the confidence that can be placed in predictions have been increasing, but have concentrated on a statistical propagation of the influence of parameter uncertainties on the calculational results. The primary objective of this Working Group of BIOMOVS II was to test user's influence on model predictions on a more systematic basis than has been done before. The main goals were as follows: To compare differences between predictions from different people all using the same model and the same scenario description with the statistical uncertainties calculated by the model. To investigate the main reasons for different interpretations by users. To create a better awareness of the potential influence of the user on the modeling results. Terrestrial food chain models driven by deposition of radionuclides from the atmosphere were used. Three codes were obtained and run with three scenarios by a maximum of 10 users. A number of conclusions can be drawn some of which are general and independent of the type of models and processes studied, while others are restricted to the few processes that were addressed directly: For any set of predictions, the variation in best estimates was greater than one order of magnitude. Often the range increased from deposition to pasture to milk probably due to additional transfer processes. The 95% confidence intervals about the predictions calculated from the parameter distributions prepared by the participants did not always overlap the observations; similarly, sometimes the confidence intervals on the predictions did not overlap. Often the 95% confidence intervals of individual predictions were smaller than the

  9. Uncertainty and validation. Effect of user interpretation on uncertainty estimates

    International Nuclear Information System (INIS)

    Kirchner, G.; Peterson, R.

    1996-11-01

    Uncertainty in predictions of environmental transfer models arises from, among other sources, the adequacy of the conceptual model, the approximations made in coding the conceptual model, the quality of the input data, the uncertainty in parameter values, and the assumptions made by the user. In recent years efforts to quantify the confidence that can be placed in predictions have been increasing, but have concentrated on a statistical propagation of the influence of parameter uncertainties on the calculational results. The primary objective of this Working Group of BIOMOVS II was to test user's influence on model predictions on a more systematic basis than has been done before. The main goals were as follows: To compare differences between predictions from different people all using the same model and the same scenario description with the statistical uncertainties calculated by the model. To investigate the main reasons for different interpretations by users. To create a better awareness of the potential influence of the user on the modeling results. Terrestrial food chain models driven by deposition of radionuclides from the atmosphere were used. Three codes were obtained and run with three scenarios by a maximum of 10 users. A number of conclusions can be drawn some of which are general and independent of the type of models and processes studied, while others are restricted to the few processes that were addressed directly: For any set of predictions, the variation in best estimates was greater than one order of magnitude. Often the range increased from deposition to pasture to milk probably due to additional transfer processes. The 95% confidence intervals about the predictions calculated from the parameter distributions prepared by the participants did not always overlap the observations; similarly, sometimes the confidence intervals on the predictions did not overlap. Often the 95% confidence intervals of individual predictions were smaller than the

  10. The effect of hepatitis C treatment and human immunodeficiency virus (HIV) co-infection on the disease burden of hepatitis C among injecting drug users in Amsterdam

    NARCIS (Netherlands)

    Matser, Amy; Urbanus, Anouk; Geskus, Ronald; Kretzschmar, Mirjam; Xiridou, Maria; Buster, Marcel; Coutinho, Roel; Prins, Maria

    2012-01-01

    Aims The hepatitis C virus (HCV) disease burden among injecting drug users (IDUs) is determined by HCV incidence, the long latency period of HCV, competing mortality causes, presence of co-infection and HCV treatment uptake. We examined the effect of these factors and estimated the HCV disease

  11. Prediction of Effective Drug Combinations by Chemical Interaction, Protein Interaction and Target Enrichment of KEGG Pathways

    Science.gov (United States)

    Chen, Lei; Zheng, Ming-Yue; Zhang, Jian; Feng, Kai-Yan; Cai, Yu-Dong

    2013-01-01

    Drug combinatorial therapy could be more effective in treating some complex diseases than single agents due to better efficacy and reduced side effects. Although some drug combinations are being used, their underlying molecular mechanisms are still poorly understood. Therefore, it is of great interest to deduce a novel drug combination by their molecular mechanisms in a robust and rigorous way. This paper attempts to predict effective drug combinations by a combined consideration of: (1) chemical interaction between drugs, (2) protein interactions between drugs' targets, and (3) target enrichment of KEGG pathways. A benchmark dataset was constructed, consisting of 121 confirmed effective combinations and 605 random combinations. Each drug combination was represented by 465 features derived from the aforementioned three properties. Some feature selection techniques, including Minimum Redundancy Maximum Relevance and Incremental Feature Selection, were adopted to extract the key features. Random forest model was built with its performance evaluated by 5-fold cross-validation. As a result, 55 key features providing the best prediction result were selected. These important features may help to gain insights into the mechanisms of drug combinations, and the proposed prediction model could become a useful tool for screening possible drug combinations. PMID:24083237

  12. [Effects of the new comprehensive system for designating illegal drug components on the abuse of designer drugs and future problems based on an online questionnaire].

    Science.gov (United States)

    Morino, Taichi; Okazaki, Mitsuhiro; Toda, Takaki; Yokoyama, Takashi

    2015-12-01

    Recently, the abuse of designer drugs has become a social problem. Designer drugs are created by modifying part of the chemical structure of drugs that have already been categorized as illegal, thereby creating a different chemical compound in order to evade Pharmaceutical Affairs Law regulations. The new comprehensive system for designating illegal drug components has been in effect since March 2013, and many designer drugs can now be regulated. We conducted an online questionnaire survey of people with a history of designer drug use to elucidate the effects of the new system on the abuse of designer drugs and to identify potential future problems. Over half the subjects obtained designer drugs only before the new system was implemented. Awareness of the system was significantly lower among subjects who obtained designer drugs for the first time after its introduction than those who obtained the drugs only before its implementation. Due to the new system, all methods of acquiring designer drugs saw decreases in activity. However, the ratio of the acquisition of designer drugs via the Internet increased. Since over 50% of the subjects never obtained designer drugs after the new system was introduced, goals that aimed to make drug procurement more difficult were achieved. However, awareness of the new system among subjects who obtained designer drugs after the new system was introduced was significantly low. Therefore, fostering greater public awareness of the new system is necessary. The results of the questionnaire also suggested that acquiring designer drugs through the Internet has hardly been affected by the new system. We strongly hope that there will be a greater push to restrict the sale of designer drugs on the Internet in the near future.

  13. Using Population Based Data on Drugs Abuse to Estimate the Relative Need for Medical Services in Thailand.

    Science.gov (United States)

    Leyatikul, Poonrut; Kanato, Manop

    2015-07-01

    Epidemiological background shows a trend in drug abuse and essential need for revising its strategic plans, allocating resources, and advocating services for populations. The relative need for drug abuse prevention and medical services across different geographic areas of Thailand, which has been examined through an analysis of existing population-based datasets and reported routinely. The objective was to develop an indicator of relative need for drug abuse prevention and medical services. Qualitative data were collected as primary data sources from 10 focus group discussions throughout Thailand. The primary data were integrated into study framework with the result from literature review. Data sets in 2011 were retrieved from the national databank to obtain variables regarding drug abuse. Multiple regression and factor analysis were undertaken using the district as the unit of analysis. A factor analysis, which revealed six factors that explained 64% of the variance in the data set. Factors identified in the analysis were taken as indicators of variation in the need for services as all of the drugs-related variables loaded strongly on these factors. The distribution of ranks for factor scores (determined through regression) obtained for these factors across districts in Thailand showed that scores were highest in urban and suburban areas. In terms of practical implications, the study results could be used for resource allocation in medical service plans for community drug abuse.

  14. Effects of chronic administration of drugs of abuse on impulsive choice (delay discounting) in animal models.

    Science.gov (United States)

    Setlow, Barry; Mendez, Ian A; Mitchell, Marci R; Simon, Nicholas W

    2009-09-01

    Drug-addicted individuals show high levels of impulsive choice, characterized by preference for small immediate over larger but delayed rewards. Although the causal relationship between chronic drug use and elevated impulsive choice in humans has been unclear, a small but growing body of literature over the past decade has shown that chronic drug administration in animal models can cause increases in impulsive choice, suggesting that a similar causal relationship may exist in human drug users. This article reviews this literature, with a particular focus on the effects of chronic cocaine administration, which have been most thoroughly characterized. The potential mechanisms of these effects are described in terms of drug-induced neural alterations in ventral striatal and prefrontal cortical brain systems. Some implications of this research for pharmacological treatment of drug-induced increases in impulsive choice are discussed, along with suggestions for future research in this area.

  15. Effect of Correlation Structure in Generalized Estimating Equation and Quasi Least Square: An Application in Type 2 Diabetes Patient

    Directory of Open Access Journals (Sweden)

    Dilip C Nath

    2011-07-01

    Full Text Available The Quasi-Least Squares (QLS is useful for different correlation structure with attachment of Generalized Estimating Equation (GEE. The purpose of this work is to compare the regression parameter in the presence of different correlation structure with respect to GEE and QLS method. The comparison of estimated regression parameter has been performed in clinical trial data set; studying the effect of drug treatment (metformin with pioglitazone Vs (gliclazide with pioglitazone in type 2 diabetes patients. In case of QLS, the correlation coefficient of post-parandinal blood sugar (PPBS under tridiagonal correlation is 0.008 while it failed to produce by GEE. It has been found that the combination of metformin with pioglitazone is more effective as compared to the combination of gliclazide with pioglitazone.

  16. Effect of Correlation Structure in Generalized Estimating Equation and Quasi Least Square: An Application in Type 2 Diabetes Patient

    Directory of Open Access Journals (Sweden)

    Dilip C Nath

    2011-08-01

    Full Text Available The Quasi-Least Squares (QLS is useful for different correlation structure with attachment of Generalized Estimating Equation (GEE. The purpose of this work is to compare the regression parameter in the presence of different correlation structure with respect to GEE and QLS method. The comparison of estimated regression parameter has been performed in clinical trial data set; studying the effect of drug treatment (metformin with pioglitazone Vs (gliclazide with pioglitazone in type 2 diabetes patients. In case of QLS, the correlation coefficient of post-parandinal blood sugar (PPBS under tridiagonal correlation is 0.008 while it failed to produce by GEE. It has been found that the combination of metformin with pioglitazone is more effective as compared to the combination of gliclazide with pioglitazone.

  17. Is it Safe? Adverse drug effects and cardiac arrhythmias

    NARCIS (Netherlands)

    Varkevisser, R.

    2014-01-01

    The potentially life-threatening polymorphic ventricular arrhythmia Torsade de Pointes (TdP) generally occurs in the setting of delayed ventricular repolarization, as reflected on the ECG by a prolonged QT interval. A growing number of drugs are associated with QT prolongation and/or TdP, as a

  18. Spillover Effects of Drug Safety Warnings on Health Behavior

    NARCIS (Netherlands)

    Meltem Daysal, N.; Orsini, C.

