WorldWideScience

Sample records for modelling treatment effects

  1. Modelling the effects of treatment and quarantine on measles

    Science.gov (United States)

    Beay, Lazarus Kalvein

    2018-03-01

    Treatment and quarantine are efforts to cure as well as to overcome the spread of diseases including measles. The spread of measles can be expressed by mathematical modelling in the form of nonlinear dynamical systems. In this study was conducted on the spread of measles by considering the effect of treatment and quarantine on the infected individuals. By using the basic reproduction number of the model, can be analyzed the effects of treatment and quarantine to reduce the spread of measles. Basic reproduction number of models is monotonically descreasing as treatment and quarantine increasing. Numerical simulations conducted on the analysis of the results. The results showed that treatment and quarantine was given to infected individuals who were infectious has a major influence to eliminate measles from the system.

  2. Treatment Effects

    DEFF Research Database (Denmark)

    Heckman, James J.; Lopes, Hedibert F.; Piatek, Rémi

    2014-01-01

    This paper contributes to the emerging Bayesian literature on treatment effects. It derives treatment parameters in the framework of a potential outcomes model with a treatment choice equation, where the correlation between the unobservable components of the model is driven by a low-dimensional v......This paper contributes to the emerging Bayesian literature on treatment effects. It derives treatment parameters in the framework of a potential outcomes model with a treatment choice equation, where the correlation between the unobservable components of the model is driven by a low...... to observe the same person in both the treated and untreated states, but it also turns out to be straightforward to implement. Formulae are provided to compute mean treatment effects as well as their distributional versions. A Monte Carlo simulation study is carried out to illustrate how the methodology can...

  3. Modelling the cost effectiveness of antidepressant treatment in primary care.

    Science.gov (United States)

    Revicki, D A; Brown, R E; Palmer, W; Bakish, D; Rosser, W W; Anton, S F; Feeny, D

    1995-12-01

    The aim of this study was to estimate the cost effectiveness of nefazodone compared with imipramine or fluoxetine in treating women with major depressive disorder. Clinical decision analysis and a Markov state-transition model were used to estimate the lifetime health outcomes and medical costs of 3 antidepressant treatments. The model, which represents ideal primary care practice, compares treatment with nefazodone to treatment with either imipramine or fluoxetine. The economic analysis was based on the healthcare system of the Canadian province of Ontario, and considered only direct medical costs. Health outcomes were expressed as quality-adjusted life years (QALYs) and costs were in 1993 Canadian dollars ($Can; $Can1 = $US0.75, September 1995). Incremental cost-utility ratios were calculated comparing the relative lifetime discounted medical costs and QALYs associated with nefazodone with those of imipramine or fluoxetine. Data for constructing the model and estimating necessary parameters were derived from the medical literature, clinical trial data, and physician judgement. Data included information on: Ontario primary care physicians' clinical management of major depression; medical resource use and costs; probabilities of recurrence of depression; suicide rates; compliance rates; and health utilities. Estimates of utilities for depression-related hypothetical health states were obtained from patients with major depression (n = 70). Medical costs and QALYs were discounted to present value using a 5% rate. Sensitivity analyses tested the assumptions of the model by varying the discount rate, depression recurrence rates, compliance rates, and the duration of the model. The base case analysis found that nefazodone treatment costs $Can1447 less per patient than imipramine treatment (discounted lifetime medical costs were $Can50,664 vs $Can52,111) and increases the number of QALYs by 0.72 (13.90 vs 13.18). Nefazodone treatment costs $Can14 less than fluoxetine

  4. Effective field treatment of the annealed bond-dilute transverse Ising model

    International Nuclear Information System (INIS)

    Silva, P.R.; Sa Barreto, F.C. de

    1983-01-01

    The dilution of the spin-1/2 transverse Ising Model is studied by means of an effective field type treatment based on an extension of Callen's relation to the present model. The thermodynamics of the diluted model is obtained and the results are shown to be an improvement over the standard mean field treatment. The results are also compared with the Monte Carlo calculation for the spin-infinite transverse Ising Model. (Author) [pt

  5. Detecting treatment-subgroup interactions in clustered data with generalized linear mixed-effects model trees.

    Science.gov (United States)

    Fokkema, M; Smits, N; Zeileis, A; Hothorn, T; Kelderman, H

    2017-10-25

    Identification of subgroups of patients for whom treatment A is more effective than treatment B, and vice versa, is of key importance to the development of personalized medicine. Tree-based algorithms are helpful tools for the detection of such interactions, but none of the available algorithms allow for taking into account clustered or nested dataset structures, which are particularly common in psychological research. Therefore, we propose the generalized linear mixed-effects model tree (GLMM tree) algorithm, which allows for the detection of treatment-subgroup interactions, while accounting for the clustered structure of a dataset. The algorithm uses model-based recursive partitioning to detect treatment-subgroup interactions, and a GLMM to estimate the random-effects parameters. In a simulation study, GLMM trees show higher accuracy in recovering treatment-subgroup interactions, higher predictive accuracy, and lower type II error rates than linear-model-based recursive partitioning and mixed-effects regression trees. Also, GLMM trees show somewhat higher predictive accuracy than linear mixed-effects models with pre-specified interaction effects, on average. We illustrate the application of GLMM trees on an individual patient-level data meta-analysis on treatments for depression. We conclude that GLMM trees are a promising exploratory tool for the detection of treatment-subgroup interactions in clustered datasets.

  6. Effects of Video Modeling on Treatment Integrity of Behavioral Interventions

    Science.gov (United States)

    DiGennaro-Reed, Florence D.; Codding, Robin; Catania, Cynthia N.; Maguire, Helena

    2010-01-01

    We examined the effects of individualized video modeling on the accurate implementation of behavioral interventions using a multiple baseline design across 3 teachers. During video modeling, treatment integrity improved above baseline levels; however, teacher performance remained variable. The addition of verbal performance feedback increased…

  7. Some consequences of assuming simple patterns for the treatment effect over time in a linear mixed model.

    Science.gov (United States)

    Bamia, Christina; White, Ian R; Kenward, Michael G

    2013-07-10

    Linear mixed models are often used for the analysis of data from clinical trials with repeated quantitative outcomes. This paper considers linear mixed models where a particular form is assumed for the treatment effect, in particular constant over time or proportional to time. For simplicity, we assume no baseline covariates and complete post-baseline measures, and we model arbitrary mean responses for the control group at each time. For the variance-covariance matrix, we consider an unstructured model, a random intercepts model and a random intercepts and slopes model. We show that the treatment effect estimator can be expressed as a weighted average of the observed time-specific treatment effects, with weights depending on the covariance structure and the magnitude of the estimated variance components. For an assumed constant treatment effect, under the random intercepts model, all weights are equal, but in the random intercepts and slopes and the unstructured models, we show that some weights can be negative: thus, the estimated treatment effect can be negative, even if all time-specific treatment effects are positive. Our results suggest that particular models for the treatment effect combined with particular covariance structures may result in estimated treatment effects of unexpected magnitude and/or direction. Methods are illustrated using a Parkinson's disease trial. Copyright © 2012 John Wiley & Sons, Ltd.

  8. Intensive treatment models and coercion

    DEFF Research Database (Denmark)

    Ohlenschlaeger, Johan; Thorup, Anne; Petersen, Lone

    2007-01-01

    . Hospital-based Rehabilitation, an intensified inpatient treatment model, Integrated Treatment, an intensified model of Assertive Community Treatment, and standard treatment were compared for patients with first-episode schizophrenia-spectrum disorders. Ninety-four patients with first-episode schizophrenia......Little evidence exists concerning the optimal treatment for patients with first-episode schizophrenia-spectrum disorders and the effect on traditional outcomes. The aim was to investigate whether optimal treatment models have an effect on the level of use of coercion and on traditional outcomes......-spectrum disorders estimated to benefit from long-term hospitalization were included consecutively from the Copenhagen OPUS-trial and randomized to the three treatment models. At 1-year follow-up, Hospital-based Rehabilitation and Integrated Treatment had better scores on symptoms in the negative dimension...

  9. Using forecast modelling to evaluate treatment effects in single-group interrupted time series analysis.

    Science.gov (United States)

    Linden, Ariel

    2018-05-11

    Interrupted time series analysis (ITSA) is an evaluation methodology in which a single treatment unit's outcome is studied serially over time and the intervention is expected to "interrupt" the level and/or trend of that outcome. ITSA is commonly evaluated using methods which may produce biased results if model assumptions are violated. In this paper, treatment effects are alternatively assessed by using forecasting methods to closely fit the preintervention observations and then forecast the post-intervention trend. A treatment effect may be inferred if the actual post-intervention observations diverge from the forecasts by some specified amount. The forecasting approach is demonstrated using the effect of California's Proposition 99 for reducing cigarette sales. Three forecast models are fit to the preintervention series-linear regression (REG), Holt-Winters (HW) non-seasonal smoothing, and autoregressive moving average (ARIMA)-and forecasts are generated into the post-intervention period. The actual observations are then compared with the forecasts to assess intervention effects. The preintervention data were fit best by HW, followed closely by ARIMA. REG fit the data poorly. The actual post-intervention observations were above the forecasts in HW and ARIMA, suggesting no intervention effect, but below the forecasts in the REG (suggesting a treatment effect), thereby raising doubts about any definitive conclusion of a treatment effect. In a single-group ITSA, treatment effects are likely to be biased if the model is misspecified. Therefore, evaluators should consider using forecast models to accurately fit the preintervention data and generate plausible counterfactual forecasts, thereby improving causal inference of treatment effects in single-group ITSA studies. © 2018 John Wiley & Sons, Ltd.

  10. Model averaging in the presence of structural uncertainty about treatment effects: influence on treatment decision and expected value of information.

    Science.gov (United States)

    Price, Malcolm J; Welton, Nicky J; Briggs, Andrew H; Ades, A E

    2011-01-01

    Standard approaches to estimation of Markov models with data from randomized controlled trials tend either to make a judgment about which transition(s) treatments act on, or they assume that treatment has a separate effect on every transition. An alternative is to fit a series of models that assume that treatment acts on specific transitions. Investigators can then choose among alternative models using goodness-of-fit statistics. However, structural uncertainty about any chosen parameterization will remain and this may have implications for the resulting decision and the need for further research. We describe a Bayesian approach to model estimation, and model selection. Structural uncertainty about which parameterization to use is accounted for using model averaging and we developed a formula for calculating the expected value of perfect information (EVPI) in averaged models. Marginal posterior distributions are generated for each of the cost-effectiveness parameters using Markov Chain Monte Carlo simulation in WinBUGS, or Monte-Carlo simulation in Excel (Microsoft Corp., Redmond, WA). We illustrate the approach with an example of treatments for asthma using aggregate-level data from a connected network of four treatments compared in three pair-wise randomized controlled trials. The standard errors of incremental net benefit using structured models is reduced by up to eight- or ninefold compared to the unstructured models, and the expected loss attaching to decision uncertainty by factors of several hundreds. Model averaging had considerable influence on the EVPI. Alternative structural assumptions can alter the treatment decision and have an overwhelming effect on model uncertainty and expected value of information. Structural uncertainty can be accounted for by model averaging, and the EVPI can be calculated for averaged models. Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights

  11. A model to describe potential effects of chemotherapy on critical radiobiological treatments

    Science.gov (United States)

    Rodríguez-Pérez, D.; Desco, M. M.; Antoranz, J. C.

    2016-08-01

    Although chemo- and radiotherapy can annihilate tumors on their own. they are also used in coadjuvancy: improving local effects of radiotherapy using chemotherapy as a radiosensit.izer. The effects of radiotherapy are well described by current radiobiological models. The goal of this work is to describe a discrete radiotherapy model, that has been previously used describe high radiation dose response as well as unusual radio-responses of some types of tumors (e.g. prostate cancer), to obtain a model of chemo+radiotherapy that can describe how the outcome of their combination is a more efficient removal of the tumor. Our hypothesis is that, although both treatments haven different mechanisms, both affect similar key points of cell metabolism and regulation, that lead to cellular death. Hence, we will consider a discrete model where chemotherapy may affect a fraction of the same targets destroyed by radiotherapy. Although radiotherapy reaches all cells equally, chemotherapy diffuses through a tumor attaining lower concentration in its center and higher in its surface. With our simulations we study the enhanced effect of combined therapy treatment and how it depends on the tissue critical parameters (the parameters of the lion-extensive radiobiological model), the number of “targets” aimed at by chemotherapy, and the concentration and diffusion rate of the drug inside the tumor. The results show that an equivalent, cliemo-radio-dose can be computed that allows the prediction of the lower radiation dose that causes the same effect than a radio-only treatment.

  12. Accounting for Heterogeneity in Relative Treatment Effects for Use in Cost-Effectiveness Models and Value-of-Information Analyses.

    Science.gov (United States)

    Welton, Nicky J; Soares, Marta O; Palmer, Stephen; Ades, Anthony E; Harrison, David; Shankar-Hari, Manu; Rowan, Kathy M

    2015-07-01

    Cost-effectiveness analysis (CEA) models are routinely used to inform health care policy. Key model inputs include relative effectiveness of competing treatments, typically informed by meta-analysis. Heterogeneity is ubiquitous in meta-analysis, and random effects models are usually used when there is variability in effects across studies. In the absence of observed treatment effect modifiers, various summaries from the random effects distribution (random effects mean, predictive distribution, random effects distribution, or study-specific estimate [shrunken or independent of other studies]) can be used depending on the relationship between the setting for the decision (population characteristics, treatment definitions, and other contextual factors) and the included studies. If covariates have been measured that could potentially explain the heterogeneity, then these can be included in a meta-regression model. We describe how covariates can be included in a network meta-analysis model and how the output from such an analysis can be used in a CEA model. We outline a model selection procedure to help choose between competing models and stress the importance of clinical input. We illustrate the approach with a health technology assessment of intravenous immunoglobulin for the management of adult patients with severe sepsis in an intensive care setting, which exemplifies how risk of bias information can be incorporated into CEA models. We show that the results of the CEA and value-of-information analyses are sensitive to the model and highlight the importance of sensitivity analyses when conducting CEA in the presence of heterogeneity. The methods presented extend naturally to heterogeneity in other model inputs, such as baseline risk. © The Author(s) 2015.

  13. Do different methods of modeling statin treatment effectiveness influence the optimal decision?

    NARCIS (Netherlands)

    B.J.H. van Kempen (Bob); B.S. Ferket (Bart); A. Hofman (Albert); S. Spronk (Sandra); E.W. Steyerberg (Ewout); M.G.M. Hunink (Myriam)

    2012-01-01

    textabstractPurpose. Modeling studies that evaluate statin treatment for the prevention of cardiovascular disease (CVD) use different methods to model the effect of statins. The aim of this study was to evaluate the impact of using different modeling methods on the optimal decision found in such

  14. [Home treatment--a treatment model of integrated care in Hamburg].

    Science.gov (United States)

    Schöttle, Daniel; Ruppelt, Friederike; Karow, Anne; Lambert, Martin

    2015-03-01

    Treatment models like "Crisis Resolution and Hometreatment (CRHT)" or "Assertive Community Treatment" (ACT), were found to be effective, enhancing the qualitative level of treatment for patients with severe mental disorders. In Germany, these are implemented only sporadically until today, often as part of a cross-sectoral Integrated Care (IC) treatment system. We will present the implementation of an "Assertive Community Treatment" embedded into an IC-treatment model in Hamburg and discuss the 3-year-outcomes. The IC-treatment model has been designed for severe mentally ill patients with psychotic disorders. Since May 2007 the model is financed by different health insurances as a managed-care "capitation-model" and its effectiveness gets continuously evaluated. The model proved to be effective in earlier studies were compared with standard care low rates of service disengagement were found as well as significantly improved psychopathology, psychosocial functioning, quality of life, satisfaction with care and adherence, while being cost effective. The rates of involuntary admissions declined to 10% in comparison to the years before. In 2011 the model was specified to the indication "first-episode adolescents and young adults in the age of 12-29" in a government-funded study "Integrated Care in Early Psychosis, ICEP Study". In this study an interdisciplinary team of child, adolescent and adult psychiatrists was implemented and since 2012 it is financed by the involved health insurances throughout an expansion of the §140 SGB V agreement. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Visualization of laser tattoo removal treatment effects in a mouse model by two-photon microscopy.

