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Sample records for estimating drug effects

  1. Elite athletes' estimates of the prevalence of illicit drug use: evidence for the false consensus effect.

    Science.gov (United States)

    Dunn, Matthew; Thomas, Johanna O; Swift, Wendy; Burns, Lucinda

    2012-01-01

    The false consensus effect (FCE) is the tendency for people to assume that others share their attitudes and behaviours to a greater extent than they actually do. The FCE has been demonstrated for a range of health behaviours, including substance use. The study aimed to explore the relationship between elite athlete's engagement in recreational drug use and their consensus estimates (the FCE) and to determine whether those who engage in the behaviour overestimate the use of others around them. The FCE was investigated among 974 elite Australian athletes who were classified according to their drug use history. Participants tended to report that there was a higher prevalence of drug use among athletes in general compared with athletes in their sport, and these estimates appeared to be influenced by participants' drug use history. While overestimation of drug use by participants was not common, this overestimation also appeared to be influenced by athletes' drug use history. The results suggest that athletes who have a history of illicit drug use overestimate the prevalence of drug use among athletes. These findings may be helpful in the formulation of normative education initiatives. © 2011 Australasian Professional Society on Alcohol and other Drugs.

  2. 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.

  3. Estimated effects of adding universal public coverage of an essential medicines list to existing public drug plans in Canada.

    Science.gov (United States)

    Morgan, Steven G; Li, Winny; Yau, Brandon; Persaud, Nav

    2017-02-27

    Canada's universal health care system does not include universal coverage of prescription drugs. We sought to estimate the effects of adding universal public coverage of an essential medicines list to existing public drug plans in Canada. We used administrative and market research data to estimate the 2015 shares of the volume and cost of prescriptions filled in the community setting that were for 117 drugs on a model list of essential medicines for Canada. We compared prices of these essential medicines in Canada with prices in the United States, Sweden and New Zealand. We estimated the cost of adding universal public drug coverage of these essential medicines based on anticipated effects on medication use and pricing. The 117 essential medicines on the model list accounted for 44% of all prescriptions and 30% of total prescription drug expenditures in 2015. Average prices of generic essential medicines were 47% lower in the US, 60% lower in Sweden and 84% lower in New Zealand; brand-name drugs were priced 43% lower in the US. Estimated savings from universal public coverage of these essential medicines was $4.27 billion per year (range $2.72 billion to $5.83 billion; 28% reduction) for patients and private drug plan sponsors, at an incremental government cost of $1.23 billion per year (range $373 million to $1.98 billion; 11% reduction). Our analysis showed that adding universal public coverage of essential medicines to the existing public drug plans in Canada could address most of Canadians' pharmaceutical needs and save billions of dollars annually. Doing so may be a pragmatic step forward while more comprehensive pharmacare reforms are planned. © 2017 Canadian Medical Association or its licensors.

  4. Considerations for effect site pharmacokinetics to estimate drug exposure: concentrations of antibiotics in the lung.

    Science.gov (United States)

    Rodvold, Keith A; Hope, William W; Boyd, Sara E

    2017-10-01

    Bronchoalveolar lavage (BAL) and microdialysis have become the most reliable and relevant methods for measuring lung concentrations of antibiotics, with the majority of BAL studies involving either healthy adult subjects or patients undergoing diagnostic bronchoscopy. Emphasis on the amount of drug that reaches the site of infection is increasingly recognized as necessary to determine whether a dose selection will translate to good clinical outcomes in the treatment of patients with pneumonia. Observed concentrations and/or parameters of exposure (e.g. area-under-the-curve) need to be incorporated with pharmacokinetic-pharmacodynamic indices so that rational dose selection can be identified for specific pathogens and types of pneumonic infection (community-acquired vs hospital-acquired bacterial pneumonia, including ventilator-associated bacterial pneumonia). Although having measured plasma or lung concentration-time data from critically ill patients to incorporate into pharmacokinetic-pharmacodynamic models is very unlikely during drug development, it is essential that altered distribution, augmented renal clearance, and renal or hepatic dysfunction should be considered. Notably, the number of published studies involving microdialysis and intrapulmonary penetration of antibiotics has been limited and mainly involve beta-lactam agents, levofloxacin, and fosfomycin. Opportunities to measure in high-resolution effect site spatial pharmacokinetics (e.g. with MALDI-MSI or PET imaging) and in vivo continuous drug concentrations (e.g. with aptamer-based probes) now exist. Going forward these studies could be incorporated into antibiotic development programs for pneumonia in order to further increase the probability of candidate success. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. 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

    of this misclassification for analysing the risk of breast cancer. MATERIALS AND METHODS: Prescription data were obtained from Danish Registry of Medicinal Products Statistics and we applied various methods to approximate treatment episodes. We analysed the duration of HT episodes to study the ability to identify......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 carry any information on the time of discontinuation of treatment.In this study, we investigated the amount of misclassification of exposure (never, current, previous use) to hormone therapy (HT) when the exposure variable was based on prescription data. Furthermore, we evaluated the significance...

  6. Estimating the health and economic effects of the proposed US Food and Drug Administration voluntary sodium reformulation: Microsimulation cost-effectiveness analysis.

    Science.gov (United States)

    Pearson-Stuttard, Jonathan; Kypridemos, Chris; Collins, Brendan; Mozaffarian, Dariush; Huang, Yue; Bandosz, Piotr; Capewell, Simon; Whitsel, Laurie; Wilde, Parke; O'Flaherty, Martin; Micha, Renata

    2018-04-01

    Sodium consumption is a modifiable risk factor for higher blood pressure (BP) and cardiovascular disease (CVD). The US Food and Drug Administration (FDA) has proposed voluntary sodium reduction goals targeting processed and commercially prepared foods. We aimed to quantify the potential health and economic impact of this policy. We used a microsimulation approach of a close-to-reality synthetic population (US IMPACT Food Policy Model) to estimate CVD deaths and cases prevented or postponed, quality-adjusted life years (QALYs), and cost-effectiveness from 2017 to 2036 of 3 scenarios: (1) optimal, 100% compliance with 10-year reformulation targets; (2) modest, 50% compliance with 10-year reformulation targets; and (3) pessimistic, 100% compliance with 2-year reformulation targets, but with no further progress. We used the National Health and Nutrition Examination Survey and high-quality meta-analyses to inform model inputs. Costs included government costs to administer and monitor the policy, industry reformulation costs, and CVD-related healthcare, productivity, and informal care costs. Between 2017 and 2036, the optimal reformulation scenario achieving the FDA sodium reduction targets could prevent approximately 450,000 CVD cases (95% uncertainty interval: 240,000 to 740,000), gain approximately 2.1 million discounted QALYs (1.7 million to 2.4 million), and produce discounted cost savings (health savings minus policy costs) of approximately $41 billion ($14 billion to $81 billion). In the modest and pessimistic scenarios, health gains would be 1.1 million and 0.7 million QALYS, with savings of $19 billion and $12 billion, respectively. All the scenarios were estimated with more than 80% probability to be cost-effective (incremental cost/QALY cost-saving by 2031. Limitations include evaluating only diseases mediated through BP, while decreasing sodium consumption could have beneficial effects upon other health burdens such as gastric cancer. Further, the effect

  7. 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.

  8. Validating estimates of problematic drug use in England

    Directory of Open Access Journals (Sweden)

    Heatlie Heath

    2007-10-01

    Full Text Available Abstract Background UK Government expenditure on combatting drug abuse is based on estimates of illicit drug users, yet the validity of these estimates is unknown. This study aims to assess the face validity of problematic drug use (PDU and injecting drug use (IDU estimates for all English Drug Action Teams (DATs in 2001. The estimates were derived from a statistical model using the Multiple Indicator Method (MIM. Methods Questionnaire study, in which the 149 English Drug Action Teams were asked to evaluate the MIM estimates for their DAT. Results The response rate was 60% and there were no indications of selection bias. Of responding DATs, 64% thought the PDU estimates were about right or did not dispute them, while 27% had estimates that were too low and 9% were too high. The figures for the IDU estimates were 52% (about right, 44% (too low and 3% (too high. Conclusion This is the first UK study to determine the validity estimates of problematic and injecting drug misuse. The results of this paper highlight the need to consider criterion and face validity when evaluating estimates of the number of drug users.

  9. 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

  10. Hypotensive anesthesia: Comparing the effects of different drug combinations on mean arterial pressure, estimated blood loss, and surgery time in orthognathic surgery.

    Science.gov (United States)

    Jeong, James; Portnof, Jason E; Kalayeh, Mona; Hardigan, Patrick

    2016-07-01

    Sevoflurane, an inhalational hypotensive anesthetic agent with a vasodilatory property, has been commonly used as a single agent to induce hypotension and effectively decrease blood loss in orthognathic surgery. However, it is common for patients to receive other hypotensive anesthetic agents in combination with sevoflurane. The purpose of our retrospective cohort study is to investigate whether administering an additional hypotensive agent has greater effect at reducing mean arterial pressure (MAP), estimated blood loss (EBL) and surgery time during orthognathic surgery. 57 subjects, aged 0-89 of both genders, who underwent orthognathic surgery were investigated in this study. Each patient's anesthesia records were reviewed to record the following variables of interest: EBL, duration of surgery, and MAP reduction in %. 41 subjects were placed in Group I and they received sevoflurane alone. 16 subjects were placed in Group II and they received sevoflurane plus a "supportive" agent. These "supportive" agents were esmolol, labetalol, metoprolol, nicardipine, and dexmedetomidine. The significant differences between two groups were assessed by using ANCOVA and p surgery time. Subjects in Group II experienced a greater reduction in MAP during surgery than subjects in Group I, 27.30% and 20.44%, respectively (p = 0.027). There was no significant difference for sex (p = 0.417) or age group (p = 0.113) in estimated blood loss, however. The mean surgery time in Group I was 1.93, 2.77, and 4.54 h with respect to LeFort, BSSO/IVRO, and double jaw surgery. Patients in Group II had a mean surgery time of 1.73, 2.07, and 5.64 h with respect to LeFort, BSSO/IVRO, and double jaw surgery. No statistically significant difference was demonstrated in surgery time between Group I vs. Group II (p > 0.05). Subjects in Group II experienced, on average, more blood loss than subjects in Group I, 355.50 ml and 238.90 ml, respectively. The use of multi-drug combination may offer

  11. Effects of Drugs

    Science.gov (United States)

    ... Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search ... who aren't yet born. Drug use can hurt the body and the brain, sometimes forever. Drug use can also lead to addiction, a long-lasting brain disease in which people ...

  12. 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

  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. Republic of Georgia estimates for prevalence of drug use: Randomized response techniques suggest under-estimation.

    Science.gov (United States)

    Kirtadze, Irma; Otiashvili, David; Tabatadze, Mzia; Vardanashvili, Irina; Sturua, Lela; Zabransky, Tomas; Anthony, James C

    2018-06-01

    Validity of responses in surveys is an important research concern, especially in emerging market economies where surveys in the general population are a novelty, and the level of social control is traditionally higher. The Randomized Response Technique (RRT) can be used as a check on response validity when the study aim is to estimate population prevalence of drug experiences and other socially sensitive and/or illegal behaviors. To apply RRT and to study potential under-reporting of drug use in a nation-scale, population-based general population survey of alcohol and other drug use. For this first-ever household survey on addictive substances for the Country of Georgia, we used the multi-stage probability sampling of 18-to-64-year-old household residents of 111 urban and 49 rural areas. During the interviewer-administered assessments, RRT involved pairing of sensitive and non-sensitive questions about drug experiences. Based upon the standard household self-report survey estimate, an estimated 17.3% [95% confidence interval, CI: 15.5%, 19.1%] of Georgian household residents have tried cannabis. The corresponding RRT estimate was 29.9% [95% CI: 24.9%, 34.9%]. The RRT estimates for other drugs such as heroin also were larger than the standard self-report estimates. We remain unsure about what is the "true" value for prevalence of using illegal psychotropic drugs in the Republic of Georgia study population. Our RRT results suggest that standard non-RRT approaches might produce 'under-estimates' or at best, highly conservative, lower-end estimates. Copyright © 2018 Elsevier B.V. All rights reserved.

  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. 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.

  18. Quantitative PET Imaging in Drug Development: Estimation of Target Occupancy.

    Science.gov (United States)

    Naganawa, Mika; Gallezot, Jean-Dominique; Rossano, Samantha; Carson, Richard E

    2017-12-11

    Positron emission tomography, an imaging tool using radiolabeled tracers in humans and preclinical species, has been widely used in recent years in drug development, particularly in the central nervous system. One important goal of PET in drug development is assessing the occupancy of various molecular targets (e.g., receptors, transporters, enzymes) by exogenous drugs. The current linear mathematical approaches used to determine occupancy using PET imaging experiments are presented. These algorithms use results from multiple regions with different target content in two scans, a baseline (pre-drug) scan and a post-drug scan. New mathematical estimation approaches to determine target occupancy, using maximum likelihood, are presented. A major challenge in these methods is the proper definition of the covariance matrix of the regional binding measures, accounting for different variance of the individual regional measures and their nonzero covariance, factors that have been ignored by conventional methods. The novel methods are compared to standard methods using simulation and real human occupancy data. The simulation data showed the expected reduction in variance and bias using the proper maximum likelihood methods, when the assumptions of the estimation method matched those in simulation. Between-method differences for data from human occupancy studies were less obvious, in part due to small dataset sizes. These maximum likelihood methods form the basis for development of improved PET covariance models, in order to minimize bias and variance in PET occupancy studies.

  19. Estimation of effective wind speed

    Science.gov (United States)

    Østergaard, K. Z.; Brath, P.; Stoustrup, J.

    2007-07-01

    The wind speed has a huge impact on the dynamic response of wind turbine. Because of this, many control algorithms use a measure of the wind speed to increase performance, e.g. by gain scheduling and feed forward. Unfortunately, no accurate measurement of the effective wind speed is online available from direct measurements, which means that it must be estimated in order to make such control methods applicable in practice. In this paper a new method is presented for the estimation of the effective wind speed. First, the rotor speed and aerodynamic torque are estimated by a combined state and input observer. These two variables combined with the measured pitch angle is then used to calculate the effective wind speed by an inversion of a static aerodynamic model.

  20. 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.

  1. Accounting for the drug life cycle and future drug prices in cost-effectiveness analysis.

    Science.gov (United States)

    Hoyle, Martin

    2011-01-01

    Economic evaluations of health technologies typically assume constant real drug prices and model only the cohort of patients currently eligible for treatment. It has recently been suggested that, in the UK, we should assume that real drug prices decrease at 4% per annum and, in New Zealand, that real drug prices decrease at 2% per annum and at patent expiry the drug price falls. It has also recently been suggested that we should model multiple future incident cohorts. In this article, the cost effectiveness of drugs is modelled based on these ideas. Algebraic expressions are developed to capture all costs and benefits over the entire life cycle of a new drug. The lifetime of a new drug in the UK, a key model parameter, is estimated as 33 years, based on the historical lifetime of drugs in England over the last 27 years. Under the proposed methodology, cost effectiveness is calculated for seven new drugs recently appraised in the UK. Cost effectiveness as assessed in the future is also estimated. Whilst the article is framed in mathematics, the findings and recommendations are also explained in non-mathematical language. The 'life-cycle correction factor' is introduced, which is used to convert estimates of cost effectiveness as traditionally calculated into estimates under the proposed methodology. Under the proposed methodology, all seven drugs appear far more cost effective in the UK than published. For example, the incremental cost-effectiveness ratio decreases by 46%, from £61, 900 to £33, 500 per QALY, for cinacalcet versus best supportive care for end-stage renal disease, and by 45%, from £31,100 to £17,000 per QALY, for imatinib versus interferon-α for chronic myeloid leukaemia. Assuming real drug prices decrease over time, the chance that a drug is publicly funded increases over time, and is greater when modelling multiple cohorts than with a single cohort. Using the methodology (compared with traditional methodology) all drugs in the UK and New

  2. 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.

  3. Estimating preferences for modes of drug administration: The case of US healthcare professionals.

    Science.gov (United States)

    Tetteh, Ebenezer K; Morris, Steve; Titchener-Hooker, Nigel

    2018-01-01

    There are hidden drug administration costs that arise from a mismatch between end-user preferences and how manufacturers choose to formulate their drug products for delivery to patients. The corollary of this is: there are "intangible benefits" from considering end-user preferences in manufacturing patient-friendly medicines. It is important then to have some idea of what pharmaceutical manufacturers should consider in making patient-friendly medicines and of the magnitude of the indirect benefits from doing so. This study aimed to evaluate preferences of healthcare professionals in the US for the non-monetary attributes of different modes of drug administration. It uses these preference orderings to compute a monetary valuation of the indirect benefits from making patient-friendly medicines. A survey collected choice preferences of a sample of 210 healthcare professionals in the US for two unlabelled drug options. These drugs were identical except in the levels of attributes of drug administration. Using the choice data collected, statistical models were estimated to compute gross welfare benefits, measured by the expected compensating variation, from making drugs in a more patient-friendly manner. The monetary value of end-user benefits from developing patient-friendly drug delivery systems is: (1) as large as the annual acquisition costs per full treatment episode for some biologic drugs; and (2) likely to fall in the "high end" of the distribution of the direct monetary costs of drug administration. An examination of end-user preferences should help manufacturers make more effective and efficient use of limited resources for innovations in drug delivery system, or manufacturing research in general. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Neurodevelopmental Effects of Antiepileptic Drugs.

    Science.gov (United States)

    Kellogg, Marissa; Meador, Kimford J

    2017-07-01

    Increasing evidence suggests that exposure to certain antiepileptic drugs (AEDs) during critical periods of development may induce transient or long-lasting neurodevelopmental deficits across cognitive, motor and behavioral domains. The developing nervous system may endure prolonged chronic exposure to AEDs during pregnancy (in utero) or during childhood, which can lead to neurodevelopmental defects such as congenital neural tube defects, lower IQ, language deficits, autism and ADHD. To date, valproate is the most widely recognized AED to significantly negatively affect neurodevelopment, and demonstrates greater adverse effects than any other AEDs that have been assessed. Although some AEDs appear to have low risk (i.e., lamotrigine, levetiracetam), other AEDs have been implicated in a variety of studies detailed below, and many AEDs have not been adequately assessed. The purpose of this review article is to summarize our current understanding of the neurodevelopmental effects of AEDs.

  5. The effects of drugs on nutrition

    African Journals Online (AJOL)

    Drug treatment can have a detrimental effect on nutritional status and drugs ... non-prescription medication dispensed due to chronic diseases such ... and cytochrome P450 in the liver, lungs and small intestine and ... Alcoholic beverages.

  6. 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.

  7. Drug Repositioning for Effective Prostate Cancer Treatment.

    Science.gov (United States)

    Turanli, Beste; Grøtli, Morten; Boren, Jan; Nielsen, Jens; Uhlen, Mathias; Arga, Kazim Y; Mardinoglu, Adil

    2018-01-01

    Drug repositioning has gained attention from both academia and pharmaceutical companies as an auxiliary process to conventional drug discovery. Chemotherapeutic agents have notorious adverse effects that drastically reduce the life quality of cancer patients so drug repositioning is a promising strategy to identify non-cancer drugs which have anti-cancer activity as well as tolerable adverse effects for human health. There are various strategies for discovery and validation of repurposed drugs. In this review, 25 repurposed drug candidates are presented as result of different strategies, 15 of which are already under clinical investigation for treatment of prostate cancer (PCa). To date, zoledronic acid is the only repurposed, clinically used, and approved non-cancer drug for PCa. Anti-cancer activities of existing drugs presented in this review cover diverse and also known mechanisms such as inhibition of mTOR and VEGFR2 signaling, inhibition of PI3K/Akt signaling, COX and selective COX-2 inhibition, NF-κB inhibition, Wnt/β-Catenin pathway inhibition, DNMT1 inhibition, and GSK-3β inhibition. In addition to monotherapy option, combination therapy with current anti-cancer drugs may also increase drug efficacy and reduce adverse effects. Thus, drug repositioning may become a key approach for drug discovery in terms of time- and cost-efficiency comparing to conventional drug discovery and development process.

  8. 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)

  9. Analysing Drug Oversue in a Prescription database: estimation Method Matters

    DEFF Research Database (Denmark)

    Andersen, Morten; Søndergaard, Jens

    2004-01-01

    20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:159......20 th International Conference on Pharmacoepiemiology and Risk Management. Bordeaux, France. Pharmacoepidemiology and Drug Safety, 2004;13:Sl 1:159...

  10. The Effects of Psychotropic Drugs.

    Science.gov (United States)

    Bonnardeaux, Jef-Louis

    1984-01-01

    Presents information on psychotropic drugs for individuals who are not specialists in pharmacology. Discusses: alcohol and barbituates; dependence and withdrawal; central nervous system depressors (anaesthetics, narcotic analgesics, sedatives and hypnotic drugs, tranquilizers), central nervous stimulants (amphetamines, cocaine, tobacco, caffeine),…

  11. [Management of adverse drug effects].

    Science.gov (United States)

    Schlienger, R G

    2000-09-01

    Adverse drug reactions (ADRs) are still considered one of the main problems of drug therapy. ADRs are associated with considerable morbidity, mortality, decreased compliance and therapeutic success as well as high direct and indirect medical costs. Several considerations have to come into play when managing a potential ADR. It is critical to establish an accurate clinical diagnosis of the adverse event. Combining information about drug exposure together with considering other possible causes of the reaction is crucial to establish a causal relationship between the reaction and the suspected drug. Identification of the underlying pathogenesis of an ADR together with the severity of the reaction will have profound implications on continuation of drug therapy after an ADR. Since spontaneous reports about ADRs are a key stone of a functioning post-marketing surveillance system and therefore play a key role in improving drug safety, health care professionals are highly encouraged to report ADRs to a local or national organization. However, because the majority of ADRs is dose-dependent and therefore preventable, individualization of pharmacotherapy may have a major impact on reducing such events.

  12. Mechanistic models enable the rational use of in vitro drug-target binding kinetics for better drug effects in patients.

    Science.gov (United States)

    de Witte, Wilhelmus E A; Wong, Yin Cheong; Nederpelt, Indira; Heitman, Laura H; Danhof, Meindert; van der Graaf, Piet H; Gilissen, Ron A H J; de Lange, Elizabeth C M

    2016-01-01

    Drug-target binding kinetics are major determinants of the time course of drug action for several drugs, as clearly described for the irreversible binders omeprazole and aspirin. This supports the increasing interest to incorporate newly developed high-throughput assays for drug-target binding kinetics in drug discovery. A meaningful application of in vitro drug-target binding kinetics in drug discovery requires insight into the relation between in vivo drug effect and in vitro measured drug-target binding kinetics. In this review, the authors discuss both the relation between in vitro and in vivo measured binding kinetics and the relation between in vivo binding kinetics, target occupancy and effect profiles. More scientific evidence is required for the rational selection and development of drug-candidates on the basis of in vitro estimates of drug-target binding kinetics. To elucidate the value of in vitro binding kinetics measurements, it is necessary to obtain information on system-specific properties which influence the kinetics of target occupancy and drug effect. Mathematical integration of this information enables the identification of drug-specific properties which lead to optimal target occupancy and drug effect in patients.

  13. Intracellular Drug Bioavailability: Effect of Neutral Lipids and Phospholipids.

    Science.gov (United States)

    Treyer, Andrea; Mateus, André; Wiśniewski, Jacek R; Boriss, Hinnerk; Matsson, Pär; Artursson, Per

    2018-06-04

    Intracellular unbound drug concentrations are the pharmacologically relevant concentrations for targets inside cells. Intracellular drug concentrations are determined by multiple processes, including the extent of drug binding to intracellular structures. The aim of this study was to evaluate the effect of neutral lipid (NL) and phospholipid (PL) levels on intracellular drug disposition. The NL and/or PL content of 3T3-L1 cells were enhanced, resulting in phenotypes (in terms of morphology and proteome) reminiscent of adipocytes (high NL and PL) or mild phospholipidosis (only high PL). Intracellular bioavailability ( F ic ) was then determined for 23 drugs in these cellular models and in untreated wild-type cells. A higher PL content led to higher intracellular drug binding and a lower F ic . The induction of NL did not further increase drug binding but led to altered F ic due to increased lysosomal pH. Further, there was a good correlation between binding to beads coated with pure PL and intracellular drug binding. In conclusion, our results suggest that PL content is a major determinant of drug binding in cells and that PL beads may constitute a simple alternative to estimating this parameter. Further, the presence of massive amounts of intracellular NLs did not influence drug binding significantly.

  14. 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 ...

  15. 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...

  16. 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...

  17. 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.

  18. Hallucinatory Side Effects of ADHD Drugs

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-04-01

    Full Text Available Clinical trial and postmarketing surveillance data for drugs used in treatment of attention deficit hyperactivity disorder were analyzed to determine the frequency of hallucinations and other psychotic side effects, in a study at the US Food and Drug Administration, and Department of Health and Human Services, Maryland.

  19. Weighing up crime: the over estimation of drug-related crime

    OpenAIRE

    Stevens, Alex

    2008-01-01

    Background: It is generally accepted that harms from crime cause a very large part of the total social harm that can be attributed to drug use. For example, crime harms accounted for 70% of the weighting of the British Drug Harm Index in 2004. This paper explores the linkage of criminal harm to drug use and challenges the current overestimation of the proportion of crime that can be causally attributed to drug use. It particularly examines the use of data from arrested drug users to estimate ...

  20. Reference drug programs: Effectiveness and policy implications☆

    Science.gov (United States)

    Schneeweiss, Sebastian

    2010-01-01

    In the current economic environment, health care systems are constantly struggling to contain rapidly rising costs. Drug costs are targeted by a wide variety of measures. Many jurisdictions have implemented reference drug programs (RDPs) or similar therapeutic substitution programs. This paper summarizes the mechanism and rationale of RDPs and presents evidence of their economic effectiveness and clinical safety. RDPs for pharmaceutical reimbursement are based on the assumption that drugs within specified medication groups are therapeutically equivalent and clinically interchangeable and that a common reimbursement level can thus be established. If the evidence documents that a higher price for a given drug does not buy greater effectiveness or reduced toxicity, then under RDP such extra costs are not covered. RDPs or therapeutic substitutions based on therapeutic equivalence are seen as logical extensions of generic substitution that is based on bioequivalence of drugs. If the goal is to achieve full drug coverage for as many patients as possible in the most efficient manner, then RDPs in combination with prior authorization programs are safer and more effective than simplistic fiscal drug policies, including fixed co-payments, co-insurances, or deductibles. RDPs will reduce spending in the less innovative but largest market, while fully covering all patients. Prior authorization will ensure that patients with a specified indication will benefit from the most innovative therapies with full coverage. In practice, however, not all patients and drugs will fit exactly into one of the two categories. Therefore, a process of medically indicated exemptions that will consider full coverage should accompany an RDP. In the current economic environment, health care systems are constantly struggling to contain rapidly rising costs. Drug costs are targeted by a wide variety of measures. Many jurisdictions have implemented reference drug programs, and others are considering

  1. 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 ...

  2. Unifying Theories of Psychedelic Drug Effects

    Directory of Open Access Journals (Sweden)

    Link R. Swanson

    2018-03-01

    Full Text Available 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.

  3. 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

  4. Estimating pharmacy level prescription drug acquisition costs for third-party reimbursement.

    Science.gov (United States)

    Kreling, D H; Kirk, K W

    1986-07-01

    Accurate payment for the acquisition costs of drug products dispensed is an important consideration in a third-party prescription drug program. Two alternative methods of estimating these costs among pharmacies were derived and compared. First, pharmacists were surveyed to determine the purchase discounts offered to them by wholesalers. A 10.00% modal and 11.35% mean discount resulted for 73 responding pharmacists. Second, cost-plus percents derived from gross profit margins of wholesalers were calculated and applied to wholesaler product costs to estimate pharmacy level acquisition costs. Cost-plus percents derived from National Median and Southwestern Region wholesaler figures were 9.27% and 10.10%, respectively. A comparison showed the two methods of estimating acquisition costs would result in similar acquisition cost estimates. Adopting a cost-plus estimating approach is recommended because it avoids potential pricing manipulations by wholesalers and manufacturers that would negate improvements in drug product reimbursement accuracy.

  5. 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...

  6. 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.

  7. 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.

  8. A practical approach to risk-benefit estimation in pediatric drug research.

    Science.gov (United States)

    Koren, Gideon

    2015-02-01

    One of the most difficult challenges in pediatric drug research is in exposing children to risk, often without a balanced chance of benefits. While the concept of risk is similar in adult research, the adult patient can decide for himself/herself on an acceptable level of risk, whereas children have to accept the decisions of their guardians. This paper attempts to put the complexities of estimating risk in pediatric drug research into their practical perspective, and to familiarize the reader with the way such processes are conducted in different parts of the world. Although there are regional differences, all authorities typically quantify risks of pediatric research in general, and drug research in particular, in three levels: those experienced in day-to-day life; risks slightly above this 'baseline' risk; and risks substantially above 'baseline risk'. Proportionally, the diligence of the ethics process depends on these levels, as well as on the potential benefits (or lack of) to the child involved in the research. Importantly, risk is context dependent, and a particular intervention may be effective or safe in one setting but not in another, based on local experience, staffing levels, and similar variabilities.

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

    DEFF Research Database (Denmark)

    Kuhn, Michael; Campillos, Monica; Letunic, Ivica

    2010-01-01

    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...

  10. 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...

  11. 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...

  12. Stop Negative Thinking Effects for Drug Dependence

    OpenAIRE

    Windiarti, Sri Endang; Indriati, Indriati; Surachmi, Fajar

    2013-01-01

    The purpose of this study was to determine the effect of therapy stop thinking negatively against drug addiction in Rehabilitation Orphanage Rumah Damai Gunung Pati Semarang. This research is quasy experiment with pretest - posttes without the control group design. Thirty respondents were taken to the reseach sujects. Stop thinking negative therapy before and after thebehavior of drug addiction there are differences (t = 0.00), so it can be stated that the therapy stop thinking negatively inf...

  13. Estimating network effects in China's mobile telecommunications

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    A model is proposed along with empirical investigation to prove the existence of network effects in China's mobile telecommunications market. Futhernore, network effects on China's mobile telecommunications are estimated with a dynamic model. The structural parameters are identified from regression coefficients and the results are analyzed and compared with another literature. Data and estimation issues are also discussed. Conclusions are drawn that network effects are significant in China's mobile telecommunications market, and that ignoring network effects leads to bad policy making.