    2012-01-01

    Abstract: We examine the impact of new medical information on drug safety on preventive health behavior. We exploit the release of the findings of the Women's Health Initiative Study (WHIS) -the largest randomized controlled trial of women's health- which demonstrated in 2002 that long-term Hormone

  19. Drug combination may be highly effective in recurrent ovarian cancer

    Science.gov (United States)

    Significant improvement with the use of a combination drug therapy for recurrent ovarian cancer was reported at the annual meeting of the American Society of Clinical Oncology meeting in Chicago. The trial compared the activity of a combination of the dru

  20. Single-enantiomer drugs: elegant science, disappointing effects.

    Science.gov (United States)

    Mansfield, Peter; Henry, David; Tonkin, Anne

    2004-01-01

    Most new drugs are marketed as single enantiomers but many older agents are still available in racemic form. As these drugs reach the end of their patent life manufacturers become interested in marketing single enantiomer equivalents. This is called 'chiral switching' and it has been claimed that it will bring clinical benefits in terms of improved efficacy, more predictable pharmacokinetics or reduced toxicity. We reviewed the clinical evidence and prices for three recently marketed single enantiomer versions of widely used racemic drugs: escitalopram, esomeprazole and levosalbutamol. Claims of increased efficacy were based on comparisons of non-equivalent doses and any advantages seemed small and clinically unimportant. Prices of esomeprazole and levosalbutamol were higher than their racemic alternatives and we predict that these prices will remain high despite the market presence of generic versions of the racemates. Patent protection and a perception of superiority based on promotion rather than evidence will maintain price premiums for single enantiomer drugs that are not justified on the basis of clinical performance.

  1. Effect of Antimalarial Drugs and Malaria Infection on Oxidative ...

    African Journals Online (AJOL)

    The increase in lipid peroxidation and decrease in GSH and ascorbic acid levels in women who were malaria positive and in those who had taken drugs is indicative of oxidative stress. (Afr. J. Reprod. Health 2010; 14[3]: 209-212). Key words: Pregnant women, malaria, lipid peroxidation, reduced glutathione, Ascorbic acid ...

  2. Effect of a brief intervention for alcohol and illicit drug use on trauma recidivism in a cohort of trauma patients.

    Directory of Open Access Journals (Sweden)

    Sergio Cordovilla-Guardia

    Full Text Available Estimate the effectiveness of brief interventions in reducing trauma recidivism in hospitalized trauma patients who screened positive for alcohol and/or illicit drug use.Dynamic cohort study based on registry data from 1818 patients included in a screening and brief intervention program for alcohol and illicit drug use for hospitalized trauma patients. Three subcohorts emerged from the data analysis: patients who screened negative, those who screened positive and were offered brief intervention, and those who screened positive and were not offered brief intervention. Follow-up lasted from 10 to 52 months. Trauma-free survival, adjusted hazard rate ratios (aHRR and adjusted incidence rate ratios (aIRR were calculated, and complier average causal effect (CACE analysis was used.We found a higher cumulative risk of trauma recidivism in the subcohort who screened positive. In this subcohort, an aHRR of 0.63 (95% CI: 0.41-0.95 was obtained for the group offered brief intervention compared to the group not offered intervention. CACE analysis yielded an estimated 52% reduction in trauma recidivism associated with the brief intervention.The brief intervention offered during hospitalization in trauma patients positive for alcohol and/or illicit drug use can halve the incidence of trauma recidivism.

  3. Simultaneous estimation of QTL effects and positions when using ...

    Indian Academy of Sciences (India)

    backcross model; EM algorithm; genotyping errors; maximum likelihood estimation; QTL mapping. ... Accurate genetic data are important prerequisite of performing genetic linkage test or association test. ... However, due to the constraint at the technical level, most of the genetic data that people used so far contain errors.

  4. Attributes Effecting Software Testing Estimation; Is Organizational Trust an Issue?

    Science.gov (United States)

    Hammoud, Wissam

    2013-01-01

    This quantitative correlational research explored the potential association between the levels of organizational trust and the software testing estimation. This was conducted by exploring the relationships between organizational trust, tester's expertise, organizational technology used, and the number of hours, number of testers, and time-coding…

  5. Estimating the effects of the factors underlying the progression of ...

    African Journals Online (AJOL)

    We designed a statistical model based on Com-‐ Poisson distribution, which can efficiently analyze such a data structure. The estimates of over-‐dispersion as well as correlation parameters confirm the nature of real data. Analysis of the model indicates that males are 50% more at risk to develop polyps than females.

  6. Effective utilization of weighting adjustment for the estimates of ...

    African Journals Online (AJOL)

    The use of response propensity and the predicted mean of the outcome variable for cell creation are stressed .The results from our empirical study emphasize the efficacy of Weighting Adjustment over the Unadjusted estimates .We adopt the following criteria: Variance, Bias and Mean Square Error in reaching our ...

  7. The effect of phantom parent groups on genetic trend estimation ...

    African Journals Online (AJOL)

    Bias in the estimation of trend was reduced when phantom parent groups were taken into account. The 109 385 base animals were replaced by 64 phantom parent groups. Phantom parent groups were constructed by combining year of birth, country of birth and selection intensity of the phantom parents. In recent years ...

  8. Treatment effect on biases in size estimation in spider phobia.

    Science.gov (United States)

    Shiban, Youssef; Fruth, Martina B; Pauli, Paul; Kinateder, Max; Reichenberger, Jonas; Mühlberger, Andreas

    2016-12-01

    The current study investigates biases in size estimations made by spider-phobic and healthy participants before and after treatment. Forty-one spider-phobic and 20 healthy participants received virtual reality (VR) exposure treatment and were then asked to rate the size of a real spider immediately before and, on average, 15days after the treatment. During the VR exposure treatment skin conductance response was assessed. Prior to the treatment, both groups tended to overestimate the size of the spider, but this size estimation bias was significantly larger in the phobic group than in the control group. The VR exposure treatment reduced this bias, which was reflected in a significantly smaller size rating post treatment. However, the size estimation bias was unrelated to the skin conductance response. Our results confirm the hypothesis that size estimation by spider-phobic patients is biased. This bias is not stable over time and can be decreased with adequate treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Effects of systematic sampling on satellite estimates of deforestation rates

    International Nuclear Information System (INIS)

    Steininger, M K; Godoy, F; Harper, G

    2009-01-01

    Options for satellite monitoring of deforestation rates over large areas include the use of sampling. Sampling may reduce the cost of monitoring but is also a source of error in estimates of areas and rates. A common sampling approach is systematic sampling, in which sample units of a constant size are distributed in some regular manner, such as a grid. The proposed approach for the 2010 Forest Resources Assessment (FRA) of the UN Food and Agriculture Organization (FAO) is a systematic sample of 10 km wide squares at every 1 deg. intersection of latitude and longitude. We assessed the outcome of this and other systematic samples for estimating deforestation at national, sub-national and continental levels. The study is based on digital data on deforestation patterns for the five Amazonian countries outside Brazil plus the Brazilian Amazon. We tested these schemes by varying sample-unit size and frequency. We calculated two estimates of sampling error. First we calculated the standard errors, based on the size, variance and covariance of the samples, and from this calculated the 95% confidence intervals (CI). Second, we calculated the actual errors, based on the difference between the sample-based estimates and the estimates from the full-coverage maps. At the continental level, the 1 deg., 10 km scheme had a CI of 21% and an actual error of 8%. At the national level, this scheme had CIs of 126% for Ecuador and up to 67% for other countries. At this level, increasing sampling density to every 0.25 deg. produced a CI of 32% for Ecuador and CIs of up to 25% for other countries, with only Brazil having a CI of less than 10%. Actual errors were within the limits of the CIs in all but two of the 56 cases. Actual errors were half or less of the CIs in all but eight of these cases. These results indicate that the FRA 2010 should have CIs of smaller than or close to 10% at the continental level. However, systematic sampling at the national level yields large CIs unless the

  10. Effects of acute doses of prosocial drugs methamphetamine and alcohol on plasma oxytocin levels.

    Science.gov (United States)

    Bershad, Anya K; Kirkpatrick, Matthew G; Seiden, Jacob A; de Wit, Harriet

    2015-06-01

    Many drugs, including alcohol and stimulants, demonstrably increase sociability and verbal interaction and are recreationally consumed in social settings. One drug, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), seems to produce its prosocial effects by increasing plasma oxytocin levels, and the oxytocin system has been implicated in responses to several other drugs of abuse. Here, we sought to investigate the effects of 2 other "social" drugs on plasma oxytocin levels--methamphetamine and alcohol. Based on their shared capacity to enhance sociability, we hypothesized that both methamphetamine and alcohol would increase plasma oxytocin levels. In study 1, 11 healthy adult volunteers attended 3 sessions during which they received methamphetamine (10 mg or 20 mg) or placebo under double-blind conditions. Subjective drug effects, cardiovascular effects, and plasma oxytocin levels were measured at regular intervals throughout the sessions. In study 2, 8 healthy adult volunteers attended a single session during which they received 1 beverage containing placebo, and then a beverage containing alcohol (0.8 g/kg). Subjective effects, breath alcohol levels, and plasma oxytocin levels were measured at regular intervals. Both methamphetamine and alcohol produced their expected physiological and subjective effects, but neither of these drugs increased plasma oxytocin levels. The neurobiological mechanisms mediating the prosocial effects of drugs such as alcohol and methamphetamine remain to be identified.

  11. Effect of weight reductions on estimated kidney function

    DEFF Research Database (Denmark)

    von Scholten, Bernt Johan; Davies, Melanie J; Persson, Frederik

    2017-01-01

    AIMS: Weight loss-induced serum creatinine reduction may increase creatinine-based estimated glomerular filtration rate (eGFR) producing incorrect estimates of kidney function. We investigated whether weight changes in the SCALE program with liraglutide 3.0mg were associated with changes in serum...... in serum creatinine was observed (P≥0.05, both trials, all tests). CONCLUSIONS: Moderate gradual body weight reductions observed in the SCALE program were not associated with changes in serum creatinine....... creatinine. METHODS: Post hoc analysis of two 56-week, randomized, double-blind trials: SCALE Obesity and Prediabetes (n=3731, without type 2 diabetes [T2D], randomized [2:1] to liraglutide 3.0mg [n=2487] or placebo [n=1244]); SCALE Diabetes (n=846 with T2D, randomized [2:1:1] to liraglutide 3.0mg [n=423], 1...

  12. Simultaneous lipolysis/permeation in vitro model, for the estimation of bioavailability of lipid based drug delivery systems

    DEFF Research Database (Denmark)

    Bibi, Hanady Ajine; Holm, René; Bauer-Brandl, Annette

    2017-01-01

    The simultaneous processes of lipid digestion and absorption together determine the oral bioavailability of drugs incorporated into lipid based drug delivery systems (LBDDS). A number of slightly different protocols for in vitro lipolysis are widely accepted; however, the permeation process has so......® during lipid digestion. Using calcein as a marker molecule the investigations demonstrated that the barrier was able to maintain its permeation properties in the presence of the SNEDDS (self-emulsifying drug delivery system) formulation, the lipolysis medium, and the lipolysis medium while digesting...... far not been included into the models due to the harsh conditions of lipid digestion compromising permeation barriers. The present study for the first time combines biomimetic permeation and lipolysis of LBDDS. The focus of the current work was on the functional stability of the barrier - Permeapad...

  13. MRI and image quantitation for drug assessment - growth effects of anabolic steroids and precursors.

    Science.gov (United States)

    Tang, Haiying; Wu, Ed; Vasselli, Joseph

    2005-01-01

    MRI and image quantitation play an expanding role in modern drug research, because MRI offers high resolution and non-invasive ability, and provides excellent soft tissue contrast. Moreover, with development of effective image segmentation and analysis methods, in-vivo and serial tissue growth measurements could be assessed. In the study, MR image acquisition and analysis protocol were established and validated for investigating the effects of anabolic steroids and precursors on muscle growth and body composition in a guinea pig model. Semi-automatic and interactive segmentation methods were developed to accurately label the tissue of interest for tissue volume estimation. In addition, a longitudinal tissue area outlining procedure was proposed for study of tissue geometric features in relation to tissue growth. Finally, a fully automatic data retrieval and analysis scheme was implemented to facilitate the overall huge amount of image quantitation, statistical analysis, as well as study group comparisons. As a result, highly significant differences in muscle and organ growth were detected between intact and castrated guinea pigs using the selected anabolic steroids, indicating the viability of employing such protocol to assess other anabolic steroids. Furthermore, the anabolic potential of selected steroid precursors and their effects on muscle growth, in comparison with that in respective positive control groups of castrated guinea pigs, were evaluated with the proposed protocol.