    Science.gov (United States)

    Jang, Won Hyuk; Yoon, Yeoreum; Kim, Wonjoong; Kwon, Soonjae; Lee, Seunghun; Song, Duke; Choi, Jong Woon; Kim, Ki Hean

    2017-08-01

    Laser tattoo removal is an effective method of eliminating tattoo particles in the skin. However, laser treatment cannot always remove the unwanted tattoo completely, and there are risks of either temporary or permanent side effects. Studies using preclinical animal models could provide detailed information on the effects of laser treatment in the skin, and might help to minimize side effects in clinical practices. In this study, two-photon microscopy (TPM) was used to visualize the laser treatment effects on tattoo particles in both phantom specimens and in vivo mouse models. Fluorescent tattoo ink was used for particle visualization by TPM, and nanosecond (ns) and picosecond (ps) lasers at 532 nm were used for treatment. In phantom specimens, TPM characterized the fragmentation of individual tattoo particles by tracking them before and after the laser treatment. These changes were confirmed by field emission scanning electron microscopy (FE-SEM). TPM was used to measure the treatment efficiency of the two lasers at different laser fluences. In the mouse model, TPM visualized clusters of tattoo particles in the skin and detected their fragmentation after the laser treatment. Longitudinal TPM imaging observed the migration of cells containing tattoo particles after the laser treatment. These results show that TPM may be useful for the assessment of laser tattoo removal treatment in preclinical studies.

  16. A model to describe potential effects of chemotherapy on critical radiobiological treatments

    International Nuclear Information System (INIS)

    Rodríguez-Pérez, D.; Desco, M.M.; Antoranz, J.C.

    2016-01-01

    Although chemo- and radiotherapy can annihilate tumors on their own. they are also used in coadjuvancy: improving local effects of radiotherapy using chemotherapy as a radiosensit.izer. The effects of radiotherapy are well described by current radiobiological models. The goal of this work is to describe a discrete radiotherapy model, that has been previously used describe high radiation dose response as well as unusual radio-responses of some types of tumors (e.g. prostate cancer), to obtain a model of chemo+radiotherapy that can describe how the outcome of their combination is a more efficient removal of the tumor. Our hypothesis is that, although both treatments haven different mechanisms, both affect similar key points of cell metabolism and regulation, that lead to cellular death. Hence, we will consider a discrete model where chemotherapy may affect a fraction of the same targets destroyed by radiotherapy. Although radiotherapy reaches all cells equally, chemotherapy diffuses through a tumor attaining lower concentration in its center and higher in its surface. With our simulations we study the enhanced effect of combined therapy treatment and how it depends on the tissue critical parameters (the parameters of the lion-extensive radiobiological model), the number of “targets” aimed at by chemotherapy, and the concentration and diffusion rate of the drug inside the tumor. The results show that an equivalent, cliemo-radio-dose can be computed that allows the prediction of the lower radiation dose that causes the same effect than a radio-only treatment. (paper)

  17. Treatment of cloud radiative effects in general circulation models

    Energy Technology Data Exchange (ETDEWEB)

    Wang, W.C.; Dudek, M.P.; Liang, X.Z.; Ding, M. [State Univ. of New York, Albany, NY (United States)] [and others

    1996-04-01

    We participate in the Atmospheric Radiation Measurement (ARM) program with two objectives: (1) to improve the general circulation model (GCM) cloud/radiation treatment with a focus on cloud verticle overlapping and layer cloud optical properties, and (2) to study the effects of cloud/radiation-climate interaction on GCM climate simulations. This report summarizes the project progress since the Fourth ARM Science Team meeting February 28-March 4, 1994, in Charleston, South Carolina.

  18. Estimating the average treatment effect on survival based on observational data and using partly conditional modeling.

    Science.gov (United States)

    Gong, Qi; Schaubel, Douglas E

    2017-03-01

    Treatments are frequently evaluated in terms of their effect on patient survival. In settings where randomization of treatment is not feasible, observational data are employed, necessitating correction for covariate imbalances. Treatments are usually compared using a hazard ratio. Most existing methods which quantify the treatment effect through the survival function are applicable to treatments assigned at time 0. In the data structure of our interest, subjects typically begin follow-up untreated; time-until-treatment, and the pretreatment death hazard are both heavily influenced by longitudinal covariates; and subjects may experience periods of treatment ineligibility. We propose semiparametric methods for estimating the average difference in restricted mean survival time attributable to a time-dependent treatment, the average effect of treatment among the treated, under current treatment assignment patterns. The pre- and posttreatment models are partly conditional, in that they use the covariate history up to the time of treatment. The pre-treatment model is estimated through recently developed landmark analysis methods. For each treated patient, fitted pre- and posttreatment survival curves are projected out, then averaged in a manner which accounts for the censoring of treatment times. Asymptotic properties are derived and evaluated through simulation. The proposed methods are applied to liver transplant data in order to estimate the effect of liver transplantation on survival among transplant recipients under current practice patterns. © 2016, The International Biometric Society.

  19. Effectiveness and cost-effectiveness of antidepressants in primary care: a multiple treatment comparison meta-analysis and cost-effectiveness model.

    Directory of Open Access Journals (Sweden)

    Joakim Ramsberg

    Full Text Available OBJECTIVE: To determine effectiveness and cost-effectiveness over a one-year time horizon of pharmacological first line treatment in primary care for patients with moderate to severe depression. DESIGN: A multiple treatment comparison meta-analysis was employed to determine the relative efficacy in terms of remission of 10 antidepressants (citalopram, duloxetine escitalopram, fluoxetine, fluvoxamine mirtazapine, paroxetine, reboxetine, sertraline and venlafaxine. The estimated remission rates were then applied in a decision-analytic model in order to estimate costs and quality of life with different treatments at one year. DATA SOURCES: Meta-analyses of remission rates from randomised controlled trials, and cost and quality-of-life data from published sources. RESULTS: The most favourable pharmacological treatment in terms of remission was escitalopram with an 8- to 12-week probability of remission of 0.47. Despite a high acquisition cost, this clinical effectiveness translated into escitalopram being both more effective and having a lower total cost than all other comparators from a societal perspective. From a healthcare perspective, the cost per QALY of escitalopram was €3732 compared with venlafaxine. CONCLUSION: Of the investigated antidepressants, escitalopram has the highest probability of remission and is the most effective and cost-effective pharmacological treatment in a primary care setting, when evaluated over a one year time-horizon. Small differences in remission rates may be important when assessing costs and cost-effectiveness of antidepressants.

  20. Effect of sclerostin antibody treatment in a mouse model of severe osteogenesis imperfecta.

    Science.gov (United States)

    Roschger, Andreas; Roschger, Paul; Keplingter, Petra; Klaushofer, Klaus; Abdullah, Sami; Kneissel, Michaela; Rauch, Frank

    2014-09-01

    Osteogenesis imperfecta (OI) is a heritable bone fragility disorder that is usually caused by mutations affecting collagen type I production in osteoblasts. Stimulation of bone formation through sclerostin antibody treatment (Sost-ab) has shown promising results in mouse models of relatively mild OI. We assessed the effect of once-weekly intravenous Sost-ab injections for 4weeks in male Col1a1(Jrt)/+mice, a model of severe dominant OI, starting either at 4weeks (growing mice) or at 20weeks (adult mice) of age. Sost-ab had no effect on weight or femur length. In OI mice, no significant treatment-associated differences in serum markers of bone formation (alkaline phosphatase activity, procollagen type I N-propeptide) or resorption (C-telopeptide of collagen type I) were found. Micro-CT analyses at the femur showed that Sost-ab treatment was associated with higher trabecular bone volume and higher cortical thickness in wild type mice at both ages and in growing OI mice, but not in adult OI mice. Three-point bending tests of the femur showed that in wild type but not in OI mice, Sost-ab was associated with higher ultimate load and work to failure. Quantitative backscattered electron imaging of the femur did not show any effect of Sost-ab on CaPeak (the most frequently occurring calcium concentration in the bone mineral density distribution), regardless of genotype, age or measurement location. Thus, Sost-ab had a larger effect in wild type than in Col1a1(Jrt)/+mice. Previous studies had found marked improvements of Sost-ab on bone mass and strength in an OI mouse model with a milder phenotype. Our data therefore suggest that Sost-ab is less effective in a more severely affected OI mouse model. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. 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.

  2. Simple, efficient estimators of treatment effects in randomized trials using generalized linear models to leverage baseline variables.

    Science.gov (United States)

    Rosenblum, Michael; van der Laan, Mark J

    2010-04-01

    Models, such as logistic regression and Poisson regression models, are often used to estimate treatment effects in randomized trials. These models leverage information in variables collected before randomization, in order to obtain more precise estimates of treatment effects. However, there is the danger that model misspecification will lead to bias. We show that certain easy to compute, model-based estimators are asymptotically unbiased even when the working model used is arbitrarily misspecified. Furthermore, these estimators are locally efficient. As a special case of our main result, we consider a simple Poisson working model containing only main terms; in this case, we prove the maximum likelihood estimate of the coefficient corresponding to the treatment variable is an asymptotically unbiased estimator of the marginal log rate ratio, even when the working model is arbitrarily misspecified. This is the log-linear analog of ANCOVA for linear models. Our results demonstrate one application of targeted maximum likelihood estimation.

  3. Simple, Efficient Estimators of Treatment Effects in Randomized Trials Using Generalized Linear Models to Leverage Baseline Variables

    Science.gov (United States)

    Rosenblum, Michael; van der Laan, Mark J.

    2010-01-01

    Models, such as logistic regression and Poisson regression models, are often used to estimate treatment effects in randomized trials. These models leverage information in variables collected before randomization, in order to obtain more precise estimates of treatment effects. However, there is the danger that model misspecification will lead to bias. We show that certain easy to compute, model-based estimators are asymptotically unbiased even when the working model used is arbitrarily misspecified. Furthermore, these estimators are locally efficient. As a special case of our main result, we consider a simple Poisson working model containing only main terms; in this case, we prove the maximum likelihood estimate of the coefficient corresponding to the treatment variable is an asymptotically unbiased estimator of the marginal log rate ratio, even when the working model is arbitrarily misspecified. This is the log-linear analog of ANCOVA for linear models. Our results demonstrate one application of targeted maximum likelihood estimation. PMID:20628636

  4. Cost-Effective Fuel Treatment Planning

    Science.gov (United States)

    Kreitler, J.; Thompson, M.; Vaillant, N.

    2014-12-01

    The cost of fighting large wildland fires in the western United States has grown dramatically over the past decade. This trend will likely continue with growth of the WUI into fire prone ecosystems, dangerous fuel conditions from decades of fire suppression, and a potentially increasing effect from prolonged drought and climate change. Fuel treatments are often considered the primary pre-fire mechanism to reduce the exposure of values at risk to wildland fire, and a growing suite of fire models and tools are employed to prioritize where treatments could mitigate wildland fire damages. Assessments using the likelihood and consequence of fire are critical because funds are insufficient to reduce risk on all lands needing treatment, therefore prioritization is required to maximize the effectiveness of fuel treatment budgets. Cost-effectiveness, doing the most good per dollar, would seem to be an important fuel treatment metric, yet studies or plans that prioritize fuel treatments using costs or cost-effectiveness measures are absent from the literature. Therefore, to explore the effect of using costs in fuel treatment planning we test four prioritization algorithms designed to reduce risk in a case study examining fuel treatments on the Sisters Ranger District of central Oregon. For benefits we model sediment retention and standing biomass, and measure the effectiveness of each algorithm by comparing the differences among treatment and no treat alternative scenarios. Our objective is to maximize the averted loss of net benefits subject to a representative fuel treatment budget. We model costs across the study landscape using the My Fuel Treatment Planner software, tree list data, local mill prices, and GIS-measured site characteristics. We use fire simulations to generate burn probabilities, and estimate fire intensity as conditional flame length at each pixel. Two prioritization algorithms target treatments based on cost-effectiveness and show improvements over those

  5. Cost and cost-effectiveness of tuberculosis treatment shortening: a model-based analysis.

    Science.gov (United States)

    Gomez, G B; Dowdy, D W; Bastos, M L; Zwerling, A; Sweeney, S; Foster, N; Trajman, A; Islam, M A; Kapiga, S; Sinanovic, E; Knight, G M; White, R G; Wells, W A; Cobelens, F G; Vassall, A

    2016-12-01

    Despite improvements in treatment success rates for tuberculosis (TB), current six-month regimen duration remains a challenge for many National TB Programmes, health systems, and patients. There is increasing investment in the development of shortened regimens with a number of candidates in phase 3 trials. We developed an individual-based decision analytic model to assess the cost-effectiveness of a hypothetical four-month regimen for first-line treatment of TB, assuming non-inferiority to current regimens of six-month duration. The model was populated using extensive, empirically-collected data to estimate the economic impact on both health systems and patients of regimen shortening for first-line TB treatment in South Africa, Brazil, Bangladesh, and Tanzania. We explicitly considered 'real world' constraints such as sub-optimal guideline adherence. From a societal perspective, a shortened regimen, priced at USD1 per day, could be a cost-saving option in South Africa, Brazil, and Tanzania, but would not be cost-effective in Bangladesh when compared to one gross domestic product (GDP) per capita. Incorporating 'real world' constraints reduces cost-effectiveness. Patient-incurred costs could be reduced in all settings. From a health service perspective, increased drug costs need to be balanced against decreased delivery costs. The new regimen would remain a cost-effective option, when compared to each countries' GDP per capita, even if new drugs cost up to USD7.5 and USD53.8 per day in South Africa and Brazil; this threshold was above USD1 in Tanzania and under USD1 in Bangladesh. Reducing the duration of first-line TB treatment has the potential for substantial economic gains from a patient perspective. The potential economic gains for health services may also be important, but will be context-specific and dependent on the appropriate pricing of any new regimen.

  6. Improving observational study estimates of treatment effects using joint modeling of selection effects and outcomes: the case of AAA repair.

    Science.gov (United States)

    O'Malley, A James; Cotterill, Philip; Schermerhorn, Marc L; Landon, Bruce E

    2011-12-01

    When 2 treatment approaches are available, there are likely to be unmeasured confounders that influence choice of procedure, which complicates estimation of the causal effect of treatment on outcomes using observational data. To estimate the effect of endovascular (endo) versus open surgical (open) repair, including possible modification by institutional volume, on survival after treatment for abdominal aortic aneurysm, accounting for observed and unobserved confounding variables. Observational study of data from the Medicare program using a joint model of treatment selection and survival given treatment to estimate the effects of type of surgery and institutional volume on survival. We studied 61,414 eligible repairs of intact abdominal aortic aneurysms during 2001 to 2004. The outcome, perioperative death, is defined as in-hospital death or death within 30 days of operation. The key predictors are use of endo, transformed endo and open volume, and endo-volume interactions. There is strong evidence of nonrandom selection of treatment with potential confounding variables including institutional volume and procedure date, variables not typically adjusted for in clinical trials. The best fitting model included heterogeneous transformations of endo volume for endo cases and open volume for open cases as predictors. Consistent with our hypothesis, accounting for unmeasured selection reduced the mortality benefit of endo. The effect of endo versus open surgery varies nonlinearly with endo and open volume. Accounting for institutional experience and unmeasured selection enables better decision-making by physicians making treatment referrals, investigators evaluating treatments, and policy makers.