  14. The nocebo effect of drugs.

    Science.gov (United States)

    Planès, Sara; Villier, Céline; Mallaret, Michel

    2016-04-01

    While the placebo effect has been studied for a long time, much less is known about its negative counterpart, named the nocebo effect. However, it may be of particular importance because of its impact on the treatment outcomes and public health. We conducted a review on the nocebo effect using PubMed and other databases up to July 2014. The nocebo effect refers by definition to the induction or the worsening of symptoms induced by sham or active therapies. Examples are numerous and concerns both clinical trials and daily practice. The underlying mechanisms are, on one hand, psychological (conditioning and negative expectations) and, on the other hand, neurobiological (role of cholecystokinin, endogenous opioids and dopamine). Nocebo effects can modulate the outcome of a given therapy in a negative way, as do placebo effects in a positive way. The verbal and nonverbal communications of physicians contain numerous unintentional negative suggestions that may trigger a nocebo response. This raises the important issue of how physicians can at the same time obtain informed consent and minimize nocebo-related risks. Every physician has to deal with this apparent contradiction between primum non nocere and to deliver truthful information about risks. Meticulous identification of patients at risk, information techniques such as positive framing, contextualized informed consent, and even noninformation, is valuable.

  15. A paradigm shift in pharmacokinetic-pharmacodynamic (PKPD) modeling: rule of thumb for estimating free drug level in tissue compared with plasma to guide drug design.

    Science.gov (United States)

    Poulin, Patrick

    2015-07-01

    A basic assumption in pharmacokinetics-pharmacodynamics research is that the free drug concentration is similar in plasma and tissue, and, hence, in vitro plasma data can be used to estimate the in vivo condition in tissue. However, in a companion manuscript, it has been demonstrated that this assumption is violated for the ionized drugs. Nonetheless, these observations focus on in vitro static environments and do not challenge data with an in vivo dynamic system. Therefore, an extension from an in vitro to an in vivo system becomes the necessary next step. The objective of this study was to perform theoretical simulations of the free drug concentration in tissue and plasma by using a physiologically based pharmacokinetics (PBPK) model reproducing the in vivo conditions in human. Therefore, the effects of drug ionization, lipophilicity, and clearance have been taken into account in a dynamic system. This modeling exercise was performed as a proof of concept to demonstrate that free drug concentration in tissue and plasma may also differ in a dynamic system for passively permeable drugs that are ionized at the physiological pH. The PBPK model simulations indicated that free drug concentrations in tissue cells and plasma significantly differ for the ionized drugs because of the pH gradient effect between cells and interstitial space. Hence, a rule of thumb for potentially performing more accurate PBPK/PD modeling is suggested, which states that the free drug concentration in tissue and plasma will differ for the ionizable drugs in contrast to the neutral drugs. In addition to the pH gradient effect for the ionizable drugs, lipophilicity and clearance effects will increase or decrease the free drug concentration in tissue and plasma for each class of drugs; thus, higher will be the drug lipophilicity and clearance, lower would be the free drug concentration in plasma, and, hence, in tissue, in a dynamic in vivo system. Therefore, only considering the value of free

  16. PockDrug: A Model for Predicting Pocket Druggability That Overcomes Pocket Estimation Uncertainties.

    Science.gov (United States)

    Borrel, Alexandre; Regad, Leslie; Xhaard, Henri; Petitjean, Michel; Camproux, Anne-Claude

    2015-04-27

    Predicting protein druggability is a key interest in the target identification phase of drug discovery. Here, we assess the pocket estimation methods' influence on druggability predictions by comparing statistical models constructed from pockets estimated using different pocket estimation methods: a proximity of either 4 or 5.5 Å to a cocrystallized ligand or DoGSite and fpocket estimation methods. We developed PockDrug, a robust pocket druggability model that copes with uncertainties in pocket boundaries. It is based on a linear discriminant analysis from a pool of 52 descriptors combined with a selection of the most stable and efficient models using different pocket estimation methods. PockDrug retains the best combinations of three pocket properties which impact druggability: geometry, hydrophobicity, and aromaticity. It results in an average accuracy of 87.9% ± 4.7% using a test set and exhibits higher accuracy (∼5-10%) than previous studies that used an identical apo set. In conclusion, this study confirms the influence of pocket estimation on pocket druggability prediction and proposes PockDrug as a new model that overcomes pocket estimation variability.

  17. 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.

  18. 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.

  19. The Drug Effects Questionnaire: Psychometric Support across Three Drug Types

    Science.gov (United States)

    Morean, Meghan E.; de Wit, Harriet; King, Andrea C.; Sofuoglu, Mehmet; Rueger, Sandra Y.; O’Malley, Stephanie S.

    2013-01-01

    Rationale The Drug Effects Questionnaire (DEQ) is widely used in studies of acute subjective response (SR) to a variety of substances, but the format of the DEQ varies widely across studies, and details of its psychometric properties are lacking. Thus, the field would benefit from demonstrating the reliability and validity of the DEQ for use across multiple substances. Objective The current study evaluated the psychometric properties of several variations of DEQ items, which assessed the extent to which participants (1) feel any substance effect(s), (2) feel high, (3) like the effects, (4) dislike the effects, and (5) want more of the substance using 100mm Visual Analog Scales. Methods DEQ data from three placebo-controlled studies were analyzed to examine SR to amphetamine, nicotine, and alcohol. We evaluated the internal structure of the DEQ for use with each substance as well as relationships between scale items, measures of similar constructs, and substance-related behaviors. Results Results provided preliminary psychometric support for items assessing each DEQ construct (FEEL, HIGH, DISLIKE, LIKE, and MORE). Conclusions Based on the study results, we identify several common limitations of extant variants of the DEQ and recommend an improved version of the measure. The simplicity and brevity of the DEQ combined with its promising psychometric properties support its use in future SR research across a variety of substances. PMID:23271193

  20. 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.

  1. Sex, Drugs, and Cognition: Effects of Marijuana†

    OpenAIRE

    Anderson, Beth M.; Rizzo, Matthew; Block, Robert I.; Pearlson, Godfrey D.; O'Leary, Daniel S.

    2010-01-01

    Despite the knowledge that many drugs affect men and women differently, few studies exploring the effects of marijuana use on cognition have included women. Findings from both animal and human studies suggest marijuana may have more marked effects in women. This study examined sex differences in the acute effects of marijuana on cognition in 70 (n= 35 male, 35 female) occasional users of marijuana. Tasks were chosen to tap a wide variety of cognitive domains affected by sex and/or marijuana i...

  2. 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, ...

  3. Effecting attitudinal change towards rational drug use.

    Science.gov (United States)

    Singh, T; Natu, M V

    1995-01-01

    Attitudes of 40 interns towards rational drug use (RDU) were assessed, using a standardized Likert type scale. The assessment was repeated after 4 months to evaluate the effect of usual working conditions of the hospital. After this period, the attitudes had slided towards negative side (p attitudes of test group returned towards positive side (p attitudes.

  4. In search of a corrected prescription drug elasticity estimate: a meta-regression approach.

    Science.gov (United States)

    Gemmill, Marin C; Costa-Font, Joan; McGuire, Alistair

    2007-06-01

    An understanding of the relationship between cost sharing and drug consumption depends on consistent and unbiased price elasticity estimates. However, there is wide heterogeneity among studies, which constrains the applicability of elasticity estimates for empirical purposes and policy simulation. This paper attempts to provide a corrected measure of the drug price elasticity by employing meta-regression analysis (MRA). The results indicate that the elasticity estimates are significantly different from zero, and the corrected elasticity is -0.209 when the results are made robust to heteroskedasticity and clustering of observations. Elasticity values are higher when the study was published in an economic journal, when the study employed a greater number of observations, and when the study used aggregate data. Elasticity estimates are lower when the institutional setting was a tax-based health insurance system.

  5. 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...

  6. 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.

  7. 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.

  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. 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.

  10. Health effects estimation for contaminated properties

    International Nuclear Information System (INIS)

    Marks, S.; Denham, D.H.; Cross, F.T.; Kennedy, W.E. Jr.

    1984-05-01

    As part of an overall remedial action program to evaluate the need for and institute actions designed to minimize health hazards from inactive tailings piles and from displaced tailings, methods for estimating health effects from tailings were developed and applied to the Salt Lake City area. 2 references, 2 tables

  11. 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.

  12. 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

  13. Estimating the effects of wages on obesity.

    Science.gov (United States)

    Kim, DaeHwan; Leigh, John Paul

    2010-05-01

    To estimate the effects of wages on obesity and body mass. Data on household heads, aged 20 to 65 years, with full-time jobs, were drawn from the Panel Study of Income Dynamics for 2003 to 2007. The Panel Study of Income Dynamics is a nationally representative sample. Instrumental variables (IV) for wages were created using knowledge of computer software and state legal minimum wages. Least squares (linear regression) with corrected standard errors were used to estimate the equations. Statistical tests revealed both instruments were strong and tests for over-identifying restrictions were favorable. Wages were found to be predictive (P low wages increase obesity prevalence and body mass.

  14. The Economic Side Effects of Dangerous Drug Announcements.

    OpenAIRE

    Dranove, David; Olsen, Chris

    1994-01-01

    Immediately prior to the passage of the 1962 Food and Drug Administration Amendments, there were a number of drugs recalled from markets worldwide. Announcements about the dangerous side effects of these drugs were associated with lower-share prices for their manufacturers and the industry as a whole. We perform several analyses to sort out alternative explanations for the observed declines. We find that dangerous drug announcements had no effect on the sales of other drugs and didn't affect ...

  15. 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...

  16. 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

  17. 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...... who were under follow-up on ART at 1 July 2008 was therefore developed by imputing data on patients with no prior resistance test results, based on the probability of detecting resistance in tested patients with similar profiles....

  18. [Effect of speech estimation on social anxiety].

    Science.gov (United States)

    Shirotsuki, Kentaro; Sasagawa, Satoko; Nomura, Shinobu

    2009-02-01

    This study investigates the effect of speech estimation on social anxiety to further understanding of this characteristic of Social Anxiety Disorder (SAD). In the first study, we developed the Speech Estimation Scale (SES) to assess negative estimation before giving a speech which has been reported to be the most fearful social situation in SAD. Undergraduate students (n = 306) completed a set of questionnaires, which consisted of the Short Fear of Negative Evaluation Scale (SFNE), the Social Interaction Anxiety Scale (SIAS), the Social Phobia Scale (SPS), and the SES. Exploratory factor analysis showed an adequate one-factor structure with eight items. Further analysis indicated that the SES had good reliability and validity. In the second study, undergraduate students (n = 315) completed the SFNE, SIAS, SPS, SES, and the Self-reported Depression Scale (SDS). The results of path analysis showed that fear of negative evaluation from others (FNE) predicted social anxiety, and speech estimation mediated the relationship between FNE and social anxiety. These results suggest that speech estimation might maintain SAD symptoms, and could be used as a specific target for cognitive intervention in SAD.

  19. Estimating scaled treatment effects with multiple outcomes.

    Science.gov (United States)

    Kennedy, Edward H; Kangovi, Shreya; Mitra, Nandita

    2017-01-01

    In classical study designs, the aim is often to learn about the effects of a treatment or intervention on a single outcome; in many modern studies, however, data on multiple outcomes are collected and it is of interest to explore effects on multiple outcomes simultaneously. Such designs can be particularly useful in patient-centered research, where different outcomes might be more or less important to different patients. In this paper, we propose scaled effect measures (via potential outcomes) that translate effects on multiple outcomes to a common scale, using mean-variance and median-interquartile range based standardizations. We present efficient, nonparametric, doubly robust methods for estimating these scaled effects (and weighted average summary measures), and for testing the null hypothesis that treatment affects all outcomes equally. We also discuss methods for exploring how treatment effects depend on covariates (i.e., effect modification). In addition to describing efficiency theory for our estimands and the asymptotic behavior of our estimators, we illustrate the methods in a simulation study and a data analysis. Importantly, and in contrast to much of the literature concerning effects on multiple outcomes, our methods are nonparametric and can be used not only in randomized trials to yield increased efficiency, but also in observational studies with high-dimensional covariates to reduce confounding bias.

  20. 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…

  1. 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....

  2. Estimating network effect in geocenter motion: Theory

    Science.gov (United States)

    Zannat, Umma Jamila; Tregoning, Paul

    2017-10-01

    Geophysical models and their interpretations of several processes of interest, such as sea level rise, postseismic relaxation, and glacial isostatic adjustment, are intertwined with the need to realize the International Terrestrial Reference Frame. However, this realization needs to take into account the geocenter motion, that is, the motion of the center of figure of the Earth surface, due to, for example, deformation of the surface by earthquakes or hydrological loading effects. Usually, there is also a discrepancy, known as the network effect, between the theoretically convenient center of figure and the physically accessible center of network frames, because of unavoidable factors such as uneven station distribution, lack of stations in the oceans, disparity in the coverage between the two hemispheres, and the existence of tectonically deforming zones. Here we develop a method to estimate the magnitude of the network effect, that is, the error introduced by the incomplete sampling of the Earth surface, in measuring the geocenter motion, for a network of space geodetic stations of a fixed size N. For this purpose, we use, as our proposed estimate, the standard deviations of the changes in Helmert parameters measured by a random network of the same size N. We show that our estimate scales as 1/√N and give an explicit formula for it in terms of the vector spherical harmonics expansion of the displacement field. In a complementary paper we apply this formalism to coseismic displacements and elastic deformations due to surface water movements.

  3. 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.

  4. 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

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

    Science.gov (United States)

    Kindermans, Jean-Marie; Vandenbergh, Daniel; Vreeke, Ed; Olliaro, Piero; D'Altilia, Jean-Pierre

    2007-07-10

    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. 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. 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). Additional studies are required to build a more robust methodology, and to assess current consumptions more accurately in order to better quantify volumes and finances for

  6. 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.

  7. Derivative Spectrophotometric Method for Estimation of Antiretroviral Drugs in Fixed Dose Combinations

    Science.gov (United States)

    P.B., Mohite; R.B., Pandhare; S.G., Khanage

    2012-01-01

    Purpose: Lamivudine is cytosine and zidovudine is cytidine and is used as an antiretroviral agents. Both drugs are available in tablet dosage forms with a dose of 150 mg for LAM and 300 mg ZID respectively. Method: The method employed is based on first order derivative spectroscopy. Wavelengths 279 nm and 300 nm were selected for the estimation of the Lamovudine and Zidovudine respectively by taking the first order derivative spectra. The conc. of both drugs was determined by proposed method. The results of analysis have been validated statistically and by recovery studies as per ICH guidelines. Result: Both the drugs obey Beer’s law in the concentration range 10-50 μg mL-1,for LAM and ZID; with regression 0.9998 and 0.9999, intercept – 0.0677 and – 0.0043 and slope 0.0457 and 0.0391 for LAM and ZID, respectively.The accuracy and reproducibility results are close to 100% with 2% RSD. Conclusion: A simple, accurate, precise, sensitive and economical procedures for simultaneous estimation of Lamovudine and Zidovudine in tablet dosage form have been developed. PMID:24312779

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

    African Journals Online (AJOL)

    Effect of Contemporary Social Environment, Drug Abuse and Cultism on the Health of ... This health situation comes as results of substance abuse which these ... the patent medicine stores, from hard drugs like (marijuana, cannabis) or others ...

  9. 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.

  10. Bayesian estimation of dose rate effectiveness

    International Nuclear Information System (INIS)

    Arnish, J.J.; Groer, P.G.

    2000-01-01

    A Bayesian statistical method was used to quantify the effectiveness of high dose rate 137 Cs gamma radiation at inducing fatal mammary tumours and increasing the overall mortality rate in BALB/c female mice. The Bayesian approach considers both the temporal and dose dependence of radiation carcinogenesis and total mortality. This paper provides the first direct estimation of dose rate effectiveness using Bayesian statistics. This statistical approach provides a quantitative description of the uncertainty of the factor characterising the dose rate in terms of a probability density function. The results show that a fixed dose from 137 Cs gamma radiation delivered at a high dose rate is more effective at inducing fatal mammary tumours and increasing the overall mortality rate in BALB/c female mice than the same dose delivered at a low dose rate. (author)

  11. 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

  12. Estimating Drug Costs: How do Manufacturer Net Prices Compare with Other Common US Price References?

    Science.gov (United States)

    Mattingly, T Joseph; Levy, Joseph F; Slejko, Julia F; Onwudiwe, Nneka C; Perfetto, Eleanor M

    2018-05-12

    Drug costs are frequently estimated in economic analyses using wholesale acquisition cost (WAC), but what is the best approach to develop these estimates? Pharmaceutical manufacturers recently released transparency reports disclosing net price increases after accounting for rebates and other discounts. Our objective was to determine whether manufacturer net prices (MNPs) could approximate the discounted prices observed by the U.S. Department of Veterans Affairs (VA). We compared the annual, average price discounts voluntarily reported by three pharmaceutical manufacturers with the VA price for specific products from each company. The top 10 drugs by total sales reported from company tax filings for 2016 were included. The discount observed by the VA was determined from each drug's list price, reported as WAC, in 2016. Descriptive statistics were calculated for the VA discount observed and a weighted price index was calculated using the lowest price to the VA (Weighted VA Index), which was compared with the manufacturer index. The discounted price as a percentage of the WAC ranged from 9 to 74%. All three indexes estimated by the average discount to the VA were at or below the manufacturer indexes (42 vs. 50% for Eli Lilly, 56 vs. 65% for Johnson & Johnson, and 59 vs. 59% for Merck). Manufacturer-reported average net prices may provide a close approximation of the average discounted price granted to the VA, suggesting they may be a useful proxy for the true pharmacy benefits manager (PBM) or payer cost. However, individual discounts for products have wide variation, making a standard discount adjustment across multiple products less acceptable.

  13. 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....

  14. 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...

  15. 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.

  16. 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)

  17. 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.

  18. 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.

  19. 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.

  20. 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, ...

  1. 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.

  2. 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…

  3. A Novel Drug-Mouse Phenotypic Similarity Method Detects Molecular Determinants of Drug Effects.

    Directory of Open Access Journals (Sweden)

    Jeanette Prinz

    2016-09-01

    Full Text Available The molecular mechanisms that translate drug treatment into beneficial and unwanted effects are largely unknown. We present here a novel approach to detect gene-drug and gene-side effect associations based on the phenotypic similarity of drugs and single gene perturbations in mice that account for the polypharmacological property of drugs. We scored the phenotypic similarity of human side effect profiles of 1,667 small molecules and biologicals to profiles of phenotypic traits of 5,384 mouse genes. The benchmarking with known relationships revealed a strong enrichment of physical and indirect drug-target connections, causative drug target-side effect links as well as gene-drug links involved in pharmacogenetic associations among phenotypically similar gene-drug pairs. The validation by in vitro assays and the experimental verification of an unknown connection between oxandrolone and prokineticin receptor 2 reinforces the ability of this method to provide new molecular insights underlying drug treatment. Thus, this approach may aid in the proposal of novel and personalized treatments.

  4. The role of drug profiles as similarity metrics: applications to repurposing, adverse effects detection and drug-drug interactions.

    Science.gov (United States)

    Vilar, Santiago; Hripcsak, George

    2017-07-01

    Explosion of the availability of big data sources along with the development in computational methods provides a useful framework to study drugs' actions, such as interactions with pharmacological targets and off-targets. Databases related to protein interactions, adverse effects and genomic profiles are available to be used for the construction of computational models. In this article, we focus on the description of biological profiles for drugs that can be used as a system to compare similarity and create methods to predict and analyze drugs' actions. We highlight profiles constructed with different biological data, such as target-protein interactions, gene expression measurements, adverse effects and disease profiles. We focus on the discovery of new targets or pathways for drugs already in the pharmaceutical market, also called drug repurposing, in the interaction with off-targets responsible for adverse reactions and in drug-drug interaction analysis. The current and future applications, strengths and challenges facing all these methods are also discussed. Biological profiles or signatures are an important source of data generation to deeply analyze biological actions with important implications in drug-related studies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Can the use of psychoactive drugs in the general adult population be estimated based on data from a roadside survey of drugs and driving?

    Directory of Open Access Journals (Sweden)

    Hallvard Gjerde

    2011-12-01

    Full Text Available A roadside survey of drugs and driving was performed in south-eastern Norway in 2005-6. Samples of saliva from a total of 10,503 drivers above 20 years of age were analysed, and the results were weighted for under- and over-sampling compared to the population distribution in the study area. Weighted results were compared with data on dispensed prescriptions of zopiclone, codeine and diazepam at Norwegian pharmacies in the same area and with self-reported use of cannabis. When using roadside data to estimate drug use, the use of medicinal drugs was under-estimated by 17-59% compared to amounts dispensed. One of the main reasons for the under-estimation may be that a large proportion of the users of psychoactive medicinal drugs are not frequent drivers. For cannabis, self-reported data corresponded approximately to the estimated prevalence range. The results indicate that roadside surveys cannot be used for accurate estima tions of drug use in the population, but may provide minimum figures.

  6. 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.

  7. 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.

  8. Anti-VEGF drugs: evidence for effectiveness

    OpenAIRE

    Evans, Jennifer; Virgili, Gianni

    2014-01-01

    Anti-vascular endothelial growth factors (anti-VEGF) are targeted biological drugs (e.g. monoclonal antibodies) that prevent the growth of new vessels by inhibiting VEGF. VEGF is a cytokine (cell-signalling protein) that promotes the growth of, and leakage from, new vessels. Currently there are three anti-VEGF drugs licensed for use in eye disease: pegaptanib, aflibercept, ranibizumab and one that is not licensed but is commonly used off-label (bevacizumab).

  9. 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 ...

  10. 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.

  11. 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)

  12. 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.

  13. 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

  14. 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.

  15. 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......% of which can be compared to the frequency under placebo treatment. SIDER furthermore contains a data set of drug indications, extracted from the package inserts using Natural Language Processing. These drug indications are used to reduce the rate of false positives by identifying medical terms that do...

  16. 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.

  17. Anxiety and dysthymia: local prevalence estimates based on drug prescriptions by general practitioners in Turin (Italy).

    Science.gov (United States)

    Mamo, C; Farina, E; Cicio, R; Fanì, M

    2014-01-01

    The aim of the study was to obtain local estimates of the prevalence of anxiety and dysthymic disorders among attendees of primary care at local level, useful to pursue a better management of the health care services. The study was conducted in the Health District no. 2 of Turin (industrial town in northwest Italy). The criteria for identification of cases were based on the drugs prescriptions made by general practitioners (GPs), selected in order to assure high specificity. The study involved 86 physicians (with 87,885 attendees). As expected, the crude and standardized prevalences were higher in women (anxiety: 2.9% vs 1.3% in men; dysthymia: 3.8% vs 1.7% in men), with a peak in women aged over 75 yrs (anxiety: 4.8%; dysthymia: 6.2%). In comparison to male GPs, female GPs had an higher prevalence of patients with anxious disorders, whereas the prevalences of dysthymia were similar. Despite the discussed limitations, the used methodology allows to obtain sufficiently reliable estimates of prevalence of common mental disorders at local level, providing informations useful for organizing the primary care in the Health district.

  18. Quantifying the effects of antiangiogenic and chemotherapy drug combinations on drug delivery and treatment efficacy.

    Science.gov (United States)

    Yonucu, Sirin; Yιlmaz, Defne; Phipps, Colin; Unlu, Mehmet Burcin; Kohandel, Mohammad

    2017-09-01

    Tumor-induced angiogenesis leads to the development of leaky tumor vessels devoid of structural and morphological integrity. Due to angiogenesis, elevated interstitial fluid pressure (IFP) and low blood perfusion emerge as common properties of the tumor microenvironment that act as barriers for drug delivery. In order to overcome these barriers, normalization of vasculature is considered to be a viable option. However, insight is needed into the phenomenon of normalization and in which conditions it can realize its promise. In order to explore the effect of microenvironmental conditions and drug scheduling on normalization benefit, we build a mathematical model that incorporates tumor growth, angiogenesis and IFP. We administer various theoretical combinations of antiangiogenic agents and cytotoxic nanoparticles through heterogeneous vasculature that displays a similar morphology to tumor vasculature. We observe differences in drug extravasation that depend on the scheduling of combined therapy; for concurrent therapy, total drug extravasation is increased but in adjuvant therapy, drugs can penetrate into deeper regions of tumor.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. Effectiveness of hepatoprotective drugs for anti-tuberculosis drug-induced hepatotoxicity: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Zenya Saito

    2016-11-01

    Full Text Available Abstract Background The effectiveness of hepatoprotective drugs for DIH (drug induced hepatotoxicity during tuberculosis treatment is not clear. We evaluated the effectiveness of hepatoprotective drugs by comparing the period until the normalization of hepatic enzymes between patients who were prescribed with the hepatoprotective drugs after DIH was occurred and patients who were not prescribed with the hepatoprotective drugs. Methods During 2006–2010, 389 patients with active tuberculosis were included in this study. DIH was defined as elevation of peak serum aspartate aminotransferase (AST and/or alanine aminotransferase (ALT of more than twice the upper limit of normal (ULN. We divided the patients into the severe (peak serum AST and/or ALT elevation of >5 times the ULN, moderate (peak serum AST and/or ALT elevation of >3 to ≤5 times the ULN, and mild DIH groups (peak serum AST and/or ALT elevation of >2 to ≤3 times the ULN. We compared the average period until the normalization of hepatic enzymes between patient subgroups with and without hepatoprotective drugs (ursodeoxycholic acid: UDCA, stronger neo-minophagen C: SNMC, and glycyrrhizin. Results In the severe group, there was no significant difference in the average period until the normalization between subgroups with and without hepatoprotective drugs (21.4 ± 10.8 vs 21.5 ± 11.1 days, P = 0.97. In the mild group, the period was longer in the subgroup with hepatoprotective drugs than that without hepatoprotective drugs (15.7 ± 6.2 vs 12.4 ± 7.9 days, P = 0.046. Conclusion Regardless of the severity, hepatoprotective drugs did not shorten the period until the normalization of hepatic enzymes.

  5. 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...

  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. Cost-effectiveness and pricing of antibacterial drugs.

    Science.gov (United States)

    Verhoef, Talitha I; Morris, Stephen

    2015-01-01

    Growing resistance to antibacterial agents has increased the need for the development of new drugs to treat bacterial infections. Given increasing pressure on limited health budgets, it is important to study the cost-effectiveness of these drugs, as well as their safety and efficacy, to find out whether or not they provide value for money and should be reimbursed. In this article, we systematically reviewed 38 cost-effectiveness analyses of new antibacterial agents. Most studies showed the new antibacterial drugs were cost-effective compared to older generation drugs. Drug pricing is a complicated process, involving different stakeholders, and has a large influence on cost-effectiveness. Value-based pricing is a method to determine the price of a drug at which it can be cost-effective. It is currently unclear what the influence of value-based pricing will be on the prices of new antibacterial agents, but an important factor will be the definition of 'value', which as well as the impact of the drug on patient health might also include other factors such as wider social impact and the health impact of disease. © 2015 The Authors. Chemical Biology & Drug Design Published by John Wiley & Sons Ltd.

  8. Illicit drugs and the media: models of media effects for use in drug policy research.

    Science.gov (United States)

    Lancaster, Kari; Hughes, Caitlin E; Spicer, Bridget; Matthew-Simmons, Francis; Dillon, Paul

    2011-07-01

    Illicit drugs are never far from the media gaze and although identified almost a decade ago as 'a new battleground' for the alcohol and other drug (AOD) field there has been limited research examining the role of the news media and its effects on audiences and policy. This paper draws together media theories from communication literature to examine media functions. We illustrate how each function is relevant for media and drugs research by drawing upon the existing literature examining Australian media coverage during the late 1990s of escalating heroin-related problems and proposed solutions. Media can influence audiences in four key ways: by setting the agenda and defining public interest; framing issues through selection and salience; indirectly shaping individual and community attitudes towards risk; and feeding into political debate and decision making. Each has relevance for the AOD field. For example, media coverage of the escalating heroin-related problems in Australia played a strong role in generating interest in heroin overdoses, framing public discourse in terms of a health and/or criminal issue and affecting political decisions. Implications AND CONCLUSION: Media coverage in relation to illicit drugs can have multifarious effects. Incorporating media communication theories into future research and actions is critical to facilitate understanding of the short- and long-term impacts of media coverage on illicit drugs and the avenues by which the AOD field can mitigate or inform future media debates on illicit drugs. © 2010 Australasian Professional Society on Alcohol and other Drugs.

  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

    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......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...

  10. 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......Although sex-specific differences in cardiovascular medicine are well-known, the exact influences of sex on the effect of cardiovascular drugs remain unclear. Women and men differ in body composition and physiology (hormonal influences during the menstrual cycle, menopause and pregnancy...... and pharmacodynamics of cardiovascular drugs and provides recommendations to close the gaps in our understanding of sex-specific differences in drug efficacy and safety....

  11. The effects of drugs on human models of emotional processing: an account of antidepressant drug treatment.

    Science.gov (United States)

    Pringle, Abbie; Harmer, Catherine J

    2015-12-01

    Human models of emotional processing suggest that the direct effect of successful antidepressant drug treatment may be to modify biases in the processing of emotional information. Negative biases in emotional processing are documented in depression, and single or short-term dosing with conventional antidepressant drugs reverses these biases in depressed patients prior to any subjective change in mood. Antidepressant drug treatments also modulate emotional processing in healthy volunteers, which allows the consideration of the psychological effects of these drugs without the confound of changes in mood. As such, human models of emotional processing may prove to be useful for testing the efficacy of novel treatments and for matching treatments to individual patients or subgroups of patients.

  12. Estimating the number of HIV-infected injection drug users in Bangkok: a capture--recapture method.

    Science.gov (United States)

    Mastro, T D; Kitayaporn, D; Weniger, B G; Vanichseni, S; Laosunthorn, V; Uneklabh, T; Uneklabh, C; Choopanya, K; Limpakarnjanarat, K

    1994-07-01

    The purpose of the study was to estimate the number of injection drug users infected with the human immunodeficiency virus (HIV) in Bangkok to allow planning for health services for this population. A two-sample capture-recapture method was used. The first capture listed all persons on methadone treatment for opiate addiction from April 17 through May 17, 1991, at 18 facilities in Bangkok. The second capture involved urine testing of persons held at 72 Bangkok police stations from June 3 through September 30, 1991. Persons whose urine tests were positive for opiate metabolites or methadone were included on the second list. The first capture comprised 4064 persons and the recapture 1540 persons. There were 171 persons included on both lists, yielding an estimate of 36,600 opiate users in Bangkok. Existing data indicate that 89% of opiate users in Bangkok inject drugs and that about one third are infected with HIV, yielding an estimate of approximately 12,000 HIV-infected injection drug users in Bangkok in 1991. During the 1990s the number of cases of acquired immunodeficiency syndrome (AIDS) and other HIV-related diseases, including tuberculosis, in the population of HIV-infected injection drug users in Bangkok will increase dramatically, placing new demands on existing health care facilities. The capture-recapture method may be useful in estimating difficult-to-count populations, including injection drug users.