  14. Metabolic and Endocrine Side Effects of Atypical Antipsychotic Drugs in Children and Adolescents

    Directory of Open Access Journals (Sweden)

    Aysegul Tahiroglu

    2011-03-01

    Full Text Available omorbid psychiatric disorders, frequent hospitalization, multiple outpatient treatment, prior history of hypertension, obesity and lipid dysregulation are associated with higher risk of metabolic syndrome in children. Side effects of antipsychotic drugs and their management have recently become a major subject of research due to enhanced antipsychotic drug usage in child and adolescents. Prevention strategies are usually preferred to secondary or tertiary strategies in the management of metabolic syndrome associated with antipsychotic drugs. Clinicians should present multidisciplinary approach to endocrine and metabolic side effects due to antipsychotic use in pediatric patient groups and avoid multiple drug use in such patients. In this paper, we briefly reviewed metabolic side effects of second generation antipsychotic drugs in child and adolescent population, possible mechanisms of susceptibility to metabolic syndrome and pharmacological and non pharmacological treatment approach to prevention of weight gain.

  15. We know very little about the subjective effects of drugs in females.

    Science.gov (United States)

    Bevins, Rick A; Charntikov, Sergios

    2015-03-18

    Pharmaceutical companies assessing the nervous system effects of candidate therapeutics often use a behavioral assay in rodents that assesses the drug's subjective (internal stimulus) effects. Variants of this so-called "drug discrimination task" have also been widely used by basic scientist for more than 50 years to study the receptor actions of a host of ligands related to disease states and neuropathologies. Notably, most published research with this task has used male rats or mice. This situation is unfortunate and severely limits the utility of the research, given the well-documented differences between women and men on drug efficacy and safety, as well as known sex differences in the neural and behavioral effects of drugs. In this Viewpoint, we highlight the need for basic researchers, as well as pharmaceutical scientists, to include females in drug discrimination studies in a manner that allows detection and interpretation of potential sex differences.

  16. The Effect of Common Therapeutic Drugs on Vision

    Science.gov (United States)

    1975-05-01

    compared to its complete the F-M 100-hue test placebo condition. For Aralen (Fg. -3a), the increased errors are most Drug Placebo prevalent around 480...Netirophysiol 21: 622(A), dhisholm, I. A. The dyschromatopsia 1966. of tobacco amblyopia . Paper read at Symposium on Colour held at Edin- Brown, J. L...Turgeon. Detection of hydramine hydrochloride (Benadryl). narcotic use: comparison of the • 54 nalorphine (pupil) test with chemical toxic amblyopia

  17. Effects of uncertainty in model predictions of individual tree volume on large area volume estimates

    Science.gov (United States)

    Ronald E. McRoberts; James A. Westfall

    2014-01-01

    Forest inventory estimates of tree volume for large areas are typically calculated by adding model predictions of volumes for individual trees. However, the uncertainty in the model predictions is generally ignored with the result that the precision of the large area volume estimates is overestimated. The primary study objective was to estimate the effects of model...

  18. A simple method for estimating the effective detection distance of camera traps

    NARCIS (Netherlands)

    Hofmeester, Tim R.; Rowcliffe, J.M.; Jansen, Patrick A.

    2017-01-01

    Estimates of animal abundance are essential for understanding animal ecology. Camera traps can be used to estimate the abundance of terrestrial mammals, including elusive species, provided that the sensitivity of the sensor, estimated as the effective detection distance (EDD), is quantified.

  19. Revised estimates for direct-effect recreational jobs in the interior Columbia River basin.

    Science.gov (United States)

    Lisa K. Crone; Richard W. Haynes

    1999-01-01

    This paper reviews the methodology used to derive the original estimates for direct employment associated with recreation on Federal lands in the interior Columbia River basin (the basin), and details the changes in methodology and data used to derive new estimates. The new analysis resulted in an estimate of 77,655 direct-effect jobs associated with recreational...

  20. Semi-parametric estimation of random effects in a logistic regression model using conditional inference

    DEFF Research Database (Denmark)

    Petersen, Jørgen Holm

    2016-01-01

    This paper describes a new approach to the estimation in a logistic regression model with two crossed random effects where special interest is in estimating the variance of one of the effects while not making distributional assumptions about the other effect. A composite likelihood is studied...

  1. Effect of reporting bias on meta-analyses of drug trials

    DEFF Research Database (Denmark)

    Hart, Beth; Lundh, Andreas; Bero, Lisa

    2012-01-01

    OBJECTIVE: To investigate the effect of including unpublished trial outcome data obtained from the Food and Drug Administration (FDA) on the results of meta-analyses of drug trials. DESIGN: Reanalysis of meta-analyses. DATA SOURCES: Drug trials with unpublished outcome data for new molecular....... Clinical guidelines, conference proceedings, duplicate systematic reviews, and systematic reviews in which included trials were not referenced or that combined trials across multiple drug classes were excluded. Systematic reviews using non-standard meta-analytic techniques (such as Bayesian or network meta...

  2. Effects of image congruency on persuasiveness and recall in direct-to-consumer prescription drug advertising.

    Science.gov (United States)

    Kiernicki, Kristen; Helme, Donald W

    2017-01-01

    Although direct-to-consumer (DTC) prescription drug advertising is regulated by the U.S. Food and Drug Administration, content analyses suggest advertisers may not disclose drug risks in the same way they describe drug benefits. This study tests the relationship between image congruency in televised DTC advertisements, recall of risks/benefits, and perceived persuasiveness. Advertisements for Nasonex, Advair, and Lunesta were shown to college students in either their original (image incongruent) or modified (image neutral) form. Risks were easier to recall with image-neutral advertisements. Gender also had a significant interaction effect, suggesting that males and females process DTC advertisement differently.

  3. The effect of anticholinergic drugs on 123I-IMP SPECT in Parkinson's disease

    International Nuclear Information System (INIS)

    Mizuno, Tomoyuki; Nishiyama, Kazutoshi; Hitoshi, Seiji; Takeda, Koichi; Sakuta, Manabu

    1992-01-01

    Anticholinergic drugs may be responsible for mental deterioration in Parkinson's disease (PD). This study was thus performed to examine effects of anticholinergic drugs on the brain by using N-isopropyl-p-[I-123] iodoamphetamine SPECT. The purpose of the study was twofold: (I) to compare regional cerebral uptake of tracer during treatment with anticholinergic drugs and one month after the discontinuation of the drugs in 7 PD patients given them for 6 months or more; and (II) to compare tracer uptake in 11 PD patients administered anticholinergic drugs and 25 PD patients not administered them. Each 16 regions in the bilateral cerebral cortexes and each one region in the bilateral basal ganglia, thalamus, and cerebellum were assigned as regions of interest (ROI). The count ratio of each ROI in the cerebrum to ROI in the cerebellum was designated as regional cerebral uptake ratio (rCUR). A mean rCUR was lower during administration of anticholinergic drugs in all ROIs, except for two in Group I and one in Group II, than during the period not administered the drugs. The administration of anticholinergic drugs was sigificantly associated with decreased rCUR in 10 ROIs in Group I, and in 15 ROIs in Group II. The rCUR in the occipital, basal ganglia, and thalamus was independent of the administration of anticholinergic drugs. These results suggest that anticholinergic drugs may inhibit the cortical cholinergic system in PD patients. (N.K.)

  4. The effects of cyclodextrins on drug release from fatty suppository bases : I. In vitro observations

    NARCIS (Netherlands)

    Frijlink, H.W.; Eissens, Anko; Schoonen, Adelbert; Lerk, C.F.

    The effect of cyclodextrins on suppository drug release was investigated. Complexes of several lipophilic drugs with β- and/or γ-cyclodextrin were prepared using the coprecipitation method. The formation of true complexes was confirmed by DSC and an 'ether-wash' method. Witepsol H15 suppositories

  5. Prediction of Effective Drug Combinations by Chemical Interaction, Protein Interaction and Target Enrichment of KEGG Pathways

    Directory of Open Access Journals (Sweden)

    Lei Chen

    2013-01-01

    Full Text Available Drug combinatorial therapy could be more effective in treating some complex diseases than single agents due to better efficacy and reduced side effects. Although some drug combinations are being used, their underlying molecular mechanisms are still poorly understood. Therefore, it is of great interest to deduce a novel drug combination by their molecular mechanisms in a robust and rigorous way. This paper attempts to predict effective drug combinations by a combined consideration of: (1 chemical interaction between drugs, (2 protein interactions between drugs’ targets, and (3 target enrichment of KEGG pathways. A benchmark dataset was constructed, consisting of 121 confirmed effective combinations and 605 random combinations. Each drug combination was represented by 465 features derived from the aforementioned three properties. Some feature selection techniques, including Minimum Redundancy Maximum Relevance and Incremental Feature Selection, were adopted to extract the key features. Random forest model was built with its performance evaluated by 5-fold cross-validation. As a result, 55 key features providing the best prediction result were selected. These important features may help to gain insights into the mechanisms of drug combinations, and the proposed prediction model could become a useful tool for screening possible drug combinations.

  6. Effect of Zeta Potential on the Properties of Nano-Drug Delivery ...

    African Journals Online (AJOL)

    Zeta potential is a scientific term for electrokinetic potential in colloidal systems which has a major effect on the various properties of nano-drug delivery systems. Presently, colloidal nano-carriers are growing at a remarkable rate owing to their strong potential for overcoming old challenges such as poor drug solubility and ...

  7. The Effectiveness of Mandatory-Random Student Drug Testing. NCEE 2010-4025

    Science.gov (United States)

    James-Burdumy, Susanne; Goesling, Brian; Deke, John; Einspruch, Eric

    2010-01-01

    To help assess the effects of school-based random drug testing programs, the U.S. Department of Education's Institute of Education Sciences (IES) contracted with RMC Research Corporation and Mathematica Policy Research to conduct an experimental evaluation of the Mandatory-Random Student Drug Testing (MRSDT) programs in 36 high schools within…

  8. New old challenges in tuberculosis: potentially effective nanotechnologies in drug delivery.

    Science.gov (United States)

    Sosnik, Alejandro; Carcaboso, Angel M; Glisoni, Romina J; Moretton, Marcela A; Chiappetta, Diego A

    2010-03-18

    Tuberculosis (TB) is the second most deadly infectious disease. Despite potentially curative pharmacotherapies being available for over 50 years, the length of the treatment and the pill burden can hamper patient lifestyle. Thus, low compliance and adherence to administration schedules remain the main reasons for therapeutic failure and contribute to the development of multi-drug-resistant (MDR) strains. Pediatric patients constitute a high risk population. Most of the first-line drugs are not commercially available in pediatric form. The design of novel antibiotics attempts to overcome drug resistance, to shorten the treatment course and to reduce drug interactions with antiretroviral therapies. On the other hand, the existing anti-TB drugs are still effective. Overcoming technological drawbacks of these therapeutic agents as well as improving the effectiveness of the drug by targeting the infection reservoirs remains the central aims of Pharmaceutical Technology. In this framework, nanotechnologies appear as one of the most promising approaches for the development of more effective and compliant medicines. The present review thoroughly overviews the state-of-the-art in the development of nano-based drug delivery systems for encapsulation and release of anti-TB drugs and discusses the challenges that are faced in the development of a more effective, compliant and also affordable TB pharmacotherapy. Copyright 2009 Elsevier B.V. All rights reserved.