  7. An Exponential Tilt Mixture Model for Time-to-Event Data to Evaluate Treatment Effect Heterogeneity in Randomized Clinical Trials.

    Science.gov (United States)

    Wang, Chi; Tan, Zhiqiang; Louis, Thomas A

    2014-01-01

    Evaluating the effect of a treatment on a time-to-event outcome is the focus of many randomized clinical trials. It is often observed that the treatment effect is heterogeneous, where only a subgroup of the patients may respond to the treatment due to some unknown mechanism such as genetic polymorphism. In this paper, we propose a semiparametric exponential tilt mixture model to estimate the proportion of patients who respond to the treatment and to assess the treatment effect. Our model is a natural extension of parametric mixture models to a semiparametric setting with a time-to-event outcome. We propose a nonparametric maximum likelihood estimation approach for inference and establish related asymptotic properties. Our method is illustrated by a randomized clinical trial on biodegradable polymer-delivered chemotherapy for malignant gliomas patients.

  8. Cost-effectiveness modeling for neuropathic pain treatments: investigating the relative importance of parameters using an open-source model.

    Science.gov (United States)

    Hirst, Matthew; Bending, Matthew W; Baio, Gianluca; Yesufu-Udechuku, Amina; Dunlop, William C N

    2018-06-08

    The study objective was to develop an open-source replicate of a cost-effectiveness model developed by National Institute for Health and Care (NICE) in order to explore uncertainties in health economic modeling of novel pharmacological neuropathic pain treatments. The NICE model, consisting of a decision tree with branches for discrete levels of pain relief and adverse event (AE) severities, was replicated using R and used to compare a hypothetical neuropathic pain drug to pregabalin. Model parameters were sourced from NICE's clinical guidelines and associated with probability distributions to account for underlying uncertainty. A simulation-based scenario analysis was conducted to assess how uncertainty in efficacy and AEs affected the net monetary benefit (NMB) for the hypothetical treatment at a cost-effectiveness threshold of £20,000 per QALY. Relative to pregabalin, an increase in efficacy was associated with greater NMB than an improvement in tolerability. A greater NMB was observed when efficacy was marginally higher than that of pregabalin while maintaining the same level of AEs than when efficacy was equivalent to pregabalin but with a more substantial reduction in AEs. In the latter scenario, the NMB was only positive at a low cost-effectiveness threshold. The replicate model shares the limitations described in the NICE guidelines. There is a lack of support in scientific literature for the assumption that increased efficacy is associated with a greater reduction in tolerability. The replicate model also included a single comparator, unlike the NICE model. Pain relief is a stronger driver of NMB than tolerability at a cost-effectiveness threshold of £20,000 per QALY. Health technology assessment decisions which are influenced by NICE's model may reward efficacy gains even if they are associated with more severe AEs. This contrasts with recommendations from clinical guidelines for neuropathic pain which place more equal weighting on improvements in

  9. Screening of effective pharmacological treatments for MELAS syndrome using yeasts, fibroblasts and cybrid models of the disease.

    Science.gov (United States)

    Garrido-Maraver, Juan; Cordero, Mario D; Moñino, Irene Domínguez; Pereira-Arenas, Sheila; Lechuga-Vieco, Ana V; Cotán, David; De la Mata, Mario; Oropesa-Ávila, Manuel; De Miguel, Manuel; Bautista Lorite, Juan; Rivas Infante, Eloy; Alvarez-Dolado, Manuel; Navas, Plácido; Jackson, Sandra; Francisci, Silvia; Sánchez-Alcázar, José A

    2012-11-01

    MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a mitochondrial disease most usually caused by point mutations in tRNA genes encoded by mitochondrial DNA (mtDNA). Approximately 80% of cases of MELAS syndrome are associated with a m.3243A > G mutation in the MT-TL1 gene, which encodes the mitochondrial tRNALeu (UUR). Currently, no effective treatments are available for this chronic progressive disorder. Treatment strategies in MELAS and other mitochondrial diseases consist of several drugs that diminish the deleterious effects of the abnormal respiratory chain function, reduce the presence of toxic agents or correct deficiencies in essential cofactors. We evaluated the effectiveness of some common pharmacological agents that have been utilized in the treatment of MELAS, in yeast, fibroblast and cybrid models of the disease. The yeast model harbouring the A14G mutation in the mitochondrial tRNALeu(UUR) gene, which is equivalent to the A3243G mutation in humans, was used in the initial screening. Next, the most effective drugs that were able to rescue the respiratory deficiency in MELAS yeast mutants were tested in fibroblasts and cybrid models of MELAS disease. According to our results, supplementation with riboflavin or coenzyme Q(10) effectively reversed the respiratory defect in MELAS yeast and improved the pathologic alterations in MELAS fibroblast and cybrid cell models. Our results indicate that cell models have great potential for screening and validating the effects of novel drug candidates for MELAS treatment and presumably also for other diseases with mitochondrial impairment. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  10. A global economic model to assess the cost-effectiveness of new treatments for advanced breast cancer in Canada.

    Science.gov (United States)

    Beauchemin, C; Letarte, N; Mathurin, K; Yelle, L; Lachaine, J

    2016-06-01

    Objective Considering the increasing number of treatment options for metastatic breast cancer (MBC), it is important to develop high-quality methods to assess the cost-effectiveness of new anti-cancer drugs. This study aims to develop a global economic model that could be used as a benchmark for the economic evaluation of new therapies for MBC. Methods The Global Pharmacoeconomics of Metastatic Breast Cancer (GPMBC) model is a Markov model that was constructed to estimate the incremental cost per quality-adjusted life years (QALY) of new treatments for MBC from a Canadian healthcare system perspective over a lifetime horizon. Specific parameters included in the model are cost of drug treatment, survival outcomes, and incidence of treatment-related adverse events (AEs). Global parameters are patient characteristics, health states utilities, disutilities, and costs associated with treatment-related AEs, as well as costs associated with drug administration, medical follow-up, and end-of-life care. The GPMBC model was tested and validated in a specific context, by assessing the cost-effectiveness of lapatinib plus letrozole compared with other widely used first-line therapies for post-menopausal women with hormone receptor-positive (HR+) and epidermal growth factor receptor 2-positive (HER2+) MBC. Results When tested, the GPMBC model led to incremental cost-utility ratios of CA$131 811 per QALY, CA$56 211 per QALY, and CA$102 477 per QALY for the comparison of lapatinib plus letrozole vs letrozole alone, trastuzumab plus anastrozole, and anastrozole alone, respectively. Results of the model testing were quite similar to those obtained by Delea et al., who also assessed the cost-effectiveness of lapatinib in combination with letrozole in HR+/HER2 + MBC in Canada, thus suggesting that the GPMBC model can replicate results of well-conducted economic evaluations. Conclusions The GPMBC model can be very valuable as it allows a quick and valid assessment of the cost-effectiveness

  11. [Treatment of cloud radiative effects in general circulation models

    International Nuclear Information System (INIS)

    Wang, W.C.

    1993-01-01

    This is a renewal proposal for an on-going project of the Department of Energy (DOE)/Atmospheric Radiation Measurement (ARM) Program. The objective of the ARM Program is to improve the treatment of radiation-cloud in GCMs so that reliable predictions of the timing and magnitude of greenhouse gas-induced global warming and regional responses can be made. The ARM Program supports two research areas: (I) The modeling and analysis of data related to the parameterization of clouds and radiation in general circulation models (GCMs); and (II) the development of advanced instrumentation for both mapping the three-dimensional structure of the atmosphere and high accuracy/precision radiometric observations. The present project conducts research in area (I) and focuses on GCM treatment of cloud life cycle, optical properties, and vertical overlapping. The project has two tasks: (1) Development and Refinement of GCM Radiation-Cloud Treatment Using ARM Data; and (2) Validation of GCM Radiation-Cloud Treatment

  12. Fluoxetine treatment is effective in a rat model of childhood-induced post-traumatic stress disorder.

    Science.gov (United States)

    Ariel, Lior; Inbar, Sapir; Edut, Schachaf; Richter-Levin, Gal

    2017-11-30

    Although selective serotonin reuptake inhibitors (SSRIs) are first-line treatment for post-traumatic stress disorder (PTSD) patients, their therapeutic efficacy is limited. Childhood adversities are considered a risk factor for developing PTSD in adulthood but may trigger PTSD without additional trauma in some individuals. Nevertheless, just as childhood is considered a vulnerable period it may also be an effective period for preventive treatment. Using a rat model of childhood-induced PTSD, pre-pubertal stress (juvenile stress, JVS), we compared the therapeutic effects of fluoxetine and examined the effectiveness of 1 month of fluoxetine treatment following JVS and into adulthood compared to treatment in adulthood. Since not all individuals develop PTSD following a trauma, comparing only group means is not the adequate type of analysis. We employed a behavioral profiling approach, which analyzes individual differences compared to the normal behavior of a control group. Animals exposed to JVS exhibited a higher proportion of affected animals as measured using the elevated plus maze 8 weeks after JVS. Fluoxetine treatment following the JVS significantly decreased the proportion of affected animals as measured in adulthood. Fluoxetine treatment in adulthood was not effective. The results support the notion that childhood is not only a vulnerable period but also an effective period for preventive treatment.

  13. Integrative psychotherapy model for treatment of Depressive Recurrent disorder without psychotic symptoms effectiveness.

    Directory of Open Access Journals (Sweden)

    Joaquín F. Márquez Pérez

    2010-10-01

    Full Text Available The investigation shows the results of the application of an integrative psychotherapy model in the treatment of Depressive Recurrent disorder without psychotic symptoms. The use of a design of a qualitative Investigation - Action was necessary for finding the psychological mechanism that explain different levels of effectiveness.

  14. Stochastic modelling to assess economic effects of treatment of chronic subclinical mastitis caused by Streptococcus uberis

    NARCIS (Netherlands)

    Steeneveld, W.; Swinkels, J.; Hogeveen, H.

    2007-01-01

    Chronic subclinical mastitis is usually not treated during the lactation. However, some veterinarians regard treatment of some types of subclinical mastitis to be effective. The goal of this research was to develop a stochastic Monte Carlo simulation model to support decisions around treatment of

  15. Models of human adamantinomatous craniopharyngioma tissue: Steps toward an effective adjuvant treatment.

    Science.gov (United States)

    Hölsken, Annett; Buslei, Rolf

    2017-05-01

    Even though ACP is a benign tumor, treatment is challenging because of the tumor's eloquent location. Today, with the exception of surgical intervention and irradiation, further treatment options are limited. However, ongoing molecular research in this field provides insights into the pathways involved in ACP pathogenesis and reveal a plethora of druggable targets. In the next step, appropriate models are essential to identify the most suitable and effective substances for clinical practice. Primary cell cultures in low passages provide a proper and rapid tool for initial drug potency testing. The patient-derived xenograft (PDX) model accommodates ACP complexity in that it shows respect to the preserved architecture and similar histological appearance to human tumors and therefore provides the most appropriate means for analyzing pharmacological efficacy. Nevertheless, further research is needed to understand in more detail the biological background of ACP pathogenesis, which provides the identification of the best targets in the hierarchy of signaling cascades. ACP models are also important for the continuous testing of new targeting drugs, to establish precision medicine. © 2017 International Society of Neuropathology.

  16. A budget-impact and cost-effectiveness model for second-line treatment of major depression.

    Science.gov (United States)

    Malone, Daniel C

    2007-07-01

    Depressed patients who initially fail to achieve remission when placed on a selective serotonin reuptake inhibitor (SSRI) may require a second treatment. The purpose of this study was to evaluate the effectiveness, cost, cost-effectiveness, and budget impact of second-line pharmacologic treatment for major depressive disorder (MDD). A cost-effectiveness analysis was conducted to evaluate second-line therapies (citalopram, escitalopram, fluoxetine, paroxetine, paroxetine controlled release [CR], sertraline, and venlafaxine extended release [XR]) for the treatment of depression. Effectiveness data were obtained from published clinical studies. The primary outcome was remission defined as a score of 7 or less on the Hamilton Rating Scale for Depression (HAM-D) or a score of 10 or less on the montgomery-Asberg Depression Rating Scale (MADRS) depression rating scales. The wholesale acquisition cost (WAC) for medications and medical treatment costs for depression were included. The perspective was derived from a managed care organization (MCO) with 500,000 members, a 1.9% annual incidence of depression, and treatment duration of 6 months. Assumptions included: second-line treatment is not as effective as first-line treatment, WAC price reflects MCO costs, and side effects were identical. Sensitivity analyses were conducted to determine variables that influenced the results. Second-line remission rates were 20.4% for venlafaxine XR, 16.9% for sertraline, 16.4% for escitalopram, 15.1% for generic SSRIs (weighted average), and 13.6% for paroxetine CR. Pharmacy costs ranged from $163 for generic SSRIs to $319 for venlafaxine SR. Total cost per patient achieving remission was $14,275 for venlafaxine SR, followed by $16,100 for escitalopram. The incremental cost-effectiveness ratio (ICER) for venlafaxine SR compared with generic SSRIs was $2,073 per patient achieving remission, followed by escitalopram with an ICER of $3,566. The model was most sensitive to other therapies

  17. Stochastic modelling to assess economic effects of treatment of chronic subclinical mastitis caused by Streptococcus uberis.

    Science.gov (United States)

    Steeneveld, Wilma; Swinkels, Jantijn; Hogeveen, Henk

    2007-11-01

    Chronic subclinical mastitis is usually not treated during the lactation. However, some veterinarians regard treatment of some types of subclinical mastitis to be effective. The goal of this research was to develop a stochastic Monte Carlo simulation model to support decisions around treatment of chronic subclinical mastitis caused by Streptococcus uberis. Factors in the model included the probability of cure after treatment, probability of the cow becoming clinically diseased, transmission of infection to other cows, and physiological effects of the infection. Using basic input parameters for Dutch circumstances, the average economic costs per cow of an untreated chronic subclinical mastitis case caused by Str. uberis in a single quarter from day of diagnosis onwards was euro109. With treatment, the average costs were higher (euro120). Thus, for the average cow, treatment was not efficient economically. However, the risk of high costs was much higher when cows with chronic subclinical mastitis were not treated. A sensitivity analysis showed that profitability of treatment of chronic subclinical Str. uberis mastitis depended on farm-specific factors (such as economic value of discarded milk) and cow-specific factors (such as day of diagnosis, duration of infection, amount of transmission to other cows and cure rate). Therefore, herd level protocols are not sufficient and decision support should be cow specific. Given the importance of cow-specific factors, information from the current model could be applied to automatic decision support systems.

  18. Effect of heteroscedasticity treatment in residual error models on model calibration and prediction uncertainty estimation

    Science.gov (United States)

    Sun, Ruochen; Yuan, Huiling; Liu, Xiaoli

    2017-11-01

    The heteroscedasticity treatment in residual error models directly impacts the model calibration and prediction uncertainty estimation. This study compares three methods to deal with the heteroscedasticity, including the explicit linear modeling (LM) method and nonlinear modeling (NL) method using hyperbolic tangent function, as well as the implicit Box-Cox transformation (BC). Then a combined approach (CA) combining the advantages of both LM and BC methods has been proposed. In conjunction with the first order autoregressive model and the skew exponential power (SEP) distribution, four residual error models are generated, namely LM-SEP, NL-SEP, BC-SEP and CA-SEP, and their corresponding likelihood functions are applied to the Variable Infiltration Capacity (VIC) hydrologic model over the Huaihe River basin, China. Results show that the LM-SEP yields the poorest streamflow predictions with the widest uncertainty band and unrealistic negative flows. The NL and BC methods can better deal with the heteroscedasticity and hence their corresponding predictive performances are improved, yet the negative flows cannot be avoided. The CA-SEP produces the most accurate predictions with the highest reliability and effectively avoids the negative flows, because the CA approach is capable of addressing the complicated heteroscedasticity over the study basin.