  13. 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)

  14. 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 ...

  15. 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…

  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. Principles that underpin effective school-based drug education.

    Science.gov (United States)

    Midford, Richard; Munro, Geoffrey; McBride, Nyanda; Snow, Pamela; Ladzinski, Ursula

    2002-01-01

    This study identifies the conceptual underpinnings of effective school-based drug education practice in light of contemporary research evidence and the practical experience of a broad range of drug education stakeholders. The research involved a review of the literature, a national survey of 210 Australian teachers and others involved in drug education, and structured interviews with 22 key Australian drug education policy stakeholders. The findings from this research have been distilled and presented as a list of 16 principles that underpin effective drug education. In broad terms, drug education should be evidence-based, developmentally appropriate, sequential, and contextual. Programs should be initiated before drug use commences. Strategies should be linked to goals and should incorporate harm minimization. Teaching should be interactive and use peer leaders. The role of the classroom teacher is central. Certain program content is important, as is social and resistance skills training. Community values, the social context of use, and the nature of drug harm have to be addressed. Coverage needs to be adequate and supported by follow-up. It is envisaged that these principles will provide all those involved in the drug education field with a set of up-to-date, research-based guidelines against which to reference decisions on program design, selection, implementation, and evaluation.

  18. Estimating Equilibrium Effects of Job Search Assistance

    DEFF Research Database (Denmark)

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

    that the nonparticipants in the experiment regions find jobs slower after the introduction of the activation program (relative to workers in other regions). We then estimate an equilibrium search model. This model shows that a large scale role out of the activation program decreases welfare, while a standard partial...... microeconometric cost-benefit analysis would conclude the opposite....

  19. Effect of oils on drug absorption

    OpenAIRE

    Palin, K.J.

    1981-01-01

    Oil and emulsion vehicles have been shown to alter the oral absorption of many drugs. This may be due to enhanced lymph flow and/or altered gastro-intestinal motility in the presence of the oils. The oral absorption of a model compound (DOT) in the presence of three chemically different oils, arachis oil, Miglyol 812 and liquid paraffin was investigated in rats, the influence of lymphatic absorption and gastro-intestinal motility being determined. The findings were applied to the for.mulation...

  20. Intratumor heterogeneity alters most effective drugs in designed combinations.

    Science.gov (United States)

    Zhao, Boyang; Hemann, Michael T; Lauffenburger, Douglas A

    2014-07-22

    The substantial spatial and temporal heterogeneity observed in patient tumors poses considerable challenges for the design of effective drug combinations with predictable outcomes. Currently, the implications of tissue heterogeneity and sampling bias during diagnosis are unclear for selection and subsequent performance of potential combination therapies. Here, we apply a multiobjective computational optimization approach integrated with empirical information on efficacy and toxicity for individual drugs with respect to a spectrum of genetic perturbations, enabling derivation of optimal drug combinations for heterogeneous tumors comprising distributions of subpopulations possessing these perturbations. Analysis across probabilistic samplings from the spectrum of various possible distributions reveals that the most beneficial (considering both efficacy and toxicity) set of drugs changes as the complexity of genetic heterogeneity increases. Importantly, a significant likelihood arises that a drug selected as the most beneficial single agent with respect to the predominant subpopulation in fact does not reside within the most broadly useful drug combinations for heterogeneous tumors. The underlying explanation appears to be that heterogeneity essentially homogenizes the benefit of drug combinations, reducing the special advantage of a particular drug on a specific subpopulation. Thus, this study underscores the importance of considering heterogeneity in choosing drug combinations and offers a principled approach toward designing the most likely beneficial set, even if the subpopulation distribution is not precisely known.

  1. Molecular Mechanism: ERK Signaling, Drug Addiction, and Behavioral Effects.

    Science.gov (United States)

    Sun, Wei-Lun; Quizon, Pamela M; Zhu, Jun

    2016-01-01

    Addiction to psychostimulants has been considered as a chronic psychiatric disorder characterized by craving and compulsive drug seeking and use. Over the past two decades, accumulating evidence has demonstrated that repeated drug exposure causes long-lasting neurochemical and cellular changes that result in enduring neuroadaptation in brain circuitry and underlie compulsive drug consumption and relapse. Through intercellular signaling cascades, drugs of abuse induce remodeling in the rewarding circuitry that contributes to the neuroplasticity of learning and memory associated with addiction. Here, we review the role of the extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase, and its related intracellular signaling pathways in drug-induced neuroadaptive changes that are associated with drug-mediated psychomotor activity, rewarding properties and relapse of drug seeking behaviors. We also discuss the neurobiological and behavioral effects of pharmacological and genetic interferences with ERK-associated molecular cascades in response to abused substances. Understanding the dynamic modulation of ERK signaling in response to drugs may provide novel molecular targets for therapeutic strategies to drug addiction. Copyright © 2016. Published by Elsevier Inc.

  2. Entry time effects and follow-on drug competition.

    Science.gov (United States)

    Andrade, Luiz Flavio; Sermet, Catherine; Pichetti, Sylvain

    2016-01-01

    Pharmaceutical firms have been criticized for concentrating efforts of R&D on the so-called me-too or follow-on drugs. There have been many comments for and against the dissemination of these incremental innovations but few papers have broached the subject from an econometric point of view, possibly because identification of me-too or follow-on drugs is not so obvious. This paper focuses on the impact of entry order on follow-on drug competition in the French market between the years 2001 and 2007. More precisely, this study examines the effects on market share of first entrants in the follow-on drug market and how this possible competitive advantage changes over time. First results are coherent with theoretical microeconomic issues concerning the importance of being first. We find evidence that first movers in the follow-on drug market have the ability to capture and maintain greater market share for a long period of time. The hierarchical market position of follow-on drugs does not seem to be affected by generic drug emergence. From a dynamic perspective, our analysis shows that market share is positively correlated with the ability of follow-on drugs to set prices higher than the average follow-on drug prices in a specific therapeutic class, which means that market power remains considerably important for first movers. Moreover, we found that the optimum level of innovation to maximize market share is the highest one.

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

    Science.gov (United States)

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

    2014-09-01

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

  4. 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...

  5. Validation of limited sampling models (LSM) for estimating AUC in therapeutic drug monitoring - is a separate validation group required?

    NARCIS (Netherlands)

    Proost, J. H.

    Objective: Limited sampling models (LSM) for estimating AUC in therapeutic drug monitoring are usually validated in a separate group of patients, according to published guidelines. The aim of this study is to evaluate the validation of LSM by comparing independent validation with cross-validation

  6. 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

  7. [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.

  8. 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.

  9. Estimation of the standardized risk difference and ratio in a competing risks framework: application to injection drug use and progression to AIDS after initiation of antiretroviral therapy.

    Science.gov (United States)

    Cole, Stephen R; Lau, Bryan; Eron, Joseph J; Brookhart, M Alan; Kitahata, Mari M; Martin, Jeffrey N; Mathews, William C; Mugavero, Michael J

    2015-02-15

    There are few published examples of absolute risk estimated from epidemiologic data subject to censoring and competing risks with adjustment for multiple confounders. We present an example estimating the effect of injection drug use on 6-year risk of acquired immunodeficiency syndrome (AIDS) after initiation of combination antiretroviral therapy between 1998 and 2012 in an 8-site US cohort study with death before AIDS as a competing risk. We estimate the risk standardized to the total study sample by combining inverse probability weights with the cumulative incidence function; estimates of precision are obtained by bootstrap. In 7,182 patients (83% male, 33% African American, median age of 38 years), we observed 6-year standardized AIDS risks of 16.75% among 1,143 injection drug users and 12.08% among 6,039 nonusers, yielding a standardized risk difference of 4.68 (95% confidence interval: 1.27, 8.08) and a standardized risk ratio of 1.39 (95% confidence interval: 1.12, 1.72). Results may be sensitive to the assumptions of exposure-version irrelevance, no measurement bias, and no unmeasured confounding. These limitations suggest that results be replicated with refined measurements of injection drug use. Nevertheless, estimating the standardized risk difference and ratio is straightforward, and injection drug use appears to increase the risk of AIDS. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. 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.

  11. Marijuana and Cocaine Effect Expectancies and Drug Use Patterns.

    Science.gov (United States)

    Schafer, John; Brown, Sandra A.

    1991-01-01

    Content analyzed self-reports from 704 college students and used results to develop Marijuana Effect Expectancy Questionnaire and Cocaine Effect Expectancy Questionnaire. Identified six marijuana expectancies and five cocaine expectancies. Drug effect expectancies distinguished between patterns of nonuse and varying degrees of use of these two…

  12. 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

  13. 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.

  14. 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

    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...

  15. 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....

  16. 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.

  17. 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…

  18. ORIGINAL ARTICLE Estimation of annual occupational effective ...

    African Journals Online (AJOL)

    Nagasaki nuclear bomb survivors, who have demonstrated increased ... atomic numbers as soft tissue, and their energy responses to absorbed radiation show little ... suitable thermal treatment, making them cost-effective and viable in the long ...

  19. Efficient nonparametric estimation of causal mediation effects

    OpenAIRE

    Chan, K. C. G.; Imai, K.; Yam, S. C. P.; Zhang, Z.

    2016-01-01

    An essential goal of program evaluation and scientific research is the investigation of causal mechanisms. Over the past several decades, causal mediation analysis has been used in medical and social sciences to decompose the treatment effect into the natural direct and indirect effects. However, all of the existing mediation analysis methods rely on parametric modeling assumptions in one way or another, typically requiring researchers to specify multiple regression models involving the treat...

  20. The effect of selection on genetic parameter estimates

    African Journals Online (AJOL)

    Unknown

    The South African Journal of Animal Science is available online at ... A simulation study was carried out to investigate the effect of selection on the estimation of genetic ... The model contained a fixed effect, random genetic and random.

  1. The use of random-effects models to identify health care center-related characteristics modifying the effect of antipsychotic drugs.

    Science.gov (United States)

    Nordon, Clementine; Battin, Constance; Verdoux, Helene; Haro, Josef Maria; Belger, Mark; Abenhaim, Lucien; van Staa, Tjeerd Pieter

    2017-01-01

    A case study was conducted, exploring methods to identify drugs effects modifiers, at a health care center level. Data were drawn from the Schizophrenia Outpatient Health Outcome cohort, including hierarchical information on 6641 patients, recruited from 899 health care centers from across ten European countries. Center-level characteristics included the following: psychiatrist's gender, age, length of practice experience, practice setting and type, countries' Healthcare System Efficiency score, and psychiatrist density in the country. Mixed multivariable linear regression models were used: 1) to estimate antipsychotic drugs' effectiveness (defined as the association between patients' outcome at 3 months - dependent variable, continuous - and antipsychotic drug initiation at baseline - drug A vs other antipsychotic drug); 2) to estimate the similarity between clustered data (using the intra-cluster correlation coefficient); and 3) to explore antipsychotic drug effects modification by center-related characteristics (using the addition of an interaction term). About 23% of the variance found for patients' outcome was explained by unmeasured confounding at a center level. Psychiatrists' practice experience was found to be associated with patient outcomes ( p =0.04) and modified the relative effect of "drug A" ( p <0.001), independent of center- or patient-related characteristics. Mixed models may be useful to explore how center-related characteristics modify drugs' effect estimates, but require numerous assumptions.

  2. 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.

  3. 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.

  4. 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.

  5. 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 ...

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

    DEFF Research Database (Denmark)

    Hornum, Mads; Feldt-Rasmussen, Bo

    2017-01-01

    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...

  7. Non-invasive assessment of the effects of drugs on acute myocardial infarct size in man

    Energy Technology Data Exchange (ETDEWEB)

    Maclean, D [Ninewells Hospital and Medical School, Dundee (UK)

    1979-06-01

    The amount of necrotic myocardium following acute coronary artery occlusion influences both the early and long-term consequences of myocardial infarction. Experiments, however, indicate that several drugs given early after the occlusion can substantially alter final infarct size. Clinical assessment of the effects of these drugs poses difficulties and an awareness of the limitations of existing methods is essential for their successful application. This discussion is restricted largely to the advantages and disadvantages of the three main methods currently used for assessing acute myocardial infarct size:-praecordial electrocardiographic mapping, serial estimates of serum creatine kinase activity, and radionuclide scintigraphy.

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

    African Journals Online (AJOL)

    School of Management Technology,. Federal University of Technology Owerri,. Imo State, Nigeria. Abstract. The study examined the effects of exchange rate and interest rate on the ... the basic values of the firm like interest margin, sales etc. ... the economy, so it provides an easy way to gauge the performance of the entire ...

  9. 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

  10. Dosimetry in Interventional Radiology - Effective Dose Estimation

    International Nuclear Information System (INIS)

    Miljanic, S.; Buls, N.; Clerinx, P.; Jarvinen, H.; Nikodemova, D.; Ranogajec-Komor, M; D'Errico, F.

    2008-01-01

    Interventional radiological procedures can lead to significant radiation doses to patients and to staff members. In order to evaluate the personal doses with respect to the regulatory dose limits, doses measured by dosimeters have to be converted to effective doses (E). Measurement of personal dose equivalent Hp(10) using a single unshielded dosimeter above the lead apron can lead to significant overestimation of the effective dose, while the measurement with dosimeter under the apron can lead to underestimation. To improve the accuracy, measurements with two dosimeters, one above and the other under the apron have been suggested ( d ouble dosimetry ) . The ICRP has recommended that interventional radiology departments develop a policy that staff should wear two dosimeters. The aim of this study was to review the double dosimetry algorithms for the calculation of effective dose in high dose interventional radiology procedures. The results will be used to develop general guidelines for personal dosimetry in interventional radiology procedures. This work has been carried out by Working Group 9 (Radiation protection dosimetry of medical staff) of the CONRAD project, which is a Coordination Action supported by the European Commission within its 6th Framework Program.(author)

  11. Brain serotonin, psychoactive drugs, and effects on reproduction.

    Science.gov (United States)

    Ayala, María Elena

    2009-12-01

    Serotonin, a biogenic amine, is present in significant amounts in many structures of the CNS. It is involved in regulation of a wide variety of physiological functions, such as sensory and motor functions, memory, mood, and secretion of hormones including reproductive hormones. It has also been implicated in the etiology of a range of psychiatric disorders such as anxiety, depression, and eating disorders, along with other conditions such as obesity and migraine. While some drugs that affect serotonin, such as fenfluramine and fluoxetine, have been successfully used in treatment of a range of psychiatric diseases, others, such as the amphetamine analogues MDMA and METH, are potent psychostimulant drugs of abuse. Alterations in serotonergic neurons caused by many of these drugs are well characterized; however, little is known about the reproductive consequences of such alterations. This review evaluates the effects of drugs such as MDMA, pCA, fenfluramine, and fluoxetine on serotonergic transmission in the brain, examines the relationships of these drug effects with the neuroendocrine mechanisms modulating reproductive events such as gonadotropin secretion, ovulation, spermatogenesis, and sexual behavior in animal models, and discusses possible reproductive implications of these drugs in humans.

  12. Drugs and Pregnancy: The Effects of Nonmedical Use of Drugs on Pregnancy, Childbirth, and Neonates. National Institute on Drug Abuse Research Issues 5.

    Science.gov (United States)

    Ferguson, Patricia, Ed.; And Others

    The National Institute on Drug Abuse presents this report as the fifth in a series intended to summarize the empirical research findings and major theoretical approaches relating to the the issues of drug use and abuse. Included in this volume are summaries of the major research findings concerning the effects of nonmedical drug use on pregnancy.…

  13. Effects of parent drug use and personality on toddler adjustment.

    Science.gov (United States)

    Brook, J S; Whiteman, M; Shapiro, J; Cohen, P

    1996-03-01

    The interrelation between parental drug use and parental personality and the effects on 18-month-old children's adjustment were examined. Data on the parents were available at four points in time: Time 1 at mean age 6.1 years, Time 2 at mean age 13.7 years, Time 3 at mean age 16.4 years, and at Time 4 at mean age 22.2 years. Data on their toddlers at 18 months of age were also available. Structured interviews were used to assess personality and drug use and the toddlers' adjustment. Time 3 parental personality traits were related to Time 4 personality traits, which in turn were related to toddler adjustment. The influence of parental alcohol involvement (Time 3) on toddler adjustment was mediated by parental personality (Times 3 and 4) and parental alcohol problems (Time 4). Interactive effects demonstrated that protective parental personality traits (nondrug conducive) enhanced the effects of low parental drug use, resulting in the highest amounts of toddler adjustment. There are significant pathways between parental personality and drug use and toddler adjustment. Parental protective factors enhance the effect of parental low drug use on toddler adjustment.

  14. 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)

  15. 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.

  16. Functional Mixed Effects Model for Small Area Estimation.

    Science.gov (United States)

    Maiti, Tapabrata; Sinha, Samiran; Zhong, Ping-Shou

    2016-09-01

    Functional data analysis has become an important area of research due to its ability of handling high dimensional and complex data structures. However, the development is limited in the context of linear mixed effect models, and in particular, for small area estimation. The linear mixed effect models are the backbone of small area estimation. In this article, we consider area level data, and fit a varying coefficient linear mixed effect model where the varying coefficients are semi-parametrically modeled via B-splines. We propose a method of estimating the fixed effect parameters and consider prediction of random effects that can be implemented using a standard software. For measuring prediction uncertainties, we derive an analytical expression for the mean squared errors, and propose a method of estimating the mean squared errors. The procedure is illustrated via a real data example, and operating characteristics of the method are judged using finite sample simulation studies.

  17. 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.

  18. 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.

  19. 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.

  20. Effect of intravenous drug administration mode on drug distribution in a tumor slab: a finite Fourier transform analysis.

    Science.gov (United States)

    Subramaniam, B; Claudius, J S

    1990-03-08

    Cancer therapy using chemotherapeutic drugs frequently involves injection of the drug into the body through some intravenous mode of administration, viz, continuous (drip) infusion or single/multiple bolus injection(s). An understanding of the effect of the various modes of administration upon tumor penetration of drug is essential to rational design of drug therapy. This paper investigates drug penetration into a model tumor of slab geometry (between two capillaries) in which the overall transport rate of drug is limited by intra-tumor transport characterized by an effective diffusion coefficient. Employing the method of Finite Fourier Transforms (FFT), analytical solutions have been obtained for transient drug distribution in both the plasma and the tumor following three modes of administration, viz, continuous infusion, single bolus injection and equally-spaced equal-dose multiple bolus injections, of a given amount of drug. The qualitative trends exhibited by the plasma drug distribution profiles are consistent with reported experimental studies. Two concepts, viz, the dimensionless decay constant and the plasma/tumor drug concentration trajectories, are found to be particularly useful in the rational design of drug therapy. The dimensionless decay constant provides a measure of the rate of drug decay in the plasma relative to the rate of drug diffusion into the tumor and is thus characteristic of the tumor/drug system. The magnitude of this parameter dictates the choice of drug administration mode for minimizing drug decay in the plasma while simultaneously maximizing drug transport into the tumor. The concentration trajectories provide a measure of the plasma drug concentration relative to the tumor drug concentration at various times following injection. When the tumor drug concentration exceeds the plasma drug concentration, the drug will begin to diffuse out of the tumor. Knowledge of the time at which this diffusion reversal occurs is especially useful

  1. 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.

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

    International Nuclear Information System (INIS)

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M.; Guwy, Alan J.

    2009-01-01

    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 -1 1000 people -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 -1 1000 people -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.

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

    Science.gov (United States)

    Kasprzyk-Hordern, Barbara; Dinsdale, Richard M; Guwy, Alan J

    2009-06-01

    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(-1) 1000 people(-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(-1) 1000 people(-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.

  4. Cost effectiveness of withdrawal of fall-risk-increasing drugs in geriatric outpatients.

    Science.gov (United States)

    van der Velde, Nathalie; Meerding, Willen Jan; Looman, Caspar W; Pols, Huibert A P; van der Cammen, Tischa J M

    2008-01-01

    Withdrawal of fall-risk-increasing drugs has been proven to be effective in older persons. However, given the enormous rise in healthcare costs in recent decades, the effect of such withdrawals on healthcare costs also needs to be considered. Within a common geriatric outpatient population, patients with a history of falls were assessed for falls risk (n = 139). Fall-risk-increasing drugs were withdrawn when appropriate (n = 75). All participants had a 2-month follow-up for fall incidents. The number of prevented falls was calculated using a loglinear regression model. The savings on health expenditures as a result of prevented injuries (estimated from a literature review) and reduced consumption of pharmaceuticals were compared with the intervention costs. After adjustment for confounders, drug withdrawal resulted in a falls risk reduction of 0.89 (95% CI 0.33, 0.98) per patient compared with the non-withdrawal group. Net cost savings were euro1691 (95% CI 662, 2181) per patient in the cohort. This resulted in a cost saving of euro491 (95% CI 465, 497) per prevented fall. Withdrawal of fall-risk-increasing drugs generates significant cost savings. Extrapolation of these findings to a national scale results in an estimated reduction of euro60 million in healthcare expenditures, that is, 15% of fall-related health costs.

  5. Instrumental variables estimates of peer effects in social networks.

    Science.gov (United States)

    An, Weihua

    2015-03-01

    Estimating peer effects with observational data is very difficult because of contextual confounding, peer selection, simultaneity bias, and measurement error, etc. In this paper, I show that instrumental variables (IVs) can help to address these problems in order to provide causal estimates of peer effects. Based on data collected from over 4000 students in six middle schools in China, I use the IV methods to estimate peer effects on smoking. My design-based IV approach differs from previous ones in that it helps to construct potentially strong IVs and to directly test possible violation of exogeneity of the IVs. I show that measurement error in smoking can lead to both under- and imprecise estimations of peer effects. Based on a refined measure of smoking, I find consistent evidence for peer effects on smoking. If a student's best friend smoked within the past 30 days, the student was about one fifth (as indicated by the OLS estimate) or 40 percentage points (as indicated by the IV estimate) more likely to smoke in the same time period. The findings are robust to a variety of robustness checks. I also show that sharing cigarettes may be a mechanism for peer effects on smoking. A 10% increase in the number of cigarettes smoked by a student's best friend is associated with about 4% increase in the number of cigarettes smoked by the student in the same time period. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. An attention-based effective neural model for drug-drug interactions extraction.

    Science.gov (United States)

    Zheng, Wei; Lin, Hongfei; Luo, Ling; Zhao, Zhehuan; Li, Zhengguang; Zhang, Yijia; Yang, Zhihao; Wang, Jian

    2017-10-10

    Drug-drug interactions (DDIs) often bring unexpected side effects. The clinical recognition of DDIs is a crucial issue for both patient safety and healthcare cost control. However, although text-mining-based systems explore various methods to classify DDIs, the classification performance with regard to DDIs in long and complex sentences is still unsatisfactory. In this study, we propose an effective model that classifies DDIs from the literature by combining an attention mechanism and a recurrent neural network with long short-term memory (LSTM) units. In our approach, first, a candidate-drug-oriented input attention acting on word-embedding vectors automatically learns which words are more influential for a given drug pair. Next, the inputs merging the position- and POS-embedding vectors are passed to a bidirectional LSTM layer whose outputs at the last time step represent the high-level semantic information of the whole sentence. Finally, a softmax layer performs DDI classification. Experimental results from the DDIExtraction 2013 corpus show that our system performs the best with respect to detection and classification (84.0% and 77.3%, respectively) compared with other state-of-the-art methods. In particular, for the Medline-2013 dataset with long and complex sentences, our F-score far exceeds those of top-ranking systems by 12.6%. Our approach effectively improves the performance of DDI classification tasks. Experimental analysis demonstrates that our model performs better with respect to recognizing not only close-range but also long-range patterns among words, especially for long, complex and compound sentences.

  7. 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…

  8. 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…

  9. 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 ...

  10. The Effects of Antiepileptic Drugs on Classroom Performance

    Science.gov (United States)

    Titus, Jeffrey B.; Thio, Liu Lin

    2009-01-01

    Epilepsy is one of the most common neurological disorders in children, and it has been associated with an increased risk of cognitive, psychiatric, and learning problems. Although side effects of antiepileptic drugs (AEDs) have been long studied in adults, an understanding of how they manifest in children is only beginning to emerge. Careful…

  11. Modulatory effect of polymer type and composition on drug release ...

    African Journals Online (AJOL)

    The purpose of this study was to investigate the effects of polymer type and composition on drug release from the matrix of diclofenac sodium sustained release tablets formulated using three different granulation methods. Ten (10) batches of diclofenac sodium tablets (F01 - F10) were prepared by melt granulation, ...

  12. Effect of drugs on the thyroid function tests

    International Nuclear Information System (INIS)

    Cardoso, G.P.; Faria, A.C.S. de; Carvalho, M.C. de; Guimaraes, M.M.; Cordeiro, J.G.H.; Santa Casa do Rio de Janeiro

    1984-01-01

    The effects of drugs in the results of thyroid function tests, which could lead to misinterpretation of the real clinical state of the patients, are reviewed. The aspects of the metabolism of the thyreoidean hormones which could be related to these alterations are presented. (Author) [pt

  13. 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,

  14. Bone effects of biologic drugs in rheumatoid arthritis.

    Science.gov (United States)

    Corrado, Addolorata; Neve, Anna; Maruotti, Nicola; Cantatore, Francesco Paolo

    2013-01-01

    Biologic agents used in the treatment of rheumatoid arthritis (RA) are able to reduce both disease activity and radiographic progression of joint disease. These drugs are directed against several proinflammatory cytokines (TNF α , IL-6, and IL-1) which are involved both in the pathogenesis of chronic inflammation and progression of joint structural damage and in systemic and local bone loss typically observed in RA. However, the role of biologic drugs in preventing bone loss in clinical practice has not yet clearly assessed. Many clinical studies showed a trend to a positive effect of biologic agents in preventing systemic bone loss observed in RA. Although the suppression of inflammation is the main goal in the treatment of RA and the anti-inflammatory effects of biologic drugs exert a positive effect on bone metabolism, the exact relationship between the prevention of bone loss and control of inflammation has not been clearly established, and if the available biologic drugs against TNF α , IL-1, and IL-6 can exert their effect on systemic and local bone loss also through a direct mechanism on bone cell metabolism is still to be clearly defined.

  15. 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...

  16. Mid-Season Influenza Vaccine Effectiveness Estimates for the 2016-2017 Influenza Season (Open Access Publisher’s Version)

    Science.gov (United States)

    2017-08-01

    VE) and findings are shared annually at the Food and Drug Administration’s advisory committee meet- ing on U.S. influenza vaccine strain selec- tion...Aeromedical Services Information Manage - ment System) and self-report from patient questionnaires. Individuals were consid- ered vaccinated if they received...surveillance are used to estimate midseason influenza vaccine effectiveness (VE) and findings are shared annually at the Food and Drug

  17. 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.

  18. 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.

  19. 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.

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

    NARCIS (Netherlands)

    Mocroft, Amanda; Kirk, Ole; Reiss, Peter; de Wit, Stephane; Sedlacek, Dalibor; Beniowski, Marek; Gatell, Jose; Phillips, Andrew N.; Ledergerber, Bruno; Lundgren, Jens D.; Losso, M.; Elias, C.; Vetter, N.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Suetnov, O.; Clumeck, N.; Poll, B.; Colebunders, R.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Begovac, J.; Machala, L.; Rozsypal, H.; Sedlacek, D.; Nielsen, J.; Kronborg, G.; Benfield, T.; Larsen, M.; Gerstoft, J.; Katzenstein, T.; Hansen, A.-B. E.; Skinhøj, P.; Pedersen, C.; Oestergaard, L.; Zilmer, K.; Smidt, Jelena; Ristola, M.; Katlama, C.; Viard, J.-P.; Girard, P.-M.; Livrozet, J. M.; Vanhems, P.; Pradier, C.; Dabis, F.; Neau, D.; Rockstroh, J.

    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 with at

  1. 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

  2. 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.

  3. [Plasma lipoproteins as drug carriers. Effect of phospholipid formulations].

    Science.gov (United States)

    Torkhovskaia, T I; Ipatova, O M; Medvedeva, N V; Ivanov, V S; Ivanova, L I

    2010-01-01

    The extensive development of nanotechnologies in the last two decades has brought about new understanding of plasma lipoproteins (LP) as natural drug nanocarriers that escape interaction with immune and reticuloendothelial systems. Drugs bound to LP (especially LDL) can more actively penetrate into cells of many cancer and inflammation tissues with enhanced expression or/and dysregulation of B,E receptors or possibly scavenger SR-BI receptors. Relevant studies are focused on the development of new dosage forms by conjugating lipophilic drugs either with isolated plasma LP or with their model formulations, such as nanoemulsions, mimetics, lipid nanospheres, etc. Some authors include in these particles serum or recombinant apoproteins, peptides, and modified polymer products. As shown recently, protein-free lipid nanoemulsions in plasma take up free apoA and apoE. Complexes with various LP also form after direct administration of lypophilic drugs into blood especially those enclosed in phospholipid formulations, e.g. liposomes. Results of evaluation of some lipophilic dugs (mainly cytostatics, amphotericin B, cyclosporine A, etc.) are discussed. Original data are presented on the influence of phospholipid formulations on the distribution of doxorubicin and indomethacin between LP classes after in vitro incubation in plasma. On the whole, the review illustrates the importance of research on LP and phospholi pid forms as drug nanocarriers to be used to enhance effect of therapy.

  4. 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

  5. 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

  6. 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

  7. Effects of regulation on drug launch and pricing in interdependent markets.

    Science.gov (United States)

    Danzon, Patricia M; Epstein, Andrew J

    2012-01-01

    This study examines the effect of price regulation and competition on launch timing and pricing of new drugs. Our data cover launch experience in 15 countries from 1992 to 2003 for drugs in 12 major therapeutic classes. We estimate a two-equation model of launch hazard and launch price of new drugs. We find that launch timing and prices of new drugs are related to a country's average prices of established products in a class. Thus to the extent that price regulation reduces price levels, such regulation directly contributes to launch delay in the regulating country. Regulation by external referencing, whereby high-price countries reference low-price countries, also has indirect or spillover effects, contributing to launch delay and higher launch prices in low-price referenced countries. Referencing policies adopted in high-price countries indirectly impose welfare loss on low-price countries. These findings have implications for US proposals to constrain pharmaceutical prices through external referencing and drug importation.