  9. The effects of cyclodextrins on drug absorption. II. In vivo observations

    NARCIS (Netherlands)

    Frijlink, H.W.; Eissens, Anko; Schoonen, A.J.M.; Lerk, C.F.

    1990-01-01

    Complex formation of diazepam and of naproxen with β-cyclodextrin results in increased aqueous solubility of the drug. The complex stability constants found were 179 and 2146 M-1, respectively. To study the effect of complex formation of drugs with β-cyclodextrin in vivo, micro-enemas containing

  10. Modelling and simulation of placebo effect : application to drug development in schizophrenia

    NARCIS (Netherlands)

    Reddy, Venkatesh Pilla; Kozielska, Magdalena; de Greef, Rik; Vermeulen, An; Proost, Johannes H.

    High and variable placebo effect (PE) within and among clinical trials can substantially affect conclusions about the efficacy of new drugs in the treatment of schizophrenia and other neuropsychiatric disorders. In recent years, it has become increasingly difficult to prove drug efficacy against

  11. Effect of clomiphene citrate (Clomid®) fertility drug on sperm ...

    African Journals Online (AJOL)

    Another group of 6 rams was given normal saline during the same period to serve as control (CON). All treatments were used to study the effect of the drug on daily sperm production, gonadal and extra-gonadal sperm reserves. The drug was given orally. The results indicated daily sperm production (109) for the control ...

  12. Changes in Effective Connectivity Network Patterns in Drug Abusers, Treated With Different Methods

    Directory of Open Access Journals (Sweden)

    Arash Zare Sadeghi

    2017-07-01

    Conclusion: This study revealed an activation network similar to the emotional and inhibitory control networks observed in drug abusers in previous works. The results of DCM analysis also support the regulatory role of frontal regions on bottom regions. Furthermore, this study demonstrates the different effective connectivity patterns after drug abuse treatment and in this way helps the experts in the field.

  13. Inhibitory effects of drugs on the metabolic activity of mouse and human aldehyde oxidases and influence on drug-drug interactions.

    Science.gov (United States)

    Takaoka, Naoki; Sanoh, Seigo; Okuda, Katsuhiro; Kotake, Yaichiro; Sugahara, Go; Yanagi, Ami; Ishida, Yuji; Tateno, Chise; Tayama, Yoshitaka; Sugihara, Kazumi; Kitamura, Shigeyuki; Kurosaki, Mami; Terao, Mineko; Garattini, Enrico; Ohta, Shigeru

    2018-04-17

    As aldehyde oxidase (AOX) plays an emerging role in drug metabolism, understanding its significance for drug-drug interactions (DDI) is important. Therefore, we tested 10 compounds for species-specific and substrate-dependent differences in the inhibitory effect of AOX activity using genetically engineered HEK293 cells over-expressing human AOX1, mouse AOX1 or mouse AOX3. The IC 50 values of 10 potential inhibitors of the three AOX enzymes were determined using phthalazine and O 6 -benzylguanine as substrates. 17β-Estradiol, menadione, norharmane and raloxifene exhibited marked differences in inhibitory effects between the human and mouse AOX isoforms when the phthalazine substrate was used. Some of the compounds tested exhibited substrate-dependent differences in their inhibitory effects. Docking simulations with human AOX1 and mouse AOX3 were conducted for six representative inhibitors. The rank order of the minimum binding energy reflected the order of the corresponding IC 50 values. We also evaluated the potential DDI between an AOX substrate (O 6 -benzylguanine) and an inhibitor (hydralazine) using chimeric mice with humanized livers. Pretreatment of hydralazine increased the maximum plasma concentration (C max ) and the area under the plasma concentration-time curve (AUC 0-24 ) of O 6 -benzylguanine compared to single administration. Our in vitro data indicate species-specific and substrate-dependent differences in the inhibitory effects on AOX activity. Our in vivo data demonstrate the existence of a DDI which may be of relevance in the clinical context. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. Effectiveness of a recent topical sialogogue in the management of drug-induced xerostomia

    OpenAIRE

    Martin-Piedra, M.A.; Aguilar Salvatierra, Antonio; Herrera, David; Gómez Moreno, Gerardo

    2011-01-01

    Objectives: Use of certain drugs is the most common aetiology of xerostomia. Systemic sialogogues provide a longer effect than topic ones, but also induce relevant side effects. Topical sialogogues, as malic acid, allow a safe use as they induce no systemic side-effects or pharmacological interactions, being especially interesting in cases of mild hyposalivation and oral dryness, mainly the chronic use of xerostomizing drugs. The aim of this study...

  15. Evaluating the Effects of Pioneer Accountable Care Organizations on Medicare Part D Drug Spending and Utilization.

    Science.gov (United States)

    Zhang, Yuting; Caines, Kadin J; Powers, Christopher A

    2017-05-01

    The improvement of medication use is a critical mechanism that accountable care organization (ACO) could use to save overall costs. Currently pharmaceutical spending is not part of the calculation for ACO-shared savings and risks. Thus, ACO providers may have strong incentives to prescribe more medications hoping to avoid expensive downstream medical costs. We designed a quasinatural experiment study to evaluate the effects of Pioneer ACOs on Medicare Part D spending and utilization. Medicare fee-for-service beneficiaries with Part D drug coverage who were aligned to a Pioneer ACO were compared with a random 5% sample of non-ACO beneficiaries. Outcomes included changes in Part D spending, number of prescription fills, percent of brand medications, and total Part A and B medical spending. We utilized a generalized linear model with a difference-in-differences approach to estimate 2011-2012 changes in these outcomes among beneficiaries aligned with Pioneer ACOs, adjusting for all beneficiary-level demographics, income and insurance status, clinical characteristics, and regional fixed effects. Being in an ACO did not significantly affect Part D spending (-$23.52; P=0.19), total prescriptions filled (-0.12; P=0.27), and the percent of claims for brand-name drugs (0.06%; P=0.23). The ACO group was associated with savings in Parts A and B spending of $345 (PPioneer ACOs were not associated with changes in pharmaceutical spending and use, but were associated with savings in Parts A and B spending in 2012.

  16. Effect of the surfactant on the availability of piroxicam as a poorly hydrosoluble drug from suppositories.

    Science.gov (United States)

    Dal Zorro, M; Franceschinis, E; Punchina, A; Realdon, N

    2012-01-01

    The use of surfactants in suppository formulations has been suggested to improve availability of poorly soluble drugs. In the present study, different kinds of surfactants have been investigated to clarify the influence on piroxicam release from suppositories formulated with both lipophilic and hydrophilic bases. Two hydrophilic glucose-derivate surfactants, and a polyoxylglyceride amphiphilic surfactant, all with high HLB values, were investigated for their use in improving drug availability. The two glucose derivate surfactants reduced drug availability from both lipophilic suppositories and hydrophilic formulations, according to longer disintegration times and drug micellization. The more complex surfactant, a lauroyl macrogolglyceride, showed an increase in piroxicam availability from lipophilic suppositories at the higher tested concentrations (15% and 20%). Otherwise, when used in hydrophilic formulations, it was less effective in promoting drug release and even reduced drug availability.

  17. Drug-releasing shape-memory polymers - the role of morphology, processing effects, and matrix degradation.

    Science.gov (United States)

    Wischke, Christian; Behl, Marc; Lendlein, Andreas

    2013-09-01

    Shape-memory polymers (SMPs) have gained interest for temporary drug-release systems that should be anchored in the body by self-sufficient active movements of the polymeric matrix. Based on the so far published scientific literature, this review highlights three aspects that require particular attention when combining SMPs with drug molecules: i) the defined polymer morphology as required for the shape-memory function, ii) the strong effects that processing conditions such as drug-loading methodologies can have on the drug-release pattern from SMPs, and iii) the independent control of drug release and degradation by their timely separation. The combination of SMPs with a drug-release functionality leads to multifunctional carriers that are an interesting technology for pharmaceutical sciences and can be further expanded by new materials such as thermoplastic SMPs or temperature-memory polymers. Experimental studies should include relevant molecules as (model) drugs and provide a thermomechanical characterization also in an aqueous environment, report on the potential effect of drug type and loading levels on the shape-memory functionality, and explore the potential correlation of polymer degradation and drug release.

  18. Comparison of the toxic and radiosensitizing effects of five therapeutic drugs on the mouse jejunum

    International Nuclear Information System (INIS)

    Veena, K.; Uma Devi, P.

    1990-01-01

    Tissue toxicity and radiosensitizing effects of five different therapeutic drugs, bleomycin (BLM), chlorpromazine (CPZ), misonidazole (MISO), metronidazole (Metro) and Cis-diamminedichloro platinum (II) (c-DDP) on the jejunal crypts of Swiss albino mice were compared. All the drugs except Metro, when used alone, showed comparable toxicity. When combined with radiation, BLM produced a pronounced enhancement in the radiation damage (DMF=1.5) while Metro did not have any effect; the other drugs lay between BLM and Metro in their radiosensitizing effect. (orig.) [de

  19. TERATOGENIC EFFECTS OF DRUGS ON THE ORGANISM OF A FUTURE CHILD DURING FETAL STAGE OF DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    S.A. Sher

    2011-01-01

    Full Text Available Article assesses the impact of adverse factors on intrauterine development of the child, first of all, drugs. The author stresses that the importance of drug safety (D is due to the large number of unintended pregnancies worldwide. A list of the D, providing proven teratogenic effects on a child organism is presenting. It is shown that the D teratogenic effect in humans can not be assessed on the basis of experimental data obtained in animals due to the difference between metabolic and detoxification processes in a different mammals and individuals. Key words: drugs, safety, teratogenic effects, fetal development, the unborn child. (Pediatric pharmacology. — 2011; 8 (6: 57–60.

  20. Estimates of genetic parameters and effect of inbreeding on milk ...

    African Journals Online (AJOL)

    The statistical model included the fixed effects of herd-year-season, age of the cow at calving, calving interval, inbreeding as a discrete or continuous variable and random effects of direct additive genetic, permanent environment of the cow and the residual effects. The multitrait derivative-free REML algorithm was used to ...