  19. 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.

  20. Measuring the individual benefit of a medical or behavioral treatment using generalized linear mixed-effects models.

    Science.gov (United States)

    Diaz, Francisco J

    2016-10-15

    We propose statistical definitions of the individual benefit of a medical or behavioral treatment and of the severity of a chronic illness. These definitions are used to develop a graphical method that can be used by statisticians and clinicians in the data analysis of clinical trials from the perspective of personalized medicine. The method focuses on assessing and comparing individual effects of treatments rather than average effects and can be used with continuous and discrete responses, including dichotomous and count responses. The method is based on new developments in generalized linear mixed-effects models, which are introduced in this article. To illustrate, analyses of data from the Sequenced Treatment Alternatives to Relieve Depression clinical trial of sequences of treatments for depression and data from a clinical trial of respiratory treatments are presented. The estimation of individual benefits is also explained. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Evaluation on the cost-effective threshold of osteoporosis treatment on elderly women in China using discrete event simulation model.

    Science.gov (United States)

    Ni, W; Jiang, Y

    2017-02-01

    This study used a simulation model to determine the cost-effective threshold of fracture risk to treat osteoporosis among elderly Chinese women. Osteoporosis treatment is cost-effective among average-risk women who are at least 75 years old and above-average-risk women who are younger than 75 years old. Aging of the Chinese population is imposing increasing economic burden of osteoporosis. This study evaluated the cost-effectiveness of osteoporosis treatment among the senior Chinese women population. A discrete event simulation model using age-specific probabilities of hip fracture, clinical vertebral fracture, wrist fracture, humerus fracture, and other fracture; costs (2015 US dollars); and quality-adjusted life years (QALYs) was used to assess the cost-effectiveness of osteoporosis treatment. Incremental cost-effectiveness ratio (ICER) was calculated. The willingness to pay (WTP) for a QALY in China was compared with the calculated ICER to decide the cost-effectiveness. To determine the absolute 10-year hip fracture probability at which the osteoporosis treatment became cost-effective, average age-specific probabilities for all fractures were multiplied by a relative risk (RR) that was systematically varied from 0 to 10 until the WTP threshold was observed for treatment relative to no intervention. Sensitivity analyses were also performed to evaluate the impacts from WTP and annual treatment costs. In baseline analysis, simulated ICERs were higher than the WTP threshold among Chinese women younger than 75, but much lower than the WTP among the older population. Sensitivity analyses indicated that cost-effectiveness could vary due to a higher WTP threshold or a lower annual treatment cost. A 30 % increase in WTP or a 30 % reduction in annual treatment costs will make osteoporosis treatment cost-effective for Chinese women population from 55 to 85. The current study provides evidence that osteoporosis treatment is cost-effective among a subpopulation of

  2. Fluoxetine treatment is effective in a rat model of childhood-induced post-traumatic stress disorder

    OpenAIRE

    Ariel, Lior; Inbar, Sapir; Edut, Schachaf; Richter-Levin, Gal

    2017-01-01

    Although selective serotonin reuptake inhibitors (SSRIs) are first-line treatment for post-traumatic stress disorder (PTSD) patients, their therapeutic efficacy is limited. Childhood adversities are considered a risk factor for developing PTSD in adulthood but may trigger PTSD without additional trauma in some individuals. Nevertheless, just as childhood is considered a vulnerable period it may also be an effective period for preventive treatment. Using a rat model of childhood-induced PTSD, ...

  3. Economic modeling of HIV treatments.

    Science.gov (United States)

    Simpson, Kit N

    2010-05-01

    To review the general literature on microeconomic modeling and key points that must be considered in the general assessment of economic modeling reports, discuss the evolution of HIV economic models and identify models that illustrate this development over time, as well as examples of current studies. Recommend improvements in HIV economic modeling. Recent economic modeling studies of HIV include examinations of scaling up antiretroviral (ARV) in South Africa, screening prior to use of abacavir, preexposure prophylaxis, early start of ARV in developing countries and cost-effectiveness comparisons of specific ARV drugs using data from clinical trials. These studies all used extensively published second-generation Markov models in their analyses. There have been attempts to simplify approaches to cost-effectiveness estimates by using simple decision trees or cost-effectiveness calculations with short-time horizons. However, these approaches leave out important cumulative economic effects that will not appear early in a treatment. Many economic modeling studies were identified in the 'gray' literature, but limited descriptions precluded an assessment of their adherence to modeling guidelines, and thus to the validity of their findings. There is a need for developing third-generation models to accommodate new knowledge about adherence, adverse effects, and viral resistance.

  4. Effective operator treatment of the Lipkin model

    International Nuclear Information System (INIS)

    Abraham, K.J.; Vary, J.P.

    2004-01-01

    We analyze the Lipkin model in the strong coupling limit using effective operator techniques. We present both analytical and numerical results for low energy effective Hamiltonians. We investigate the reliability of various approximations used to simplify the nuclear many body problem, such as the cluster approximation. We demonstrate, in explicit examples, certain limits to the validity of the cluster approximation but caution that these limits may be particular to this model where the interactions are of unlimited range

  5. Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors

    International Nuclear Information System (INIS)

    Juliachs, Mercè; Viñals, Francesc; Vidal, August; Muro, Xavier Garcia del; Piulats, Josep M; Condom, Enric; Casanovas, Oriol; Graupera, Mariona; Germà, Jose R; Villanueva, Alberto

    2013-01-01

    Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs. We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated. TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth. We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies

  6. Stability analysis of an HIV/AIDS epidemic model with treatment

    Science.gov (United States)

    Cai, Liming; Li, Xuezhi; Ghosh, Mini; Guo, Baozhu

    2009-07-01

    An HIV/AIDS epidemic model with treatment is investigated. The model allows for some infected individuals to move from the symptomatic phase to the asymptomatic phase by all sorts of treatment methods. We first establish the ODE treatment model with two infective stages. Mathematical analyses establish that the global dynamics of the spread of the HIV infectious disease are completely determined by the basic reproduction number [real]0. If [real]01. Then, we introduce a discrete time delay to the model to describe the time from the start of treatment in the symptomatic stage until treatment effects become visible. The effect of the time delay on the stability of the endemically infected equilibrium is investigated. Moreover, the delay model exhibits Hopf bifurcations by using the delay as a bifurcation parameter. Finally, numerical simulations are presented to illustrate the results.

  7. Inhalational Gentamicin Treatment Is Effective Against Pneumonic Plague in a Mouse Model

    Directory of Open Access Journals (Sweden)

    David Gur

    2018-04-01

    Full Text Available Pneumonic plague is an infectious disease characterized by rapid and fulminant development of acute pneumonia and septicemia that results in death within days of exposure. The causative agent of pneumonic plague, Yersinia pestis (Y. pestis, is a Tier-1 bio-threat agent. Parenteral antibiotic treatment is effective when given within a narrow therapeutic window after symptom onset. However, the non-specific “flu-like” symptoms often lead to delayed diagnosis and therapy. In this study, we evaluated inhalational gentamicin therapy in an infected mouse model as a means to improve antibiotic treatment efficacy. Inhalation is an attractive route for treating lung infections. The advantages include directly dosing the main infection site, the relative accessibility for administration and the lack of extensive enzymatic drug degradation machinery. In this study, we show that inhalational gentamicin treatment administered 24 h post-infection, prior to the appearance of symptoms, protected against lethal intranasal challenge with the fully virulent Y. pestis Kimberley53 strain (Kim53. Similarly, a high survival rate was demonstrated in mice treated by inhalation with another aminoglycoside, tobramycin, for which an FDA-approved inhaled formulation is clinically available for cystic fibrosis patients. Inhalational treatment with gentamicin 48 h post-infection (to symptomatic mice was also successful against a Y. pestis challenge dose of 10 i.n.LD50. Whole-body imaging using IVIS technology demonstrated that adding inhalational gentamicin to parenteral therapy accelerated the clearance of Y. pestis from the lungs of infected animals. This may reduce disease severity and the risk of secondary infections. In conclusion, our data suggest that inhalational therapy with aerosolized gentamicin may be an effective prophylactic treatment against pneumonic plague. We also demonstrate the benefit of combining this treatment with a conventional parenteral

  8. Cost-effectiveness in Clostridium difficile treatment decision-making.

    Science.gov (United States)

    Nuijten, Mark Jc; Keller, Josbert J; Visser, Caroline E; Redekop, Ken; Claassen, Eric; Speelman, Peter; Pronk, Marja H

    2015-11-16

    To develop a framework for the clinical and health economic assessment for management of Clostridium difficile infection (CDI). CDI has vast economic consequences emphasizing the need for innovative and cost effective solutions, which were aim of this study. A guidance model was developed for coverage decisions and guideline development in CDI. The model included pharmacotherapy with oral metronidazole or oral vancomycin, which is the mainstay for pharmacological treatment of CDI and is recommended by most treatment guidelines. A design for a patient-based cost-effectiveness model was developed, which can be used to estimate the cost-effectiveness of current and future treatment strategies in CDI. Patient-based outcomes were extrapolated to the population by including factors like, e.g., person-to-person transmission, isolation precautions and closing and cleaning wards of hospitals. The proposed framework for a population-based CDI model may be used for clinical and health economic assessments of CDI guidelines and coverage decisions for emerging treatments for CDI.

  9. Patient perspectives on breast cancer treatment side effects and the prospective surveillance model for physical rehabilitation for women with breast cancer.

    Science.gov (United States)

    Binkley, Jill M; Harris, Susan R; Levangie, Pamela K; Pearl, Marcia; Guglielmino, Janine; Kraus, Valerie; Rowden, Diana

    2012-04-15

    Women's experience of breast cancer is complex, affecting all aspects of life during and after treatment. Patients' perspectives about common impairments and functional limitations secondary to breast cancer treatment, including upper extremity motion restriction, lymphedema, fatigue, weight gain, pain, and chemotherapy-induced peripheral neuropathy, are addressed. Women often report being uninformed regarding these side effects and surprised that they do not always disappear after treatment, but remain part of their lives. Breast cancer patients express strong, unmet needs for education, information, and intervention for these side effects. Evidence suggests that rehabilitation and exercise are effective in preventing and managing many physical side effects of breast cancer treatment. Nevertheless, few women are referred to rehabilitation during or after treatment, and fewer receive baseline assessments of impairment and function to facilitate early detection of impairment and functional limitations. The prospective surveillance model of rehabilitation will serve the needs of women with breast cancer by providing education and information about treatment side effects, reducing the incidence and burden of side effects through early identification and treatment, and enhancing access to timely rehabilitation. Integration of exercise as a component of the model benefits patients at every phase of survivorship, by addressing individual concerns about exercise during and after treatment and highlighting the important contribution of exercise to overall health and survival. The prospective surveillance model of rehabilitation can meet the evident and often expressed needs of survivors for information, guidance, and intervention--thus addressing, and potentially improving, overall quality of life for individuals diagnosed with and treated for breast cancer. Copyright © 2012 American Cancer Society.

  10. Effects of Methadone Maintenance Treatment on Decision-Making Processes in Heroin-Abusers: A Cognitive Modeling Analysis

    Directory of Open Access Journals (Sweden)

    Arash Khodadadi

    2010-05-01

    Full Text Available A B S T R A C TIntroduction: Although decision-making processes have become a principal target of study among addiction researchers, few researches are published according to effects of different treatment methods on the cognitive processes underlying decision making up to now. Utilizing cognitive modeling method, in this paper we examine the effects of Methadone maintenance treatment (MMT on cognitive processes underlying decision-making disorders in heroin-abusers. Methods: For this purpose, for the first time, we use the balloon analog risk task (BART to assess the decision-making ability of heroin-abusers before and after treatment and compare it to the non heroin-dependent subjects. Results: Results demonstrate that heroin-abusers show more risky behavior than other groups. But, there is no difference between the performance of heroin-abusers after 6 months of MMT and control group. Modeling subjects’ behavior in BART reveals that poor performance in heroin-abusers is due to reward-dependency and insensitivity to evaluation. Discussion: Results show that 6 months of MMT decreases reward-dependency and increases sensitivity to evaluation.

  11. Ionic imbalance and lack of effect of adjuvant treatment with methylene blue in the hamster model of leptospirosis

    Directory of Open Access Journals (Sweden)

    Cleiton Silva Santos

    2013-06-01

    Full Text Available Leptospirosis in humans usually involves hypokalaemia and hypomagnesaemia and the putative mechanism underlying such ionic imbalances may be related to nitric oxide (NO production. We previously demonstrated the correlation between serum levels of NO and the severity of renal disease in patients with severe leptospirosis. Methylene blue inhibits soluble guanylyl cyclase (downstream of the action of any NO synthase isoforms and was recently reported to have beneficial effects on clinical and experimental sepsis. We investigated the occurrence of serum ionic changes in experimental leptospirosis at various time points (4, 8, 16 and 28 days in a hamster model. We also determined the effect of methylene blue treatment when administered as an adjuvant therapy, combined with late initiation of standard antibiotic (ampicillin treatment. Hypokalaemia was not reproduced in this model: all of the groups developed increased levels of serum potassium (K. Furthermore, hypermagnesaemia, rather than magnesium (Mg depletion, was observed in this hamster model of acute infection. These findings may be associated with an accelerated progression to acute renal failure. Adjuvant treatment with methylene blue had no effect on survival or serum Mg and K levels during acute-phase leptospirosis in hamsters.

  12. Modelling of volumetric composition and mechanical properties of unidirectional hemp/epoxy composites - Effect of enzymatic fibre treatment

    DEFF Research Database (Denmark)

    Liu, Ming; Thygesen, Anders; Meyer, Anne S.

    2016-01-01

    The objective of the present study is to assess the effect of enzymatic fibre treatments on the fibre performance in unidirectional hemp/epoxy composites by modelling the volumetric composition and mechanical properties of the composites. It is shown that the applied models can well predict...... the changes in volumetric composition and mechanical properties of the composites when differently treated hemp fibres are used. The decrease in the fibre correlated porosity factor with the enzymatic fibre treatments shows that the removal of pectin by pectinolytic enzymes results in a better fibre...

  13. Modelling of ultrasonic impact treatment (UIT of welded joints and its effect on fatigue strength

    Directory of Open Access Journals (Sweden)

    K.L. Yuan

    2015-10-01

    Full Text Available Ultrasonic impact treatment (UIT is a remarkable post-weld technique applying mechanical impacts in combination with ultrasound into the welded joints. In the present work, a 3D simulation method including welding simulation, numerical modelling of UIT-process and an evaluation of fatigue crack growth has been developed. In the FE model, the actual treatment conditions and local mechanical characteristics due to acoustic softening are set as input parameters. The plastic deformation and compressive stress layer are found to be more pronounced when acoustic softening takes place. The predicted internal residual stress distributions of welded joint before and after UIT are compared with experimental results, showing a fairly good agreement with each other. Finally, simulated results of fatigue crack growth in various residual stress fields are well compared with test results, so that the proposed model may provide an effective tool to simulate UIT-process in engineering structures.