  8. Estimating linear effects in ANOVA designs: the easy way.

    Science.gov (United States)

    Pinhas, Michal; Tzelgov, Joseph; Ganor-Stern, Dana

    2012-09-01

    Research in cognitive science has documented numerous phenomena that are approximated by linear relationships. In the domain of numerical cognition, the use of linear regression for estimating linear effects (e.g., distance and SNARC effects) became common following Fias, Brysbaert, Geypens, and d'Ydewalle's (1996) study on the SNARC effect. While their work has become the model for analyzing linear effects in the field, it requires statistical analysis of individual participants and does not provide measures of the proportions of variability accounted for (cf. Lorch & Myers, 1990). In the present methodological note, using both the distance and SNARC effects as examples, we demonstrate how linear effects can be estimated in a simple way within the framework of repeated measures analysis of variance. This method allows for estimating effect sizes in terms of both slope and proportions of variability accounted for. Finally, we show that our method can easily be extended to estimate linear interaction effects, not just linear effects calculated as main effects.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. Estimating the Effects of Exchange Rate Volatility on Export Volumes

    OpenAIRE

    Wang, Kai-Li; Barrett, Christopher B.

    2007-01-01

    This paper takes a new empirical look at the long-standing question of the effect of exchange rate volatility on international trade flows by studying the case of Taiwan's exports to the United States from 1989-1998. In particular, we employ sectoral-level, monthly data and an innovative multivariate GARCH-M estimator with corrections for leptokurtic errors. This estimator allows for the possibility that traders' forward-looking contracting behavior might condition the way in which exchange r...

  15. Instrumental variable estimation of treatment effects for duration outcomes

    NARCIS (Netherlands)

    G.E. Bijwaard (Govert)

    2007-01-01

    textabstractIn this article we propose and implement an instrumental variable estimation procedure to obtain treatment effects on duration outcomes. The method can handle the typical complications that arise with duration data of time-varying treatment and censoring. The treatment effect we

  16. The contribution of the hydrogen bond acidity on the lipophilicity of drugs estimated from chromatographic measurements.

    Science.gov (United States)

    Pallicer, Juan M; Pascual, Rosalia; Port, Adriana; Rosés, Martí; Ràfols, Clara; Bosch, Elisabeth

    2013-02-14

    The influence of the hydrogen bond acidity when the 1-octanol/water partition coefficient (log P(o/w)) of drugs is determined from chromatographic measurements was studied in this work. This influence was firstly evaluated by means of the comparison between the Abraham solvation parameter model when it is applied to express the 1-octanol/water partitioning and the chromatographic retention, expressed as the solute polarity p. Then, several hydrogen bond acidity descriptors were compared in order to determine properly the log P(o/w) of drugs. These descriptors were obtained from different software and comprise two-dimensional parameters such as the calculated Abraham hydrogen bond acidity A and three-dimensional descriptors like HDCA-2 from CODESSA program or WO1 and DRDODO descriptors calculated from Volsurf+software. The additional HOMO-LUMO polarizability descriptor should be added when the three-dimensional descriptors are used to complement the chromatographic retention. The models generated using these descriptors were compared studying the correlations between the determined log P(o/w) values and the reference ones. The comparison showed that there was no significant difference between the tested models and any of them was able to determine the log P(o/w) of drugs from a single chromatographic measurement and the correspondent molecular descriptors terms. However, the model that involved the calculated A descriptor was simpler and it is thus recommended for practical uses. Copyright © 2012 Elsevier B.V. All rights reserved.

  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. 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.

  19. 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

  20. Drugs affecting prelamin A processing: Effects on heterochromatin organization

    International Nuclear Information System (INIS)

    Mattioli, Elisabetta; Columbaro, Marta; Capanni, Cristina; Santi, Spartaco; Maraldi, Nadir M.; D'Apice, M. Rosaria; Novelli, Giuseppe; Riccio, Massimo; Squarzoni, Stefano; Foisner, Roland; Lattanzi, Giovanna

    2008-01-01

    Increasing interest in drugs acting on prelamin A has derived from the finding of prelamin A involvement in severe laminopathies. Amelioration of the nuclear morphology by inhibitors of prelamin A farnesylation has been widely reported in progeroid laminopathies. We investigated the effects on chromatin organization of two drugs inhibiting prelamin A processing by an ultrastructural and biochemical approach. The farnesyltransferase inhibitor FTI-277 and the non-peptidomimetic drug N-acetyl-S-farnesyl-L-cysteine methylester (AFCMe) were administered to cultured control human fibroblasts for 6 or 18 h. FTI-277 interferes with protein farnesylation causing accumulation of non-farnesylated prelamin A, while AFCMe impairs the last cleavage of the lamin A precursor and is expected to accumulate farnesylated prelamin A. FTI-277 caused redistribution of heterochromatin domains at the nuclear interior, while AFCMe caused loss of heterochromatin domains, increase of nuclear size and nuclear lamina thickening. At the biochemical level, heterochromatin-associated proteins and LAP2α were clustered at the nuclear interior following FTI-277 treatment, while they were unevenly distributed or absent in AFCMe-treated nuclei. The reported effects show that chromatin is an immediate target of FTI-277 and AFCMe and that dramatic remodeling of chromatin domains occurs following treatment with the drugs. These effects appear to depend, at least in part, on the accumulation of prelamin A forms, since impairment of prelamin A accumulation, here obtained by 5-azadeoxycytidine treatment, abolishes the chromatin effects. These results may be used to evaluate downstream effects of FTIs or other prelamin A inhibitors potentially useful for the therapy of laminopathies

  1. 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. 

  2. Estimation of the Continuous and Discontinuous Leverage Effects.

    Science.gov (United States)

    Aït-Sahalia, Yacine; Fan, Jianqing; Laeven, Roger J A; Wang, Christina Dan; Yang, Xiye

    2017-01-01

    This paper examines the leverage effect, or the generally negative covariation between asset returns and their changes in volatility, under a general setup that allows the log-price and volatility processes to be Itô semimartingales. We decompose the leverage effect into continuous and discontinuous parts and develop statistical methods to estimate them. We establish the asymptotic properties of these estimators. We also extend our methods and results (for the continuous leverage) to the situation where there is market microstructure noise in the observed returns. We show in Monte Carlo simulations that our estimators have good finite sample performance. When applying our methods to real data, our empirical results provide convincing evidence of the presence of the two leverage effects, especially the discontinuous one.

  3. The effect of antiepileptic drugs on cognitive functions

    Directory of Open Access Journals (Sweden)

    A. S. Kotov

    2013-01-01

    Full Text Available Impaired cognitive function is a common problem in epileptic patients. The exact cause of cognitive impairment in case of epilepsy has not been explored fully, but there is no doubt that a role in this is played by three factors: the disease underlying epilepsy; epileptic seizures proper; and negative side effects of antiepileptic drugs. Their cognitive effects are one of the major problems affecting the tolerance of therapy. The review considers the effects of phenobarbital, phenytoin, carbamazepine, valproates, oxcarbazepine, topiramate, lamotrigine, and levetiracetam in terms of their action on the cognitive function of healthy volunteers and epileptic patients.

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

    Science.gov (United States)

    Hijazi, Karolin; Cuppone, Anna M; Smith, Kieron; Stincarelli, Maria A; Ekeruche-Makinde, Julia; De Falco, Giulia; Hold, Georgina L; Shattock, Robin; Kelly, Charles G; Pozzi, Gianni; Iannelli, Francesco

    2015-01-01

    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 expression of drug

  5. [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.

  6. Effectiveness of multiple sclerosis treatment with current immunomodulatory drugs.

    Science.gov (United States)

    Milo, Ron

    2015-04-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of the CNS of a putative autoimmune origin characterized by neurologic dysfunction disseminated in space and time due to demyelination and axonal loss that results in progressive disability. Recent advances in understanding the immune pathogenesis of the disease resulted in the introduction of numerous effective immunomodulatoty drugs having diverse mechanisms of action, modes of administration and risk-benefit profiles. This results in more complex albeit more promising treatment selection and choices. The epidemiology, clinical features, pathogenesis and diagnosis of the disease are discussed. The mode of action and main characteristics of current immunomodulatory drugs for MS and their place in the therapeutic algorithm of the disease based on evidence from clinical trials are described. Speculation on new paradigms, treatment goals and outcome measures aimed at improving the landscape of MS treatment is presented. Multiple disease, drug and patient-related factors should be taken into consideration when selecting the appropriate drug and treatment strategy to the appropriate patient, thus paving the road for personalized medicine in MS.

  7. 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

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

    OpenAIRE

    E. V. Moroz; A. E. Karateev

    2016-01-01

    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 gast...

  9. Methodology development for the radioecological monitoring effectiveness estimation

    International Nuclear Information System (INIS)

    Gusev, A.E.; Kozlov, A.A.; Lavrov, K.N.; Sobolev, I.A.; Tsyplyakova, T.P.

    1997-01-01

    A general model for estimation of the programs assuring radiation and ecological public protection is described. The complex of purposes and criteria characterizing and giving an opportunity to estimate the effectiveness of environment protection program composition is selected. An algorithm for selecting the optimal management decision from the view point of work cost connected with population protection improvement is considered. The position of radiation-ecological monitoring in general problem of environment pollution is determined. It is shown that the monitoring organizing effectiveness is closely connected with population radiation and ecological protection

  10. 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....

  11. 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

  12. 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.

  13. 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.

  14. A new method to assess Pavlovian conditioning of psychostimulant drug effects.

    Science.gov (United States)

    Damianopoulos, E N; Carey, R J

    1994-07-01

    Experimental studies of psychoactive drugs by pavlovian drug-conditioning methods, which originally began with investigations of drug-induced responses mediated by the autonomic nervous system, have now been expanded to include drug-induced response effects expressed as modulations of spontaneous motoric behaviors. In the latter application, however, equivalent behavioral response outcomes in post-treatment tests for conditioning can occur following a psychostimulant drug treatment either through drug interference effects on habituation processes, drug-induced stress effects and/or by pavlovian conditioning of the drug-induced motoric activation effect. Current methodologies for the study of pavlovian conditioned drug effects and/or drug sensitization cannot distinguish among these possibilities. This methodological inadequacy was addressed by a modification of the conventional paired-unpaired treatment protocol. In the new protocol, the animal is sequentially placed into two test compartments with the drug treatment administered in conjunction with placement into the second test compartment. This design permits a differentiation of a pavlovian conditioned drug responses from non-conditioned drug effects through continuous measurement of the non-drug behavioral baseline in both the drug and non-drug control treatment groups combined with multiple response measurements and post-treatment tests for conditioning at variable post-conditioning intervals. The present study details the use of the new modified pavlovian protocol with repeated cocaine (10 mg/kg) treatment. A cocaine conditioned response at 1, 7, and 21 days post-conditioning was identified and distinguished from habituation and stress effects.

  15. 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

  16. 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

  17. Does the Drug Facts Label for nonprescription drugs meet its design objectives? A new procedure for assessing label effectiveness

    Directory of Open Access Journals (Sweden)

    Michael P Ryan

    2017-07-01

    Full Text Available We demonstrate an expanded procedure for assessing drug-label comprehension. Innovations include a pretest of drug preconceptions, verbal ability and label attentiveness measures, a label-scanning task, a free-recall test, category-clustering measures, and preconception-change scores. In total, 55 female and 39 male undergraduates read a facsimile Drug Facts Label for aspirin, a Cohesive-Prose Label, or a Scrambled-Prose Label. The Drug Facts Label outperformed the Scrambled-Prose Label, but not the Cohesive-Prose Label, in scanning effectiveness. The Drug Facts Label was no better than the Cohesive-Prose Label or the Scrambled-Prose Label in promoting attentiveness, recall and organization of drug facts, or misconception refutation. Discussion focuses on the need for refutational labels based on a sequence-of-events text schema.

  18. 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.

  19. New Estimates of the Effect of Unemployment on Enlisted Retention

    Science.gov (United States)

    1985-07-01

    S14cw’tity lafication) New Estimates of the Effect of Umemployment on Enlisted Retention 12. PERSONAL AUTHOR(S) Ile, TYPE OF REPORT 3b~. TIME COVERED...wider swings in the umemployment rate during recent years, relative military pay has played at least as important a role as the unemployment rate in

  20. 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...

  1. Error Estimates for the Approximation of the Effective Hamiltonian

    International Nuclear Information System (INIS)

    Camilli, Fabio; Capuzzo Dolcetta, Italo; Gomes, Diogo A.

    2008-01-01

    We study approximation schemes for the cell problem arising in homogenization of Hamilton-Jacobi equations. We prove several error estimates concerning the rate of convergence of the approximation scheme to the effective Hamiltonian, both in the optimal control setting and as well as in the calculus of variations setting

  2. 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

  3. Efficient estimation of feedback effects with application to climate models

    International Nuclear Information System (INIS)

    Cacugi, D.G.; Hall, M.C.G.

    1984-01-01

    This work presents an efficient method for calculating the sensitivity of a mathematical model's result to feedback. Feedback is defined in terms of an operator acting on the model's dependent variables. The sensitivity to feedback is defined as a functional derivative, and a method is presented to evaluate this derivative using adjoint functions. Typically, this method allows the individual effect of many different feedbacks to be estimated with a total additional computing time comparable to only one recalculation. The effects on a CO 2 -doubling experiment of actually incorporating surface albedo and water vapor feedbacks in radiative-convective model are compared with sensivities calculated using adjoint functions. These sensitivities predict the actual effects of feedback with at least the correct sign and order of magnitude. It is anticipated that this method of estimation the effect of feedback will be useful for more complex models where extensive recalculations for each of a variety of different feedbacks is impractical

  4. Model based on GRID-derived descriptors for estimating CYP3A4 enzyme stability of potential drug candidates

    Science.gov (United States)

    Crivori, Patrizia; Zamora, Ismael; Speed, Bill; Orrenius, Christian; Poggesi, Italo

    2004-03-01

    A number of computational approaches are being proposed for an early optimization of ADME (absorption, distribution, metabolism and excretion) properties to increase the success rate in drug discovery. The present study describes the development of an in silico model able to estimate, from the three-dimensional structure of a molecule, the stability of a compound with respect to the human cytochrome P450 (CYP) 3A4 enzyme activity. Stability data were obtained by measuring the amount of unchanged compound remaining after a standardized incubation with human cDNA-expressed CYP3A4. The computational method transforms the three-dimensional molecular interaction fields (MIFs) generated from the molecular structure into descriptors (VolSurf and Almond procedures). The descriptors were correlated to the experimental metabolic stability classes by a partial least squares discriminant procedure. The model was trained using a set of 1800 compounds from the Pharmacia collection and was validated using two test sets: the first one including 825 compounds from the Pharmacia collection and the second one consisting of 20 known drugs. This model correctly predicted 75% of the first and 85% of the second test set and showed a precision above 86% to correctly select metabolically stable compounds. The model appears a valuable tool in the design of virtual libraries to bias the selection toward more stable compounds. Abbreviations: ADME - absorption, distribution, metabolism and excretion; CYP - cytochrome P450; MIFs - molecular interaction fields; HTS - high throughput screening; DDI - drug-drug interactions; 3D - three-dimensional; PCA - principal components analysis; CPCA - consensus principal components analysis; PLS - partial least squares; PLSD - partial least squares discriminant; GRIND - grid independent descriptors; GRID - software originally created and developed by Professor Peter Goodford.

  5. Effects of Antidiabetic Drugs on Gut Microbiota Composition

    Directory of Open Access Journals (Sweden)

    Sophie A. Montandon

    2017-09-01

    Full Text Available Gut microbiota forms a catalog of about 1000 bacterial species; which mainly belong to the Firmicutes and Bacteroidetes phyla. Microbial genes are essential for key metabolic processes; such as the biosynthesis of short-chain fatty acids (SCFA; amino acids; bile acids or vitamins. It is becoming clear that gut microbiota is playing a prevalent role in pathologies such as metabolic syndrome; type 2 diabetes (T2D; inflammatory and bowel diseases. Obesity and related diseases; notably type 2 diabetes, induce gut dysbiosis. In this review; we aim to cover the current knowledge about the effects of antidiabetic drugs on gut microbiota diversity and composition as well as the potential beneficial effects mediated by specific taxa. Metformin is the first-line treatment against T2D. In addition to its glucose-lowering and insulin sensitizing effects, metformin promotes SCFA-producing and mucin-degrading bacteria. Other antidiabetic drugs discussed in this review show positive effects on dysbiosis; but without any consensus specifically regarding the Firmicutes to Bacteroidetes ratio. Thus, beneficial effects might be mediated by specific taxa.

  6. 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

  7. Estimation of effective thermal conductivity tensor from composite microstructure images

    International Nuclear Information System (INIS)

    Thomas, M; Boyard, N; Jarny, Y; Delaunay, D

    2008-01-01

    The determination of the effective thermal properties of inhomogeneous materials is a long-standing problem of continuously interest. The impressive number of methods developed to measure or estimate the thermal properties of composite materials clearly exhibits the importance given to their knowledge. Homogenization models are a cheap way to determine or predict them. Many different approaches of homogenization were developed, but the last advances are credited to numerical methods. In this study, a new computational model is developed to estimate the 2D thermal conductivity tensor and the thermal main directions of a pure carbon/epoxy unidirectional composite. This tool is based on real composite microstructure.

  8. Cosmological perturbation effects on gravitational-wave luminosity distance estimates

    Science.gov (United States)

    Bertacca, Daniele; Raccanelli, Alvise; Bartolo, Nicola; Matarrese, Sabino

    2018-06-01

    Waveforms of gravitational waves provide information about a variety of parameters for the binary system merging. However, standard calculations have been performed assuming a FLRW universe with no perturbations. In reality this assumption should be dropped: we show that the inclusion of cosmological perturbations translates into corrections to the estimate of astrophysical parameters derived for the merging binary systems. We compute corrections to the estimate of the luminosity distance due to velocity, volume, lensing and gravitational potential effects. Our results show that the amplitude of the corrections will be negligible for current instruments, mildly important for experiments like the planned DECIGO, and very important for future ones such as the Big Bang Observer.

  9. 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

  10. 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.

  11. 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.

  12. Effect of stress on turbine fish passage mortality estimates

    International Nuclear Information System (INIS)

    Ruggles, C.P.

    1993-01-01

    Tests were conducted with juvenile alewife to determine the effects of four experimental protocols upon turbine fish passage mortality estimates. Three protocols determined the effect of cumulative stresses upon fish, while the fourth determined the effect of long range truck transportation prior to release into the penstock or tailrace. The wide range in results were attributed to the presence or absence of additional stress factors associated with the experiments. For instance, fish may survive passage through a turbine, or non-turbine related stresses imposed by the investigator; however, when both are imposed, the cumulative stresses may be lethal. The impact of protocol stress on turbine mortality estimates becomes almost exponential after control mortality exceeds 10%. Valid turbine related mortalities may be determined only after stresses associated with experimental protocol are adequately reduced. This is usually indicated by a control mortality of less than 10%. 14 refs., 5 figs., 6 tabs

  13. 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.

  14. 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

    with at least three serum creatinine measurements and corresponding body weight measurements from 2004 onwards. METHODS:: CKD was defined as either confirmed (two measurements >/=3 months apart) estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m or below for persons with baseline eGFR of above...... cumulative exposure to tenofovir [incidence rate ratio (IRR) per year 1.16, 95% CI 1.06-1.25, P ... increased rate of CKD. Consistent results were observed in wide-ranging sensitivity analyses, although of marginal statistical significance for lopinavir/r. No other antiretroviral dugs were associated with increased incidence of CKD. CONCLUSION:: In this nonrandomized large cohort, increasing exposure...

  15. 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.

  16. 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.

  17. Estimating the rebound effect in US manufacturing energy consumption

    International Nuclear Information System (INIS)

    Bentzen, Jan

    2004-01-01

    The energy price shocks of the 1970s are usually assumed to have increased the search for new energy saving technologies where eventual gains in energy efficiencies will reduce the real per unit price of energy services and hence, the consumption of energy will rise and partially offset the initial reduction in the usage of energy sources. This is the 'rebound effect', which is estimated for the US manufacturing sector using time series data applying the dynamic OLS method (DOLS). When allowing for asymmetric price effects the rebound effect is found to be approximately 24% for the US manufacturing sector

  18. 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

    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...

  19. Effect of Antiretroviral Drug (arved) on the Kidney in Albino Rat ...

    African Journals Online (AJOL)

    African studies on effect of antiretroviral drugs on the kidney are limited resulting to scanty information on the safety of these drugs. This study was therefore designed to evaluate the effects of antiretroviral drugs arved®, on creatinine, urea, potassium and sodium ions as well as histological effect on the kidney. A total of fifty ...

  20. 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

  1. Functionality Effect of Pressure Sensitive Adhesives on In Vitro Drug Release Behavior of Fentanyl Drug in an Adhesive Patch

    Directory of Open Access Journals (Sweden)

    S.M. Taghizadeh

    2009-12-01

    Full Text Available Some formulations of drug in adhesive transdermal drug delivery systems (TDDSs( with different functional and non-functional acrylic pressure sensitive adhesives PSAs( were prepared. For this purpose fentanyl was used as a drug component. The effects of PSAs type on skin permeation and in vitro drug release from devices were evaluated using hydrodynamically well-characterized Chien permeation system fitted with excised rat abdominal skin. The adhesion properties of devices (peel strength and tack values( were obtained. It was found that TDDS with –COOH functional PSA had the lowest steady state flux. Drug release was followed by Higuchi's kinetic model. Adhesion properties of the samples were improved by addition of functional PSA in the formulations.

  2. 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.

  3. 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.

  4. 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...

  5. 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 ...

  6. 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.)

  7. 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 ...

  8. 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 ...

  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. 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

  11. 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)

  12. 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

  13. 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

  14. 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

  15. The effects of antiepileptic drugs on the growth of glioblastoma cell lines

    OpenAIRE

    Lee, Ching-Yi; Lai, Hung-Yi; Chiu, Angela; Chan, She-Hung; Hsiao, Ling-Ping; Lee, Shih-Tseng

    2016-01-01

    To determine the effects of antiepileptic drug compounds on glioblastoma cellular growth, we exposed glioblastoma cell lines to select antiepileptic drugs. The effects of selected antiepileptic drugs on glioblastoma cells were measured by MTT assay. For compounds showing significant inhibition, cell cycle analysis was performed. Statistical analysis was performed using SPSS. The antiepileptic compounds selected for screening included carbamazepine, ethosuximide, gabapentin, lamotrigine, levet...

  16. 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...

  17. Effect of Anionic Polymers on Drug Loading and Release from ...

    African Journals Online (AJOL)

    Purpose: To develop and characterize solid lipid nanoparticle (SLN) systems containing dextran sulfate or sodium ... SLNs. Drug release from SLNs is also dependent on the polymer type. ..... nanoparticles for parenteral drug delivery. Adv.

  18. 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)

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

    Science.gov (United States)

    Ojala, Karita E; Janssen, Lieneke K; Hashemi, Mahur M; Timmer, Monique H M; Geurts, Dirk E M; Ter Huurne, Niels P; Cools, Roshan; Sescousse, Guillaume

    2018-01-01

    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 D 2 /D 3 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 D 2 /D 3 receptor antagonism modulates the subjective weighting of probabilities in the gain domain, in the direction of more objective, economically rational decision making.

  20. 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

  1. On estimating the effective diffusive properties of hardened cement pastes

    International Nuclear Information System (INIS)

    Stora, E.; Bary, B.; Stora, E.; He, Qi-Chang

    2008-01-01

    The effective diffusion coefficients of hardened cement pastes can vary between a few orders of magnitude. The paper aims at building a homogenization model to estimate these macroscopic diffusivities and capture such strong variations. For this purpose, a three-scale description of the paste is proposed, relying mainly on the fact that the initial cement grains hydrate forming a complex microstructure with a multi-scale pore structure. In particular, porosity is found to be well connected at a fine scale. However, only a few homogenization schemes are shown to be adequate to account for such connectivity. Among them, the mixed composite spheres assemblage estimate (Stora, E., He, Q.-C., Bary, B.: J. Appl. Phys. 100(8), 084910, 2006a) seems to be the only one that always complies with rigorous bounds and is consequently employed to predict the effects of this fine porosity on the material effective diffusivities. The model proposed provides predictions in good agreement with experimental results and is consistent with the numerous measurements of critical pore diameters issued from mercury intrusion porosimetry tests. The evolution of the effective diffusivities of cement pastes subjected to leaching is also assessed by adopting a simplified scenario of the decalcification process. (authors)

  2. Fear Conditioning Effects on Sensitivity to Drug Reward

    Science.gov (United States)

    2010-06-01

    motivational responses and self-administration behaviors (Robbins et al., 2008). Pavlovian conditioning mechanisms link unconditioned drug responses...model. Induction of fear conditioning is followed by measurement of sensitivity to drug reward using a conditioned place preference (CPP) model to...morphine. Conditioned drug reward is a relevant model in addiction because environmental cues (e.g. a barroom) induce craving and persistent

  3. Effect of contraindicated drugs for heart failure on hospitalization among seniors with heart failure

    Science.gov (United States)

    Girouard, Catherine; Grégoire, Jean-Pierre; Poirier, Paul; Moisan, Jocelyne

    2017-01-01

    Abstract Little is known about the effect of nonsteroidal anti-inflammatory drugs (NSAIDs), thiazolidinediones (TZDs), nifedipine and nondihydropyridine calcium channel blockers (CCBs) usage on the risk of all-cause hospitalization among seniors with heart failure (HF). We assessed the risk of all-cause hospitalization associated with exposure to each of these drug classes, in a population of seniors with HF. Using the Quebec provincial databases, we conducted a nested case-control study in a population of individuals aged ≥65 with a first HF diagnosis between 2000 and 2009. Patients were considered users of a potentially inappropriate drug class if their date of hospital admission occurred in the interval between the date of the last drug claim and the end date of its days’ supply. The risks of hospitalization were estimated using multivariate conditional logistic regression. Of the 128,853 individuals included in the study population, 101,273 (78.6%) were hospitalized. When compared to nonusers, users of NSAIDs (adjusted odds ratio: 1.16; 95% confidence interval: 1.13–1.20), TZD (1.09; 1.04–1.14), and CCBs (1.03; 1.01–1.05) had an increased risk of all-cause hospitalization, but not the users of nifedipine (1.00; 0.97–1.03). Seniors with HF exposed to a potentially inappropriate drug class are at increased risk of worse health outcomes. Treatment alternatives should be considered, as they are available. PMID:28248890

  4. 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.

  5. Effect of survey design and catch rate estimation on total catch estimates in Chinook salmon fisheries

    Science.gov (United States)

    McCormick, Joshua L.; Quist, Michael C.; Schill, Daniel J.

    2012-01-01

    Roving–roving and roving–access creel surveys are the primary techniques used to obtain information on harvest of Chinook salmon Oncorhynchus tshawytscha in Idaho sport fisheries. Once interviews are conducted using roving–roving or roving–access survey designs, mean catch rate can be estimated with the ratio-of-means (ROM) estimator, the mean-of-ratios (MOR) estimator, or the MOR estimator with exclusion of short-duration (≤0.5 h) trips. Our objective was to examine the relative bias and precision of total catch estimates obtained from use of the two survey designs and three catch rate estimators for Idaho Chinook salmon fisheries. Information on angling populations was obtained by direct visual observation of portions of Chinook salmon fisheries in three Idaho river systems over an 18-d period. Based on data from the angling populations, Monte Carlo simulations were performed to evaluate the properties of the catch rate estimators and survey designs. Among the three estimators, the ROM estimator provided the most accurate and precise estimates of mean catch rate and total catch for both roving–roving and roving–access surveys. On average, the root mean square error of simulated total catch estimates was 1.42 times greater and relative bias was 160.13 times greater for roving–roving surveys than for roving–access surveys. Length-of-stay bias and nonstationary catch rates in roving–roving surveys both appeared to affect catch rate and total catch estimates. Our results suggest that use of the ROM estimator in combination with an estimate of angler effort provided the least biased and most precise estimates of total catch for both survey designs. However, roving–access surveys were more accurate than roving–roving surveys for Chinook salmon fisheries in Idaho.

  6. CAN MELATONIN BE EFFECTIVELY USED TO DIMINISH SIDE EFFECTS OF VARIOUS PSYCHOTROPIC DRUGS AND ELECTROCONVULSIVE THERAPY?

    Directory of Open Access Journals (Sweden)

    Roman Aleksandrovich Bekker

    2017-10-01

    Full Text Available Purpose. To study and summarize the existing evidence base for the use of melatonin as a mean to counteract or diminish the side effects of various psychotropic drugs and electroconvulsive therapy, and to provide the reader with relevant conclusions. Methodology. The authors have searched for the scientific literature regarding the use of melatonin as a mean to counteract or diminish the side effects of various psychotropic drugs and electroconvulsive therapy, using the PubMed and Google Scholar as a search tool. Then the authors thoroughly reviewed the data they found. The resulting review is presented in this article. Results. The data we have obtained from this review of the literature indicate that melatonin can be effectively used both in monotherapy and in combination with other therapeutic means in order to reduce several different side effects of psychotropic drugs and electroconvulsive therapy. Melatonin also deserves further study in this regard. The evidence base for its use in this manner is very variable in quality for different side effects. For now, the greatest evidence base exists regarding the potential effectiveness of melatonin in the prevention and treatment of drug-induced insomnia, memory and cognitive impairment, akathisia, tardive dyskinesias, and metabolic syndrome. Practical implications. The results we have obtained can be widely applied in psychiatry, neurology and addiction medicine, as well as in all those areas of general medicine, which make use of psychotropic drugs.