  1. Effects of Administered Cardioprotective Drugs on Treatment Response of Breast Cancer Cells.

    Science.gov (United States)

    Smith, Tim A D; Phyu, Su M; Akabuogu, Emmanuel U

    2016-01-01

    Anticancer drug treatment, particularly with anthracyclines, is frequently associated with cardiotoxicity, an effect exacerbated by trastuzumab. Several compounds are in use clinically to attenuate the cardiac-damaging effects of chemotherapy drugs, including angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, the anti-diabetic drug metformin, and dexrazoxane. However, there is concern that the cardiac-preserving mechanisms of these drugs may also limit the anticancer efficacy of the chemotherapeutic agents. Herein two breast cancer cell lines, SKBr3 and BT474, overexpressing human epithelial receptor 2 (HER2), the target of the humanised antibody trastuzumab, were treated with a range of concentrations (20-2000 nM) of doxorubicin with and without trastuzumab in the presence of clinically relevant doses of the ACE inhibitor enalapril, the beta-blocker carvedilol, metformin or dexrazoxane, and cell survival determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. None of the drugs reduced the anticancer effect of doxorubicin or trastuzumab (nor of the two drugs combined). Using Chou and Talalay's combination index, dexrazoxane and doxorubicin were found to act synergistically on the SKBr3 cells. (18)F-Fluoro-2-deoxy-D-glucose ((18)F-FDG) incorporation was reduced by treatment of SKBr3 cells with doxorubicin and this was shown to be due to reduced phosphorylation of (18)F-FDG in doxorubicin-treated cells. Treatment of SKBr3 cells with doxorubicin and dexrazoxane further reduced (18)F-FDG incorporation, indicating that the synergy in the cytotoxicity of these two drugs was reflected in their combined effect on (18)F-FDG incorporation. Commonly administered cardioprotective drugs do not interfere with anticancer activity of doxorubicin or tratsuzumab. Further studies to establish the effect of cardioprotective drugs on anticancer drug efficacy would be beneficial. Copyright© 2016 International Institute of Anticancer Research

  2. Cost-effectiveness of Drugs to Treat Relapsed/Refractory Multiple Myeloma in the United States.

    Science.gov (United States)

    Carlson, Josh J; Guzauskas, Gregory F; Chapman, Richard H; Synnott, Patricia G; Liu, Shanshan; Russo, Elizabeth T; Pearson, Steven D; Brouwer, Elizabeth D; Ollendorf, Daniel A

    2018-01-01

    New 3-drug regimens have been developed and approved to treat multiple myeloma (MM). The absence of direct comparative data and the high cost of treatment support the need to assess the relative clinical and economic outcomes across all approved regimens. To evaluate the cost-effectiveness of treatments for relapsed and/or refractory MM from a U.S. health system perspective. We developed a partition survival model with 3 health states (progression-free, progression, and death) to evaluate the following regimens: carfilzomib (CFZ), elotuzumab (ELO), ixazomib (IX), daratumumab (DAR), and panobinostat (PAN) in combination with lenalidomide (LEN) or bortezomib (BOR) plus dexamethasone (DEX) in the second and/or third line of therapy. To estimate relative treatment effects, we developed a network meta-analysis and applied progression-free survival hazard ratios to baseline parametric progression-free survival functions derived from pooled data on LEN+DEX. We estimated overall survival using data on the relationship between progression-free survival and overall survival from a large meta-analysis of MM patients. Modeled costs included those related to drug treatment, administration, monitoring, adverse events, and progression. Utilities were from publicly available data and manufacturer data, if published sources were unavailable. Model results showed that regimens containing DAR yielded the highest expected life years (DAR range: 6.71-7.38 vs. non-DAR range: 3.25-5.27) and quality-adjusted life-years (QALY; DAR range: 4.38-5.44 vs. non-DAR range: 2.04-3.46), with DAR+BOR+DEX (second line) and PAN+BOR+DEX (third line) as the most cost-effective options (incremental cost-effectiveness ratio: $50,700 and cost saving, respectively). The applicability of the PAN+BOR+DEX result may be challenging, however, because of ongoing toxicity concerns. In the probabilistic sensitivity analysis, second-line DAR+BOR+DEX and third-line PAN+BOR+DEX had an 89% and 87% probability of being

  3. The Effect of Digestion and Drug Load on Halofantrine Absorption from Self-nanoemulsifying Drug Delivery System (SNEDDS)

    DEFF Research Database (Denmark)

    Michaelsen, Maria Hotoft; Wasan, Kishor M.; Sivak, Olena

    2016-01-01

    A super-saturated self-nanoemulsifying drug delivery system (super-SNEDDS), containing the poorly water-soluble drug halofantrine (Hf) at 150% of equilibrium solubility (Seq), was compared in vitro and in vivo with a conventional SNEDDS (75% of Seq) with respect to bioavailability and digestibility....... Further, the effect of digestion on oral absorption of Hf from SNEDDS and super-SNEDDS was assessed by incorporation of the lipase inhibitor tetrahydrolipstatin (orlistat) into the SNEDDS. The SNEDDS contained soybean oil/Maisine 34-I (1:1), Kolliphor RH40, and ethanol at a ratio of 55:35:10, w/w percent....... For the dynamic in vitro lipolysis, the precipitation of Hf at 60 min was significantly larger for the super-SNEDDS (66.8 ± 16.4%) than for the SNEDDS (18.5 ± 9.2%). The inhibition of the in vitro digestion by orlistat (1% (w/w)) lowered drug precipitation significantly for both the super-SNEDDS (36.8 ± 1...

  4. Cost-effectiveness of routine measuring of serum drug concentrations and anti-drug antibodies in treatment of rheumatoid arthritis patients with TNF-α blockers

    Directory of Open Access Journals (Sweden)

    Laine J

    2016-04-01

    Full Text Available Juha Laine,1 T Sakari Jokiranta,2,3 Kari K Eklund,4,5 Merja Väkeväinen,1 Kari Puolakka6 1Pfizer Oy, Helsinki, 2United Medix Laboratories Ltd, Espoo, 3Research Programs Unit, Immunobiology, 4Department of Rheumatology, University of Helsinki, 5Helsinki University Central Hospital, Helsinki, 6Department of Medicine, South Karelia, Finland Abstract: Monitoring of anti-drug antibodies (ADAbs or serum concentrations of biologicals in treatment of rheumatoid arthritis could provide an explanation for a loss of efficacy and help in the choice of subsequent medication. Current clinical practices do not generally include such monitoring of tumor necrosis factor (TNF-α blockers on a routine basis. The main aims of this study were to estimate the probabilities of optimal and nonoptimal treatment decisions if infliximab or adalimumab drug trough level (DL and ADAbs are tested or not in rheumatoid arthritis, and to model cost-effectiveness of performing such monitoring on a routine basis. Data on DLs and ADAbs concentrations were obtained in Finland from clinically requested monitoring analyses of 486 and 1,137 samples from patients on adalimumab and infliximab, respectively. DL was within the target range in 42% of samples from adalimumab- and 50.4% of infliximab-treated patients. ADAbs were detected in approximately 20% and 13.5% of samples from adalimumab- and infliximab-treated patients, respectively. ADAbs were found in 52.3% and 41.3% of those with low adalimumab or infliximab DLs, respectively. The monitoring data were incorporated into probabilities for making the optimal treatment decision. Economic impact of clinical decision-making was modeled in a short-term (3–6 months scenario with 100 hypothetical patients. In the model, the combined measurement of DLs and ADAbs was cost-saving compared to the nontesting scenario when the monitoring results affected the treatment decision in at least 2–5 of 100 patients, a proportion which is easily

  5. Information Technology-Based Interventions to Improve Drug-Drug Interaction Outcomes: A Systematic Review on Features and Effects.

    Science.gov (United States)

    Nabovati, Ehsan; Vakili-Arki, Hasan; Taherzadeh, Zhila; Saberi, Mohammad Reza; Medlock, Stephanie; Abu-Hanna, Ameen; Eslami, Saeid

    2017-01-01

    The purpose of this systematic review was to identify features and effects of information technology (IT)-based interventions on outcomes related to drug-drug interactions (DDI outcomes). A literature search was conducted in Medline, EMBASE, and the Cochrane Library for published English-language studies. Studies were included if a main outcome was related to DDIs, the intervention involved an IT-based system, and the study design was experimental or observational with controls. Study characteristics, including features and effects of IT-based interventions, were extracted. Nineteen studies comprising five randomized controlled trials (RCT), five non-randomized controlled trials (NRCT) and nine observational studies with controls (OWC) were included. Sixty-four percent of prescriber-directed interventions, and all non-prescriber interventions, were effective. Each of the following characteristics corresponded to groups of studies of which a majority were effective: automatic provision of recommendations within the providers' workflow, intervention at the time of decision-making, integration into other systems, and requiring the reason for not following the recommendations. Only two studies measured clinical outcomes: an RCT that showed no significant improvement and an OWC that showed improvement, but did not statistically assess the effect. Most studies that measured surrogate outcomes (e.g. potential DDIs) and other outcomes (e.g. adherence to alerts) showed improvements. IT-based interventions improve surrogate clinical outcomes and adherence to DDI alerts. However, there is lack of robust evidence about their effectiveness on clinical outcomes. It is recommended that researchers consider the identified features of effective interventions in the design of interventions and evaluate the effectiveness on DDI outcomes, particularly clinical outcomes.

  6. Off-target effects of psychoactive drugs revealed by genome-wide assays in yeast.

    Directory of Open Access Journals (Sweden)

    Elke Ericson

    2008-08-01

    Full Text Available To better understand off-target effects of widely prescribed psychoactive drugs, we performed a comprehensive series of chemogenomic screens using the budding yeast Saccharomyces cerevisiae as a model system. Because the known human targets of these drugs do not exist in yeast, we could employ the yeast gene deletion collections and parallel fitness profiling to explore potential off-target effects in a genome-wide manner. Among 214 tested, documented psychoactive drugs, we identified 81 compounds that inhibited wild-type yeast growth and were thus selected for genome-wide fitness profiling. Many of these drugs had a propensity to affect multiple cellular functions. The sensitivity profiles of half of the analyzed drugs were enriched for core cellular processes such as secretion, protein folding, RNA processing, and chromatin structure. Interestingly, fluoxetine (Prozac interfered with establishment of cell polarity, cyproheptadine (Periactin targeted essential genes with chromatin-remodeling roles, while paroxetine (Paxil interfered with essential RNA metabolism genes, suggesting potential secondary drug targets. We also found that the more recently developed atypical antipsychotic clozapine (Clozaril had no fewer off-target effects in yeast than the typical antipsychotics haloperidol (Haldol and pimozide (Orap. Our results suggest that model organism pharmacogenetic studies provide a rational foundation for understanding the off-target effects of clinically important psychoactive agents and suggest a rational means both for devising compound derivatives with fewer side effects and for tailoring drug treatment to individual patient genotypes.

  7. Effects of parameter estimation on maximum-likelihood bootstrap analysis.

    Science.gov (United States)

    Ripplinger, Jennifer; Abdo, Zaid; Sullivan, Jack

    2010-08-01

    Bipartition support in maximum-likelihood (ML) analysis is most commonly assessed using the nonparametric bootstrap. Although bootstrap replicates should theoretically be analyzed in the same manner as the original data, model selection is almost never conducted for bootstrap replicates, substitution-model parameters are often fixed to their maximum-likelihood estimates (MLEs) for the empirical data, and bootstrap replicates may be subjected to less rigorous heuristic search strategies than the original data set. Even though this approach may increase computational tractability, it may also lead to the recovery of suboptimal tree topologies and affect bootstrap values. However, since well-supported bipartitions are often recovered regardless of method, use of a less intensive bootstrap procedure may not significantly affect the results. In this study, we investigate the impact of parameter estimation (i.e., assessment of substitution-model parameters and tree topology) on ML bootstrap analysis. We find that while forgoing model selection and/or setting substitution-model parameters to their empirical MLEs may lead to significantly different bootstrap values, it probably would not change their biological interpretation. Similarly, even though the use of reduced search methods often results in significant differences among bootstrap values, only omitting branch swapping is likely to change any biological inferences drawn from the data. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Method of estimating investment decisions effectiveness in power engineering

    International Nuclear Information System (INIS)

    Kamrat, W.