  14. Incorporating model parameter uncertainty into inverse treatment planning

    International Nuclear Information System (INIS)

    Lian Jun; Xing Lei

    2004-01-01

    Radiobiological treatment planning depends not only on the accuracy of the models describing the dose-response relation of different tumors and normal tissues but also on the accuracy of tissue specific radiobiological parameters in these models. Whereas the general formalism remains the same, different sets of model parameters lead to different solutions and thus critically determine the final plan. Here we describe an inverse planning formalism with inclusion of model parameter uncertainties. This is made possible by using a statistical analysis-based frameset developed by our group. In this formalism, the uncertainties of model parameters, such as the parameter a that describes tissue-specific effect in the equivalent uniform dose (EUD) model, are expressed by probability density function and are included in the dose optimization process. We found that the final solution strongly depends on distribution functions of the model parameters. Considering that currently available models for computing biological effects of radiation are simplistic, and the clinical data used to derive the models are sparse and of questionable quality, the proposed technique provides us with an effective tool to minimize the effect caused by the uncertainties in a statistical sense. With the incorporation of the uncertainties, the technique has potential for us to maximally utilize the available radiobiology knowledge for better IMRT treatment

  15. Modelling of treatment couch top with prowess panther treatment planning system for external beam radiotherapy

    International Nuclear Information System (INIS)

    Owusu-Agyapong, Linus

    2016-07-01

    The aim of this work is to evaluate the attenuation effects of a treatment couch and to alternatively model the couch top material with a Prowess Panther treatment planning system which does not support couch top modelling. The Hounsfield Unit classification of the couch structure was determined using a PMMA phantom by comparing ion chamber measurements with the dose forecasted by the treatment planning system (TPS). The transmission factor (TF) of the couch top was determined and was used as a TF for a treatment accessory that represented the treatment couch in the TPS. A treatment plan was done for various angles with and without the interference of the couch top and a simulated treatment was done using the PMMA phantom. Ion chamber measurement were made and compared with dose predicted by the TPS to evaluate the accuracy of the couch top modelling in the treatment planning system TPS. These investigations were done for various field sizes. The ideal set of HU for the couch was established to be -674. The measured TF was 0.956042 and the TPS calculated Transmission factor was 0.951456. The percentage difference between the measured and calculated TFs was 0.48% and this agrees perfectly with the IAEA recommended tolerance of 2%. Relative attenuation measurements were as high as 54.16% and as low as 0.63% for the beams that exited the couch before interacting with the phantom. In comparing couch modelling by couch simulation and couch TF insert, it was observed that the normalized doses were the same for 5×5 square field but deviated approximately 1% for the other field sizes. The highest deviation was observed at 10×10 square field. This study demonstrates that the couch simulation method of couch modelling is the best method that can be used to account for the effect of the treatment couch top on intersecting posterior beam fields. Thus, the attenuation effects of the treatment couch was effectively evaluated and the couch top material accurately modelled in

  16. Population cost-effectiveness of the Triple P parenting programme for the treatment of conduct disorder: an economic modelling study.

    Science.gov (United States)

    Sampaio, Filipa; Barendregt, Jan J; Feldman, Inna; Lee, Yong Yi; Sawyer, Michael G; Dadds, Mark R; Scott, James G; Mihalopoulos, Cathrine

    2017-12-29

    Parenting programmes are the recommended treatments of conduct disorders (CD) in children, but little is known about their longer term cost-effectiveness. This study aimed to evaluate the population cost-effectiveness of one of the most researched evidence-based parenting programmes, the Triple P-Positive Parenting Programme, delivered in a group and individual format, for the treatment of CD in children. A population-based multiple cohort decision analytic model was developed to estimate the cost per disability-adjusted life year (DALY) averted of Triple P compared with a 'no intervention' scenario, using a health sector perspective. The model targeted a cohort of 5-9-year-old children with CD in Australia currently seeking treatment, and followed them until they reached adulthood (i.e., 18 years). Multivariate probabilistic and univariate sensitivity analyses were conducted to incorporate uncertainty in the model parameters. Triple P was cost-effective compared to no intervention at a threshold of AU$50,000 per DALY averted when delivered in a group format [incremental cost-effectiveness ratio (ICER) = $1013 per DALY averted; 95% uncertainty interval (UI) 471-1956] and in an individual format (ICER = $20,498 per DALY averted; 95% UI 11,146-39,470). Evidence-based parenting programmes, such as the Triple P, for the treatment of CD among children appear to represent good value for money, when delivered in a group or an individual face-to-face format, with the group format being the most cost-effective option. The current model can be used for economic evaluations of other interventions targeting CD and in other settings.

  17. Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy

    Directory of Open Access Journals (Sweden)

    Julia M. Post

    2018-03-01

    Full Text Available Research on the antiepileptic effects of (endo-cannabinoids has remarkably progressed in the years following the discovery of fundamental role of the endocannabinoid (eCB system in controlling neural excitability. Moreover, an increasing number of well-documented cases of epilepsy patients exhibiting multi-drug resistance report beneficial effects of cannabis use. Pre-clinical and clinical research has increasingly focused on the antiepileptic effectiveness of exogenous administration of cannabinoids and/or pharmacologically induced increase of eCBs such as anandamide (also known as arachidonoylethanolamide [AEA]. Concomitant research has uncovered the contribution of neuroinflammatory processes and peripheral immunity to the onset and progression of epilepsy. Accordingly, modulation of inflammatory pathways such as cyclooxygenase-2 (COX-2 was pursued as alternative therapeutic strategy for epilepsy. Palmitoylethanolamide (PEA is an endogenous fatty acid amide related to the centrally and peripherally present eCB AEA, and is a naturally occurring nutrient that has long been recognized for its analgesic and anti-inflammatory properties. Neuroprotective and anti-hyperalgesic properties of PEA were evidenced in neurodegenerative diseases, and antiepileptic effects in pentylenetetrazol (PTZ, maximal electroshock (MES and amygdaloid kindling models of epileptic seizures. Moreover, numerous clinical trials in chronic pain revealed that PEA treatment is devoid of addiction potential, dose limiting side effects and psychoactive effects, rendering PEA an appealing candidate as antiepileptic compound or adjuvant. In the present study, we aimed at assessing antiepileptic properties of PEA in a mouse model of acute epileptic seizures induced by systemic administration of kainic acid (KA. KA-induced epilepsy in rodents is assumed to resemble to different extents human temporal lobe epilepsy (TLE depending on the route of KA administration; intracerebral (i

  18. TU-G-210-00: Treatment Planning Strategies, Modeling, Control

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2015-06-15

    Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such as the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)

  19. TU-G-210-00: Treatment Planning Strategies, Modeling, Control

    International Nuclear Information System (INIS)

    2015-01-01

    Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such as the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)

  20. Modeling the Cost Effectiveness of Neuroimaging-Based Treatment of Acute Wake-Up Stroke.

    Directory of Open Access Journals (Sweden)

    Ankur Pandya

    Full Text Available Thrombolytic treatment (tissue-type plasminogen activator [tPA] is only recommended for acute ischemic stroke patients with stroke onset time 4.5 hours, 46.3% experienced a good stroke outcome. Lifetime discounted QALYs and costs were 5.312 and $88,247 for the no treatment strategy and 5.342 and $90,869 for the MRI-based strategy, resulting in an ICER of $88,000/QALY. Results were sensitive to variations in patient- and provider-specific factors such as sleep duration, hospital travel and door-to-needle times, as well as onset probability distribution, MRI specificity, and mRS utility values.Our model-based findings suggest that an MRI-based treatment strategy for this population could be cost-effective and quantifies the impact that patient- and provider-specific factors, such as sleep duration, hospital travel and door-to-needle times, could have on the optimal decision for wake-up stroke patients.

  1. A mathematical model for CTL effect on a latently infected cell inclusive HIV dynamics and treatment

    Science.gov (United States)

    Tarfulea, N. E.

    2017-10-01

    This paper investigates theoretically and numerically the effect of immune effectors, such as the cytotoxic lymphocyte (CTL), in modeling HIV pathogenesis (via a newly developed mathematical model); our results suggest the significant impact of the immune response on the control of the virus during primary infection. Qualitative aspects (including positivity, boundedness, stability, uncertainty, and sensitivity analysis) are addressed. Additionally, by introducing drug therapy, we analyze numerically the model to assess the effect of treatment consisting of a combination of several antiretroviral drugs. Our results show that the inclusion of the CTL compartment produces a higher rebound for an individual's healthy helper T-cell compartment than drug therapy alone. Furthermore, we quantitatively characterize successful drugs or drug combination scenarios.

  2. Modeling of ion beam surface treatment

    Energy Technology Data Exchange (ETDEWEB)

    Stinnett, R W [Quantum Manufacturing Technologies, Inc., Albuquerque, NM (United States); Maenchen, J E; Renk, T J [Sandia National Laboratories, Albuquerque, NM (United States); Struve, K W [Mission Research Corporation, Albuquerque, NM (United States); Campbell, M M [PASTDCO, Albuquerque, NM (United States)

    1997-12-31

    The use of intense pulsed ion beams is providing a new capability for surface engineering based on rapid thermal processing of the top few microns of metal, ceramic, and glass surfaces. The Ion Beam Surface Treatment (IBEST) process has been shown to produce enhancements in the hardness, corrosion, wear, and fatigue properties of surfaces by rapid melt and re-solidification. A new code called IBMOD was created, enabling the modeling of intense ion beam deposition and the resulting rapid thermal cycling of surfaces. This code was used to model the effect of treatment of aluminum, iron, and titanium using different ion species and pulse durations. (author). 3 figs., 4 refs.

  3. Cost-effectiveness of root caries preventive treatments.

    Science.gov (United States)

    Schwendicke, Falk; Göstemeyer, Gerd

    2017-01-01

    With a growing number of individuals retaining their teeth lifelong, often with periodontitis-induced root surface exposure, there is the need for cost-effective management strategies for root caries lesions. The present study aimed to assess the cost-effectiveness of root caries preventive treatments. Patients were simulated over 10 years using a Markov model. Four treatments were compared: No treatment, daily 225-800ppm fluoride rinses, chlorhexidine (CHX) varnish (2×/year), silver diamine fluoride (SDF) varnish (2×/year). Data from a systematic review were submitted to network meta-analysis for inferring relative efficacies of treatments. The health outcome was years of teeth being free of root caries. A mixed public-private payer perspective within 2016 German healthcare was taken, with costs being estimated from fee item catalogues or based on market prices. Populations with different numbers of teeth and tooth-level risks were modelled. Monte-Carlo microsimulations, univariate- and probabilistic sensitivity analyses were performed. In populations with 16 teeth at risk and low tooth-level risk for root caries, providing no preventive treatment was least costly, but also least effective (130 Euro, 144 years). SDF ranked next, being more costly (180 Euro), but also more effective (151 years). Payers willing to invest 8.30 Euro per root caries-free tooth-year found SDF most cost-effective. CHX varnish and fluoride rinse were not cost-effective. In populations with more teeth and high tooth-level risk, SDF was the most effective and least costly option. Root caries preventive treatments (like SDF) are effective and might even be cost-saving in high risk populations. Application of SDF can be recommended as a cost-saving treatment for prevention of root caries in patients with high risk of root caries. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Accounting for treatment use when validating a prognostic model: a simulation study.

    Science.gov (United States)

    Pajouheshnia, Romin; Peelen, Linda M; Moons, Karel G M; Reitsma, Johannes B; Groenwold, Rolf H H

    2017-07-14

    Prognostic models often show poor performance when applied to independent validation data sets. We illustrate how treatment use in a validation set can affect measures of model performance and present the uses and limitations of available analytical methods to account for this using simulated data. We outline how the use of risk-lowering treatments in a validation set can lead to an apparent overestimation of risk by a prognostic model that was developed in a treatment-naïve cohort to make predictions of risk without treatment. Potential methods to correct for the effects of treatment use when testing or validating a prognostic model are discussed from a theoretical perspective.. Subsequently, we assess, in simulated data sets, the impact of excluding treated individuals and the use of inverse probability weighting (IPW) on the estimated model discrimination (c-index) and calibration (observed:expected ratio and calibration plots) in scenarios with different patterns and effects of treatment use. Ignoring the use of effective treatments in a validation data set leads to poorer model discrimination and calibration than would be observed in the untreated target population for the model. Excluding treated individuals provided correct estimates of model performance only when treatment was randomly allocated, although this reduced the precision of the estimates. IPW followed by exclusion of the treated individuals provided correct estimates of model performance in data sets where treatment use was either random or moderately associated with an individual's risk when the assumptions of IPW were met, but yielded incorrect estimates in the presence of non-positivity or an unobserved confounder. When validating a prognostic model developed to make predictions of risk without treatment, treatment use in the validation set can bias estimates of the performance of the model in future targeted individuals, and should not be ignored. When treatment use is random, treated

  5. Hydraulic modelling of drinking water treatment plant operations

    Directory of Open Access Journals (Sweden)

    L. C. Rietveld

    2009-06-01

    Full Text Available The flow through a unit of a drinking water treatment plant is one of the most important parameters in terms of a unit's effectiveness. In the present paper, a new EPAnet library is presented with the typical hydraulic elements for drinking water treatment processes well abstraction, rapid sand filtration and cascade and tower aeration. Using this treatment step library, a hydraulic model was set up, calibrated and validated for the drinking water treatment plant Harderbroek. With the actual valve position and pump speeds, the flows were calculated through the several treatment steps. A case shows the use of the model to calculate the new setpoints for the current frequency converters of the effluent pumps during a filter backwash.

  6. Fuel treatment effects on tree-based forest carbon storage and emissions under modeled wildfire scenarios

    Science.gov (United States)

    M. Hurteau; M. North

    2009-01-01

    Forests are viewed as a potential sink for carbon (C) that might otherwise contribute to climate change. It is unclear, however, how to manage forests with frequent fire regimes to maximize C storage while reducing C emissions from prescribed burns or wildfire. We modeled the effects of eight different fuel treatments on treebased C storage and release over a century,...

  7. In silico modelling of radiation effects towards personalised treatment in radiotherapy

    Science.gov (United States)

    Marcu, Loredana G.; Marcu, David

    2017-12-01

    In silico models applied in medical physics are valuable tools to assist in treatment optimization and personalization, which represent the ultimate goal of today's radiotherapy. Next to several biological and biophysical factors that influence tumour response to ionizing radiation, hypoxia and cancer stem cells are critical parameters that dictate the final outcome. The current work presents the results of an in silico model of tumour growth and response to radiation developed using Monte Carlo techniques. We are presenting the impact of partial oxygen tension and repopulation via cancer stem cells on tumour control after photon irradiation, highlighting some of the gaps that clinical research needs to fill for better customized treatment.

  8. The Trimeric Model: A New Model of Periodontal Treatment Planning

    Science.gov (United States)

    Tarakji, Bassel

    2014-01-01

    Treatment of periodontal disease is a complex and multidisciplinary procedure, requiring periodontal, surgical, restorative, and orthodontic treatment modalities. Several authors attempted to formulate models for periodontal treatment that orders the treatment steps in a logical and easy to remember manner. In this article, we discuss two models of periodontal treatment planning from two of the most well-known textbook in the specialty of periodontics internationally. Then modify them to arrive at a new model of periodontal treatment planning, The Trimeric Model. Adding restorative and orthodontic interrelationships with periodontal treatment allows us to expand this model into the Extended Trimeric Model of periodontal treatment planning. These models will provide a logical framework and a clear order of the treatment of periodontal disease for general practitioners and periodontists alike. PMID:25177662

  9. Effect of sodium aescinate treatment on PCOS rat model with insulin resistance.

    Science.gov (United States)

    Chen, L; Hu, L M; Wang, Y F; Yang, H Y; Huang, X Y; Zhou, W; Sun, H X

    2017-01-01

    Recent studies indicated that insulin resistance may contribute to the pathogenesis of polycystic ovary syndrome (PCOS); however, the specific mechanism is still unclear. To investigate the effect of sodium aescinate (SA) on PCOS-IR rat models. Sixty rats were randomly divided into the five groups: un-treated rats (n = 12), PCOS-IR group (n = 12), PCOS-IR group plus 50 mg/kg SA (n = 12), PCOS-IR group plus 10 mg/kg SA (n = 12), PCOS-IR group plus 150 mg/kg metformin (n = 12). On day 21, rats were sacrificed, and H(and)E staining was performed for histopathologic examination of the ovaries; moreover, the serum level of follicle-stimulating hormone (FSH), testosterone, and luteotropic hormone (LH) were measured, and the expression as well as phosphorylation of PI3K, Akt and Gsk-3β were examined using western blot assay. High dosage of SA treatment improved the morphological features of the ovaries in PCOS rats, and also induced significant decrease in serum expression of testosterone and LH/FSH ratio and significant decrease in the expression of p-PI3K, p-Akt and p-Gsk-3β. Our results demonstrated that SA treatment could alleviate the symptom of PCOS in rat model through regulating the PI3K/Akt/GSK3-β pathway (Fig. 4, Ref. 22).