  7. Prediction of Effective Drug Combinations by an Improved Naïve Bayesian Algorithm.

    Science.gov (United States)

    Bai, Li-Yue; Dai, Hao; Xu, Qin; Junaid, Muhammad; Peng, Shao-Liang; Zhu, Xiaolei; Xiong, Yi; Wei, Dong-Qing

    2018-02-05

    Drug combinatorial therapy is a promising strategy for combating complex diseases due to its fewer side effects, lower toxicity and better efficacy. However, it is not feasible to determine all the effective drug combinations in the vast space of possible combinations given the increasing number of approved drugs in the market, since the experimental methods for identification of effective drug combinations are both labor- and time-consuming. In this study, we conducted systematic analysis of various types of features to characterize pairs of drugs. These features included information about the targets of the drugs, the pathway in which the target protein of a drug was involved in, side effects of drugs, metabolic enzymes of the drugs, and drug transporters. The latter two features (metabolic enzymes and drug transporters) were related to the metabolism and transportation properties of drugs, which were not analyzed or used in previous studies. Then, we devised a novel improved naïve Bayesian algorithm to construct classification models to predict effective drug combinations by using the individual types of features mentioned above. Our results indicated that the performance of our proposed method was indeed better than the naïve Bayesian algorithm and other conventional classification algorithms such as support vector machine and K-nearest neighbor.

  8. Prediction of Effective Drug Combinations by an Improved Naïve Bayesian Algorithm

    Directory of Open Access Journals (Sweden)

    Li-Yue Bai

    2018-02-01

    Full Text Available Drug combinatorial therapy is a promising strategy for combating complex diseases due to its fewer side effects, lower toxicity and better efficacy. However, it is not feasible to determine all the effective drug combinations in the vast space of possible combinations given the increasing number of approved drugs in the market, since the experimental methods for identification of effective drug combinations are both labor- and time-consuming. In this study, we conducted systematic analysis of various types of features to characterize pairs of drugs. These features included information about the targets of the drugs, the pathway in which the target protein of a drug was involved in, side effects of drugs, metabolic enzymes of the drugs, and drug transporters. The latter two features (metabolic enzymes and drug transporters were related to the metabolism and transportation properties of drugs, which were not analyzed or used in previous studies. Then, we devised a novel improved naïve Bayesian algorithm to construct classification models to predict effective drug combinations by using the individual types of features mentioned above. Our results indicated that the performance of our proposed method was indeed better than the naïve Bayesian algorithm and other conventional classification algorithms such as support vector machine and K-nearest neighbor.

  9. Microbiological aspects of the effectiveness of antimicrobial drugs

    Directory of Open Access Journals (Sweden)

    Oleksandr Nazarchuk

    2015-06-01

      Abstract Introduction. It is well known, that patients with deep burns belong to the category of critically ill ones. According to the data of National Nosocomial Infections Surveillance (2004, Staphylococcus spp. are among leading opportunistic pathogens of infectious complications in such patients. Nowadays much attention is given to the problem of antibiotic resistance of Staphylococcus clinical strains. More often antiseptics are used in treatment of infectious complications, caused by antibiotic resistant miсroorganisms. The aim of the research was to study microbiological aspects of the effectiveness of antimicrobial drugs. Materials and methods. There were examined 372 critically ill patients with burns, having infectious complications. In all patients microbiological examinations were carried out during the first 7 days after burn trauma. There were isolated 115 clinical strains of Staphylococcus spp.. Their morphological, cultural, biochemical qualities and sensitivity to antibiotics, antiseptics were studied. Rresults of the study. We found, that clinical strains of S. aureus, S. epidermidis were highly resistant to oxacillin (46,9; 59,1 % respectively; were insensitive to clavulanate and sulbactam potentiated beta-lactams; ceftriaxone; meropenem, imipenem; ciprofloxacin. Sensitivity of Staphylococcus to amikacin, linezolid, vancomycin was found. There was shown the sensitivity of antibiotic resistant strains of Staphylococcus to decamethoxin, its polymer composition, chlorhexidine digluconate. In the research there was proved the decreasing of the effectiveness of chlorhexidine digluconate against Staphylococcus in conditions of increasing microbial load to 109 CFU/ml in 6,6 times comparably to decamethoxin drugs (p<0,001. Conclusions Resistant to the majority of antibiotics strains of Staphylococcus spp. store their high sensitivity to antiseptic decamethoxin and its polymeric composition, chlorhexidine digluconate. Microbial load increase up to 109

  10. 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.

  11. 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.

  12. 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

  13. Methodological challenges to control for immortal time bias in addressing drug effects in type 2 diabetes

    OpenAIRE

    Yang, Xi-Lin; Huo, Xiao-Xu; Chan, Juliana CN

    2015-01-01

    There are multiple biases in using observational studies to examine treatment effects such as those from prevalent drug users, immortal time and drug indications. We used renin angiotensin system (RAS) inhibitors and statins as reference drugs with proven efficacies in randomized clinical trials (RCTs) and examined their effectiveness in the prospective Hong Kong Diabetes Registry using adjustment methods proposed in the literature. Using time-dependent exposures to drug treatments yielded gr...

  14. 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.)

  15. 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)

  16. 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.

  17. Estimating effective doses to children from CT examinations

    International Nuclear Information System (INIS)

    Heron, J.C.L.

    2000-01-01

    Full text: Assessing doses to patients in diagnostic radiology is an integral part of implementing optimisation of radiation protection. Sources of normalised data are available for estimating doses to adults undergoing CT examinations, but for children this is not the case. This paper describes a simple method for estimating effective doses arising from paediatric CT examinations. First the effective dose to an adult is calculated, having anatomically matched the scanned regions of the child and the adult and also matched the irradiation conditions. A conversion factor is then applied to the adult effective dose, based on the region of the body being scanned - head, upper or lower trunk. This conversion factor is the child-to-adult ratio of the ratios of effective dose per entrance air kerma (in the absence of the patient) at the FAD. The values of these conversion factors were calculated by deriving effective dose per entrance air kerma at the FAD for new-born, 1, 5, 10, 15 and adult phantoms using four projections (AP, PA, left and right laterals) over a range of beam qualities and FADs.The program PCXMC was used for this purpose. Results to date suggest that the conversion factors to give effective doses for children undergoing CT examinations of the upper trunk are approximately 1.3, 1.2, 1.15, 1.1 and 1.05 for ages 0, 1, 5, 10 and 15 years respectively; CT of the lower trunk - 1.4, 1.3, 1.2, 1.2, 1.1; and CT of the head - 2.3, 2.0, 1.5, 1.3, 1.1. The dependence of these factors on beam quality (HVL from 4 to 10 mm Al) is less than 10%, with harder beams resulting in slightly smaller conversion factors. Dependence on FAD is also less than 10%. Major sources of uncertainties in the conversion factors include matching anatomical regions across the phantoms, and the presence of beam divergence in the z-direction when deriving the factors. The method described provides a simple means of estimating effective doses arising from paediatric CT examinations with

  18. Using pharmacokinetics to predict the effects of pregnancy and maternal-infant transfer of drugs during lactation.

    Science.gov (United States)

    Anderson, Gail D

    2006-12-01

    Knowledge of pharmacokinetics and the use of a mechanistic-based approach can improve our ability to predict the effects of pregnancy for medications when data are limited. Despite the many physiological changes that occur during pregnancy that could theoretically affect absorption, bioavailability does not appear to be altered. Decreased albumin and alpha(1)-acid glycoprotein concentrations during pregnancy will result in decreased protein binding for highly bound drugs. For drugs metabolised by the liver, this can result in misinterpretation of total plasma concentrations of low extraction ratio drugs and overdosing of high extraction ratio drugs administered by non-oral routes. Renal clearance and the activity of the CYP isozymes, CYP3A4, 2D6 and 2C9, and uridine 5'-diphosphate glucuronosyltransferase are increased during pregnancy. In contrast, CYP1A2 and 2C19 activity is decreased. The dose of a drug an infant receives during breastfeeding is dependent on the amount excreted into the breast milk, the daily volume of milk ingested and the average plasma concentration of the mother. The lipophilicity, protein binding and ionisation properties of a drug will determine how much is excreted into the breast milk. The milk to plasma concentration ratio has large inter- and intrasubject variability and is often not known. In contrast, protein binding is usually known. An extensive literature review was done to identify case reports including infant concentrations from breast-fed infants exposed to maternal drugs. For drugs that were at least 85% protein bound, measurable concentrations of drug in the infant did not occur if there was no placental exposure immediately prior to or during delivery. Knowledge of the protein binding properties of a drug can provide a quick and easy tool to estimate exposure of an infant to medication from breastfeeding.

  19. Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation.

    Science.gov (United States)

    Wilby, J; Kainth, A; Hawkins, N; Epstein, D; McIntosh, H; McDaid, C; Mason, A; Golder, S; O'Meara, S; Sculpher, M; Drummond, M; Forbes, C

    2005-04-01

    treatments for patients with generalised seizures. LTG and VPA showed similar health benefits when used as monotherapy. VPA was less costly and was likely to be cost-effective. The analysis indicated that TPM might be cost-effective when used as an adjunctive therapy, with an estimated incremental cost-effectiveness ratio of 34,500 pounds compared with continuing current treatment alone. There was little good-quality evidence from clinical trials to support the use of newer monotherapy or adjunctive therapy AEDs over older drugs, or to support the use of one newer AED in preference to another. In general, data relating to clinical effectiveness, safety and tolerability failed to demonstrate consistent and statistically significant differences between the drugs. The exception was comparisons between newer adjunctive AEDs and placebo, where significant differences favoured newer AEDs. However, trials often had relatively short-term treatment durations and often failed to limit recruitment to either partial or generalised onset seizures, thus limiting the applicability of the data. Newer AEDs, used as monotherapy, may be cost-effective for the treatment of patients who have experienced adverse events with older AEDs, who have failed to respond to the older drugs, or where such drugs are contraindicated. The integrated economic analysis also suggested that newer AEDs used as adjunctive therapy may be cost-effective compared with the continuing current treatment alone given a QALY of about 20,000 pounds. There is a need for more direct comparisons of the different AEDs within clinical trials, considering different treatment sequences within both monotherapy and adjunctive therapy. Length of follow-up also needs to be considered. Trials are needed that recruit patients with either partial or generalised seizures; that investigate effectiveness and cost-effectiveness in patients with generalised onset seizures and that investigate effectiveness in specific populations of epilepsy

  20. 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)

  1. 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.

  2. 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.

  3. 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.

  4. Identification and estimation of survivor average causal effects.

    Science.gov (United States)

    Tchetgen Tchetgen, Eric J

    2014-09-20

    In longitudinal studies, outcomes ascertained at follow-up are typically undefined for individuals who die prior to the follow-up visit. In such settings, outcomes are said to be truncated by death and inference about the effects of a point treatment or exposure, restricted to individuals alive at the follow-up visit, could be biased even if as in experimental studies, treatment assignment were randomized. To account for truncation by death, the survivor average causal effect (SACE) defines the effect of treatment on the outcome for the subset of individuals who would have survived regardless of exposure status. In this paper, the author nonparametrically identifies SACE by leveraging post-exposure longitudinal correlates of survival and outcome that may also mediate the exposure effects on survival and outcome. Nonparametric identification is achieved by supposing that the longitudinal data arise from a certain nonparametric structural equations model and by making the monotonicity assumption that the effect of exposure on survival agrees in its direction across individuals. A novel weighted analysis involving a consistent estimate of the survival process is shown to produce consistent estimates of SACE. A data illustration is given, and the methods are extended to the context of time-varying exposures. We discuss a sensitivity analysis framework that relaxes assumptions about independent errors in the nonparametric structural equations model and may be used to assess the extent to which inference may be altered by a violation of key identifying assumptions. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons, Ltd.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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…

  12. 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...

  13. 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…

  14. 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

  15. 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…

  16. The "War on drugs" in Nigeria: How effective and beneficial is it in ...

    African Journals Online (AJOL)

    Since drugs became both a public and social issue in Nigeria, fear about both the real ... research literature, published documents and media reports on drug policy matters. ... The shift will provide far more cost-effective drug control results and ...

  17. 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.

  18. Potential Effects of a Ban on Direct-to-Consumer Advertising of New Prescription Drugs

    OpenAIRE

    Congressional Budget Office

    2011-01-01

    Concerns about direct-to-consumer advertising of prescription drugs have spurred recent proposals for a moratorium on advertising brand-name prescription drugs to consumers during the first two years following a drug's approval by the Food and Drug Administration. This Congressional Budget Office brief examines some of the effects of such a moratorium, drawing on data documenting direct-to-consumer advertising and other promotional activities used by pharmaceutical producers as well as academ...

  19. 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

  20. 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)

  1. 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.

  2. 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.

  3. 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.

  4. The effect of an interactive e-drug calculations package on nursing students' drug calculation ability and self-efficacy.

    Science.gov (United States)

    McMullan, Miriam; Jones, Ray; Lea, Susan

    2011-06-01

    Nurses need to be competent and confident in performing drug calculations to ensure patient safety. The purpose of this study is to compare an interactive e-drug calculations package, developed using Cognitive Load Theory as its theoretical framework, with traditional handout learning support on nursing students' drug calculation ability, self-efficacy and support material satisfaction. A cluster randomised controlled trial comparing the e-package with traditional handout learning support was conducted with a September cohort (n=137) and a February cohort (n=92) of second year diploma nursing students. Students from each cohort were geographically dispersed over 3 or 4 independent sites. Students from each cohort were invited to participate, halfway through their second year, before and after a 12 week clinical practice placement. During their placement the intervention group received the e-drug calculations package while the control group received traditional 'handout' support material. Drug calculation ability and self-efficacy tests were given to the participants pre- and post-intervention. Participants were given the support material satisfaction scale post-intervention. Students in both cohorts randomised to e-learning were more able to perform drug calculations than those receiving the handout (September: mean 48.4% versus 34.7%, p=0.027; February: mean 47.6% versus 38.3%, p=0.024). February cohort students using the e-package were more confident in performing drug calculations than those students using handouts (self-efficacy mean 56.7% versus 45.8%, p=0.022). There was no difference in improved self-efficacy between intervention and control for students in the September cohort. Students who used the package were more satisfied with its use than the students who used the handout (mean 29.6 versus 26.5, p=0.001), particularly with regard to the package enhancing their learning (p=0.023), being an effective way to learn (p=0.005), providing practice and

  5. Estimation of Aging Effects on LOHS for CANDU-6

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Yong Ki; Moon, Bok Ja; Kim, Seoung Rae [Nuclear Engineering Service and Solution Co. Ltd., Daejeon (Korea, Republic of)

    2014-05-15

    To evaluate the Wolsong Unit 1's capacity to respond to large-scale natural disaster exceeding design, the loss of heat sink(LOHS) accident accompanied by loss of all electric power is simulated as a beyond design basis accident. This analysis is considered the aging effects of plant as the consequences of LOHS accident. Various components of primary heat transport system(PHTS) get aged and some of the important aging effects of CANDU reactor are pressure tube(PT) diametral creep, steam generator(SG) U-tube fouling, increased feeder roughness, and feeder orifice degradation. These effects result in higher inlet header temperatures, reduced flows in some fuel channels, and higher void fraction in fuel channel outlets. Fresh and aged models are established for the analysis where fresh model is the circuit model simulating the conditions at retubing and aged model corresponds to the model reflecting the aged condition at 11 EFPY after retubing. CATHENA computer code[1] is used for the analysis of the system behavior under LOHS condition. The LOHS accident is analyzed for fresh and aged models using CATHENA thermal hydraulic computer code. The decay heat removal is one of the most important factors for mitigation of this accident. The major aging effect on decay heat removal is the reduction of heat transfer efficiency by steam generator. Thus, the channel failure time cannot be conservatively estimated if aged model is applied for the analysis of this accident.

  6. Estimation of effective dose for children in interventional cardiology

    Directory of Open Access Journals (Sweden)

    S. S. Sarycheva

    2017-01-01

    Full Text Available This study is devoted to the estimation of effective dose for children undergoing interventional cardiology examinations. The conversion coefficients (CC from directly measured dose area product (DAP value to effective dose (ED were calculated within the approved effective dose assessment methodology (Guidelines 2.6.1. 2944-11. The CC, Ed K , [mSv / (Gy • cm2] for newborn infants and children of 1, 5, 10 and 15 years old (main(range were calculated as 2.5 (1.8-3.2; 1.1 (0.8-1.3; 0.6 (0.4-0.7; 0.4 (0.3-0.5; and 0,22 (0,18-0,30 respectively. A special Finnish computer program PCXMC 2.0 was used for calculating the dose CC. The series of calculations were made for different values of the physical and geometrical parameters based on their real-existing range of values. The value of CC from DAP to ED were calculated for all pediatric age groups. This work included 153 pediatric interventional studies carried out in two hospitals of the city of St. Petersburg for the period of one year from the summer of 2015. The dose CC dependency from the patient’s age and parameters of the examinations were under the study. The dependence from the beam quality (filtration and tube voltage and age of the patient were found. The younger is the patient, stronger is the filtration and higher is the voltage, the higher is the CC value. The CC in the younger (newborn and older (15 years age groups are different by the factor of 10. It was shown that the changes of the geometric parameters (in the scope of their real existing range have small effect on the value of the effective dose, not exceed 30-50% allowable for radiation protection purpose. The real values of effective doses of children undergoing cardiac interventions were estimated. In severe cases, the values of ED can reach several tens of mSv.

  7. 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_vol, 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

  8. Apollo Video Photogrammetry Estimation Of Plume Impingement Effects

    Science.gov (United States)

    Immer, Christopher; Lane, John; Metzger, Philip T.; Clements, Sandra

    2008-01-01

    The Constellation Project's planned return to the moon requires numerous landings at the same site. Since the top few centimeters are loosely packed regolith, plume impingement from the Lander ejects the granular material at high velocities. Much work is needed to understand the physics of plume impingement during landing in order to protect hardware surrounding the landing sites. While mostly qualitative in nature, the Apollo Lunar Module landing videos can provide a wealth of quantitative information using modem photogrammetry techniques. The authors have used the digitized videos to quantify plume impingement effects of the landing exhaust on the lunar surface. The dust ejection angle from the plume is estimated at 1-3 degrees. The lofted particle density is estimated at 10(exp 8)- 10(exp 13) particles per cubic meter. Additionally, evidence for ejection of large 10-15 cm sized objects and a dependence of ejection angle on thrust are presented. Further work is ongoing to continue quantitative analysis of the landing videos.

  9. 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 ...

  10. Systematic review: ursodeoxycholic acid--adverse effects and drug interactions

    NARCIS (Netherlands)

    Hempfling, W.; Dilger, K.; Beuers, U.

    2003-01-01

    BACKGROUND: Ursodeoxycholic acid is increasingly being used for the treatment of chronic cholestatic liver diseases. It appears to be generally well tolerated, but a systematic review on drug safety is lacking. AIM: As experimental data suggest a role of bile acids in the regulation of hepatic drug

  11. Mixing pleasures: review of the effects of drugs on sex behavior in humans and animal models.

    Science.gov (United States)

    Frohmader, Karla S; Pitchers, Kyle K; Balfour, Margaret E; Coolen, Lique M

    2010-06-01

    Drugs of abuse act on the brain circuits mediating motivation and reward associated with natural behaviors. There is ample evidence that drugs of abuse impact male and female sexual behavior. First, the current review discusses the effect of drugs of abuse on sexual motivation and performance in male and female humans. In particular, we discuss the effects of commonly abused drugs including psychostimulants, opiates, marijuana/THC, and alcohol. In general, drug use affects sexual motivation, arousal, and performance and is commonly associated with increased sexual risk behaviors. Second, studies on effects of systemic administration of drugs of abuse on sexual behavior in animals are reviewed. These studies analyze the effects on sexual performance and motivation but do not investigate the effects of drugs on risk-taking behavior, creating a disconnect between human and animal studies. For this reason, we discuss two studies that focus on the effects of alcohol and methamphetamine on inhibition of maladaptive sex-seeking behaviors in rodents. Third, this review discusses potential brain areas where drugs of abuse may be exerting their effect on sexual behavior with a focus on the mesolimbic system as the site of action. Finally, we discuss recent studies that have brought to light that sexual experience in turn can affect drug responsiveness, including a sensitized locomotor response to amphetamine in female and male rodents as well as enhanced drug reward in male rats. Copyright 2009 Elsevier Inc. All rights reserved.

  12. [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

  13. 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

  14. 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

  15. Estimating effects of improved drinking water and sanitation on cholera.

    Science.gov (United States)

    Leidner, Andrew J; Adusumilli, Naveen C

    2013-12-01

    Demand for adequate provision of drinking-water and sanitation facilities to promote public health and economic growth is increasing in the rapidly urbanizing countries of the developing world. With a panel of data on Asia and Africa from 1990 to 2008, associations are estimated between the occurrence of cholera outbreaks, the case rates in given outbreaks, the mortality rates associated with cholera and two disease control mechanisms, drinking-water and sanitation services. A statistically significant and negative effect is found between drinking-water services and both cholera case rates as well as cholera-related mortality rates. A relatively weak statistical relationship is found between the occurrence of cholera outbreaks and sanitation services.

  16. Cost effectiveness of drug eluting coronary artery stenting in a UK setting: cost-utility study.

    Science.gov (United States)

    Bagust, A; Grayson, A D; Palmer, N D; Perry, R A; Walley, T

    2006-01-01

    To assess the cost effectiveness of drug eluting stents (DES) compared with conventional stents for treatment of symptomatic coronary artery disease in the UK. Cost-utility analysis of audit based patient subgroups by means of a simple economic model. Tertiary care. 12 month audit data for 2884 patients receiving percutaneous coronary intervention with stenting at the Cardiothoracic Centre Liverpool between January 2000 and December 2002. Risk of repeat revascularisation within 12 months of index procedure and reduction in risk from use of DES. Economic modelling was used to estimate the cost-utility ratio and threshold price premium. Four factors were identified for patients undergoing elective surgery (n = 1951) and two for non-elective surgery (n = 933) to predict risk of repeat revascularisation within 12 months. Most patients fell within the subgroup with lowest risk (57% of the elective surgery group with 5.6% risk and 91% of the non-elective surgery group with 9.9% risk). Modelled cost-utility ratios were acceptable for only one group of high risk patients undergoing non-elective surgery (only one patient in audit data). Restricting the number of DES for each patient improved results marginally: 4% of stents could then be drug eluting on economic grounds. The threshold price premium justifying 90% substitution of conventional stents was estimated to be 112 pound sterling (212 USD, 162 pound sterling) (sirolimus stents) or 89 pound sterling (167 USD, 130 pound sterling) (paclitaxel stents). At current UK prices, DES are not cost effective compared with conventional stents except for a small minority of patients. Although the technology is clearly effective, general substitution is not justified unless the price premium falls substantially.

  17. 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.

  18. 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%.

  19. 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.

  20. 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)

  1. A qualitative examination of the effects of international counter-drug interdictions.

    Science.gov (United States)

    Toth, Alexander G; Mitchell, Ojmarrh

    2018-05-01

    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.

  2. Estimating causal effects with a non-paranormal method for the design of efficient intervention experiments.

    Science.gov (United States)

    Teramoto, Reiji; Saito, Chiaki; Funahashi, Shin-ichi

    2014-06-30

    Knockdown or overexpression of genes is widely used to identify genes that play important roles in many aspects of cellular functions and phenotypes. Because next-generation sequencing generates high-throughput data that allow us to detect genes, it is important to identify genes that drive functional and phenotypic changes of cells. However, conventional methods rely heavily on the assumption of normality and they often give incorrect results when the assumption is not true. To relax the Gaussian assumption in causal inference, we introduce the non-paranormal method to test conditional independence in the PC-algorithm. Then, we present the non-paranormal intervention-calculus when the directed acyclic graph (DAG) is absent (NPN-IDA), which incorporates the cumulative nature of effects through a cascaded pathway via causal inference for ranking causal genes against a phenotype with the non-paranormal method for estimating DAGs. We demonstrate that causal inference with the non-paranormal method significantly improves the performance in estimating DAGs on synthetic data in comparison with the original PC-algorithm. Moreover, we show that NPN-IDA outperforms the conventional methods in exploring regulators of the flowering time in Arabidopsis thaliana and regulators that control the browning of white adipocytes in mice. Our results show that performance improvement in estimating DAGs contributes to an accurate estimation of causal effects. Although the simplest alternative procedure was used, our proposed method enables us to design efficient intervention experiments and can be applied to a wide range of research purposes, including drug discovery, because of its generality.

  3. 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

  4. Spillover Effects of Drug Safety Warnings on Preventive Health Care Use

    DEFF Research Database (Denmark)

    Daysal, N. Meltem; Orsini, Chiara

    2015-01-01

    We examine how new medical information on drug safety impacts preventive health care use. 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 the health risks associated...... with the long-term use of hormone replacement therapy (HRT). We first show that, after the release of the WHIS findings, HRT use dropped sharply among post-menopausal women. We then estimate the spillover effects of the WHIS findings on preventive care by means of a difference-in-differences methodology...... comparing changes in preventive care use among 60 to 69 year-old women (who have high rates of HRT use) with the change among women aged 75 and above (who have much lower rates of HRT use). Using data from the Behavioral Risk Factor Surveillance System for the period 1998–2007, we find that women aged 60...

  5. Stigma, discrimination, treatment effectiveness, and policy: public views about drug addiction and mental illness.

    Science.gov (United States)

    Barry, Colleen L; McGinty, Emma E; Pescosolido, Bernice A; Goldman, Howard H

    2014-10-01

    Public attitudes about drug addiction and mental illness were compared. A Web-based national survey (N=709) was conducted to compare attitudes about stigma, discrimination, treatment effectiveness, and policy support in regard to drug addiction and mental illness. Respondents held significantly more negative views toward persons with drug addiction. More respondents were unwilling to have a person with drug addiction marry into their family or work closely with them. Respondents were more willing to accept discriminatory practices against persons with drug addiction, more skeptical about the effectiveness of treatments, and more likely to oppose policies aimed at helping them. Drug addiction is often treated as a subcategory of mental illness, and insurance plans group them together under the rubric of "behavioral health." Given starkly different public views about drug addiction and mental illness, advocates may need to adopt differing approaches to reducing stigma and advancing public policy.

  6. Effects of exposure estimation errors on estimated exposure-response relations for PM2.5.

    Science.gov (United States)

    Cox, Louis Anthony Tony

    2018-07-01

    Associations between fine particulate matter (PM2.5) exposure concentrations and a wide variety of undesirable outcomes, from autism and auto theft to elderly mortality, suicide, and violent crime, have been widely reported. Influential articles have argued that reducing National Ambient Air Quality Standards for PM2.5 is desirable to reduce these outcomes. Yet, other studies have found that reducing black smoke and other particulate matter by as much as 70% and dozens of micrograms per cubic meter has not detectably affected all-cause mortality rates even after decades, despite strong, statistically significant positive exposure concentration-response (C-R) associations between them. This paper examines whether this disconnect between association and causation might be explained in part by ignored estimation errors in estimated exposure concentrations. We use EPA air quality monitor data from the Los Angeles area of California to examine the shapes of estimated C-R functions for PM2.5 when the true C-R functions are assumed to be step functions with well-defined response thresholds. The estimated C-R functions mistakenly show risk as smoothly increasing with concentrations even well below the response thresholds, thus incorrectly predicting substantial risk reductions from reductions in concentrations that do not affect health risks. We conclude that ignored estimation errors obscure the shapes of true C-R functions, including possible thresholds, possibly leading to unrealistic predictions of the changes in risk caused by changing exposures. Instead of estimating improvements in public health per unit reduction (e.g., per 10 µg/m 3 decrease) in average PM2.5 concentrations, it may be essential to consider how interventions change the distributions of exposure concentrations. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. 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,

  8. Drugs with anticholinergic side‑effects in primary care

    African Journals Online (AJOL)

    2014-05-31

    May 31, 2014 ... retention or hesitancy, visual impairment, falls, confusion, drowsiness ... updated in 2012; as drugs, which may cause dementia and cognitive ... Two questions were asked to determine physicians' attention ... Even if selective.

  9. 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.

  10. 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

  11. 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.

  12. Estimated effects of temperature on secondary organic aerosol concentrations.

    Science.gov (United States)

    Sheehan, P E; Bowman, F M

    2001-06-01

    The temperature-dependence of secondary organic aerosol (SOA) concentrations is explored using an absorptive-partitioning model under a variety of simplified atmospheric conditions. Experimentally determined partitioning parameters for high yield aromatics are used. Variation of vapor pressures with temperature is assumed to be the main source of temperature effects. Known semivolatile products are used to define a modeling range of vaporization enthalpy of 10-25 kcal/mol-1. The effect of diurnal temperature variations on model predictions for various assumed vaporization enthalpies, precursor emission rates, and primary organic concentrations is explored. Results show that temperature is likely to have a significant influence on SOA partitioning and resulting SOA concentrations. A 10 degrees C decrease in temperature is estimated to increase SOA yields by 20-150%, depending on the assumed vaporization enthalpy. In model simulations, high daytime temperatures tend to reduce SOA concentrations by 16-24%, while cooler nighttime temperatures lead to a 22-34% increase, compared to constant temperature conditions. Results suggest that currently available constant temperature partitioning coefficients do not adequately represent atmospheric SOA partitioning behavior. Air quality models neglecting the temperature dependence of partitioning are expected to underpredict peak SOA concentrations as well as mistime their occurrence.

  13. 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)

  14. Adverse effects of sympathomimetic drugs in a group of adolescents

    OpenAIRE

    Jerí, F. Raúl; Carbajal, Carlos; Sánchez M., César

    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...

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

    Science.gov (United States)

    2013-06-01

    today, customers have easy access to information, products, and services from numerous companies simply by using the Internet or a smartphone , so...customers in the smartphone 81 Campbell, Drug War Zone, 245. 82 Paul Gootenberg, “Talking About The...Drug addictions bring people back once they become hooked. Cartels have been known to allow contractors to use the “bait and hook” technique, a method

  16. Estimating overall exposure effects for the clustered and censored outcome using random effect Tobit regression models.

    Science.gov (United States)

    Wang, Wei; Griswold, Michael E

    2016-11-30

    The random effect Tobit model is a regression model that accommodates both left- and/or right-censoring and within-cluster dependence of the outcome variable. Regression coefficients of random effect Tobit models have conditional interpretations on a constructed latent dependent variable and do not provide inference of overall exposure effects on the original outcome scale. Marginalized random effects model (MREM) permits likelihood-based estimation of marginal mean parameters for the clustered data. For random effect Tobit models, we extend the MREM to marginalize over both the random effects and the normal space and boundary components of the censored response to estimate overall exposure effects at population level. We also extend the 'Average Predicted Value' method to estimate the model-predicted marginal means for each person under different exposure status in a designated reference group by integrating over the random effects and then use the calculated difference to assess the overall exposure effect. The maximum likelihood estimation is proposed utilizing a quasi-Newton optimization algorithm with Gauss-Hermite quadrature to approximate the integration of the random effects. We use these methods to carefully analyze two real datasets. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  17. 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.