    1996-01-01

    A new concept of determining efficient power plants investment decision-making is proposed.The results of research on capital expenditures for building and modernization of power plants are presented. The model introduced is based on the well-known Annual Cost Model which is modified by adding annual risk costs. So the formula for annual costs is: K = K f + K v + K r , where: K f are annual fixed costs, K v - annual variables costs, K r -annual risk costs. The annual risk costs can be calculated by the expression: K r = e i x K c , where e i is the investment risk factor, and K c - leveled capital investment. The risk factor was created on the basis of some elements of the taxonometric method with a high level of estimation probability. The essential problem is the selection of risk investment variables, most important of which are economic, financial, technical, social, political, legal. These variables create a multidimensional space. A so called 'ideal' model of the power plant is created taking into account capacity, type, fuel used, etc. The values of the multidimensional risk factor e i lie within limit and make it possible to rank the planned plants in series according to the estimated level of risk. This method can be used not only for risk evaluation in power engineering but also for investment efficiency studies in different industrial branches

  9. Effects of Drugs and Drug Combinations in Pigeons Trained to Discriminate among Pentobarbital, Dizocilpine, a Combination of These Drugs, and Saline

    Science.gov (United States)

    McMillan, D. E.; Wessinger, William D.; Li, Mi

    2009-01-01

    Drugs with multiple actions can have complex discriminative-stimulus properties. An approach to studying such drugs is to train subjects to discriminate among drug combinations and individual drugs in the combination so that all of the complex discriminative stimuli are present during training. In the current experiments, a four-choice procedure…

  10. Estimating the Value of New Technologies That Provide More Accurate Drug Adherence Information to Providers for Their Patients with Schizophrenia.

    Science.gov (United States)

    Shafrin, Jason; Schwartz, Taylor T; Lakdawalla, Darius N; Forma, Felicia M

    2016-11-01

    Nonadherence to antipsychotic medication among patients with schizophrenia results in poor symptom management and increased health care and other costs. Despite its health impact, medication adherence remains difficult to accurately assess. New technologies offer the possibility of real-time patient monitoring data on adherence, which may in turn improve clinical decision making. However, the economic benefit of accurate patient drug adherence information (PDAI) has yet to be evaluated. To quantify how more accurate PDAI can generate value to payers by improving health care provider decision making in the treatment of patients with schizophrenia. A 3-step decision tree modeling framework was used to measure the effect of PDAI on annual costs (2016 U.S. dollars) for patients with schizophrenia who initiated therapy with an atypical antipsychotic. The first step classified patients using 3 attributes: adherence to antipsychotic medication, medication tolerance, and response to therapy conditional on medication adherence. The prevalence of each characteristic was determined from claims database analysis and literature reviews. The second step modeled the effect of PDAI on provider treatment decisions based on health care providers' survey responses to schizophrenia case vignettes. In the survey, providers were randomized to vignettes with access to PDAI and with no access. In the third step, the economic implications of alternative provider decisions were identified from published peer-reviewed studies. The simulation model calculated the total economic value of PDAI as the difference between expected annual patient total cost corresponding to provider decisions made with or without PDAI. In claims data, 75.3% of patients with schizophrenia were found to be nonadherent to their antipsychotic medications. Review of the literature revealed that 7% of patients cannot tolerate medication, and 72.9% would respond to antipsychotic medication if adherent. Survey responses by

  11. Estimation of HIV-1 incidence among five focal populations in Dehong, Yunnan: a hard hit area along a major drug trafficking route.

    Science.gov (United States)

    Duan, Song; Shen, Sheng; Bulterys, Marc; Jia, Yujiang; Yang, Yuecheng; Xiang, Lifeng; Tian, Fei; Lu, Lin; Xiao, Yao; Wang, Minjie; Jia, Manhong; Jiang, Huazhou; Vermund, Sten H; Jiang, Yan

    2010-04-07

    Since 1989 when the first 146 HIV positives in China were identified, Dehong Prefecture had been one of the areas hardest-hit by HIV in China. The local and national governments have put substantial financial resources into tackling the HIV epidemic in Dehong from 2004. The objective of this study was to track dynamic changes in HIV-1 prevalence and incidence among five focal populations in Dehong and to assess the impact of HIV prevention and control efforts. Consecutive cross-sectional surveys conducted in five focal populations between 2004 and 2008. Specimens seropositive for HIV were tested with the BED IgG capture enzyme immunoassay to identify recent seroconversions (median, 155 days) using normalized optical density of 0.8 and adjustments. From 2004 to 2008, estimated annual HIV incidence among injecting drug users (IDUs) decreased significantly [from 15.0% (95% CI = 11.4%-18.5%) in 2004 to 4.3% (95% CI = 2.4%-6.2%) in 2008; trend test P < 0.0001]. The incidence among other focal populations, such as HIV discordant couples (varying from 5.5% to 4.7%), female sex workers (varying from 1.4% to 1.3%), pregnant women (0.1%), and pre-marital couples (0.2 to 0.1%) remained stable. Overall, the proportion of recent HIV-1 infections was higher among females than males (P < 0.0001). The HIV epidemic in Dehong continued to expand during a five-year period but at a slowing rate among IDUs, and HIV incidence remains high among IDUs and discordant couples. Intensive prevention measures should target sub-groups at highest risk to further slow the epidemic and control the migration of HIV to other areas of China, and multivariate analysis is needed to explore which measures are more effective for different populations.

  12. Psychomotor developmental effects of prenatal exposure to psychotropic drugs: a study in EFEMERIS database.

    Science.gov (United States)

    Hurault-Delarue, Caroline; Damase-Michel, Christine; Finotto, Laurent; Guitard, Claudine; Vayssière, Christophe; Montastruc, Jean-Louis; Montastruc, François; Lacroix, Isabelle

    2016-10-01

    Little is known about neurodevelopment of children exposed to psychotropic drugs during pregnancy. The purpose of this study was to evaluate the effects of prenatal exposure to psychotropic drugs on psychomotor development in children. This observational study used the EFEMERIS database. The database records the drugs prescribed and delivered during pregnancy and the resulting outcomes. Neurodevelopment at nine and 24 months of children born to women exposed to psychotropic drugs (anxiolytics, antidepressants, neuroleptics and anti-epileptics) during the second and/or third trimesters of pregnancy was compared to children who were not exposed to these drugs. Psychomotor development of 493 children (1.5%) exposed to psychotropic drugs during pregnancy was compared to 32 303 unexposed children. Exposure to psychotropic drugs during pregnancy was associated with an increased risk of abnormal motor development at 9 months (OR = 1.3 [1.1-2.2]) and abnormal motor and mental development at 24 months (OR = 4.8 [2.1-11.0] and OR = 2.3 [1.05-4.9]). Increased risk was observed in children born to women exposed to anti-epileptic drugs, neuroleptics or antidepressants during pregnancy. This study found a higher rate of deviation from the normal developmental milestones in children born to women exposed to psychotropic drugs during pregnancy and more particularly antidepressants, neuroleptics and anti-epileptics. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  13. Predictive tools for the evaluation of microbial effects on drugs during gastrointestinal passage.

    Science.gov (United States)

    Pieper, Ines A; Bertau, Martin

    2010-06-01

    Predicting drug metabolism after oral administration is highly complex, yet indispensable. Hitherto, drug metabolism mainly focuses on hepatic processes. In the intestine, drug molecules encounter the metabolic activity of microorganisms prior to absorption through the gut wall. Drug biotransformation through the gastrointestinal microflora has the potential to evoke serious problems because the metabolites formed may cause unexpected and undesired side effects in patients. Hence, in the course of drug development, the question has to be addressed if microbially formed metabolites are physiologically active, pharmaceutically active or even toxic. In order to provide answers to these questions and to keep the number of laboratory tests needed low, predictive tools - in vivo as well as in silico - are invaluable. This review gives an outline of the current state of the art in the field of predicting the drug biotransformation through the gastrointestinal microflora on several levels of modelling. A comprehensive review of the literature with a thorough discussion on assets and drawbacks of the different modelling approaches. The impact of the gastrointestinal drug biotransformation on patients' health will grow with increasing complexity of drug entities. Predicting metabolic fates of drugs by combining in vitro and in silico models provides invaluable information which will be suitable to particularly reduce in vivo studies.

  14. The cost-effectiveness of direct-to-consumer advertising for prescription drugs.

    Science.gov (United States)

    Atherly, Adam; Rubin, Paul H

    2009-12-01

    In this paper we use published information to analyze the economic value of Direct to Consumer Advertising (DTCA). The reviewed research finds that DTCA leads to increased demand for the advertised drug and that the effect of the drug tends to be class-wide rather than product specific. There is weak evidence that DTCA may increase compliance and improve clinical outcomes. However, there is little research on the effect of DTCA on inappropriate prescribing or on the characteristics of patients who respond to treatment. On net, if the advertised drugs are cost effective on average and the patients using the drugs in response to the advertisement are similar to other users, DTCA is likely cost effective. Overall, the literature to date is consistent with the idea that DTCA is beneficial, but further research is needed before definitive conclusions can be drawn.

  15. Deciphering the clinical effect of drugs through large-scale data integration

    DEFF Research Database (Denmark)

    Kjærulff, Sonny Kim

    chemical biology database. ChemProt integrates different chemical-protein annotation resources for disease-associated proteins and protein-protein interaction data. ChemProt is developed to assist in silico evaluation of environmental chemicals, natural products and approved drugs, as well as to aid......-effect data have been implemented. Chapter 3 presents two articles that showcase the application of systems chemical biology approaches to understand and model drug side-effect data. The first approach applies machine learning methods to cluster side-effects, drugs, proteins and clinical outcomes in networks......This thesis presents the work carried out at the Center for Biological Sequence Analysis, Technical University of Denmark. The thesis includes four articles describing large-scale data integration and methods for the prediction of drug side-effects. Chapter 2 presents ChemProt, a novel disease...

  16. Unfavorable side effects to first line anti-tuberculosis drugs

    OpenAIRE

    N. A. Stepanova; E. N. Streltsova; Kh. M. Galimzyanov; B. I. Kantemirova

    2016-01-01

    The article presents the study of frequency of unfavorable side effects to anti-tuberculosis drugs in new pulmonary tuberculosis patients in Regional Clinical TB Dispensary in Astrakhan in 2012-2013. The study reflects the type and nature of unfavorable side effects to specific drugs. It has been found out that side effect occur more often in case of combination of TB drugs compared to one TB drugs. The efficiency of specific therapy in case of side effects has been demonstrated....