  10. Perspectives on modelling micropollutants in wastewater treatment plants

    DEFF Research Database (Denmark)

    Clouzot, Ludiwine; Cloutier, Frédéric; Vanrolleghem, Peter A.

    2013-01-01

    Models for predicting the fate of micropollutants (MPs) in wastewater treatment plants (WWTPs) have been developed to provide engineers and decision-makers with tools that they can use to improve their understanding of, and evaluate how to optimize, the removal of MPs and determine their impact......) addressing advancements in WWTP treatment technologies, (iii) making use of common approaches to data acquisition for model calibration and (iv) integrating ecotoxicological effects of MPs in receiving waters....... on the receiving waters. This paper provides an overview of such models, and discusses the impact of regulation, engineering practice and research on model development. A review of the current status of MP models reveals that a single model cannot represent the wide range of MPs that are present in wastewaters...

  11. The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model.

    Science.gov (United States)

    Birnbaum, Jeanette; Gadi, Vijayakrishna K; Markowitz, Elan; Etzioni, Ruth

    2016-02-16

    Mammography trials, which are the primary sources of evidence for screening benefit, were conducted decades ago. Whether advances in systemic therapies have rendered previously observed benefits of screening less significant is unknown. To compare the outcomes of breast cancer screening trials had they been conducted using contemporary systemic treatments with outcomes of trials conducted with previously used treatments. Computer simulation model of 3 virtual screening trials with similar reductions in advanced-stage cancer cases but reflecting treatment patterns in 1975 (prechemotherapy era), 1999, or 2015 (treatment according to receptor status). Meta-analyses of screening and treatment trials; study of dissemination of primary systemic treatments; SEER (Surveillance, Epidemiology, and End Results) registry. U.S. women aged 50 to 74 years. 10 and 25 years. Population. Mammography, chemotherapy, tamoxifen, aromatase inhibitors, and trastuzumab. Breast cancer mortality rate ratio (MRR) and absolute risk reduction (ARR) obtained by the difference in cumulative breast cancer mortality between control and screening groups. At 10 years, screening in a 1975 trial yielded an MRR of 90% and an ARR of 5 deaths per 10,000 women. A 2015 screening trial yielded a 10-year MRR of 90% and an ARR of 3 deaths per 10,000 women. Greater reductions in advanced-stage disease yielded a greater screening effect, but MRRs remained similar across trials. However, ARRs were consistently lower under contemporary treatments. When contemporary treatments were available only for early-stage cases, the MRR was 88%. Disease models simplify reality and cannot capture all breast cancer subtypes. Advances in systemic therapies for breast cancer have not substantively reduced the relative benefits of screening but have likely reduced the absolute benefits because of their positive effect on breast cancer survival. University of Washington and National Cancer Institute.

  12. Accounting for treatment use when validating a prognostic model: a simulation study

    Directory of Open Access Journals (Sweden)

    Romin Pajouheshnia

    2017-07-01

    Full Text Available Abstract Background Prognostic models often show poor performance when applied to independent validation data sets. We illustrate how treatment use in a validation set can affect measures of model performance and present the uses and limitations of available analytical methods to account for this using simulated data. Methods We outline how the use of risk-lowering treatments in a validation set can lead to an apparent overestimation of risk by a prognostic model that was developed in a treatment-naïve cohort to make predictions of risk without treatment. Potential methods to correct for the effects of treatment use when testing or validating a prognostic model are discussed from a theoretical perspective.. Subsequently, we assess, in simulated data sets, the impact of excluding treated individuals and the use of inverse probability weighting (IPW on the estimated model discrimination (c-index and calibration (observed:expected ratio and calibration plots in scenarios with different patterns and effects of treatment use. Results Ignoring the use of effective treatments in a validation data set leads to poorer model discrimination and calibration than would be observed in the untreated target population for the model. Excluding treated individuals provided correct estimates of model performance only when treatment was randomly allocated, although this reduced the precision of the estimates. IPW followed by exclusion of the treated individuals provided correct estimates of model performance in data sets where treatment use was either random or moderately associated with an individual's risk when the assumptions of IPW were met, but yielded incorrect estimates in the presence of non-positivity or an unobserved confounder. Conclusions When validating a prognostic model developed to make predictions of risk without treatment, treatment use in the validation set can bias estimates of the performance of the model in future targeted individuals, and

  13. A Method for Measuring Treatment Effects on the Treated without Randomization

    Directory of Open Access Journals (Sweden)

    P.A.V.B. Swamy

    2016-03-01

    Full Text Available This paper contributes to the literature on the estimation of causal effects by providing an analytical formula for individual specific treatment effects and an empirical methodology that allows us to estimate these effects. We derive the formula from a general model with minimal restrictions, unknown functional form and true unobserved variables such that it is a credible model of the underlying real world relationship. Subsequently, we manipulate the model in order to put it in an estimable form. In contrast to other empirical methodologies, which derive average treatment effects, we derive an analytical formula that provides estimates of the treatment effects on each treated individual. We also provide an empirical example that illustrates our methodology.

  14. Effects of Electroacupuncture Treatment on Bone Cancer Pain Model with Morphine Tolerance

    Directory of Open Access Journals (Sweden)

    Lei Sima

    2016-01-01

    Full Text Available Objective. To explore the efficacy of electroacupuncture treatment in cancer induced bone pain (CIBP rat model with morphine tolerance and explore changes of calcitonin-gene related peptide (CGRP expression in dorsal root ganglion (DRG. Methods. Forty SD rats were divided into five groups: sham, CIBP (B, CIBP + morphine (BM, CIBP + electroacupuncture (BE, and CIBP + morphine + electroacupuncture (BME. B, BM, BE, and BME groups were prepared CIBP model. The latter three groups then accepted morphine, electroacupuncture, and morphine combined electroacupuncture, separately, nine days consecutively (M1 to M9. Mechanical withdraw threshold (MWT was evaluated. Results. BE group only had differences in M1, M2, and M3 compared to B group (P<0.01. From M5, BM group showed significantly decreased MWT. Electroacupuncture could obtain analgesic effects only at early stage (M1 to M5. From M5 to M9, BME had the differences with BM group (P<0.01. IOD value of CGRP in BM and BME was substantially less than in B group. CGRP in BME was significantly lower than that in BM group (P<0.01. Conclusion. When used in combination with electroacupuncture, morphine could result in improving analgesic effects and reducing tolerance. CGRP may be associated with pain behaviors.

  15. Detrimental effects of rat mesenchymal stromal cell pre-treatment in a model of acute kidney rejection

    Directory of Open Access Journals (Sweden)

    Martina eSeifert

    2012-07-01

    Full Text Available Mesenchymal stromal cells (MSC have shown immunomodulatory and tissue repair potential including partial tolerance induction by pre-treatment of donor-specific cells in a rat heart transplantation model. Very recently, we could show that autologous MSC attenuated ischemia reperfusion injury in a highly mismatched donor-recipient rat kidney transplant model. Therefore, we investigated donor-specific MSC pre-treatment in this rat kidney transplantation model to study whether graft function could be improved, or if tolerance could be induced.Donor- and recipient-type MSC or PBS as a control were injected i.v. four days before kidney transplantation. Mycophenolate mofetil (MMF immunosuppression (20 mg/kg body weight was applied for 7 days. Kidney grafts and spleens were harvested between days 8-10 and analyzed by quantitative RT-PCR and immunohistology. In addition, creatinine levels in the blood were measured and serum was screened for the presence of donor-specific antibodies.Surprisingly, application of both donor- and recipient-specific MSC resulted in enhanced humoral immune responses verified by intragraft B cell infiltration and complement factor C4d deposits. Moreover, signs of inflammation and rejection were generally enhanced in both MSC-treated groups relative to PBS control group. Additionally, pre-treatment with donor-specific MSC significantly enhanced the level of donor-specific antibody formation when compared with PBS- or recipient-MSC-treated groups. Pre-treatment with both MSC types resulted in a higher degree of kidney cortex tissue damage and elevated creatinine levels at the time point of rejection. Thus, MSC pre-sensitization in this model impairs the allograft outcome.Our data from this pre-clinical kidney transplantation model indicate that pre-operative MSC administration may not be optimal in kidney transplantation and caution must be exerted before moving forward with clinical studies in order to avoid adverse effects.

  16. Beyond the treatment effect: Evaluating the effects of patient preferences in randomised trials.

    Science.gov (United States)

    Walter, S D; Turner, R; Macaskill, P; McCaffery, K J; Irwig, L

    2017-02-01

    The treatments under comparison in a randomised trial should ideally have equal value and acceptability - a position of equipoise - to study participants. However, it is unlikely that true equipoise exists in practice, because at least some participants may have preferences for one treatment or the other, for a variety of reasons. These preferences may be related to study outcomes, and hence affect the estimation of the treatment effect. Furthermore, the effects of preferences can sometimes be substantial, and may even be larger than the direct effect of treatment. Preference effects are of interest in their own right, but they cannot be assessed in the standard parallel group design for a randomised trial. In this paper, we describe a model to represent the impact of preferences on trial outcomes, in addition to the usual treatment effect. In particular, we describe how outcomes might differ between participants who would choose one treatment or the other, if they were free to do so. Additionally, we investigate the difference in outcomes depending on whether or not a participant receives his or her preferred treatment, which we characterise through a so-called preference effect. We then discuss several study designs that have been proposed to measure and exploit data on preferences, and which constitute alternatives to the conventional parallel group design. Based on the model framework, we determine which of the various preference effects can or cannot be estimated with each design. We also illustrate these ideas with some examples of preference designs from the literature.

  17. Effects of Combined Milrinone and Levosimendan Treatment on Systolic and Diastolic Function During Postischemic Myocardial Dysfunction in a Porcine Model.

    Science.gov (United States)

    Axelsson, Birger; Häggmark, Sören; Svenmarker, Staffan; Johansson, Göran; Gupta, Anil; Tydén, Hans; Wouters, Patrick; Haney, Michael

    2016-09-01

    It is not known whether there are positive or negative interactions on ventricular function when a calcium-sensitizing inotrope is added to a phosphodiesterase inhibitor in the clinical setting of acute left ventricular (LV) dysfunction. We hypothesized that when levosimendan is added to milrinone treatment, there will be synergetic inotropic and lusitropic effects. This was tested in an anesthetized porcine postischemic global LV injury model, where ventricular pressures and volumes (conductance volumetry) were measured. A global ischemic injury was induced by repetitive left main stem coronary artery occlusions. Load-independent indices of LV function were assessed before and after ventricular injury, after milrinone treatment, and finally after addition of levosimendan to the milrinone treatment. Nonparametric, within-group comparisons were made. The protocol was completed in 12 pigs, 7 of which received the inotrope treatment and 5 of which served as controls. Milrinone led to positive lusitropic effects seen by improvement in tau after myocardial stunning. The addition of levosimendan to milrinone further increased lusitropic state. The latter effect could however not be attributed solely to levosimendan, since lusitropic state also improved spontaneously in time-matched controls at the same rate during the corresponding period. When levosimendan was added to milrinone infusion, there was no increase in systolic function (preload recruitable stroke work) compared to milrinone treatment alone. We conclude that in this model of postischemic LV dysfunction, there appears to be no clear improvement in systolic or diastolic function after addition of levosimendan to established milrinone treatment but also no negative effects of levosimendan in this context. © The Author(s) 2016.

  18. The effects of psychotherapy treatment on outcome in bulimia nervosa: Examining indirect effects through emotion regulation, self-directed behavior, and self-discrepancy within the mediation model.

    Science.gov (United States)

    Peterson, Carol B; Berg, Kelly C; Crosby, Ross D; Lavender, Jason M; Accurso, Erin C; Ciao, Anna C; Smith, Tracey L; Klein, Marjorie; Mitchell, James E; Crow, Scott J; Wonderlich, Stephen A

    2017-06-01

    The purpose of this investigation was to examine the indirect effects of Integrative Cognitive-Affective Therapy (ICAT-BN) and Cognitive-Behavioral Therapy-Enhanced (CBT-E) on bulimia nervosa (BN) treatment outcome through three hypothesized maintenance variables: emotion regulation, self-directed behavior, and self-discrepancy. Eighty adults with BN were randomized to 21 sessions of ICAT-BN or CBT-E. A regression-based bootstrapping approach was used to test the indirect effects of treatment on outcome at end of treatment through emotion regulation and self-directed behavior measured at mid-treatment, as well as the indirect effects of treatment at follow-up through emotion regulation, self-directed behavior, and self-discrepancy measured at end of treatment. No significant differences in outcome between treatment conditions were observed, and no significant direct or indirect effects were found. Examination of the individual paths within the indirect effects models revealed comparable treatment effects. Across treatments, improvements in emotion regulation and self-directed behavior between baseline and mid-treatment predicted improvements in global eating disorder scores but not binge eating and purging frequency at end of treatment. Baseline to end of treatment improvements in emotion regulation and self-directed behavior also predicted improvements in global eating disorder scores at follow-up. Baseline to end of treatment improvements in emotion regulation predicted improvements in binge eating and baseline to end of treatment increases in positive self-directed behavior predicted improvements in purging at follow-up. These findings suggest that emotion regulation and self-directed behavior are important treatment targets and that ICAT-BN and CBT-E are comparable in modifying these psychological processes among individuals with BN. © 2017 Wiley Periodicals, Inc.

  19. The proposed 'concordance-statistic for benefit' provided a useful metric when modeling heterogeneous treatment effects.

    Science.gov (United States)

    van Klaveren, David; Steyerberg, Ewout W; Serruys, Patrick W; Kent, David M

    2018-02-01

    Clinical prediction models that support treatment decisions are usually evaluated for their ability to predict the risk of an outcome rather than treatment benefit-the difference between outcome risk with vs. without therapy. We aimed to define performance metrics for a model's ability to predict treatment benefit. We analyzed data of the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial and of three recombinant tissue plasminogen activator trials. We assessed alternative prediction models with a conventional risk concordance-statistic (c-statistic) and a novel c-statistic for benefit. We defined observed treatment benefit by the outcomes in pairs of patients matched on predicted benefit but discordant for treatment assignment. The 'c-for-benefit' represents the probability that from two randomly chosen matched patient pairs with unequal observed benefit, the pair with greater observed benefit also has a higher predicted benefit. Compared to a model without treatment interactions, the SYNTAX score II had improved ability to discriminate treatment benefit (c-for-benefit 0.590 vs. 0.552), despite having similar risk discrimination (c-statistic 0.725 vs. 0.719). However, for the simplified stroke-thrombolytic predictive instrument (TPI) vs. the original stroke-TPI, the c-for-benefit (0.584 vs. 0.578) was similar. The proposed methodology has the potential to measure a model's ability to predict treatment benefit not captured with conventional performance metrics. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Assessment of Antimicrobial Treatment Strategies in Pig Production Using Mathematical Models

    DEFF Research Database (Denmark)

    Ahmad, Amais

    strategies. Dosing factors, along with the in vivo epidemiological parameters, govern the relation between resistance and antimicrobial use. Mathematical modeling and simulation techniques have been used over the past two decades to evaluate the effect of these factors on the development of resistance......, and are considered to be powerful tools in designing treatment strategies. The overall aim of the thesis was to develop an in vivo bacterial growth model to predict and assess the effect of dosing factor on resistance growth in order to optimize treatment strategies. Specific aims were to a) estimate pharmacodynamic...... concentration (MIC). These parameters along with MIC should be taken into account when studying the effect of antimicrobials on the bacterial growth. These parameters were used as an input to the in vivo growth model of multiple bacterial strains. For almost all treatments, high resistance levels were found...