  18. 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 ...

  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

    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. Evaluation of Anti-Inflammatory Drug-Conjugated Silicon Quantum Dots: Their Cytotoxicity and Biological Effect

    Directory of Open Access Journals (Sweden)

    Kenji Yamamoto

    2013-01-01

    Full Text Available Silicon quantum dots (Si-QDs have great potential for biomedical applications, including their use as biological fluorescent markers and carriers for drug delivery systems. Biologically inert Si-QDs are less toxic than conventional cadmium-based QDs, and can modify the surface of the Si-QD with covalent bond. We synthesized water-soluble alminoprofen-conjugated Si-QDs (Ap-Si. Alminoprofen is a non-steroid anti-inflammatory drug (NSAID used as an analgesic for rheumatism. Our results showed that the “silicon drug” is less toxic than the control Si-QD and the original drug. These phenomena indicate that the condensed surface integration of ligand/receptor-type drugs might reduce the adverse interaction between the cells and drug molecules. In addition, the medicinal effect of the Si-QDs (i.e., the inhibition of COX-2 enzyme was maintained compared to that of the original drug. The same drug effect is related to the integration ratio of original drugs, which might control the binding interaction between COX-2 and the silicon drug. We conclude that drug conjugation with biocompatible Si-QDs is a potential method for functional pharmaceutical drug development.

  1. 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)

  2. 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...

  3. 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.

  4. A Monte Carlo estimation of effective dose in chest tomosynthesis

    International Nuclear Information System (INIS)

    Sabol, John M.

    2009-01-01

    calculated to be 0.124 mSv (ICRP60) [0.134 mSv (ICRP103)]. This is less than 75% of that predicted by scaling of the PA mA s ratio. This lower dose was due to changes in the focal-spot-to-skin distance, effective changes in collimation with projection angle, rounding down of the mA s step, and variations in organ exposure to the primary x-ray beam for each view. Large errors in dose estimation can occur if these factors are not accurately modeled. Conclusions: The effective dose of a chest examination with this chest tomosynthesis system is about twice that of a two-view chest examination and less than 2% of the published average values for thoracic CT. It is shown that complete consideration of the tomosynthesis acquisition technique and geometry is required for accurate determination of the effective dose to the patient. Tomosynthesis provides three-dimensional imaging at a dose level comparable to a two-view chest x-ray examination and may provide a low dose alternative to thoracic CT for obtaining depth information in chest imaging.

  5. 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...

  6. Effect of nonsteroidal antiinflammatory drugs on the C-reactive protein level in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Tarp, Simon; Bartels, Else M.; Bliddal, Henning

    2012-01-01

    To evaluate the effects of oral nonsteroidal antiinflammatory drugs (NSAIDs) on C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients, with a prespecified focus on the different NSAIDs.......To evaluate the effects of oral nonsteroidal antiinflammatory drugs (NSAIDs) on C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients, with a prespecified focus on the different NSAIDs....

  7. Quiet please! Drug round tabards: are they effective and accepted? A mixed method study

    NARCIS (Netherlands)

    Verweij, Lotte; Smeulers, Marian; Maaskant, Jolanda M.; Vermeulen, Hester

    2014-01-01

    The use of drug round tabards is a widespread intervention that is implemented to reduce the number of interruptions and medication administration errors (MAEs) by nurses; however, evidence for their effectiveness is scarce. Evaluation of the effect of drug round tabards on the frequency and type of

  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, lowachieving 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, low-achieving students are harmed by high-achieving peers. Analyzing students’ course evaluations suggests that peer effects are driven by

  10. 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.

  11. Prediction of drug-related cardiac adverse effects in humans--A: creation of a database of effects and identification of factors affecting their occurrence.

    Science.gov (United States)

    Matthews, Edwin J; Frid, Anna A

    2010-04-01

    This is the first of two reports that describes the compilation of a database of drug-related cardiac adverse effects (AEs) that was used to construct quantitative structure-activity relationship (QSAR) models to predict these AEs, to identify properties of pharmaceuticals correlated with the AEs, and to identify plausible mechanisms of action (MOAs) causing the AEs. This database of 396,985 cardiac AE reports was linked to 1632 approved drugs and their chemical structures, 1851 clinical indications (CIs), 997 therapeutic targets (TTs), 432 pharmacological MOAs, and 21,180 affinity coefficients (ACs) for the MOA receptors. AEs were obtained from the Food and Drug Administration's (FDA's) Spontaneous Reporting System (SRS) and Adverse Event Reporting System (AERS) and publicly available medical literature. Drug TTs were obtained from Integrity; drug MOAs and ACs were predicted by BioEpisteme. Significant cardiac AEs and patient exposures were estimated based on the proportional reporting ratios (PRRs) for each drug and each AE endpoint as a percentage of the total AEs. Cardiac AE endpoints were bundled based on toxicological mechanism and concordance of drug-related findings. Results revealed that significant cardiac AEs formed 9 clusters affecting Purkinje nerve fibers (arrhythmia, bradycardia, conduction disorder, electrocardiogram, palpitations, QT prolongation, rate rhythm composite, tachycardia, and Torsades de pointes), and 5 clusters affecting the heart muscle (coronary artery disorders, heart failure, myocardial disorders, myocardial infarction, and valve disorders). Based on the observation that each drug had one TT and up to 9 off-target MOAs, cardiac AEs were highly correlated with drugs affecting cardiovascular and cardioneurological functions and certain MOAs (e.g., alpha- and beta-adeno, dopamine, and hydroxytryptomine receptors). Copyright 2010. Published by Elsevier Inc.

  12. 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

    2018-04-01

    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.

  13. Drug-drug Interactions of Statins Potentially Leading to Muscle-Related Side Effects in Hospitalized Patients.

    Science.gov (United States)

    Bucsa, Camelia; Farcas, Andreea; Leucuta, D; Mogosan, Cristina; Bojita, M; Dumitrascu, D L

    2015-01-01

    The associations of drugs that may interact with the statins resulting in elevated serum concentration of the statins are an important risk factor for statin induced muscle disorders. We aimed to determine the prevalence of these associations in all hospitalized patients that had been prescribed statins before/during hospitalization and to find out how often they are associated with muscle-related side effects. This prospective, non-interventional study performed in two internal medicine departments included patients with statin therapy before/during hospitalization. Data on each patient demographic characteristics, co-morbidities and treatment was collected from medical charts and interviews. We evaluated patients' therapy for the targeted associations using Thomson Micromedex Drug Interactions checker and we ranked the identified drug-drug interactions (DDIs) accordingly. Each patient with statin treatment before admission was additionally interviewed in order to identify muscular symptoms. In 109 patients on statin treatment we found 35 potential (p) DDIs of statins in 30 (27.5%) patients, most of which were in the therapy before admission (27 pDDIs). The pDDIs were moderate (20 pDDIs) and major (15 pDDIs). Of the total number of pDDIs, 24 were targeting the muscular system. The drugs most frequently involved in the statins' pDDIs were amiodarone and fenofibrate. Two of the patients with pDDIs reported muscle pain, both having additional risk factors for statin induced muscular effects. The prevalence of statins' pDDIs was high in our study, mostly in the therapy before admission, with only a small number of pDDIs resulting in clinical outcome.

  14. 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.

  15. 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 phy......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...

  16. Renal Side Effects of Non-Steroidal Anti-Inflammatory Drugs in Neonates

    Directory of Open Access Journals (Sweden)

    Marc Gewillig

    2010-02-01

    Full Text Available Non-steroidal anti-inflammatory drugs like ibuprofen or indomethacin are commonly prescribed drugs to induce pharmacologic closure of a patent ductus arteriosus in preterm neonates. Based on a recently published Cochrane meta-analysis, both drugs are equally effective to induce closure. Drug choice can therefore be based on differences in side effects or pharmaco-economic arguments. The current review quantifies the negative impact of either ibuprofen or indomethacin on renal function, including diuresis, glomerular filtration rate and renal tubular function. Both ibuprofen and indomethacin have a quantifiable impact on renal function. However, compared to ibuprofen, the negative impact of indomethacin is more pronounced.

  17. [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.

  18. National Estimates of Marijuana Use and Related Indicators - National Survey on Drug Use and Health, United States, 2002-2014.

    Science.gov (United States)

    Azofeifa, Alejandro; Mattson, Margaret E; Schauer, Gillian; McAfee, Tim; Grant, Althea; Lyerla, Rob

    2016-09-02

    In the United States, marijuana is the most commonly used illicit drug. In 2013, 7.5% (19.8 million) of the U.S. population aged ≥12 years reported using marijuana during the preceding month. Because of certain state-level policies that have legalized marijuana for medical or recreational use, population-based data on marijuana use and other related indicators are needed to help monitor behavioral health changes in the United States. 2002-2014. The National Survey on Drug Use and Health (NSDUH) is a national- and state-level survey of a representative sample of the civilian, noninstitutionalized U.S. population aged ≥12 years. NSDUH collects information about the use of illicit drugs, alcohol, and tobacco; initiation of substance use; frequency of substance use; substance dependence and abuse; perception of substance harm risk or no risk; and other related behavioral health indicators. This report describes national trends for selected marijuana use and related indicators, including prevalence of marijuana use; initiation; perception of harm risk, approval, and attitudes; perception of availability and mode of acquisition; dependence and abuse; and perception of legal penalty for marijuana possession. In 2014, a total of 2.5 million persons aged ≥12 years had used marijuana for the first time during the preceding 12 months, an average of approximately 7,000 new users each day. During 2002-2014, the prevalence of marijuana use during the past month, past year, and daily or almost daily increased among persons aged ≥18 years, but not among those aged 12-17 years. Among persons aged ≥12 years, the prevalence of perceived great risk from smoking marijuana once or twice a week and once a month decreased and the prevalence of perceived no risk increased. The prevalence of past year marijuana dependence and abuse decreased, except among persons aged ≥26 years. Among persons aged ≥12 years, the percentage reporting that marijuana was fairly easy or very easy

  19. 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.

  20. A side-effect free method for identifying cancer drug targets.

    Science.gov (United States)

    Ashraf, Md Izhar; Ong, Seng-Kai; Mujawar, Shama; Pawar, Shrikant; More, Pallavi; Paul, Somnath; Lahiri, Chandrajit

    2018-04-27

    Identifying effective drug targets, with little or no side effects, remains an ever challenging task. A potential pitfall of failing to uncover the correct drug targets, due to side effect of pleiotropic genes, might lead the potential drugs to be illicit and withdrawn. Simplifying disease complexity, for the investigation of the mechanistic aspects and identification of effective drug targets, have been done through several approaches of protein interactome analysis. Of these, centrality measures have always gained importance in identifying candidate drug targets. Here, we put forward an integrated method of analysing a complex network of cancer and depict the importance of k-core, functional connectivity and centrality (KFC) for identifying effective drug targets. Essentially, we have extracted the proteins involved in the pathways leading to cancer from the pathway databases which enlist real experimental datasets. The interactions between these proteins were mapped to build an interactome. Integrative analyses of the interactome enabled us to unearth plausible reasons for drugs being rendered withdrawn, thereby giving future scope to pharmaceutical industries to potentially avoid them (e.g. ESR1, HDAC2, F2, PLG, PPARA, RXRA, etc). Based upon our KFC criteria, we have shortlisted ten proteins (GRB2, FYN, PIK3R1, CBL, JAK2, LCK, LYN, SYK, JAK1 and SOCS3) as effective candidates for drug development.

  1. Stem cells as anticancer drug carrier to reduce the chemotherapy side effect

    Science.gov (United States)

    Salehi, Hamideh; Al-Arag, Siham; Middendorp, Elodie; Gergley, Csilla; Cuisinier, Frederic

    2017-02-01

    Chemotherapy used for cancer treatment, due to the lack of specificity of drugs, is associated to various damaging side effects that have severe impact on patients' quality of life. Over the past 30 years, increasing efforts have been placed on optimizing chemotherapy dosing with the main goal of increasing antitumor efficacy while reducing drug-associated toxicity. A novel research shows that stem cells may act as a reservoir for the anticancer agent, which will subsequently release some of the drug's metabolites, or even the drug in its original form, in vicinity of the cancer cells. These cells may play a dual role in controlling drug toxicity depending on their capacity to uptake and release the chemotherapeutic drug. In our study, we show that Dental Pulp Stem Cells DPSCs are able to rapidly uptake Paclitaxel PTX, and to release it in the culture medium in a time-dependent manner. This resulting conditioned culture medium is to be transferred to breast cancer cells, the MCF-7. By applying Confocal Raman Microscopy, the anticancer drug uptake by the MCF-7 was measured. Surprisingly, the cancer cells -without any direct contact with PTX- showed a drug uptake. This proves that the stem cells carried and delivered the anticancer drug without its modification. It could be a revolution in chemotherapy to avoid the drug's side effects and increase its efficacy.

  2. Estimating the Effects of Parental Divorce and Death With Fixed Effects Models

    OpenAIRE

    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 o...

  3. The Paradoxical and Unintended Effects of the War on Drugs

    Science.gov (United States)

    1993-04-01

    of coca leaves; 2) heroin, derived from the opium poppy; and, 3) marijuana and hashish from the cannabis plant. Cocaine and crack come into the U.S...example, is 28 to 43 per cent of its total exports, and generates more money than its major export, coffee . 52 Moreover, the drug business is a major source

  4. 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

  5. [Adverse muscle effects of a podofyllotoxin-containing cytotoxic drug product with simvastatin].

    Science.gov (United States)

    Kaipiainen-Seppänen, Oili; Savolainen, Elina; Elfving, Pia; Kononoff, Aulikki

    2009-01-01

    With the ageing population, drug interactions pose an increasing challenge to health professionals. We describe four patients, for whom concurrent administration of a podofyllotoxin-containing cytotoxic drug product and simvastatin caused severe adverse effects on muscles, including muscle pain, soreness or fatigue or weakness, and in some patients also disintegration of muscle tissue, i.e. rhabdomyolysis. The metabolism of both drugs proceeds via the common CYP3A4 enzyme pathway.

  6. Nonparametric Estimation of Distributions in Random Effects Models

    KAUST Repository

    Hart, Jeffrey D.; Cañ ette, Isabel

    2011-01-01

    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

  7. 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.

  8. Tumor Volume Estimation and Quasi-Continuous Administration for Most Effective Bevacizumab Therapy.

    Science.gov (United States)

    Sápi, Johanna; Kovács, Levente; Drexler, Dániel András; Kocsis, Pál; Gajári, Dávid; Sápi, Zoltán

    2015-01-01

    Bevacizumab is an exogenous inhibitor which inhibits the biological activity of human VEGF. Several studies have investigated the effectiveness of bevacizumab therapy according to different cancer types but these days there is an intense debate on its utility. We have investigated different methods to find the best tumor volume estimation since it creates the possibility for precise and effective drug administration with a much lower dose than in the protocol. We have examined C38 mouse colon adenocarcinoma and HT-29 human colorectal adenocarcinoma. In both cases, three groups were compared in the experiments. The first group did not receive therapy, the second group received one 200 μg bevacizumab dose for a treatment period (protocol-based therapy), and the third group received 1.1 μg bevacizumab every day (quasi-continuous therapy). Tumor volume measurement was performed by digital caliper and small animal MRI. The mathematical relationship between MRI-measured tumor volume and mass was investigated to estimate accurate tumor volume using caliper-measured data. A two-dimensional mathematical model was applied for tumor volume evaluation, and tumor- and therapy-specific constants were calculated for the three different groups. The effectiveness of bevacizumab administration was examined by statistical analysis. In the case of C38 adenocarcinoma, protocol-based treatment did not result in significantly smaller tumor volume compared to the no treatment group; however, there was a significant difference between untreated mice and mice who received quasi-continuous therapy (p = 0.002). In the case of HT-29 adenocarcinoma, the daily treatment with one-twelfth total dose resulted in significantly smaller tumors than the protocol-based treatment (p = 0.038). When the tumor has a symmetrical, solid closed shape (typically without treatment), volume can be evaluated accurately from caliper-measured data with the applied two-dimensional mathematical model. Our results

  9. Deciphering the clinical effect of drugs through large-scale data integration

    DEFF Research Database (Denmark)

    Kjærulff, Sonny Kim

    . This work demonstrates the power of a strategy that uses clinical data mining in association with chemical biology in order to reduce the search space and aid identification of novel drug actions. The second article described in chapter 3 outlines a high confidence side-effect-drug interaction dataset. We...... demonstrates the importance of using high-confidence drug-side-effect data in deciphering the effect of small molecules in humans. In summary, this thesis presents computational systems chemical biology approaches that can help identify clinical effects of small molecules through large-scale data integration...

  10. 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.

  11. Effect of a brief intervention for alcohol and illicit drug use on trauma recidivism in a cohort of trauma patients.

    Science.gov (United States)

    Cordovilla-Guardia, Sergio; Fernández-Mondéjar, Enrique; Vilar-López, Raquel; Navas, Juan F; Portillo-Santamaría, Mónica; Rico-Martín, Sergio; Lardelli-Claret, Pablo

    2017-01-01

    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.

  12. Effect of a brief intervention for alcohol and illicit drug use on trauma recidivism in a cohort of trauma patients

    Science.gov (United States)

    Fernández-Mondéjar, Enrique; Vilar-López, Raquel; Navas, Juan F.; Portillo-Santamaría, Mónica; Rico-Martín, Sergio; Lardelli-Claret, Pablo

    2017-01-01

    Objective Estimate the effectiveness of brief interventions in reducing trauma recidivism in hospitalized trauma patients who screened positive for alcohol and/or illicit drug use. Methods 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. Results 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. Conclusion The brief intervention offered during hospitalization in trauma patients positive for alcohol and/or illicit drug use can halve the incidence of trauma recidivism. PMID:28813444

  13. 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.

  14. 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

  15. 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...

  16. Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; policies, requirements, and administrative procedures; delay of effective date; reopening of administrative record. Food and Drug Administration, HHS. Final rule; delay of effective date; reopening of administrative record.

    Science.gov (United States)

    2000-05-03

    The Food and Drug Administration (FDA) is delaying until October 1, 2001, the effective date and reopening the administrative record to receive additional comments regarding certain requirements of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720). The other provisions of the final rule become effective on December 4, 2000. The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA) and the FDA Modernization Act of 1997 (the Modernization Act). FDA is delaying the effective date for certain requirements relating to wholesale distribution of prescription drugs by distributors that are not authorized distributors of record. FDA is also delaying the effective date of another requirement that would prohibit blood centers functioning as "health care entities" to act as wholesale distributors of blood derivatives. The agency is taking this action to address numerous concerns about the provisions raised by affected parties.

  17. The use of random-effects models to identify health care center-related characteristics modifying the effect of antipsychotic drugs

    Directory of Open Access Journals (Sweden)

    Nordon C

    2017-12-01

    Full Text Available Clementine Nordon,1 Constance Battin,1 Helene Verdoux,2 Josef Maria Haro,3 Mark Belger,4 Lucien Abenhaim,1 Tjeerd Pieter van Staa5 On behalf of the IMI GetReal WP2 Group 1Epidemiological Research, Analytica LASER, Paris, 2Population Health Research Center, Team Pharmaco-Epidemiology, UMR 1219, Bordeaux-2 University, INSERM, Bordeaux, France; 3Parc Sanitari Sant Joan de Deu, CIBERSAM, University of Barcelona, Barcelona, Spain; 4Eli Lilly and Company Limited, Erl Wood Manor, Windlesham, 5Farr Institute, University of Manchester, Manchester, UK Purpose: A case study was conducted, exploring methods to identify drugs effects modifiers, at a health care center level.Patients and methods: Data were drawn from the Schizophrenia Outpatient Health Outcome cohort, including hierarchical information on 6641 patients, recruited from 899 health care centers from across ten European countries. Center-level characteristics included the following: psychiatrist’s gender, age, length of practice experience, practice setting and type, countries’ Healthcare System Efficiency score, and psychiatrist density in the country. Mixed multivariable linear regression models were used: 1 to estimate antipsychotic drugs’ effectiveness (defined as the association between patients’ outcome at 3 months – dependent variable, continuous – and antipsychotic drug initiation at baseline – drug A vs other antipsychotic drug; 2 to estimate the similarity between clustered data (using the intra-cluster correlation coefficient; and 3 to explore antipsychotic drug effects modification by center-related characteristics (using the addition of an interaction term.Results: About 23% of the variance found for patients’ outcome was explained by unmeasured confounding at a center level. Psychiatrists’ practice experience was found to be associated with patient outcomes (p=0.04 and modified the relative effect of “drug A” (p<0.001, independent of center- or patient

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

    Science.gov (United States)

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

    2003-10-01

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

  19. Personalizing oncology treatments by predicting drug efficacy, side-effects, and improved therapy: mathematics, statistics, and their integration.

    Science.gov (United States)

    Agur, Zvia; Elishmereni, Moran; Kheifetz, Yuri

    2014-01-01

    Despite its great promise, personalized oncology still faces many hurdles, and it is increasingly clear that targeted drugs and molecular biomarkers alone yield only modest clinical benefit. One reason is the complex relationships between biomarkers and the patient's response to drugs, obscuring the true weight of the biomarkers in the overall patient's response. This complexity can be disentangled by computational models that integrate the effects of personal biomarkers into a simulator of drug-patient dynamic interactions, for predicting the clinical outcomes. Several computational tools have been developed for personalized oncology, notably evidence-based tools for simulating pharmacokinetics, Bayesian-estimated tools for predicting survival, etc. We describe representative statistical and mathematical tools, and discuss their merits, shortcomings and preliminary clinical validation attesting to their potential. Yet, the individualization power of mathematical models alone, or statistical models alone, is limited. More accurate and versatile personalization tools can be constructed by a new application of the statistical/mathematical nonlinear mixed effects modeling (NLMEM) approach, which until recently has been used only in drug development. Using these advanced tools, clinical data from patient populations can be integrated with mechanistic models of disease and physiology, for generating personal mathematical models. Upon a more substantial validation in the clinic, this approach will hopefully be applied in personalized clinical trials, P-trials, hence aiding the establishment of personalized medicine within the main stream of clinical oncology. © 2014 Wiley Periodicals, Inc.

  20. 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.

  1. Cost-effectiveness analysis of microdose clinical trials in drug development.

    Science.gov (United States)

    Yamane, Naoe; Igarashi, Ataru; Kusama, Makiko; Maeda, Kazuya; Ikeda, Toshihiko; Sugiyama, Yuichi

    2013-01-01

    Microdose (MD) clinical trials have been introduced to obtain human pharmacokinetic data early in drug development. Here we assessed the cost-effectiveness of microdose integrated drug development in a hypothetical model, as there was no such quantitative research that weighed the additional effectiveness against the additional time and/or cost. First, we calculated the cost and effectiveness (i.e., success rate) of 3 types of MD integrated drug development strategies: liquid chromatography-tandem mass spectrometry, accelerator mass spectrometry, and positron emission tomography. Then, we analyzed the cost-effectiveness of 9 hypothetical scenarios where 100 drug candidates entering into a non-clinical toxicity study were selected by different methods as the conventional scenario without MD. In the base-case, where 70 drug candidates were selected without MD and 30 selected evenly by one of the three MD methods, incremental cost-effectiveness ratio per one additional drug approved was JPY 12.7 billion (US$ 0.159 billion), whereas the average cost-effectiveness ratio of the conventional strategy was JPY 24.4 billion, which we set as a threshold. Integrating MD in the conventional drug development was cost-effective in this model. This quantitative analytical model which allows various modifications according to each company's conditions, would be helpful for guiding decisions early in clinical development.

  2. Uncertainties in effective dose estimates of adult CT head scans: The effect of head size

    International Nuclear Information System (INIS)

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

    2009-01-01

    Purpose: This study is an extension of a previous study where the uncertainties in effective dose estimates from adult CT head scans were calculated using four CT effective dose estimation methods, three of which were computer programs (CT-EXPO, CTDOSIMETRY, and IMPACTDOSE) and one that involved the dose length product (DLP). However, that study did not include the uncertainty contribution due to variations in head sizes. Methods: The uncertainties due to head size variations were estimated by first using the computer program data to calculate doses to small and large heads. These doses were then compared with doses calculated for the phantom heads used by the computer programs. An uncertainty was then assigned based on the difference between the small and large head doses and the doses of the phantom heads. Results: The uncertainties due to head size variations alone were found to be between 4% and 26% depending on the method used and the patient gender. When these uncertainties were included with the results of the previous study, the overall uncertainties in effective dose estimates (stated at the 95% confidence interval) were 20%-31% (CT-EXPO), 15%-30% (CTDOSIMETRY), 20%-36% (IMPACTDOSE), and 31%-40% (DLP). Conclusions: For the computer programs, the lower overall uncertainties were still achieved when measured values of CT dose index were used rather than tabulated values. For DLP dose estimates, head size variations made the largest (for males) and second largest (for females) contributions to effective dose uncertainty. An improvement in the uncertainty of the DLP method dose estimates will be achieved if head size variation can be taken into account.

  3. Uncertainties in effective dose estimates of adult CT head scans: The effect of head size

    Energy Technology Data Exchange (ETDEWEB)

    Gregory, Kent J.; Bibbo, Giovanni; Pattison, John E. [Department of Medical Physics, Royal Adelaide Hospital, Adelaide, South Australia 5000 (Australia) and School of Electrical and Information Engineering (Applied Physics), University of South Australia, Mawson Lakes, South Australia 5095 (Australia); Division of Medical Imaging, Women' s and Children' s Hospital, North Adelaide, South Australia 5006 (Australia) and School of Electrical and Information Engineering (Applied Physics), University of South Australia, Mawson Lakes, South Australia 5095 (Australia); School of Electrical and Information Engineering (Applied Physics), University of South Australia, Mawson Lakes, South Australia 5095 (Australia)

    2009-09-15

    Purpose: This study is an extension of a previous study where the uncertainties in effective dose estimates from adult CT head scans were calculated using four CT effective dose estimation methods, three of which were computer programs (CT-EXPO, CTDOSIMETRY, and IMPACTDOSE) and one that involved the dose length product (DLP). However, that study did not include the uncertainty contribution due to variations in head sizes. Methods: The uncertainties due to head size variations were estimated by first using the computer program data to calculate doses to small and large heads. These doses were then compared with doses calculated for the phantom heads used by the computer programs. An uncertainty was then assigned based on the difference between the small and large head doses and the doses of the phantom heads. Results: The uncertainties due to head size variations alone were found to be between 4% and 26% depending on the method used and the patient gender. When these uncertainties were included with the results of the previous study, the overall uncertainties in effective dose estimates (stated at the 95% confidence interval) were 20%-31% (CT-EXPO), 15%-30% (CTDOSIMETRY), 20%-36% (IMPACTDOSE), and 31%-40% (DLP). Conclusions: For the computer programs, the lower overall uncertainties were still achieved when measured values of CT dose index were used rather than tabulated values. For DLP dose estimates, head size variations made the largest (for males) and second largest (for females) contributions to effective dose uncertainty. An improvement in the uncertainty of the DLP method dose estimates will be achieved if head size variation can be taken into account.

  4. Studying Disease Occurrence and Drug Effects in Children: A global approach

    NARCIS (Netherlands)

    O.U. Osokogu (Osemeke)

    2017-01-01

    markdownabstractChildhood diseases result from different causes and exhibit different characteristics. The occurrence of such diseases can be estimated from electronic healthcare records but the characteristics of both the diseases and the databases should be considered. Licensed drugs have limited

  5. 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.

  6. Effect of some radiosensitising drugs on human erythrocyte membrane - - spin label study

    Energy Technology Data Exchange (ETDEWEB)

    Mishra, K P [Bhabha Atomic Research Centre, Bombay (India). Biology and Agriculture Div.

    1982-02-01

    Electron spin resonance and spin label techniques have been employed to study the effects of local anaesthetic drugs, procaine and tetracaine, on human erythrocyte membrane. Both the drugs altered the protein and lipid arrangements in the membrane and these changes were reversible. Procaine had greater effect on the labels attached to proteins while tetracaine fluidized interior of lipid bilayer to a greater extent. The differential effects of these drugs on the protein and lipid labels have been interpreted in terms of their relative penetrability in the membrane. Present results have explained that radiation induced enhanced killing of cells in the presence of these drugs might be due to the alterations in membrane, particularly proteins both structural and enzymatic. In addition, these results indicate a possible relationship between drug-induced structural changes in membrane and their anaesthetic potency.

  7. 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...... it with bioinformatics. With this approach, the assessment of chemical safety can be done across multiple scales of complexity from molecular to cellular and system levels in human health. Network biology can be used at several levels of complexity. Areas covered: This review describes the strengths and limitations...... of network biology. The authors specifically assess this approach across different biological scales when it is applied to toxicity. Expert opinion: There has been much progress made with the amount of data that is generated by various omics technologies. With this large amount of useful data, network...

  8. 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.)

  9. The effect of anticholinergic drugs on [sup 123]I-IMP SPECT in Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Mizuno, Tomoyuki; Nishiyama, Kazutoshi; Hitoshi, Seiji; Takeda, Koichi; Sakuta, Manabu [Japan Red Cross Central Hospital, Tokyo (Japan)

    1992-04-01

    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.).

  10. 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.

  11. Consumers' reports on the health effects of direct-to-consumer drug advertising.

    Science.gov (United States)

    Weissman, Joel S; Blumenthal, David; Silk, Alvin J; Zapert, Kinga; Newman, Michael; Leitman, Robert

    2003-01-01

    We conducted a national telephone survey about health care experiences associated with direct-to-consumer advertising (DTCA) of prescription drugs. Among the 35 percent of our sample who had a physician visit during which DTCA was discussed, 25 percent received a new diagnosis, of which 43 percent were considered high priority according to authoritative sources. More than half also reported actions taken by their physician other than prescribing the advertised drug. Despite concerns about DTCA's negative consequences, we found no differences in health effects between patients who took advertised drugs and those who took other prescription drugs.

  12. Estimated cost savings associated with the transfer of office-administered specialty pharmaceuticals to a specialty pharmacy provider in a Medical Injectable Drug program.