  17. Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects

    International Nuclear Information System (INIS)

    Florea, Ana-Maria; Büsselberg, Dietrich

    2011-01-01

    Platinum complexes are clinically used as adjuvant therapy of cancers aiming to induce tumor cell death. Depending on cell type and concentration, cisplatin induces cytotoxicity, e.g., by interference with transcription and/or DNA replication mechanisms. Additionally, cisplatin damages tumors via induction of apoptosis, mediated by the activation of various signal transduction pathways, including calcium signaling, death receptor signaling, and the activation of mitochondrial pathways. Unfortunately, neither cytotoxicity nor apoptosis are exclusively induced in cancer cells, thus, cisplatin might also lead to diverse side-effects such as neuro- and/or renal-toxicity or bone marrow-suppression. Moreover, the binding of cisplatin to proteins and enzymes may modulate its biochemical mechanism of action. While a combination-chemotherapy with cisplatin is a cornerstone for the treatment of multiple cancers, the challenge is that cancer cells could become cisplatin-resistant. Numerous mechanisms of cisplatin resistance were described including changes in cellular uptake, drug efflux, increased detoxification, inhibition of apoptosis and increased DNA repair. To minimize cisplatin resistance, combinatorial therapies were developed and have proven more effective to defeat cancers. Thus, understanding of the biochemical mechanisms triggered by cisplatin in tumor cells may lead to the design of more efficient platinum derivates (or other drugs) and might provide new therapeutic strategies and reduce side effects

  18. EFFECTS OF THALLIUM ON THE LARVAL DEVELOPMENT OF LUCILIA SERICATA MEIGEN 1826 AND PMI ESTIMATION

    Directory of Open Access Journals (Sweden)

    Arif Gökhan BAŞARAN

    2011-08-01

    Full Text Available Determination of larval growth rate of and forensic analysis of the age of Calliphoridae larvae on a corpse are useful evidence in legal investigations for the estimation of exact death time and time duration after death; post mortem interval. However many factors, such as temperature, tissue type and contamination of drugs and toxins, effect larval development of blow fly larvae and consequently theestimation of post mortem interval. The present study examined the larval growth rate of a forensically important blow fly species, Lucilia sericata Meigen 1826 in different concentrations (0,12; 0,25; 0,50; 1 and 2 μg/g of toxic heavy metal Thallium under controlled laboratory conditions. Body length and weight, death ratio of larvae and pupa between experimental and control groups were compared. Results demonstrated that the development rate of larvae between uncontaminated and contaminated diets varies significantly. In short, they molted later, reached maximum length more slowly and sometimesproduced significantly smaller pupae in contaminated food source. These results emphasized that the importance of determining the contamination rate of toxins in tissue for the forensic entomologist,while using development rates from standard curves based on larvae fed non-contaminated mediums.

  19. A High Effective Fuzzy Synthetic Evaluation Multi-model Estimation

    Directory of Open Access Journals (Sweden)

    Yang LIU

    2014-01-01

    Full Text Available In view of the questions that the algorithm flow of variable structure multi-model method (VSMM is too complex and the tracking performance is inefficient and therefore it is so difficult to apply VSMM into installing equipment. The paper presents a high-performance variable structure multi-model method basing on multi-factor fuzzy synthetic evaluation (HEFS_VSMM. Under the guidance of variable structure method, HEFS_VSMM uses the technique of multi-factor fuzzy synthetic evaluation in the strategy of model set adaptive to select the appropriate model set in real time and reduce the computation complexity of the model evaluation, firstly. Secondly, select the model set center according to the evaluation results of each model and set the property value for current model set. Thirdly, choose different processes basing on the current model set property value to simplify the logical complexity of the algorithm. At last, the algorithm gets the total estimation by the theories of optimal information fusion on the above-mentioned processing results. The results of simulation show that, compared with the FSMM and EMA, the mean of estimation error belonging to position, velocity and acceleration in the HEFS_VSMM is improved from -0.029 (m, -0.350 (m/s, -10.051(m/s2 to -0.023 (m, 0.052 (m/s, -5.531 (m/s2. The algorithm cycle is reduced from 0.0051(s to 0.0025 (s.

  20. Drug Pricing Reforms

    DEFF Research Database (Denmark)

    Kaiser, Ulrich; Mendez, Susan J.; Rønde, Thomas

    2015-01-01

    Reference price systems for prescription drugs have found widespread use as cost containment tools. Under such regulatory regimes, patients co-pay a fraction of the difference between pharmacy retail price of the drug and a reference price. Reference prices are either externally (based on drug...... prices in other countries) or internally (based on domestic drug prices) determined. In a recent study, we analysed the effects of a change from external to internal reference pricing in Denmark in 2005, finding that the reform led to substantial reductions in prices, producer revenues, and expenditures...... for patients and the health insurance system. We also estimated an increase in consumer welfare but the size effect depends on whether or not perceived quality differences between branded and other drugs are taken into account....

  1. School Processes Mediate School Compositional Effects: Model Specification and Estimation

    Science.gov (United States)

    Liu, Hongqiang; Van Damme, Jan; Gielen, Sarah; Van Den Noortgate, Wim

    2015-01-01

    School composition effects have been consistently verified, but few studies ever attempted to study how school composition affects school achievement. Based on prior research findings, we employed multilevel mediation modeling to examine whether school processes mediate the effect of school composition upon school outcomes based on the data of 28…

  2. Private Returns on Education in Ghana: Estimating the Effects of ...

    African Journals Online (AJOL)

    This paper draws on the latest and most comprehensive survey data in Ghana, the fifth round of the Ghana Living Standards Survey (GLSS 5), to assess the effects of education on employability in Ghana. This paper argues that education has a positive effect on employability in Ghana. Analysis of the GLSS 5 data shows ...

  3. Effectiveness of mindfulness-based stress reduction in drug relapse prevention

    Directory of Open Access Journals (Sweden)

    Ali Hamedi

    2014-02-01

    Full Text Available Objective: The present study was designed to investigate the effectiveness of mindfulness in the prevention of relapse in drug abusers. Method: Using a quasi experimental design, 90 male drug abusers who had undergone detoxification were selected from among all detoxified individuals referred to drug rehabilitation centers in the City of Tehran. Patients were placed randomly in three groups: Mindfulness training intervention, behavioral drug reduction counseling and a control group in which no intervention was applied. Diagnosis of drug abuse was made using structured clinical interview for diagnosing axis I disorders on DSMIV (SCID-I as well as tests to measure morphine levels in the blood. Fisher test was used to compare groups. Patients were assessed two weeks and two months after the intervention as follow up measure. Findings: Results show that both intervention groups were effective in preventing relapse as compared to the control group. Furthermore, the effectiveness of mindfulness training and BDRC was about the same. There were no significant differences between patients with and without experience of drug abuse and married and single patients. Conclusion: Both mindfulness training and BDRC may be considered effective practical methods in reducing the risk of relapse in male drug abusers.

  4. Effect of heterogeneous microvasculature distribution on drug delivery to solid tumour

    International Nuclear Information System (INIS)

    Zhan, Wenbo; Xu, Xiao Yun; Gedroyc, Wladyslaw

    2014-01-01

    Most of the computational models of drug transport in vascular tumours assume a uniform distribution of blood vessels through which anti-cancer drugs are delivered. However, it is well known that solid tumours are characterized by dilated microvasculature with non-uniform diameters and irregular branching patterns. In this study, the effect of heterogeneous vasculature on drug transport and uptake is investigated by means of mathematical modelling of the key physical and biochemical processes in drug delivery. An anatomically realistic tumour model accounting for heterogeneous distribution of blood vessels is reconstructed based on magnetic resonance images of a liver tumour. Numerical simulations are performed for different drug delivery modes, including direct continuous infusion and thermosensitive liposome-mediated delivery, and the anti-cancer effectiveness is evaluated through changes in tumour cell density based on predicted intracellular concentrations. Comparisons are made between regions of different vascular density, and between the two drug delivery modes. Our numerical results show that both extra- and intra-cellular concentrations in the liver tumour are non-uniform owing to the heterogeneous distribution of tumour vasculature. Drugs accumulate faster in well-vascularized regions, where they are also cleared out more quickly, resulting in less effective tumour cell killing in these regions. Compared with direct continuous infusion, the influence of heterogeneous vasculature on anti-cancer effectiveness is more pronounced for thermosensitive liposome-mediated delivery. (paper)

  5. The effect of construction cost estimating (CCE software on job performance: An improvement plan

    Directory of Open Access Journals (Sweden)

    Mohd Mukelas M.F.

    2014-01-01

    Full Text Available This paper presents a comprehensive statistical research on the effect of construction cost estimating software’s features towards estimating job performance. The objectives of this study are identification of cost estimating software features, analyzing the significant relation of cost estimating software’s features towards job performance, Explore the problem faced during the implementation and lastly propose a plan to improve the cost estimating software usage among contractors in Malaysia. The study statistically reveals four features of cost estimating software that significantly impact towards changes in cost estimating job performance. These features were refined by performing interview to focus group of respondent to observe the actual possible problems during the implementation. Eventually, the proposed improvement plan was validated by the focus group of respondents to enhance the cost estimating software implementation among contractors in Malaysia.

  6. Effects of antidepressant drugs on histamine-H1 receptors in the brain

    International Nuclear Information System (INIS)

    Hall, H.; Oegren, S.O.

    1984-01-01

    The histamine-H 1 receptor blocking properties of a number of structurally different antidepressant drugs have been evaluated using a 3 H-mepyramine binding assay and a guinea-pig ileum preparation. The tricyclic antidepressants all inhibited the histamine-H 1 receptor. Some newer antidepressant drugs, such as zimeldine and nomifensine were devoid of activity while others, such as iprindole and mianserin were very potent. It is concluded that antagonistic effects on the histamine-H 1 receptor is not associated with the therapeutic efficacy in depression, but may contribute to the sedative effects of the antidepressant drugs

  7. Comparative effectiveness of antiepileptic drugs in patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

    Science.gov (United States)

    Androsova, Ganna; Krause, Roland; Borghei, Mojgansadat; Wassenaar, Merel; Auce, Pauls; Avbersek, Andreja; Becker, Felicitas; Berghuis, Bianca; Campbell, Ellen; Coppola, Antonietta; Francis, Ben; Wolking, Stefan; Cavalleri, Gianpiero L; Craig, John; Delanty, Norman; Koeleman, Bobby P C; Kunz, Wolfram S; Lerche, Holger; Marson, Anthony G; Sander, Josemir W; Sills, Graeme J; Striano, Pasquale; Zara, Federico; Sisodiya, Sanjay M; Depondt, Chantal

    2017-10-01

    Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) is a common epilepsy syndrome that is often poorly controlled by antiepileptic drug (AED) treatment. Comparative AED effectiveness studies in this condition are lacking. We report retention, efficacy, and tolerability in a cohort of patients with MTLE-HS. Clinical data were collected from a European database of patients with epilepsy. We estimated retention, 12-month seizure freedom, and adverse drug reaction (ADR) rates for the 10 most commonly used AEDs in patients with MTLE-HS. Seven hundred sixty-seven patients with a total of 3,249 AED trials were included. The highest 12-month retention rates were observed with carbamazepine (85.9%), valproate (85%), and clobazam (79%). Twelve-month seizure freedom rates varied from 1.2% for gabapentin and vigabatrin to 11% for carbamazepine. Response rates were highest for AEDs that were prescribed as initial treatment and lowest for AEDs that were used in a third or higher instance. ADRs were reported in 47.6% of patients, with the highest rates observed with oxcarbazepine (35.7%), topiramate (30.9%), and pregabalin (27.4%), and the lowest rates with clobazam (6.5%), gabapentin (8.9%), and lamotrigine (16.6%). The most commonly reported ADRs were lethargy and drowsiness, dizziness, vertigo and ataxia, and blurred vision and diplopia. Our results did not demonstrate any clear advantage of newer versus older AEDs. Our results provide useful insights into AED retention, efficacy, and ADR rates in patients with MTLE-HS. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  8. Effect of wide spectrum anti-helminthic drugs upon Schistosoma mansoni experimentally infected mice

    Directory of Open Access Journals (Sweden)

    PANCERA Christiane Finardi

    1997-01-01

    Full Text Available Mebendazole, albendazole, levamisole and thiabendazole are well known as active drugs against several nematode species, and against cestodes as well, when the first two drugs are considered. None of the drugs have proven activity, however, against trematodes. We tested the effect of these drugs on the fecal shedding of schistosome eggs and the recovering of adult schistosomes, after portal perfusion in Schistosoma mansoni experimentally infected mice. Balb/c mice infected with 80 S. mansoni cercariae were divided into three groups, each in turn subdivided into four other groups, for each tested drug. The first group was treated with each one of the studied drugs 25 days after S. mansoni infection; the second group was submitted to treatment with each one of the drugs 60 days after infection. Finally, the third group, considered as control, received no treatment. No effect upon fecal shedding of S. mansoni eggs and recovering of schistosomes after portal perfusion was observed when mice were treated with either mebendazole or albendazole. Mice treated with either levamisole or thiabendazole, on the other hand, showed a significant reduction in the recovering of adult schistosomes after portal perfusion, mainly when both drugs were given during the schistosomula evolution period, i.e., 25 days after cercariae penetration, probably due to unspecific immunomodulation

  9. Effects of uremic toxins on transport and metabolism of different biopharmaceutics drug disposition classification system xenobiotics.