  1. Estimating the best laser parameters for skin cancer treatment using finite element models

    International Nuclear Information System (INIS)

    El-Berry, A.A.; El-Berry, A.A.; Solouma, N.H.; Hassan, F.; Ahmed, A.S.

    2010-01-01

    Skin cancer is an intimidating disease which necessitates the presence of a non-invasive treatment. Laser-induced thermo therapy is one of the recent noninvasive modalities of superficial lesion treatment. Although of its promising effect, this method still needs more effort to be quantized. Many studies are being conducted for this purpose. Modeling and simulating the process of skin lesion treatment by laser can lead to the best quantization of the treatment protocol. In this paper, we provide finite element models for the treatment of skin cancer using laser thermal effect. A comparison between the effects of using different laser parameters of diode laser (800nm) and Nd: Yag laser (1064 nm) revealed that Nd: Yag laser can be used effectively foe skin cancer treatment specially with high intensities of about 106 w/m 2 .

  2. The effects of surface treatments on rapid chloride permeability tests

    KAUST Repository

    Yoon, Seyoon

    2012-08-01

    Surface treatments are commonly applied to improve the chloride resistance of concrete structures exposed to saline environments. Information on chloride ingress to surface-treated concrete is mostly provided by application of the rapid chloride permeability test (RCPT); this test is short in duration and provides rapid results. This study presents a numerical formulation, based on the extended Nernst-Plank/Poisson (NPP) equation, to model the effect of the surface treatment on a sample tested by RCPT. Predictions of the model are compared to experimental measurements. The simulations show that the results from RCPT, in terms of ionic profiles and measurement of the electric field, are dependent on the effectiveness of surface treatments. During RCPT, highly effective surface treatments cause both cations and anions to flocculate at the interface between the surface treatment and the concrete, creating a local electric field. Our numerical model includes these phenomena and presents a methodology to obtain more accurate diffusivities of the surface-treated- concrete from RCPT. © 2012 Elsevier B.V. All rights reserved.

  3. The effects of surface treatments on rapid chloride permeability tests

    KAUST Repository

    Yoon, Seyoon; Oh, Sang-gyun; Ha, Juyoung; Monteiro, Paulo M.

    2012-01-01

    Surface treatments are commonly applied to improve the chloride resistance of concrete structures exposed to saline environments. Information on chloride ingress to surface-treated concrete is mostly provided by application of the rapid chloride permeability test (RCPT); this test is short in duration and provides rapid results. This study presents a numerical formulation, based on the extended Nernst-Plank/Poisson (NPP) equation, to model the effect of the surface treatment on a sample tested by RCPT. Predictions of the model are compared to experimental measurements. The simulations show that the results from RCPT, in terms of ionic profiles and measurement of the electric field, are dependent on the effectiveness of surface treatments. During RCPT, highly effective surface treatments cause both cations and anions to flocculate at the interface between the surface treatment and the concrete, creating a local electric field. Our numerical model includes these phenomena and presents a methodology to obtain more accurate diffusivities of the surface-treated- concrete from RCPT. © 2012 Elsevier B.V. All rights reserved.

  4. A novel model to study neonatal Escherichia coli sepsis and the effect of treatment on the human immune system using humanized mice.

    Science.gov (United States)

    Schlieckau, Florian; Schulz, Daniela; Fill Malfertheiner, Sara; Entleutner, Kathrin; Seelbach-Goebel, Birgit; Ernst, Wolfgang

    2018-04-19

    Neonatal sepsis is a serious threat especially for preterm infants. As existing in vitro and in vivo models have limitations, we generated a novel neonatal sepsis model using humanized mice and tested the effect of Betamethasone and Indomethacin which are used in the clinic in case of premature birth. Humanized mice were infected with Escherichia coli (E. coli). Subsequently, the effect of the infection itself, and treatment with Betamethasone and Indomethacin on survival, recovery, bacterial burden, leukocyte populations, and cytokine production, was analyzed. The human immune system in the animals responded with leukocyte trafficking to the site of infection and granulopoiesis in the bone marrow. Treatment with Indomethacin had no pronounced effect on the immune system or bacterial burden. Betamethasone induced a decline of splenocytes. The human immune system in humanized mice responds to the infection, making them a suitable model to study neonatal E. coli sepsis and the immune response of the neonatal immune system. Treatment with Betamethasone could have potential negative long-term effects for the immune system of the child. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Incorporating Psychological Predictors of Treatment Response into Health Economic Simulation Models: A Case Study in Type 1 Diabetes.

    Science.gov (United States)

    Kruger, Jen; Pollard, Daniel; Basarir, Hasan; Thokala, Praveen; Cooke, Debbie; Clark, Marie; Bond, Rod; Heller, Simon; Brennan, Alan

    2015-10-01

    . Health economic modeling has paid limited attention to the effects that patients' psychological characteristics have on the effectiveness of treatments. This case study tests 1) the feasibility of incorporating psychological prediction models of treatment response within an economic model of type 1 diabetes, 2) the potential value of providing treatment to a subgroup of patients, and 3) the cost-effectiveness of providing treatment to a subgroup of responders defined using 5 different algorithms. . Multiple linear regressions were used to investigate relationships between patients' psychological characteristics and treatment effectiveness. Two psychological prediction models were integrated with a patient-level simulation model of type 1 diabetes. Expected value of individualized care analysis was undertaken. Five different algorithms were used to provide treatment to a subgroup of predicted responders. A cost-effectiveness analysis compared using the algorithms to providing treatment to all patients. . The psychological prediction models had low predictive power for treatment effectiveness. Expected value of individualized care results suggested that targeting education at responders could be of value. The cost-effectiveness analysis suggested, for all 5 algorithms, that providing structured education to a subgroup of predicted responders would not be cost-effective. . The psychological prediction models tested did not have sufficient predictive power to make targeting treatment cost-effective. The psychological prediction models are simple linear models of psychological behavior. Collection of data on additional covariates could potentially increase statistical power. . By collecting data on psychological variables before an intervention, we can construct predictive models of treatment response to interventions. These predictive models can be incorporated into health economic models to investigate more complex service delivery and reimbursement strategies.

  6. Knowledge-Management-Based-Nursing Care Model Improves Patient Adherence to Tuberculosis Treatment

    Directory of Open Access Journals (Sweden)

    Ninuk Dian Kurniawati

    2016-04-01

    Full Text Available Introduction. Pulmonary tuberculosis remains prominent as one of public health problems in the world. Patients’ non-compliance to treatment is a significant contributor to drug resistance. This study aimed to develop and to test the efficacy of a nursing care model to prevent non-compliance. Method This study consisted of two phases: phase one, model development, used a descriptive analytic, and phase two, model testing, employed a quasi-experimental design. Participants, comprised both patients and nurses at two health care centres in Surabaya, were recruited by consecutive sampling. Data were collected by interview, self-administered-questionnaires, check-list and focused group discussion. Data analyses were performed using both partial least squares and Wilcoxon signed rank test. Results. The model was statistically effective to improve nearly all aspects of patients’ compliance to TB treatment (knowledge, discipline in taking medications regularity of controls, and abilities to monitor the results of treatment with p < 0.05, except for abilities to cope with drug adverse effects (p = 1.000. This is possible because seldom do patients aware of the medication side effects, so their experiences were probably limited. Conclusion. This study concludes that the KM nursing care model was proven effective to improve patients’ adherence to treatment. Future study is suggested to evaluate the impact of the KM nursing care model in bigger population.

  7. A random effects meta-analysis model with Box-Cox transformation.

    Science.gov (United States)

    Yamaguchi, Yusuke; Maruo, Kazushi; Partlett, Christopher; Riley, Richard D

    2017-07-19

    In a random effects meta-analysis model, true treatment effects for each study are routinely assumed to follow a normal distribution. However, normality is a restrictive assumption and the misspecification of the random effects distribution may result in a misleading estimate of overall mean for the treatment effect, an inappropriate quantification of heterogeneity across studies and a wrongly symmetric prediction interval. We focus on problems caused by an inappropriate normality assumption of the random effects distribution, and propose a novel random effects meta-analysis model where a Box-Cox transformation is applied to the observed treatment effect estimates. The proposed model aims to normalise an overall distribution of observed treatment effect estimates, which is sum of the within-study sampling distributions and the random effects distribution. When sampling distributions are approximately normal, non-normality in the overall distribution will be mainly due to the random effects distribution, especially when the between-study variation is large relative to the within-study variation. The Box-Cox transformation addresses this flexibly according to the observed departure from normality. We use a Bayesian approach for estimating parameters in the proposed model, and suggest summarising the meta-analysis results by an overall median, an interquartile range and a prediction interval. The model can be applied for any kind of variables once the treatment effect estimate is defined from the variable. A simulation study suggested that when the overall distribution of treatment effect estimates are skewed, the overall mean and conventional I 2 from the normal random effects model could be inappropriate summaries, and the proposed model helped reduce this issue. We illustrated the proposed model using two examples, which revealed some important differences on summary results, heterogeneity measures and prediction intervals from the normal random effects model. The

  8. A random effects meta-analysis model with Box-Cox transformation

    Directory of Open Access Journals (Sweden)

    Yusuke Yamaguchi

    2017-07-01

    Full Text Available Abstract Background In a random effects meta-analysis model, true treatment effects for each study are routinely assumed to follow a normal distribution. However, normality is a restrictive assumption and the misspecification of the random effects distribution may result in a misleading estimate of overall mean for the treatment effect, an inappropriate quantification of heterogeneity across studies and a wrongly symmetric prediction interval. Methods We focus on problems caused by an inappropriate normality assumption of the random effects distribution, and propose a novel random effects meta-analysis model where a Box-Cox transformation is applied to the observed treatment effect estimates. The proposed model aims to normalise an overall distribution of observed treatment effect estimates, which is sum of the within-study sampling distributions and the random effects distribution. When sampling distributions are approximately normal, non-normality in the overall distribution will be mainly due to the random effects distribution, especially when the between-study variation is large relative to the within-study variation. The Box-Cox transformation addresses this flexibly according to the observed departure from normality. We use a Bayesian approach for estimating parameters in the proposed model, and suggest summarising the meta-analysis results by an overall median, an interquartile range and a prediction interval. The model can be applied for any kind of variables once the treatment effect estimate is defined from the variable. Results A simulation study suggested that when the overall distribution of treatment effect estimates are skewed, the overall mean and conventional I 2 from the normal random effects model could be inappropriate summaries, and the proposed model helped reduce this issue. We illustrated the proposed model using two examples, which revealed some important differences on summary results, heterogeneity measures and

  9. Dosimetric Effects Of Different Treatment Tables During Radiotherapy

    International Nuclear Information System (INIS)

    Murkovic, M.; Grego, T.; Bibic, J.

    2015-01-01

    The aim of our study was to measure the effect of mega-voltage photon beam attenuation when treating patients through carbon fibre treatment table with and without the carbon laminate base plate on it. We also examined the ability of XiO treatment planning system in modelling this effect. Direct attenuation measurements were made for two treatment tables, Siemens TxT 550 treatment table with TT-A table top and Elekta Precise table with iBEAM evo table top. On both treatment tables we used Orfit Base Plate (32301). Measurements were taken for two photon energies (6 MV and 18 MV), at two different field sizes (5 x 5 cm 2 and 10 x 10 cm 2 ) and different gantry angles in 50 intervals using stationary water phantom and Farmer type ionization chamber. These values were compared to values calculated in XiO. In order to account for the effect of table and base plate during treatment planning in XiO, customized table and base plate templates were develop in Focal planning system. To construct these customized templates, table and base plate contours as well as respective relative electron density's to water were obtained on CT scanner. The largest attenuation effect was seen for oblique treatment angles using low energy and small field sizes, 6.6 percent for the Elekta table top and 8.4 percent for Siemens table top. In this paper we show that customized table and base plate templates introduced in the patient treatment plan can accurately model the attenuation due to their presence to within 0.3 percent. Since dose modifications due to such carbon fiber accessories can be significant, it can be concluded that introduction of customized table and base plate templates into TPS brings an important improvement to patient treatment planning, and should be included in dose calculations whenever possible. (author).

  10. Treatment of pathological gambling - integrative systemic model.

    Science.gov (United States)

    Mladenović, Ivica; Lažetić, Goran; Lečić-Toševski, Dušica; Dimitrijević, Ivan

    2015-03-01

    Pathological gambling was classified under impulse control disorders within the International Classification of Diseases (ICD-10) (WHO 1992), but the most recent Diagnostic and Statistical Manual, 5th edition (DSM-V), (APA 2013), has recognized pathological gambling as a first disorder within a new diagnostic category of behavioral addictions - Gambling disorder. Pathological gambling is a disorder in progression, and we hope that our experience in the treatment of pathological gambling in the Daily Hospital for Addictions at The Institute of Mental Health, through the original "Integrative - systemic model" would be of use to colleagues, dealing with this pathology. This model of treatment of pathological gambling is based on multi-systemic approach and it primarily represents an integration of family and cognitive-behavioral therapy, with traces of psychodynamic, existential and pharmacotherapy. The model is based on the book "Pathological gambling - with self-help manual" by Dr Mladenovic and Dr Lazetic, and has been designed in the form of a program that lasts 10 weeks in the intensive phase, and then continues for two years in the form of "extended treatment" ("After care"). The intensive phase is divided into three segments: educational, insight with initial changes and analysis of the achieved changes with the definition of plans and areas that need to be addressed in the extended treatment. "Extended treatment" lasts for two years in the form of group therapy, during which there is a second order change of the identified patient, but also of other family members. Pathological gambling has been treated in the form of systemic-family therapy for more than 10 years at the Institute of Mental Health (IMH), in Belgrade. For second year in a row the treatment is carried out by the modern "Integrative-systemic model". If abstinence from gambling witihin the period of one year after completion of the intensive phase of treatment is taken as the main criterion of

  11. Wastewater treatment models

    DEFF Research Database (Denmark)

    Gernaey, Krist; Sin, Gürkan

    2011-01-01

    description of biological phosphorus removal, physicalchemical processes, hydraulics and settling tanks. For attached growth systems, biofilm models have progressed from analytical steady-state models to more complex 2D/3D dynamic numerical models. Plant-wide modeling is set to advance further the practice......The state-of-the-art level reached in modeling wastewater treatment plants (WWTPs) is reported. For suspended growth systems, WWTP models have evolved from simple description of biological removal of organic carbon and nitrogen in aeration tanks (ASM1 in 1987) to more advanced levels including...

  12. Wastewater Treatment Models

    DEFF Research Database (Denmark)

    Gernaey, Krist; Sin, Gürkan

    2008-01-01

    description of biological phosphorus removal, physical–chemical processes, hydraulics, and settling tanks. For attached growth systems, biofilm models have progressed from analytical steady-state models to more complex 2-D/3-D dynamic numerical models. Plant-wide modeling is set to advance further......The state-of-the-art level reached in modeling wastewater treatment plants (WWTPs) is reported. For suspended growth systems, WWTP models have evolved from simple description of biological removal of organic carbon and nitrogen in aeration tanks (ASM1 in 1987) to more advanced levels including...