    Science.gov (United States)

    Baldini, Christopher G; Culley, Eric J

    2011-01-01

    A large managed care organization (MCO) in western Pennsylvania initiated a Medical Injectable Drug (MID) program in 2002 that transferred a specific subset of specialty drugs from physician reimbursement under the traditional "buy-and-bill" model in the medical benefit to MCO purchase from a specialty pharmacy provider (SPP) that supplied physician offices with the MIDs. The MID program was initiated with 4 drugs in 2002 (palivizumab and 3 hyaluronate products/derivatives) growing to more than 50 drugs by 2007-2008. To (a) describe the MID program as a method to manage the cost and delivery of this subset of specialty drugs, and (b) estimate the MID program cost savings in 2007 and 2008 in an MCO with approximately 4.6 million members. Cost savings generated by the MID program were calculated by comparing the total actual expenditure (plan cost plus member cost) on medications included in the MID program for calendar years 2007 and 2008 with the total estimated expenditure that would have been paid to physicians during the same time period for the same medication if reimbursement had been made using HCPCS (J code) billing under the physician "buy-and-bill" reimbursement rates. For the approximately 50 drugs in the MID program in 2007 and 2008, the drug cost savings in 2007 were estimated to be $15.5 million (18.2%) or $290 per claim ($0.28 per member per month [PMPM]) and about $13 million (12.7%) or $201 per claim ($0.23 PMPM) in 2008. Although 28% of MID claims continued to be billed by physicians using J codes in 2007 and 22% in 2008, all claims for MIDs were limited to the SPP reimbursement rates. This MID program was associated with health plan cost savings of approximately $28.5 million over 2 years, achieved by the transfer of about 50 physician-administered injectable pharmaceuticals from reimbursement to physicians to reimbursement to a single SPP and payment of physician claims for MIDs at the SPP reimbursement rates.

  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. 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 ...

  15. Money Matters: Cost-Effectiveness of Juvenile Drug Court with and without Evidence-Based Treatments

    Science.gov (United States)

    Sheidow, Ashli J.; Jayawardhana, Jayani; Bradford, W. David; Henggeler, Scott W.; Shapiro, Steven B.

    2012-01-01

    The 12-month cost-effectiveness of juvenile drug court and evidence-based treatments within court were compared with traditional Family Court for 128 substance-abusing/dependent juvenile offenders participating in a 4-condition randomized trial. Intervention conditions included Family Court with community services (FC), Drug Court with community…

  16. What Will Happen if . . . A Programmed Instruction Course on Drugs and Their Effects.

    Science.gov (United States)

    Health Services and Mental Health Administration (DHEW), Bethesda, MD.

    Developed by the National Institute of Mental Health, this booklet offers a programed instruction course on drugs and their effects. The purpose of the text is to learn about specific drugs which are currently being used and abused by a large group of people in our society. Narcotics, stimulants, depressants, hallucinogens, and marihuana are…

  17. 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.

  18. 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

  19. Meta-analysis of recent studies on patients admitted to hospital due to adverse drug effects

    NARCIS (Netherlands)

    Atiqi, R.; Cleophas, T. J.; van Bommel, E.; Zwinderman, A. H.

    2009-01-01

    The use of drugs has expanded during the previous decade. However, earlier studies oil patients admitted for adverse drugs effects (ADEs) have been heterogeneous. The objectives of this Study were to assess the number of recent admissions to hospital Clue to ADEs and to assess the degree of

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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)

  5. Estimating the effect of urban density on fuel demand

    Energy Technology Data Exchange (ETDEWEB)

    Karathodorou, Niovi; Graham, Daniel J. [Imperial College London, London, SW7 2AZ (United Kingdom); Noland, Robert B. [Rutgers University, New Brunswick, NJ 08901 (United States)

    2010-01-15

    Much of the empirical literature on fuel demand presents estimates derived from national data which do not permit any explicit consideration of the spatial structure of the economy. Intuitively we would expect the degree of spatial concentration of activities to have a strong link with transport fuel consumption. The present paper addresses this theme by estimating a fuel demand model for urban areas to provide a direct estimate of the elasticity of demand with respect to urban density. Fuel demand per capita is decomposed into car stock per capita, fuel consumption per kilometre and annual distance driven per car per year. Urban density is found to affect fuel consumption, mostly through variations in the car stock and in the distances travelled, rather than through fuel consumption per kilometre. (author)

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. Fall in hematocrit per 1000 parasites cleared from peripheral blood: a simple method for estimating drug-related fall in hematocrit after treatment of malaria infections.

    Science.gov (United States)

    Gbotosho, Grace Olusola; Okuboyejo, Titilope; Happi, Christian Tientcha; Sowunmi, Akintunde

    2014-01-01

    A simple method to estimate antimalarial drug-related fall in hematocrit (FIH) after treatment of Plasmodium falciparum infections in the field is described. The method involves numeric estimation of the relative difference in hematocrit at baseline (pretreatment) and the first 1 or 2 days after treatment begun as numerator and the corresponding relative difference in parasitemia as the denominator, and expressing it per 1000 parasites cleared from peripheral blood. Using the method showed that FIH/1000 parasites cleared from peripheral blood (cpb) at 24 or 48 hours were similar in artemether-lumefantrine and artesunate-amodiaquine-treated children (0.09; 95% confidence interval, 0.052-0.138 vs 0.10; 95% confidence interval, 0.069-0.139%; P = 0.75) FIH/1000 parasites cpb in patients with higher parasitemias were significantly (P 1000 parasites cpb were similar in anemic and nonanemic children. Estimation of FIH/1000 parasites cpb is simple, allows estimation of relatively conserved hematocrit during treatment, and can be used in both observational studies and clinical trials involving antimalarial drugs.

  11. Type 2 diabetes and metabolic syndrome - adipokine levels and effect of drugs.

    Science.gov (United States)

    Farooq, Rabia; Amin, Shajrul; Hayat Bhat, M; Malik, Rawoof; Wani, Hilal Ahmad; Majid, Sabhiya

    2017-01-01

    Type 2 diabetes mellitus (T2DM) is a consequence of complex interactions among multiple genetic variants and environmental risk factors. This complex disorder is also characterized by changes in various adipokines. In this study, our objective was to estimate the levels of adiponectin, leptin, and resistin (ALR) in T2DM patients, besides studying the effect of various drugs on their levels. Study participants included 400 diabetic and 300 normal patients from the Department of Endocrinology and Department of Biochemistry, Govt Medical College Srinagar. Subjects were categorized under various groups, i.e., Group 1 (metformin treated) and Group 2 (glimepiride treated), and cases were also categorized as obese with T2DM (Group A), obese without T2DM (Group B), and T2DM only (Group C). The serum ALR levels were estimated by ELISA (Alere), and biochemical parameters were also evaluated before and after treatment. Adiponectin levels were found to be significantly lower in T2DM cases as compared to controls (12 ± 5.5 versus 22.5 ± 7.9 μg/ml), while leptin and resistin levels were found to be significantly higher than controls (14.3 ± 7.4 versus 7.36 ± 3.73 ng/ml) (13.4 ± 1.56 versus 7.236 ± 2.129 pg/ml). Taking the effect of drugs into consideration, the effect on adiponectin and resistin levels was found to be highly significant in Group 2 before and after treatment (11 ± 5 versus 19.2 ± 4.5 μg/ml) (13.6 ± 2.5 versus 7.3 ± 2.9 pg/ml), while more effect was observed in leptin among Group 1 (metformin)-treated cases (27 ± 15 ng/ml versus 15 ± 15 ng/ml). Further the adiponectin levels were found to be significantly lower in Group B, while leptin and resistin levels were found to be significantly higher among obese cases when compared to T2DM cases only. Glimepiride also shows more effect on FBG, HbA1c% levels, while metformin shows more effect on Lipid profile levels. From the study, it can be

  12. 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...

  13. Reduced Effectiveness of Interruptive Drug-Drug Interaction Alerts after Conversion to a Commercial Electronic Health Record.

    Science.gov (United States)

    Wright, Adam; Aaron, Skye; Seger, Diane L; Samal, Lipika; Schiff, Gordon D; Bates, David W

    2018-05-15

    Drug-drug interaction (DDI) alerts in electronic health records (EHRs) can help prevent adverse drug events, but such alerts are frequently overridden, raising concerns about their clinical usefulness and contribution to alert fatigue. To study the effect of conversion to a commercial EHR on DDI alert and acceptance rates. Two before-and-after studies. 3277 clinicians who received a DDI alert in the outpatient setting. Introduction of a new, commercial EHR and subsequent adjustment of DDI alerting criteria. Alert burden and proportion of alerts accepted. Overall interruptive DDI alert burden increased by a factor of 6 from the legacy EHR to the commercial EHR. The acceptance rate for the most severe alerts fell from 100 to 8.4%, and from 29.3 to 7.5% for medium severity alerts (P fell by 50.5%, and acceptance of Tier 1 alerts rose from 9.1 to 12.7% (P < 0.01). Changing from a highly tailored DDI alerting system to a more general one as part of an EHR conversion decreased acceptance of DDI alerts and increased alert burden on users. The decrease in acceptance rates cannot be fully explained by differences in the clinical knowledge base, nor can it be fully explained by alert fatigue associated with increased alert burden. Instead, workflow factors probably predominate, including timing of alerts in the prescribing process, lack of differentiation of more and less severe alerts, and features of how users interact with alerts.

  14. 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 ...

  15. ADHD and math - The differential effect on calculation and estimation.

    Science.gov (United States)

    Ganor-Stern, Dana; Steinhorn, Ofir

    2018-05-31

    Adults with ADHD were compared to controls when solving multiplication problems exactly and when estimating the results of multidigit multiplication problems relative to reference numbers. The ADHD participants were slower than controls in the exact calculation and in the estimation tasks, but not less accurate. The ADHD participants were similar to controls in showing enhanced accuracy and speed for smaller problem sizes, for trials in which the reference numbers were smaller (vs. larger) than the exact answers and for reference numbers that were far (vs. close) from the exact answer. The two groups similarly used the approximated calculation and the sense of magnitude strategies. They differed however in strategy execution, mainly of the approximated calculation strategy, which requires working memory resources. The increase in reaction time associated with using the approximated calculation strategy was larger for the ADHD compared to the control participants. Thus, ADHD seems to selectively impair calculation processes in estimation tasks that rely on working memory, but it does not hamper estimation skills that are based on sense of magnitude. The educational implications of these findings are discussed. Copyright © 2018. Published by Elsevier B.V.

  16. 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

    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...

  17. 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

  18. Evidence behind FDA alerts for drugs with adverse cardiovascular effects: implications for clinical practice.

    Science.gov (United States)

    Rackham, Daniel M; C Herink, Megan; Stevens, Ian G; Cardoza, Natalie M; Singh, Harleen

    2014-01-01

    The U.S. Food and Drug Administration (FDA) periodically publishes Drug Safety Communications and Drug Alerts notifying health care practitioners and the general public of important information regarding drug therapies following FDA approval. These alerts can result in both positive and negative effects on patient care. Most clinical trials are not designed to detect long-term safety end points, and postmarketing surveillance along with patient reported events are often instrumental in signaling the potential harmful effect of a drug. Recently, many cardiovascular (CV) safety announcements have been released for FDA-approved drugs. Because a premature warning could discourage a much needed treatment or prompt a sudden discontinuation, it is essential to evaluate the evidence supporting these FDA alerts to provide effective patient care and to avoid unwarranted changes in therapy. Conversely, paying attention to these warnings in cases involving high-risk patients can prevent adverse effects and litigation. This article reviews the evidence behind recent FDA alerts for drugs with adverse CV effects and discusses the clinical practice implications. © 2013 Pharmacotherapy Publications, Inc.

  19. 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.

  20. Cost-effectiveness analysis of introducing malaria diagnostic testing in drug shops

    DEFF Research Database (Denmark)

    Hansen, Kristian Schultz; Clarke, Siân E.; Lal, Sham

    2017-01-01

    Background Private sector drug shops are an important source of malaria treatment in Africa, yet diagnosis without parasitological testing is common among these providers. Accurate rapid diagnostic tests for malaria (mRDTs) require limited training and present an opportunity to increase access...... to correct diagnosis. The present study was a cost-effectiveness analysis of the introduction of mRDTs in Ugandan drug shops. Methods Drug shop vendors were trained to perform and sell subsidised mRDTs and artemisinin-based combination therapies (ACTs) in the intervention arm while vendors offered ACTs...... following presumptive diagnosis of malaria in the control arm. The effect on the proportion of customers with fever ‘appropriately treated of malaria with ACT’ was captured during a randomised trial in drug shops in Mukono District, Uganda. Health sector costs included: training of drug shop vendors...

  1. 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

    landscapes (nelfinavir [NFV] and zidovudine [AZT] plus lamivudine [3TC]) to predict week 12 viral load (VL) change for 176 treatment change episodes (TCEs) and probability of week 48 virological failure for 90 TCEs, in treatment experienced patients starting these drugs in combination. RESULTS: A higher...

  2. Mechanistic models enable the rational use of in vitro drug-target binding kinetics for better drug effects in patients.

    NARCIS (Netherlands)

    Witte, W.E.; Wong, Y.C.; Nederpelt, I.; Heitman, L.H.; Danhof, M.; Graaf, van der P.H.; Gilissen, R.A.; de, Lange E.C.

    2016-01-01

    INTRODUCTION Drug-target binding kinetics are major determinants of the time course of drug action for several drugs, as clearly described for the irreversible binders omeprazole and aspirin. This supports the increasing interest to incorporate newly developed high-throughput assays for drug-target

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects

    Energy Technology Data Exchange (ETDEWEB)

    Florea, Ana-Maria [Department of Neuropathology, Heinrich-Heine University, Düsseldorf (Germany); Büsselberg, Dietrich, E-mail: dib2015@qatar-med.cornell.edu [Weil Cornell Medical College in Qatar, Qatar Foundation-Education City, P.O. Box 24144, Doha (Qatar)

    2011-03-15

    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.

  8. 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....

  9. 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.

  10. 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.

  11. 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)

  12. 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

  13. A review of illicit psychoactive drug use in elective surgery patients: Detection, effects, and policy.

    Science.gov (United States)

    Selvaggi, Gennaro; Spagnolo, Antonio G; Elander, Anna

    2017-12-01

    Limited information is present in literature regarding detection of illicit drug users visiting physicians when planning elective surgery; also, there is no update manuscript that is illustrating the effects of illicit drugs use that require reconstructive surgery interventions. Aims of this manuscript are: 1) to summarize existing knowledge, and give surgeons information how to detect patients who might possible use illicit drugs; 2) to review the effects of illicit drug use that specifically require reconstructive surgery interventions; 3) to assess on existing policies on asymptomatic illicit drug users when planning elective surgery. Studies were identified by searching systematically in the electronic databases PubMed, Medline, The Cochrane Library and SveMed+. Because of the nature of research questions to be investigated (drug policy and surgery), a "systematic review" was not possible. In spite of some existing policies to detect illicit drug use in specific situations such as workplaces or acute trauma patients, there is a lack of data and lack of information, and subsequently no policy has ever been made, for detection and management of illicit drug use asymptomatic patients requesting or referred for plastic surgery interventions. This manuscript poses questions for further ethical evaluations and future policy. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

  14. Effect of electron beam irradiation on bacterial cellulose membranes used as transdermal drug delivery systems

    Energy Technology Data Exchange (ETDEWEB)

    Stoica-Guzun, Anicuta [Department of Chemical Engineering, ' Politehnica' University Bucharest, 313 Splaiul Independentei, 060042 Bucharest (Romania)], E-mail: astoica@mt.pub.ro; Stroescu, Marta; Tache, Florin [Department of Chemical Engineering, ' Politehnica' University Bucharest, 313 Splaiul Independentei, 060042 Bucharest (Romania); Zaharescu, Traian [Advanced Research Institute for Electrical Engineering, 313 Splaiul Unirii, 030138 Bucharest (Romania)], E-mail: zaharescut@icpe-ca.ro; Grosu, Elena [Department of Chemical Engineering, ' Politehnica' University Bucharest, 313 Splaiul Independentei, 060042 Bucharest (Romania)

    2007-12-15

    Ionizing radiation is an effective energetic source for polymer surfaces modification in order to obtain transdermal systems with different controlled release properties. In this work, gamma rays have been applied to induce changes in bacterial cellulose membranes. Permeation of drug (tetracycline) was theoretically and experimentally investigated starting from the effect of {gamma}-irradiation on membranes permeability. Release and permeation of drug from irradiated and non-irradiated membranes have been performed using a diffusion cell.

  15. Effect of electron beam irradiation on bacterial cellulose membranes used as transdermal drug delivery systems

    International Nuclear Information System (INIS)

    Stoica-Guzun, Anicuta; Stroescu, Marta; Tache, Florin; Zaharescu, Traian; Grosu, Elena

    2007-01-01

    Ionizing radiation is an effective energetic source for polymer surfaces modification in order to obtain transdermal systems with different controlled release properties. In this work, gamma rays have been applied to induce changes in bacterial cellulose membranes. Permeation of drug (tetracycline) was theoretically and experimentally investigated starting from the effect of γ-irradiation on membranes permeability. Release and permeation of drug from irradiated and non-irradiated membranes have been performed using a diffusion cell

  16. Effect of electron beam irradiation on bacterial cellulose membranes used as transdermal drug delivery systems

    Science.gov (United States)

    Stoica-Guzun, Anicuta; Stroescu, Marta; Tache, Florin; Zaharescu, Traian; Grosu, Elena

    2007-12-01

    Ionizing radiation is an effective energetic source for polymer surfaces modification in order to obtain transdermal systems with different controlled release properties. In this work, gamma rays have been applied to induce changes in bacterial cellulose membranes. Permeation of drug (tetracycline) was theoretically and experimentally investigated starting from the effect of γ-irradiation on membranes permeability. Release and permeation of drug from irradiated and non-irradiated membranes have been performed using a diffusion cell.

  17. Using a 3-d model system to screen for drugs effective on solid tumors

    OpenAIRE

    Fayad, Walid

    2011-01-01

    There is a large medical need for the development of effective anticancer agents with minimal side effects. The present thesis represents an attempt to identify potent drugs for treatment of solid tumors. We used a strategy where 3-D multicellular tumor spheroids (cancer cells grown in three dimensional culture) were utilized as in vitro models for solid tumors. Drug libraries were screened using spheroids as targets and using apoptosis induction and loss of cell viability as endpoints. The h...

  18. Drug side effect extraction from clinical narratives of psychiatry and psychology patients.

    Science.gov (United States)

    Sohn, Sunghwan; Kocher, Jean-Pierre A; Chute, Christopher G; Savova, Guergana K

    2011-12-01

    To extract physician-asserted drug side effects from electronic medical record clinical narratives. Pattern matching rules were manually developed through examining keywords and expression patterns of side effects to discover an individual side effect and causative drug relationship. A combination of machine learning (C4.5) using side effect keyword features and pattern matching rules was used to extract sentences that contain side effect and causative drug pairs, enabling the system to discover most side effect occurrences. Our system was implemented as a module within the clinical Text Analysis and Knowledge Extraction System. The system was tested in the domain of psychiatry and psychology. The rule-based system extracting side effects and causative drugs produced an F score of 0.80 (0.55 excluding allergy section). The hybrid system identifying side effect sentences had an F score of 0.75 (0.56 excluding allergy section) but covered more side effect and causative drug pairs than individual side effect extraction. The rule-based system was able to identify most side effects expressed by clear indication words. More sophisticated semantic processing is required to handle complex side effect descriptions in the narrative. We demonstrated that our system can be trained to identify sentences with complex side effect descriptions that can be submitted to a human expert for further abstraction. Our system was able to extract most physician-asserted drug side effects. It can be used in either an automated mode for side effect extraction or semi-automated mode to identify side effect sentences that can significantly simplify abstraction by a human expert.

  19. 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...

  20. 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.

  1. 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...

  2. Two-Level Designs to Estimate All Main Effects and Two-Factor Interactions

    NARCIS (Netherlands)

    Eendebak, P.T.; Schoen, E.D.

    2017-01-01

    We study the design of two-level experiments with N runs and n factors large enough to estimate the interaction model, which contains all the main effects and all the two-factor interactions. Yet, an effect hierarchy assumption suggests that main effect estimation should be given more prominence

  3. Combining automatic table classification and relationship extraction in extracting anticancer drug-side effect pairs from full-text articles.

    Science.gov (United States)

    Xu, Rong; Wang, QuanQiu

    2015-02-01

    Anticancer drug-associated side effect knowledge often exists in multiple heterogeneous and complementary data sources. A comprehensive anticancer drug-side effect (drug-SE) relationship knowledge base is important for computation-based drug target discovery, drug toxicity predication and drug repositioning. In this study, we present a two-step approach by combining table classification and relationship extraction to extract drug-SE pairs from a large number of high-profile oncological full-text articles. The data consists of 31,255 tables downloaded from the Journal of Oncology (JCO). We first trained a statistical classifier to classify tables into SE-related and -unrelated categories. We then extracted drug-SE pairs from SE-related tables. We compared drug side effect knowledge extracted from JCO tables to that derived from FDA drug labels. Finally, we systematically analyzed relationships between anti-cancer drug-associated side effects and drug-associated gene targets, metabolism genes, and disease indications. The statistical table classifier is effective in classifying tables into SE-related and -unrelated (precision: 0.711; recall: 0.941; F1: 0.810). We extracted a total of 26,918 drug-SE pairs from SE-related tables with a precision of 0.605, a recall of 0.460, and a F1 of 0.520. Drug-SE pairs extracted from JCO tables is largely complementary to those derived from FDA drug labels; as many as 84.7% of the pairs extracted from JCO tables have not been included a side effect database constructed from FDA drug labels. Side effects associated with anticancer drugs positively correlate with drug target genes, drug metabolism genes, and disease indications. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. “On-Target” Cardiac Effects of Anticancer Drugs

    Science.gov (United States)

    Simons, Michael; Eichmann, Anne

    2014-01-01

    The development of new biological therapeutics such as neutralizing antibodies and small molecule inhibitors of receptors signaling is revolutionizing many fields of medicine—and creating new insights into normal biology. In particular, inhibition of blood vessel growth has been vigorously pursued in a number of fields, including oncology and ophthalmology. To date, most experience with this class of drugs centers on anti-vascular endothelial growth factor (VEGF) agents such as a neutralizing antibody bevacizumab and small molecule inhibitors of VEGF receptor-2 (VEGFR2). Anti-VEGF therapies have been spectacularly successful for treatment of macular degeneration, and somewhat less so in the treatment of cancer. Hand in hand with these advances is the emergence of new cardiac illnesses directly related to the activity of these agents. PMID:22703925

  5. [Application of reversed-phase ion-pair chromatography for universal estimation of octanol-water partition coefficients of acid, basic and amphoteric drugs].

    Science.gov (United States)

    Zhu, Hui; Yang, Ri-Fang; Yun, Liu-Hong; Jiang, Yu; Li, Jin

    2009-09-01

    This paper is to establish a reversed-phase ion-pair chromatography (RP-IPC) method for universal estimation of the octanol/water partition coefficients (logP) of a wide range of structurally diverse compounds including acidic, basic, neutral and amphoteric species. The retention factors corresponding to 100% water (logk(w)) were derived from the linear part of the logk'/phi relationship, using at least four isocratic logk' values containing different organic compositions. The logk(w) parameters obtained were close to the corresponding logP values obtained with the standard "shake flask" methods. The mean deviation for test drugs is 0.31. RP-IPC with trifluoroacetic acid as non classic ion-pair agents can be applicable to determine the logP values for a variety of drug-like molecules with increased accuracy.

  6. Legal Drugs Are Good Drugs and Illegal Drugs Are Bad Drugs

    OpenAIRE

    Indrati, Dina; Prasetyo, Herry

    2011-01-01

    ABSTRACT : Labelling drugs are important issue nowadays in a modern society. Although it is generally believed that legal drugs are good drugs and illegal drugs are bad drugs, it is evident that some people do not aware about the side effects of drugs used. Therefore, a key contention of this philosophical essay is that explores harms minimisation policy, discuss whether legal drugs are good drugs and illegal drugs are bad drugs and explores relation of drugs misuse in a psychiatric nursing s...

  7. Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; policies, requirements, and administrative procedures; delay of effective date. Final rule; delay of effective date.

    Science.gov (United States)

    2004-02-23

    The Food and Drug Administration (FDA) is further delaying, until December 1, 2006, the effective date of certain requirements of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720). In the Federal Register of May 3, 2000 (65 FR 25639), the agency delayed until October 1, 2001, the effective date of certain requirements in the final rule relating to wholesale distribution of prescription drugs by distributors that are not authorized distributors of record, and distribution of blood derivatives by entities that meet the definition of a "health care entity" in the final rule. The agency further delayed the effective date of these requirements in three subsequent Federal Register notices. Most recently, in the Federal Register of January 31, 2003 (68 FR 4912), FDA delayed the effective date until April 1, 2004. This action further delays the effective date of these requirements until December 1, 2006. The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA), and the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). The agency is taking this action to address concerns about the requirements in the final rule raised by affected parties. As explained in the SUPPLEMENTARY INFORMATION section, FDA is working with stakeholders through its counterfeit drug initiative to facilitate widespread, voluntary adoption of track and trace technologies that will generate a de facto electronic pedigree, including prior transaction history back to the original manufacturer, as a routine course of business. If this technology is widely adopted, it is expected to help fulfill the pedigree requirements of the PDMA and obviate or resolve many of the concerns that have been raised with respect to the final rule by ensuring that an electronic pedigree travels with a drug product at all times. Therefore, it is necessary to delay the effective date of Sec

  8. Drug repurposing based on drug-drug interaction.

    Science.gov (United States)

    Zhou, Bin; Wang, Rong; Wu, Ping; Kong, De-Xin

    2015-02-01

    Given the high risk and lengthy procedure of traditional drug development, drug repurposing is gaining more and more attention. Although many types of drug information have been used to repurpose drugs, drug-drug interaction data, which imply possible physiological effects or targets of drugs, remain unexploited. In this work, similarity of drug interaction was employed to infer similarity of the physiological effects or targets for the drugs. We collected 10,835 drug-drug interactions concerning 1074 drugs, and for 700 of them, drug similarity scores based on drug interaction profiles were computed and rendered using a drug association network with 589 nodes (drugs) and 2375 edges (drug similarity scores). The 589 drugs were clustered into 98 groups with Markov Clustering Algorithm, most of which were significantly correlated with certain drug functions. This indicates that the network can be used to infer the physiological effects of drugs. Furthermore, we evaluated the ability of this drug association network to predict drug targets. The results show that the method is effective for 317 of 561 drugs that have known targets. Comparison of this method with the structure-based approach shows that they are complementary. In summary, this study demonstrates the feasibility of drug repurposing based on drug-drug interaction data. © 2014 John Wiley & Sons A/S.

  9. 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.

  10. Estimating the effect of treatment rate changes when treatment benefits are heterogeneous: antibiotics and otitis media.

    Science.gov (United States)

    Park, Tae-Ryong; Brooks, John M; Chrischilles, Elizabeth A; Bergus, George

    2008-01-01

    Contrast methods to assess the health effects of a treatment rate change when treatment benefits are heterogeneous across patients. Antibiotic prescribing for children with otitis media (OM) in Iowa Medicaid is the empirical example. Instrumental variable (IV) and linear probability model (LPM) are used to estimate the effect of antibiotic treatments on cure probabilities for children with OM in Iowa Medicaid. Local area physician supply per capita is the instrument in the IV models. Estimates are contrasted in terms of their ability to make inferences for patients whose treatment choices may be affected by a change in population treatment rates. The instrument was positively related to the probability of being prescribed an antibiotic. LPM estimates showed a positive effect of antibiotics on OM patient cure probability while IV estimates showed no relationship between antibiotics and patient cure probability. Linear probability model estimation yields the average effects of the treatment on patients that were treated. IV estimation yields the average effects for patients whose treatment choices were affected by the instrument. As antibiotic treatment effects are heterogeneous across OM patients, our estimates from these approaches are aligned with clinical evidence and theory. The average estimate for treated patients (higher severity) from the LPM model is greater than estimates for patients whose treatment choices are affected by the instrument (lower severity) from the IV models. Based on our IV estimates it appears that lowering antibiotic use in OM patients in Iowa Medicaid did not result in lost cures.

  11. The effect of weak lensing on distance estimates from supernovae

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Mathew; Maartens, Roy [Department of Physics, University of the Western Cape, Cape Town 7535 (South Africa); Bacon, David J.; Nichol, Robert C.; Campbell, Heather; D' Andrea, Chris B. [Institute of Cosmology and Gravitation, University of Portsmouth, Portsmouth, PO1 3FX (United Kingdom); Clarkson, Chris [Astrophysics, Cosmology and Gravity Centre (ACGC), Department of Mathematics and Applied Mathematics, University of Cape Town, Rondebosch 7701 (South Africa); Bassett, Bruce A. [South African Astronomical Observatory, P.O. Box 9, Observatory 7935 (South Africa); Cinabro, David [Wayne State University, Department of Physics and Astronomy, Detroit, MI 48202 (United States); Finley, David A.; Frieman, Joshua A. [Center for Particle Astrophysics, Fermi National Accelerator Laboratory, P.O. Box 500, Batavia, IL 60510 (United States); Galbany, Lluis [CENTRA Centro Multidisciplinar de Astrofísica, Instituto Superior Técnico, Av. Rovisco Pais 1, 1049-001 Lisbon (Portugal); Garnavich, Peter M. [Department of Physics, University of Notre Dame, Notre Dame, IN 46556 (United States); Olmstead, Matthew D. [Department of Physics and Astronomy, University of Utah, Salt Lake City, UT 84112 (United States); Schneider, Donald P. [Department of Astronomy and Astrophysics, The Pennsylvania State University, University Park, PA 16802 (United States); Shapiro, Charles [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, La Canada Flintridge, CA 91109 (United States); Sollerman, Jesper, E-mail: matsmith2@gmail.com [The Oskar Klein Centre, Department of Astronomy, AlbaNova, SE-106 91 Stockholm (Sweden)

    2014-01-01

    Using a sample of 608 Type Ia supernovae from the SDSS-II and BOSS surveys, combined with a sample of foreground galaxies from SDSS-II, we estimate the weak lensing convergence for each supernova line of sight. We find that the correlation between this measurement and the Hubble residuals is consistent with the prediction from lensing (at a significance of 1.7σ). Strong correlations are also found between the residuals and supernova nuisance parameters after a linear correction is applied. When these other correlations are taken into account, the lensing signal is detected at 1.4σ. We show, for the first time, that distance estimates from supernovae can be improved when lensing is incorporated, by including a new parameter in the SALT2 methodology for determining distance moduli. The recovered value of the new parameter is consistent with the lensing prediction. Using cosmic microwave background data from WMAP7, H {sub 0} data from Hubble Space Telescope and Sloan Digital Sky Survey (SDSS) Baryon acoustic oscillations measurements, we find the best-fit value of the new lensing parameter and show that the central values and uncertainties on Ω {sub m} and w are unaffected. The lensing of supernovae, while only seen at marginal significance in this low-redshift sample, will be of vital importance for the next generation of surveys, such as DES and LSST, which will be systematics-dominated.