    Science.gov (United States)

    Reyes, Maribel; Benet, Leslie Z

    2011-09-01

    Chronic kidney disease (CKD) is recognized to cause pharmacokinetic changes in renally excreted drugs; however, pharmacokinetic changes are also reported for drugs that are nonrenally eliminated. Few studies have investigated how uremic toxins may affect drug transporters and metabolizing enzymes and how these may result in pharmacokinetic/metabolic changes in CKD. Here, we investigated the effects of uremic toxins and human uremic serum on the transport of the prototypical transporter substrate [(3) H]-estrone sulfate and three Biopharmaceutics Drug Disposition Classification System (BDDCS) drugs, propranolol, losartan, and eprosartan. We observed a significant decrease in [(3) H]-estrone sulfate, losartan, and eprosartan uptake with some uremic toxins in both transfected cells and rat hepatocytes. The uptake of losartan was decreased in rat and human hepatocytes (28% and 48%, respectively) in the presence of hemodialysis (HD) serum. Time-course studies of losartan showed a 27%, 65%, and 68% increase in area under the curve (AUC) in the presence of HD serum, rifampin, and sulfaphenazole, respectively. Intracellular losartan AUC decreased significantly in the treatment groups, and the metabolite AUC decreased by 41% and 26% in rifampin- and sulfaphenazole-treated group, respectively. The intracellular AUC of eprosartan increased 190% in the presence of HD serum. These studies indicate that the uremic toxins contained in HD serum play an important role in drug disposition through drug transporters, and that there would be differential effects depending on the BDDCS classification of the drug. Copyright © 2011 Wiley-Liss, Inc.

  10. Anticoagulant effects of phytotherapeutic drugs and their importance in surgical dental procedures

    OpenAIRE

    MACHADO, Ricardo; SILVA, Leopoldo COSME; CUBA, Leticia de Freitas; OLIVEIRA, Jonatas Rafael de; MARTINHO, Frederico Canato; FERRARI, Carlos Henrique

    2017-01-01

    ABSTRACT Phytotherapeutic drugs are plant-derived products with medicinal properties. They are used for treating or preventing several diseases. However, patients who use these substances and even health professionals are unaware of their negative effects. One of the most common negative effects of phytotherapeutic drugs reported in the literature is the inhibition of natural coagulation factors in the human body. Therefore, the aim of this study was to perform a brief review of the literatur...

  11. Identifying Drugs

    Science.gov (United States)

    ... and Affect Teens The Negative Health Effects of Marijuana Use State and Federal Drug Laws Treatment and Recovery Federal Student Aid and Consequences of a Drug Conviction School Failure VIDEO: Taking Prescription Drugs to Get High—A Bad Idea Drugged Driving—What You Should Know How ...

  12. Estimated Effects of the October 1979 Change in Monetary Policy on the 1980 Economy

    OpenAIRE

    Ray C* Fair

    1980-01-01

    On October 6. 1979, the Federal Reserve announced what most people interpreted as a change in monetary policy. The purpose of this paper is to estimate the effects of this change on the 1980-81 economy. The effects of the change are estimated from simulations with my model of the U.S. economy (1976, 1980b).

  13. Estimated nation wide effects of pesticide spray drift on terrestrial habitats in the Netherlands

    NARCIS (Netherlands)

    Jong, de F.M.W.; Snoo, de G.R.; Zande, van de J.C.

    2008-01-01

    This study estimated the potential effects of pesticide drift on terrestrial ecosystems outside target areas, for the Dutch situation. A series of field trials was conducted to estimate the effects of drift on different species groups at different distances from a treated plot for different

  14. Estimation of Effect Size from a Series of Experiments Involving Paired Comparisons.

    Science.gov (United States)

    Gibbons, Robert D.; And Others

    1993-01-01

    A distribution theory is derived for a G. V. Glass-type (1976) estimator of effect size from studies involving paired comparisons. The possibility of combining effect sizes from studies involving a mixture of related and unrelated samples is also explored. Resulting estimates are illustrated using data from previous psychiatric research. (SLD)

  15. Flexible Approaches to Computing Mediated Effects in Generalized Linear Models: Generalized Estimating Equations and Bootstrapping

    Science.gov (United States)

    Schluchter, Mark D.

    2008-01-01

    In behavioral research, interest is often in examining the degree to which the effect of an independent variable X on an outcome Y is mediated by an intermediary or mediator variable M. This article illustrates how generalized estimating equations (GEE) modeling can be used to estimate the indirect or mediated effect, defined as the amount by…

  16. Effects of anthropomorphic images and narration styles in promotional messages for generic prescription drugs.

    Science.gov (United States)

    Muzumdar, Jagannath M; Schommer, Jon C; Hadsall, Ronald S; Huh, Jisu

    2013-01-01

    Anthropomorphism is attribution of human characteristics to nonhuman objects or events. Marketers have used anthropomorphized characters to promote products and services. To promote use of generic drugs to save on prescription drug costs, health systems are in the process of developing informational materials to influence consumer's perceptions about generic prescription drugs. To evaluate the effects of anthropomorphic images (control vs caring vs authoritative) and information narration styles (first person vs third person) on (1) social presence, (2) attitude toward the overall promotional message, (3) perceived informativeness of the message content, (4) attitude toward specific message, (5) intent to seek information, and (6) intention to switch to a generic prescription drug. A 3×2 between-subject factorial design was used. Student participants were administered a mock promotional message regarding generic prescription drugs. Following the promotional message, they were asked to respond to items developed to measure the effects of the promotional message. Manipulation checks were conducted to test the desired effects of the independent variables. Pilot testing, exploratory factor analysis, and reliability testing of the item measures were conducted before their use in the study. Analysis of variance was used to analyze the data and test the proposed effects of the independent variables. Anthropomorphic images showed a positive effect on social presence and attitude toward the specific message. Narration styles had a positive effect on attitude toward the overall promotional message. Neither anthropomorphic images nor narration styles had a significant effect on perceived informativeness, intent to seek information, and intention to switch to a generic prescription drug. This research reveals that anthropomorphism of medications and narration styles could play a significant role in promotional messages for generic prescription drugs. These findings provide a

  17. Effect of Antiepileptic Drugs for Acute and Chronic Seizures in Children with Encephalitis.

    Directory of Open Access Journals (Sweden)

    Kuang-Lin Lin

    Full Text Available Encephalitis presents with seizures in the acute phase and increases the risk of late unprovoked seizures and epilepsy. This study aimed to evaluate the effect of antiepileptic drugs in pediatric patients with acute seizures due to encephalitis and epilepsy.Cases of acute pediatric encephalitis between January 2000 and December 2010 were reviewed. Clinical data, including onset at age, seizure type, seizure frequency, effects of antiepileptic drugs, and prognosis were analyzed.During the study period, 1038 patients (450 girls, 588 boys were enrolled. Among them, 44.6% (463 had seizures in the acute phase, 33% had status epilepticus, and 26% (251 developed postencephalitic epilepsy. At one year of follow-up, 205 of the 251 patients with postencephalitic epilepsy were receiving antiepileptic drugs while 18% were seizure free even after discontinuing the antiepileptic drugs. Among those with postencephalitic epilepsy, 67% had favorable outcomes and were using <2 anti-epileptic drugs while 15% had intractable seizures and were using ≥ 2 antiepileptic drugs. After benzodiazepines, intravenous phenobarbital was preferred over phenytoin as treatment of postencephalitic seizures in the acute phase. For refractory status epilepticus, high-dose topiramate combined with intravenous high-dose phenobarbital or high-dose lidocaine had less side effects.Children with encephalitis have a high rate of postencephalitic epilepsy. Phenobarbital and clonazepam are the most common drugs used, alone or in combination, for postencephalitic epilepsy.

  18. Lipids in the Stomach - Implications for the Evaluation of Food Effects on Oral Drug Absorption.

    Science.gov (United States)

    Koziolek, Mirko; Carrière, Frédéric; Porter, Christopher J H

    2018-02-08

    Food effects on oral drug bioavailability can have significant impact on the provision of safe and reliable oral pharmacotherapy. A mechanistic understanding of the events that contribute to the occurrence of food effects is therefore critical. An increased oral bioavailability is often seen for poorly water-soluble drugs after co-administration with lipids, including lipids in food, and is commonly explained by the ability of lipids to enhance drug solubility in intestinal luminal fluids. In contrast, the impact of lipids on drug solubilisation in the stomach has received less attention. This is in spite of the fact that lipid digestion is initiated in the stomach by human gastric lipase and that gastric events also initiate emulsification of lipids in the gastrointestinal tract. The stomach therefore acts to 'pre-process' lipids for subsequent events in the intestine and may significantly affect downstream events at intestinal drug absorption sites. In this article, the mechanisms by which lipids are processed in the stomach are reviewed and the potential impact of these processes on drug absorption discussed. Attention is also focused on in vitro methods that are used to assess gastric processing of lipids and their application to better understand food effects on drug release and absorption.

  19. Feasibility of the estimation of octanol-water distribution coefficients of acidic drugs by microemulsion electrokinetic chromatography

    Directory of Open Access Journals (Sweden)

    Alejandro Fernández-Pumarega1

    2018-03-01

    Full Text Available Previous studies have shown that a microemulsion electrokinetic chromatography (MEEKC system can estimate the logarithm of the octanol-water partition coefficient (log Po/w of neutral solutes. In the present work, the applicability of the method to partially and fully ionized acids has been evaluated. Naproxen, a monoprotic acid, has been used as test solute. The retention factor (k of this compound has been measured in MEEKC at several values of pH and the retention factor-pH profile has been established. As log Po/w correlates with log kMEEKC for neutral compounds, this correlation has been used to estimate the logarithm of the octanol-water partition coefficient of the neutral (log Po/w(HA, and the fully ionized (log P o/w(A- forms of naproxen. Then, the logarithm of the octanol-water distribution coefficient (log Do/w of the partially ionized form of the acid has been estimated. The comparison of the estimated values with the ones obtained experimentally using the classical procedures, such as the shake-flask method, shows differences under 0.4 log Do/w units either if the acid is partially ionized or in its neutral form in the most part of the pH range. However, the method overestimates the log Do/w of the highly (>99.5 % or fully ionized form of naproxen.

  20. Estimating medication stopping fraction and real-time prevalence of drug use in pharmaco-epidemiologic databases

    DEFF Research Database (Denmark)

    Støvring, Henrik; Pottegård, Anton; Hallas, Jesper

    2017-01-01

    Purpose: To introduce the reverse waiting time distribution (WTD) and show how it can be used to estimate stopping fractions and real-time prevalence of treatment in pharmacoepidemiological studies. Methods: The reverse WTD is the distribution of time from the last dispensed prescription of each...