  12. 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

  13. The effect of depression and side effects of antiepileptic drugs on injuries in patients with epilepsy.

    Science.gov (United States)

    Gur-Ozmen, S; Mula, M; Agrawal, N; Cock, H R; Lozsadi, D; von Oertzen, T J

    2017-09-01

    People with epilepsy are at increased risk of accidents and injuries but, despite several studies on this subject, data regarding preventable causes are still contradictory. The aim of this study was to investigate the relationship between injuries, side effects of antiepileptic drugs (AEDs) and depression. Data from a consecutive sample of adult patients with epilepsy attending the outpatient clinics at St George's University Hospital in London were included. All patients were asked if they had had any injury since the last clinic appointment and completed the Liverpool Adverse Event Profile (LAEP) and Neurological Disorders Depression Inventory for Epilepsy. Among 407 patients (243 females, mean age 43.1 years), 71 (17.4%) reported injuries since the last appointment. A two-step cluster analysis revealed two clusters with the major cluster (53.5% of the injured group) showing a total score for LAEP ≥45, a positive Neurological Disorders Depression Inventory for Epilepsy screening and presence of AED polytherapy. A total score for LAEP ≥45 was the most important predictor. Antiepileptic drug treatment should be reviewed in patients reporting injuries in order to evaluate the potential contribution and burden of AED side effects. © 2017 EAN.

  14. Drug research methodology. Volume 5, Experimentation in drugs and highway safety : the study of drug effects on skills related to driving

    Science.gov (United States)

    1980-06-01

    This report presents the findings of a workshop on experimental research in the area of drugs and highway safety. Complementing studies of drug use in different driving populations, experimentation here refers to studies performed under controlled co...

  15. Is drug insurance status an effect modifier in epidemiologic database studies? The case of maternal asthma and major congenital malformations.

    Science.gov (United States)

    Blais, Lucie; Kettani, Fatima-Zohra; Forget, Amélie; Beauchesne, Marie-France; Lemière, Catherine

    2015-12-01

    Our previous work on the association between maternal asthma and congenital malformations was based on cohorts formed by women with public drug insurance, i.e., over-represented by women with lower socioeconomic status, questioning the generalizability of our findings. This study aimed to evaluate whether or not drug insurance status, as a proxy of socioeconomic status, is an effect modifier for the association between maternal asthma and major congenital malformations. A cohort of 36,587 pregnancies from asthmatic women and 198,935 pregnancies from nonasthmatic women selected independently of their drug insurance status was reconstructed with Québec administrative databases (1998-2009). Asthmatic women were identified using a validated case definition of asthma. Cases of major congenital malformations were identified using diagnostic codes recorded in the hospitalization database. Drug insurance status at the beginning of pregnancy was classified into three groups: publicly insured with social welfare, publicly insured without social welfare, and privately insured. Adjusted odds ratios were estimated with generalized estimation equations, including an interaction term between maternal asthma and drug insurance status. The prevalence of congenital malformations was 6.8% among asthmatic women and 5.8% among nonasthmatics. The impact of asthma on the prevalence of congenital malformations was significantly greater in women publicly insured with social welfare (odds ratio = 1.42; 95% confidence interval, 1.25-1.61) than in the other two groups ([odds ratio = 1.10; 1.00-1.21] in the publicly insured without social welfare and [odds ratio = 1.13; 1.07-1.20] in the privately insured group). The increased risk of major congenital malformation associated with asthma was significantly higher among pregnant women publicly insured with social welfare than among those privately insured. As a result of this effect modification by drug insurance status, findings

  16. Effect of water resource development and management on lymphatic filariasis, and estimates of populations at risk.

    Science.gov (United States)

    Erlanger, Tobias E; Keiser, Jennifer; Caldas De Castro, Marcia; Bos, Robert; Singer, Burton H; Tanner, Marcel; Utzinger, Jürg

    2005-09-01

    Lymphatic filariasis (LF) is a debilitating disease overwhelmingly caused by Wuchereria bancrofti, which is transmitted by various mosquito species. Here, we present a systematic literature review with the following objectives: (i) to establish global and regional estimates of populations at risk of LF with particular consideration of water resource development projects, and (ii) to assess the effects of water resource development and management on the frequency and transmission dynamics of the disease. We estimate that globally, 2 billion people are at risk of LF. Among them, there are 394.5 million urban dwellers without access to improved sanitation and 213 million rural dwellers living in close proximity to irrigation. Environmental changes due to water resource development and management consistently led to a shift in vector species composition and generally to a strong proliferation of vector populations. For example, in World Health Organization (WHO) subregions 1 and 2, mosquito densities of the Anopheles gambiae complex and Anopheles funestus were up to 25-fold higher in irrigated areas when compared with irrigation-free sites. Although the infection prevalence of LF often increased after the implementation of a water project, there was no clear association with clinical symptoms. Concluding, there is a need to assess and quantify changes of LF transmission parameters and clinical manifestations over the entire course of water resource developments. Where resources allow, integrated vector management should complement mass drug administration, and broad-based monitoring and surveillance of the disease should become an integral part of large-scale waste management and sanitation programs, whose basic rationale lies in a systemic approach to city, district, and regional level health services and disease prevention.

  17. Effect of temperature and ph on the drug release rate from a polymer conjugate system

    International Nuclear Information System (INIS)

    Kenawy, E.; Abdel-Hay, F.I.; El-Newehy, M.H.; Ottenbrite, R.M.

    2005-01-01

    Hydroximide and A-methylhydroxamic acid of poly(ethylene-altmaleic anhydride) (average MW 100-500 k) were used as a carrier for a new drug delivery system. The synthesis of the hydroximide and N methylhydroxamic acid of poly(ethylene-alt-maleic anhydride) were carried out by chemical modification of poly(ethylene-alt-maleic anhydride) with hydroxylamine and N-methyl hydroxylamine, respectively, in N,N- dimethylformamide at room temperature to yield water soluble copolymer. Ketoprofen was reacted with hydroximide and N-methylhydroxamic acid derivatives of poly(ethylene-alt-maleic anhydride) using dicyclohexylcarbodiimide as condensation agent at -5 degree C to yield water insoluble ketoprofen conjugates. All products were characterized by elemental analysis, FTIR and 1HNMR spectra. The in-vitro ketoprofen release was carried out by UV spectrophotometer at max =260 nm. The results demonstrated the effectiveness of hydroximide and N-methylhydroxamic acid of polyethylene-alt-maleic anhydride) as a drug delivery system. The release rates were studied at various ph and temperatures. The copolymer-drug adducts released the drug very slowly at the low ph found in the stomach thus protecting the drug from the action of high concentrations of digestive acids. These results showed the usefulness of hydroxamic acid polymer-drug conjugates as a new drug delivery system for drugs to be targeted to sites in the GI system

  18. The Effect of Muscle Dysmorphia and Social Physique Anxiety on the Use of Supplements and Drugs

    Directory of Open Access Journals (Sweden)

    Yadollah Khorramabady

    2017-09-01

    Full Text Available Background The use of dietary supplements and drugs to improve performance and physical appearance has recently increased among professional and recreational ‎athletes. Literature shows that bodybuilders, more than other athletes use supplements and drugs. Objectives This study aims to predict the use of supplements and drugs by muscle dysmorphia and social physique anxiety variables among Hamedan bodybuilders. Methods This cross-sectional investigation was conducted with 438 bodybuilders in Hamedan province. For collecting data, we used a demographic questionnaire, muscle dysmorphia scale, and social ‎physique anxiety scale. Results The results showed that 79.2% of the subjects used supplements, and vitamins (22.1% and protein powders (21.9% had the highest rates of use among supplements. Moreover, 145 subjects (33.1% used drugs, and steroid derivatives (16.2% and peptide hormones and growth factors (12.6% had the highest rates of use among drugs. The results of t-test showed that muscle dysmorphia and social physique anxiety were significantly higher in the subjects who used supplements and drugs than those who did not. Additionally, the results of logistic regression indicated that muscle dysmorphia and social physique anxiety can predict the likelihood of drug abuse. Conclusions The present study provides novel findings of the effect of social physique anxiety and muscle ‎dysmorphia on nutritional supplement and drugs use among bodybuilders. ‎

  19. 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.

  20. Nonlinear mixed effects dose response modeling in high throughput drug screens: application to melanoma cell line analysis.

    Science.gov (United States)

    Ding, Kuan-Fu; Petricoin, Emanuel F; Finlay, Darren; Yin, Hongwei; Hendricks, William P D; Sereduk, Chris; Kiefer, Jeffrey; Sekulic, Aleksandar; LoRusso, Patricia M; Vuori, Kristiina; Trent, Jeffrey M; Schork, Nicholas J

    2018-01-12

    Cancer cell lines are often used in high throughput drug screens (HTS) to explore the relationship between cell line characteristics and responsiveness to different therapies. Many current analysis methods infer relationships by focusing on one aspect of cell line drug-specific dose-response curves (DRCs), the concentration causing 50% inhibition of a phenotypic endpoint (IC 50 ). Such methods may overlook DRC features and do not simultaneously leverage information about drug response patterns across cell lines, potentially increasing false positive and negative rates in drug response associations. We consider the application of two methods, each rooted in nonlinear mixed effects (NLME) models, that test the relationship relationships between estimated cell line DRCs and factors that might mitigate response. Both methods leverage estimation and testing techniques that consider the simultaneous analysis of different cell lines to draw inferences about any one cell line. One of the methods is designed to provide an omnibus test of the differences between cell line DRCs that is not focused on any one aspect of the DRC (such as the IC 50 value). We simulated different settings and compared the different methods on the simulated data. We also compared the proposed methods against traditional IC 50 -based methods using 40 melanoma cell lines whose transcriptomes, proteomes, and, importantly, BRAF and related mutation profiles were available. Ultimately, we find that the NLME-based methods are more robust, powerful and, for the omnibus test, more flexible, than traditional methods. Their application to the melanoma cell lines reveals insights into factors that may be clinically useful.

  1. The role of the seven crude drug components in the sleep-promoting effect of Yokukansan.

    Science.gov (United States)

    Ogawa, Yuko; Fujii, Yuuko; Sugiyama, Reina; Konishi, Tenji

    2016-01-11

    Yokukansan is a traditional Japanese "Kampo" medicine derived from Yi-Gan San in traditional Chinese medicine. Many studies have been published on its effects and mechanisms. In this study, we focused on the sleep-promoting effects of Yokukansan. Yokukansan composes of seven crude drugs: Uncaria Hook, Bupleurm Root, Cnidium Rhizome, Japanese Angelica Root, Poria Sclerotium, Atractylodes Lancea Rhizome, and Glycyrrhiza. Although each has distinctive effects in isolation, they combine to work as a sleep aid in the Yokukansan formula. We examined the roles of the seven crude drug components in the sleep-promoting effect of Yokukansan. In this study, we used an easy in vivo assay method which we developed previously to screen sleeping substances using thermography. This assay method focuses on the decrease in skin temperature of mice during sleep inducement. By administering the crude drug components of Yokukansan one at a time, it was possible to separate them into two groups: those that caused a decrease in body temperature (Uncaria Hook, Bupleurm Root, Cnidium rhizome, and Japanese Angelica root) and those that did not (Poria Sclerotium, Atractylodes Lancea Rhizome, and Glycyrrhiza). Accordingly, it was thought that the crude drugs causing a drop in body temperature were responsible for promoting sleep, while those in the other group would have no such effect in isolation. To investigate whether the crude drugs that did not cause a decrease in body temperature might be unnecessary for the sleep-promoting effect of Yokukansan, a number of decoctions were prepared using only six of the seven crude drug components, excluding a different crude drug in each case. Results showed that when any of the three components (Poria Sclerotium, Atractylodes Lancea Rhizome, or Glycyrrhiza) of Yokukansan that had no effect on body temperature in isolation were removed from Yokukansan, the resulting extract no longer had any of Yokukansan's sleep-promoting effects. This result

  2. The effect of response-delay on estimating reachability.

    Science.gov (United States)

    Gabbard, Carl; Ammar, Diala

    2008-11-01

    The experiment was conducted to compare visual imagery (VI) and motor imagery (MI) reaching tasks in a response-delay paradigm designed to explore the hypothesized dissociation between vision for perception and vision for action. Although the visual systems work cooperatively in motor control, theory suggests that they operate under different temporal constraints. From this perspective, we expected that delay would affect MI but not VI because MI operates in real time and VI is postulated to be memory-driven. Following measurement of actual reach, right-handers were presented seven (imagery) targets at midline in eight conditions: MI and VI with 0-, 1-, 2-, and 4-s delays. Results indicted that delay affected the ability to estimate reachability with MI but not with VI. These results are supportive of a general distinction between vision for perception and vision for action.

  3. Protein microarray: sensitive and effective immunodetection for drug residues

    Directory of Open Access Journals (Sweden)

    Zer Cindy

    2010-02-01

    Full Text Available Abstract Background Veterinary drugs such as clenbuterol (CL and sulfamethazine (SM2 are low molecular weight ( Results The artificial antigens were spotted on microarray slides. Standard concentrations of the compounds were added to compete with the spotted antigens for binding to the antisera to determine the IC50. Our microarray assay showed the IC50 were 39.6 ng/ml for CL and 48.8 ng/ml for SM2, while the traditional competitive indirect-ELISA (ci-ELISA showed the IC50 were 190.7 ng/ml for CL and 156.7 ng/ml for SM2. We further validated the two methods with CL fortified chicken muscle tissues, and the protein microarray assay showed 90% recovery while the ci-ELISA had 76% recovery rate. When tested with CL-fed chicken muscle tissues, the protein microarray assay had higher sensitivity (0.9 ng/g than the ci-ELISA (0.1 ng/g for detection of CL residues. Conclusions The protein microarrays showed 4.5 and 3.5 times lower IC50 than the ci-ELISA detection for CL and SM2, respectively, suggesting that immunodetection of small molecules with protein microarray is a better approach than the traditional ELISA technique.

  4. The estimation of occupational effective dose in diagnostic radiology with two dosimeters

    International Nuclear Information System (INIS)

    Niklason, L.T.; Marx, M.V.; Chan, Heang-Ping

    1994-01-01

    Annual effective dose limits have been proposed by national and international radiation protection committees. Radiation protection agencies must decide upon a method of converting the radiation dose measured from dosimeters to an estimate of effective dose. A proposed method for the estimation of effective dose from the radiation dose to two dosimeters is presented. Correction factors are applied to an over-apron collar dose and an under-apron dose to estimate the effective dose. Correction factors are suggested for two cases, both with and without a thyroid shield. Effective dose may be estimated by the under-apron dose plus 6% of the over-collar dose if a thyroid shield is not worn or plus 2% of the over-collar dose if a thyroid shield is worn. This method provides a reasonable estimate of effective dose that is independent of lead apron thickness and accounts for the use of a thyroid shield. 17 refs., 3 tabs

  5. Dual drug-loaded paclitaxel–thymoquinone nanoparticles for effective breast cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Soni, Parth; Kaur, Jasmine; Tikoo, Kulbhushan, E-mail: tikoo.k@gmail.com [National Institute of Pharmaceutical Education and Research (NIPER), Laboratory of Epigenetics and Diseases, Department of Pharmacology and Toxicology (India)

    2015-01-15

    The present study highlights the beneficial synergistic blend of anticancer drug paclitaxel (PTX) and thymoquinone (TQ) in MCF-7 breast cancer cells. We aimed to augment the therapeutic index of PTX using a polymeric nanoparticle system loaded with PTX and TQ. PLGA nanoparticles encapsulating the two drugs, individually or in combination, were prepared by single emulsion solvent evaporation method. The formulated nanoparticles were homogenous with an overall negative charge and their size ranging between 200 and 300 nm. Entrapment efficiency of PTX and TQ in the dual drug-loaded nanoparticles was found to be 82.4 ± 2.18 and 65.8 ± 0.45 %, respectively. The release kinetics of PTX and TQ from the nanoparticles exhibited a biphasic pattern characterised by an initial burst, followed by a gradual and continuous release. The anticancer activity of nanoparticles encapsulating both the drugs was higher as compared to the free drugs in MCF-7 breast cancer cells. The combination index for the dual drug-loaded NPs was found to be 0.688 which is indicative of synergistic interaction. Thus, here, we propose the synthesis and use of dual drug-loaded TQ and PTX NPs which exhibits enhanced anticancer activity and can additionally help to alleviate the toxic effects of PTX by lowering its effective dose.

  6. Fractured families: parental perspectives of the effects of adolescent drug abuse on family life.

    Science.gov (United States)

    Jackson, Debra; Usher, Kim; O'Brien, Louise

    Drug use in young people has serious ramifications for health and well-being of young people and their families and continues to be an area of major concern for health workers. Though the task of dealing with drug-related problems falls on families, particularly parents, very little literature has explored parental experiences of managing drug use within the context of family life. Eighteen parents of drug-abusing young people were recruited into this qualitative study that aimed to develop understandings into the effects of adolescent drug use on family life. Findings revealed that the experience of having a drug-abusing adolescent family member had a profound effect on other members of the immediate family. Family relationships were fractured and split as a result of the on-going destructive and damaging behaviour of the drug-abusing young person. Five themes were identified that captured the concept of fractured families. These are: betrayal and loss of trust: 'You had to have the doors locked'; abuse, threats and violence: 'there were holes in the wall'; sibling anger and resentment: 'Better off now with him gone'; isolated, disgraced and humiliated: 'You are on your own with it'; and, feeling blamed: 'You are not a good parent'. Implications for practice and further research are drawn from the findings of this paper.

  7. Dual drug-loaded paclitaxel–thymoquinone nanoparticles for effective breast cancer therapy

    International Nuclear Information System (INIS)

    Soni, Parth; Kaur, Jasmine; Tikoo, Kulbhushan

    2015-01-01

    The present study highlights the beneficial synergistic blend of anticancer drug paclitaxel (PTX) and thymoquinone (TQ) in MCF-7 breast cancer cells. We aimed to augment the therapeutic index of PTX using a polymeric nanoparticle system loaded with PTX and TQ. PLGA nanoparticles encapsulating the two drugs, individually or in combination, were prepared by single emulsion solvent evaporation method. The formulated nanoparticles were homogenous with an overall negative charge and their size ranging between 200 and 300 nm. Entrapment efficiency of PTX and TQ in the dual drug-loaded nanoparticles was found to be 82.4 ± 2.18 and 65.8 ± 0.45 %, respectively. The release kinetics of PTX and TQ from the nanoparticles exhibited a biphasic pattern characterised by an initial burst, followed by a gradual and continuous release. The anticancer activity of nanoparticles encapsulating both the drugs was higher as compared to the free drugs in MCF-7 breast cancer cells. The combination index for the dual drug-loaded NPs was found to be 0.688 which is indicative of synergistic interaction. Thus, here, we propose the synthesis and use of dual drug-loaded TQ and PTX NPs which exhibits enhanced anticancer activity and can additionally help to alleviate the toxic effects of PTX by lowering its effective dose

  8. 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…

  9. Estimation of biological effects of phytocenosis radioactive contamination

    International Nuclear Information System (INIS)

    Suvorova, L.I.; Smirnov, E.G.; Shejn, G.N.

    1990-01-01

    Biological effects of argicultural field contamination in the Chernobyl NPP 30-km zone in the period of 1986-1988 are studies. Depth of some kings of herbs is noted in spite of natural phytocenosis high stability. It is revealed that increased mutageneous effect is observed for seeds from phytocenosis subjected to radiation factor effects. The genetic radiation effects at cell level will be observed in the nearest years as the radiation factor will not disappear in the 30-km zone (chronic irradiation of plants in the dose range from 0.1x10 -4 up to 0.1 Gy/day). These injuries visually will not effect greatly on natural populations

  10. Machine learning-based prediction of adverse drug effects: An example of seizure-inducing compounds

    Directory of Open Access Journals (Sweden)

    Mengxuan Gao

    2017-02-01

    Full Text Available Various biological factors have been implicated in convulsive seizures, involving side effects of drugs. For the preclinical safety assessment of drug development, it is difficult to predict seizure-inducing side effects. Here, we introduced a machine learning-based in vitro system designed to detect seizure-inducing side effects. We recorded local field potentials from the CA1 alveus in acute mouse neocortico-hippocampal slices, while 14 drugs were bath-perfused at 5 different concentrations each. For each experimental condition, we collected seizure-like neuronal activity and merged their waveforms as one graphic image, which was further converted into a feature vector using Caffe, an open framework for deep learning. In the space of the first two principal components, the support vector machine completely separated the vectors (i.e., doses of individual drugs that induced seizure-like events and identified diphenhydramine, enoxacin, strychnine and theophylline as “seizure-inducing” drugs, which indeed were reported to induce seizures in clinical situations. Thus, this artificial intelligence-based classification may provide a new platform to detect the seizure-inducing side effects of preclinical drugs.

  11. EFFECTS OF PSYCHOTROPIC DRUGS AS BACTERIAL EFFLUX PUMP INHIBITORS ON QUORUM SENSING REGULATED BEHAVIORS

    Directory of Open Access Journals (Sweden)

    Aynur Aybey

    2014-10-01

    Full Text Available Psychotropic drugs are known to have antimicrobial activity against several groups of microorganisms. The antidepressant agents such as duloxetine, paroxetine, hydroxyzine and venlafaxine are shown to act as efflux pump inhibitors in bacterial cells. In order to the investigation of the effects of psychotropic drugs were determined for clinically significant pathogens by using standart broth microdillusion method. The anti-quorum sensing (anti-QS activity of psychotropic drugs was tested against four test pathogens using the agar well diffusion method. All drugs showed strong inhibitory effect on the growth of S. typhimurium. Additionally, quorum sensing-regulated behaviors of Pseudomonas aeruginosa, including swarming, swimming and twitching motility and alkaline protease production were investigated. Most effective drugs on swarming, swimming and twitching motility and alkaline protease production, respectively, were paroxetine and duloxetine; duloxetine; hydroxyzine and venlafaxine; paroxetine and venlafaxine; venlafaxine. Accordingly, psychotropic drugs were shown strongly anti-QS activity by acting as bacterial efflux pump inhibitors and effection on motility and alkaline protease production of P. aeruginosa.

  12. Biological therapies (immunomodulatory drugs), worsening of psoriasis and rebound effect: new evidence of similitude.

    Science.gov (United States)

    Teixeira, Marcus Zulian

    2016-11-01

    Employing the secondary action or adaptative reaction of the organism as therapeutic response, homeopathy uses the treatment by similitude (similia similibus curentur) administering to sick individuals the medicines that caused similar symptoms in healthy individuals. Such homeostatic or paradoxical reaction of the organism is scientifically explained through the rebound effect of drugs, which cause worsening of symptoms after withdrawal of several palliative treatments. Despite promoting an improvement in psoriasis at the beginning of the treatment, modern biological therapies provoke worsening of the psoriasis (rebound psoriasis) after discontinuation of drugs. Exploratory qualitative review of the literature on the occurrence of the rebound effect with the use of immunomodulatory drugs [T-cell modulating agents and tumor necrosis factor (TNF) inhibitors drugs] in the treatment of psoriasis. Several researches indicate the rebound effect as the mechanism of worsening of psoriasis with the use of efalizumab causing the suspension of its marketing authorization in 2009, in view of some severe cases. Other studies also have demonstrated the occurrence of rebound psoriasis with the use of alefacept, etanercept and infliximab. As well as studied in other classes of drugs, the rebound effect of biologic agents supports the principle of similitude (primary action of the drugs followed by secondary action and opposite of the organism). Copyright © 2016 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  13. "It Ruined My Life": The effects of the War on Drugs on people who inject drugs (PWID) in rural Puerto Rico.

    Science.gov (United States)

    Abadie, R; Gelpi-Acosta, C; Davila, C; Rivera, A; Welch-Lazoritz, M; Dombrowski, K

    2018-01-01

    The War on Drugs has raised the incarceration rates of racial minorities for non-violent drug-related crimes, profoundly stigmatized drug users, and redirected resources from drug prevention and treatment to militarizing federal and local law enforcement. Yet, while some states consider shifting their punitive approach to drug use, to one based on drug treatment and rehabilitation, nothing suggests that these policy shifts are being replicated in Puerto Rico. This paper utilizes data from 360 PWID residing in four rural towns in the mountainous area of central Puerto Rico. We initially recruited 315 PWID using respondent-driven sampling (RDS) and collected data about risk practices and conducted HIV and HCV testing. During a second phase, we conducted 34 micro-ethnographic assays, in which we randomly recruited 34 participants from the first phase and included their ego networks in this phase. Our ethnographic inquiry produced significant data regarding the effects of the war on drugs on the local drug trade, drug availability, and injectors' social networks. Findings suggest that repressive policing has been ineffective in preventing drug distribution and use among those in our study. This type of law enforcement approach has resulted in the disproportionate incarceration of poor drug users in rural Puerto Rico, and mainly for nonviolent drug-related crimes. In addition, incarceration exposes PWID to a form of a cruel and unusual punishment: having to quit heroin "cold turkey" while the prison environment also represents a HIV/HCV risk. In turn, the war on drugs not only diverts resources from treatment but also shapes treatment ideologies, punishing non-compliant patients. Shifting the emphasis from repression to treatment and rehabilitation is likely to have a positive impact on the health and overall quality of life of PWID and their communities. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Cost-effectiveness of antiplatelet drugs after percutaneous coronary intervention.

    Science.gov (United States)

    Wisløff, Torbjørn; Atar, Dan

    2016-01-01

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

  15. Effects of drugs on beta-endorphin and cortisol in smokers

    International Nuclear Information System (INIS)

    Du Tongxin; Wang Zizheng; Wang Shukui

    2001-01-01

    The authors observed the effects of drugs on beta-endorphin and cortisol in smokers and their correlation. The levels of plasma beta-endorphin and cortisol of smokers before and after cigarette withdrawal were detected by radioimmunoassay (RIA). The Levels of plasma beta-endorphin and cortisol in smokers is significantly higher than in controls. After natural withdrawal, the levels of plasma cortisol increased significantly, while beta-endorphin decreased significantly. After drug treatment, the levels of beta-endorphin and cortisol balanced. The drugs may play the role of cigarette withdrawal by improving the secretion of endogenous opium and the axis of hypothalamus-pituitary adrenal

  16. Oral adverse effects of gastrointestinal drugs and considerations for dental management in patients with gastrointestinal disorders

    Directory of Open Access Journals (Sweden)

    Ramya Karthik

    2012-01-01

    Full Text Available Gastrointestinal disease is associated with alterations in the mouth or influence the course of the dental diseases, and the dental health care workers are expected to recognize, diagnose, and treat oral conditions associated with gastrointestinal diseases and also provide safe and appropriate dental care for afflicted individuals. Drugs used in the management of these diseases result in oral adverse effects and also are known to interact with those prescribed during dental care. Hence, this article has reviewed the drug considerations and guidelines for drug use during dental management of patients with gastrointestinal diseases.

  17. The persuasion network is modulated by drug-use risk and predicts anti-drug message effectiveness

    Science.gov (United States)

    Mangus, J Michael; Turner, Benjamin O

    2017-01-01

    Abstract While a persuasion network has been proposed, little is known about how network connections between brain regions contribute to attitude change. Two possible mechanisms have been advanced. One hypothesis predicts that attitude change results from increased connectivity between structures implicated in affective and executive processing in response to increases in argument strength. A second functional perspective suggests that highly arousing messages reduce connectivity between structures implicated in the encoding of sensory information, which disrupts message processing and thereby inhibits attitude change. However, persuasion is a multi-determined construct that results from both message features and audience characteristics. Therefore, persuasive messages should lead to specific functional connectivity patterns among a priori defined structures within the persuasion network. The present study exposed 28 subjects to anti-drug public service announcements where arousal, argument strength, and subject drug-use risk were systematically varied. Psychophysiological interaction analyses provide support for the affective-executive hypothesis but not for the encoding-disruption hypothesis. Secondary analyses show that video-level connectivity patterns among structures within the persuasion network predict audience responses in independent samples (one college-aged, one nationally representative). We propose that persuasion neuroscience research is best advanced by considering network-level effects while accounting for interactions between message features and target audience characteristics. PMID:29140500

  18. The persuasion network is modulated by drug-use risk and predicts anti-drug message effectiveness.

    Science.gov (United States)

    Huskey, Richard; Mangus, J Michael; Turner, Benjamin O; Weber, René

    2017-12-01

    While a persuasion network has been proposed, little is known about how network connections between brain regions contribute to attitude change. Two possible mechanisms have been advanced. One hypothesis predicts that attitude change results from increased connectivity between structures implicated in affective and executive processing in response to increases in argument strength. A second functional perspective suggests that highly arousing messages reduce connectivity between structures implicated in the encoding of sensory information, which disrupts message processing and thereby inhibits attitude change. However, persuasion is a multi-determined construct that results from both message features and audience characteristics. Therefore, persuasive messages should lead to specific functional connectivity patterns among a priori defined structures within the persuasion network. The present study exposed 28 subjects to anti-drug public service announcements where arousal, argument strength, and subject drug-use risk were systematically varied. Psychophysiological interaction analyses provide support for the affective-executive hypothesis but not for the encoding-disruption hypothesis. Secondary analyses show that video-level connectivity patterns among structures within the persuasion network predict audience responses in independent samples (one college-aged, one nationally representative). We propose that persuasion neuroscience research is best advanced by considering network-level effects while accounting for interactions between message features and target audience characteristics. © The Author (2017). Published by Oxford University Press.

  19. The effect of high leverage points on the logistic ridge regression estimator having multicollinearity

    Science.gov (United States)

    Ariffin, Syaiba Balqish; Midi, Habshah

    2014-06-01

    This article is concerned with the performance of logistic ridge regression estimation technique in the presence of multicollinearity and high leverage points. In logistic regression, multicollinearity exists among predictors and in the information matrix. The maximum likelihood estimator suffers a huge setback in the presence of multicollinearity which cause regression estimates to have unduly large standard errors. To remedy this problem, a logistic ridge regression estimator is put forward. It is evident that the logistic ridge regression estimator outperforms the maximum likelihood approach for handling multicollinearity. The effect of high leverage points are then investigated on the performance of the logis