  13. Modeling Hepatitis C treatment policy.

    Energy Technology Data Exchange (ETDEWEB)

    Kuypers, Marshall A.; Lambert, Gregory Joseph; Moore, Thomas W.; Glass, Robert John,; Finley, Patrick D.; Ross, David; Chartier, Maggie

    2013-09-01

    Chronic infection with Hepatitis C virus (HCV) results in cirrhosis, liver cancer and death. As the nations largest provider of care for HCV, US Veterans Health Administration (VHA) invests extensive resources in the diagnosis and treatment of the disease. This report documents modeling and analysis of HCV treatment dynamics performed for the VHA aimed at improving service delivery efficiency. System dynamics modeling of disease treatment demonstrated the benefits of early detection and the role of comorbidities in disease progress and patient mortality. Preliminary modeling showed that adherence to rigorous treatment protocols is a primary determinant of treatment success. In depth meta-analysis revealed correlations of adherence and various psycho-social factors. This initial meta-analysis indicates areas where substantial improvement in patient outcomes can potentially result from VA programs which incorporate these factors into their design.

  14. Treatment of Sexual Offenders: Research, Best Practices, and Emerging Models

    Science.gov (United States)

    Yates, Pamela M.

    2013-01-01

    Treatment of sexual offenders has evolved substantially over the years; various theoretical and practice models of treatment been developed, modified, refined, and proposed over time. The predominant current recommended approach, supported by research, adheres to specific principles of effective correctional intervention, follows a…

  15. Electrokinetic Treatment for Model Caissons with Increasing Dimensions

    Directory of Open Access Journals (Sweden)

    Eltayeb Mohamedelhassan

    2012-01-01

    Full Text Available Electrokinetic treatment has been known in geotechnical engineering for over six decades, yet, the technique is rarely used. This stems from the absence of design guidelines and specifications for electrokinetic treatment systems. An important issue that need to be investigated and understood in order to devise guidelines from experimental results is the effect of the foundation element size on the outcome of the treatment. Also important is determining the optimum distance between the electrodes and estimating the energy consumption prior to treatment. This experimental study is a preliminary step in understanding some of the issues critical for the guidelines and specifications. Four model caissons with surface areas between 16000 and 128000 mm2 were embedded in soft clayey soil under water and treated for 168 hr with a dc voltage of 6 V. From the results, a distance between the anode (model caisson and the cathode equal 0.25 times the outside diameter of the model caisson was identified as optimum. Relationships between the surface area and axial capacity of the model caisson and the surface area and energy consumption were presented. The equations can be used to preliminary estimate the load capacity and the energy consumption for full-scale applications.

  16. Robust estimation of the proportion of treatment effect explained by surrogate marker information.

    Science.gov (United States)

    Parast, Layla; McDermott, Mary M; Tian, Lu

    2016-05-10

    In randomized treatment studies where the primary outcome requires long follow-up of patients and/or expensive or invasive obtainment procedures, the availability of a surrogate marker that could be used to estimate the treatment effect and could potentially be observed earlier than the primary outcome would allow researchers to make conclusions regarding the treatment effect with less required follow-up time and resources. The Prentice criterion for a valid surrogate marker requires that a test for treatment effect on the surrogate marker also be a valid test for treatment effect on the primary outcome of interest. Based on this criterion, methods have been developed to define and estimate the proportion of treatment effect on the primary outcome that is explained by the treatment effect on the surrogate marker. These methods aim to identify useful statistical surrogates that capture a large proportion of the treatment effect. However, current methods to estimate this proportion usually require restrictive model assumptions that may not hold in practice and thus may lead to biased estimates of this quantity. In this paper, we propose a nonparametric procedure to estimate the proportion of treatment effect on the primary outcome that is explained by the treatment effect on a potential surrogate marker and extend this procedure to a setting with multiple surrogate markers. We compare our approach with previously proposed model-based approaches and propose a variance estimation procedure based on a perturbation-resampling method. Simulation studies demonstrate that the procedure performs well in finite samples and outperforms model-based procedures when the specified models are not correct. We illustrate our proposed procedure using a data set from a randomized study investigating a group-mediated cognitive behavioral intervention for peripheral artery disease participants. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Modelling of environmental impacts from biological treatment of organic municipal waste in EASEWASTE

    DEFF Research Database (Denmark)

    Boldrin, Alessio; Neidel, Trine Lund; Damgaard, Anders

    2011-01-01

    The waste-LCA model EASEWASTE quantifies potential environmental effects from biological treatment of organic waste, based on mass and energy flows, emissions to air, water, soil and groundwater as well as effects from upstream and downstream processes. Default technologies for composting......, anaerobic digestion and combinations hereof are available in the model, but the user can change all key parameters in the biological treatment module so that specific local plants and processes can be modelled. EASEWASTE is one of the newest waste LCA models and the biological treatment module was built...... partly on features of earlier waste-LCA models, but offers additional facilities, more flexibility, transparency and user-friendliness. The paper presents the main features of the module and provides some examples illustrating the capability of the model in environmentally assessing and discriminating...

  18. Effect of Treatment Education Based on the Roy Adaptation Model on Adjustment of Hemodialysis Patients.

    Science.gov (United States)

    Kacaroglu Vicdan, Ayse; Gulseven Karabacak, Bilgi

    2016-01-01

    The Roy Adaptation Model examines the individual in 4 fields: physiological mode, self-concept mode, role function mode, and interdependence mode. Hemodialysis treatment is associated with the Roy Adaptation Model as it involves fields that might be needed by the individual with chronic renal disease. This research was conducted as randomized controlled experiment with the aim of determining the effect of the education given in accordance with the Roy Adaptation Model on physiological, psychological, and social adaptation of individuals undergoing hemodialysis treatment. This was a random controlled experimental study. The study was conducted at a dialysis center in Konya-Aksehir in Turkey between July 1 and December 31, 2012. The sample was composed of 82 individuals-41 experimental and 41 control. In the second interview, there was a decrease in the systolic blood pressures and body weights of the experimental group, an increase in the scores of functional performance and self-respect, and a decrease in the scores of psychosocial adaptation. In the control group, on the other hand, there was a decrease in the scores of self-respect and an increase in the scores of psychosocial adaptation. The 2 groups were compared in terms of adaptation variables and a difference was determined on behalf of the experimental group. The training that was provided and evaluated for individuals receiving hemodialysis according to 4 modes of the Roy Adaptation Model increased physical, psychological, and social adaptation.

  19. Autism Treatment and Family Support Models Review

    Directory of Open Access Journals (Sweden)

    Mehrnoush Esbati

    2009-04-01

    Full Text Available Autism is a lifelong neurological disability of unknown etiology. The criteria for a diagnosis of autism are based on a triad of impairments in social interaction, communication and a lack of flexibility in thinking and behavior There are several factors which are likely to contribute to this variation including the definition of autism and variability in diagnosis amongst professionals, however anecdotally there appears to have been a steadily increasing demand for services. The purpose of this review of research literature relating to the management and treatment of children with autism is to identify the most effective models of best practice. The review includes Comparative evidence supporting a range of treatment and intervention models, across the range of individuals included within autism spectrum disorders, psychodynamic treatment/management which are based on the assumption that autism is the result of emotional damage to the child, usually because of failure to develop a close attachment to parents, especially the mother, biological treatments, educational and behavioral interventions, communication therapies, cost benefits and supporting families.The research is examined for evidence to support best practice models in supporting families at the time of diagnosis and assessment and an overview of the nature of comprehensive supports that help reduce stresses that may be experienced by families of a child with autism and promote inclusion in community activities.

  20. Optimal chemotherapy for leukemia: a model-based strategy for individualized treatment.

    Directory of Open Access Journals (Sweden)

    Devaraj Jayachandran

    Full Text Available Acute Lymphoblastic Leukemia, commonly known as ALL, is a predominant form of cancer during childhood. With the advent of modern healthcare support, the 5-year survival rate has been impressive in the recent past. However, long-term ALL survivors embattle several treatment-related medical and socio-economic complications due to excessive and inordinate chemotherapy doses received during treatment. In this work, we present a model-based approach to personalize 6-Mercaptopurine (6-MP treatment for childhood ALL with a provision for incorporating the pharmacogenomic variations among patients. Semi-mechanistic mathematical models were developed and validated for i 6-MP metabolism, ii red blood cell mean corpuscular volume (MCV dynamics, a surrogate marker for treatment efficacy, and iii leukopenia, a major side-effect. With the constraint of getting limited data from clinics, a global sensitivity analysis based model reduction technique was employed to reduce the parameter space arising from semi-mechanistic models. The reduced, sensitive parameters were used to individualize the average patient model to a specific patient so as to minimize the model uncertainty. Models fit the data well and mimic diverse behavior observed among patients with minimum parameters. The model was validated with real patient data obtained from literature and Riley Hospital for Children in Indianapolis. Patient models were used to optimize the dose for an individual patient through nonlinear model predictive control. The implementation of our approach in clinical practice is realizable with routinely measured complete blood counts (CBC and a few additional metabolite measurements. The proposed approach promises to achieve model-based individualized treatment to a specific patient, as opposed to a standard-dose-for-all, and to prescribe an optimal dose for a desired outcome with minimum side-effects.

  1. TU-G-210-01: Modeling for Breast and Brain HIFU Treatment Planning

    International Nuclear Information System (INIS)

    Christensen, D.

    2015-01-01

    Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such as the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)

  2. TU-G-210-01: Modeling for Breast and Brain HIFU Treatment Planning

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, D. [University of Utah (United States)

    2015-06-15

    Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such as the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)

  3. Use of opioid substitution therapies in the treatment of opioid use disorder: results of a UK cost-effectiveness modelling study.

    Science.gov (United States)

    Kenworthy, James; Yi, Yunni; Wright, Antony; Brown, Jim; Maria Madrigal, Ana; Dunlop, William C N

    2017-07-01

    This study investigated the cost-effectiveness of buprenorphine maintenance treatment (BMT) and methadone maintenance treatment (MMT) vs no opioid substitution therapy (OST) for the treatment of opioid use disorder, from the UK National Health Service (NHS)/personal social services (PSS) and societal perspectives over 1 year. Cost-effectiveness of OST vs no OST was evaluated by first replicating and then expanding an existing UK health technology assessment model. The expanded model included the impact of OST on infection rates of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. Versus no OST, incremental cost-effectiveness ratios (ICERs) for BMT and MMT were £13,923 and £14,206 per quality-adjusted life year (QALY), respectively, from a NHS/PSS perspective. When total costs (NHS/PSS and societal) are considered, there are substantial savings associated with adopting OST; these savings are in excess of £14,032 for BMT vs no OST and £17,174 for MMT vs no OST over 1 year. This is primarily driven by a reduction in victim costs. OST treatment also impacted other aspects of criminality and healthcare resource use. The model's 1-year timeframe means long-term costs and benefits, and the influence of changes over time are not captured. OST can be considered cost-effective vs no OST from the UK NHS/PSS perspective, with a cost per QALY well below the UK's willingness-to-pay threshold. There were only small differences between BMT and MMT. The availability of two or more cost-effective options is beneficial to retaining patients in OST programs. From a societal perspective, OST is estimated to save over £14,032 and £17,174 per year for BMT and MMT vs no OST, respectively, due to savings in victim costs. Further work is required to fully quantify the clinical and health economic impacts of different OST formulations and their societal impact over the long-term.

  4. Treatment of an actual slaughterhouse wastewater by integration of biological and advanced oxidation processes: Modeling, optimization, and cost-effectiveness analysis.

    Science.gov (United States)

    Bustillo-Lecompte, Ciro Fernando; Mehrvar, Mehrab

    2016-11-01

    Biological and advanced oxidation processes are combined to treat an actual slaughterhouse wastewater (SWW) by a sequence of an anaerobic baffled reactor, an aerobic activated sludge reactor, and a UV/H2O2 photoreactor with recycle in continuous mode at laboratory scale. In the first part of this study, quadratic modeling along with response surface methodology are used for the statistical analysis and optimization of the combined process. The effects of the influent total organic carbon (TOC) concentration, the flow rate, the pH, the inlet H2O2 concentration, and their interaction on the overall treatment efficiency, CH4 yield, and H2O2 residual in the effluent of the photoreactor are investigated. The models are validated at different operating conditions using experimental data. Maximum TOC and total nitrogen (TN) removals of 91.29 and 86.05%, respectively, maximum CH4 yield of 55.72%, and minimum H2O2 residual of 1.45% in the photoreactor effluent were found at optimal operating conditions. In the second part of this study, continuous distribution kinetics is applied to establish a mathematical model for the degradation of SWW as a function of time. The agreement between model predictions and experimental values indicates that the proposed model could describe the performance of the combined anaerobic-aerobic-UV/H2O2 processes for the treatment of SWW. In the final part of the study, the optimized combined anaerobic-aerobic-UV/H2O2 processes with recycle were evaluated using a cost-effectiveness analysis to minimize the retention time, the electrical energy consumption, and the overall incurred treatment costs required for the efficient treatment of slaughterhouse wastewater effluents. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. The stochastic system approach for estimating dynamic treatments effect.

    Science.gov (United States)

    Commenges, Daniel; Gégout-Petit, Anne

    2015-10-01

    The problem of assessing the effect of a treatment on a marker in observational studies raises the difficulty that attribution of the treatment may depend on the observed marker values. As an example, we focus on the analysis of the effect of a HAART on CD4 counts, where attribution of the treatment may depend on the observed marker values. This problem has been treated using marginal structural models relying on the counterfactual/potential response formalism. Another approach to causality is based on dynamical models, and causal influence has been formalized in the framework of the Doob-Meyer decomposition of stochastic processes. Causal inference however needs assumptions that we detail in this paper and we call this approach to causality the "stochastic system" approach. First we treat this problem in discrete time, then in continuous time. This approach allows incorporating biological knowledge naturally. When working in continuous time, the mechanistic approach involves distinguishing the model for the system and the model for the observations. Indeed, biological systems live in continuous time, and mechanisms can be expressed in the form of a system of differential equations, while observations are taken at discrete times. Inference in mechanistic models is challenging, particularly from a numerical point of view, but these models can yield much richer and reliable results.

  6. An investigation of scale effects in family substance abuse treatment programs

    Directory of Open Access Journals (Sweden)

    Lee A James

    2010-07-01

    Full Text Available Abstract This short report investigates scale effects in family substance abuse treatment programs. In Massachusetts, the family substance abuse treatment programs were much more costly than other adult residential treatment models. State officials were concerned that the "scale" or size of these programs (averaging just eight families was too small to be economical. Although the sample size (just nine programs was too small to permit reliable inference, the data clearly signalled the importance of "scale effects" in these family substance abuse treatment programs. To further investigate scale effects in family substance abuse treatment programs, data from the Center for Substance Abuse Treatment's (CSAT's Residential Women and Children and Pregnant and Postpartum Women (RWC-PPW Demonstration were re-analyzed, focusing on the relationship between cost per family-day and the estimated average family census. This analysis indicates strong economies of scale up until an average family census of about 14, and less apparent scale effects beyond that point. In consideration of these and other study findings, a multidisciplinary interagency team redesigned the Massachusetts' family treatment program model. The new programs are larger than the former family treatment programs, with each new program having capacity to treat 11 to 15 families depending on family makeup.

  7. Subpopulation Treatment Effect Pattern Plot (STEPP) analysis for continuous, binary, and count outcomes.

    Science.gov (United States)

    Yip, Wai-Ki; Bonetti, Marco; Cole, Bernard F; Barcella, William; Wang, Xin Victoria; Lazar, Ann; Gelber, Richard D

    2016-08-01

    For the past few decades, randomized clinical trials have provided evidence for effective treatments by comparing several competing therapies. Their successes have led to numerous new therapies to combat many diseases. However, since their conclusions are based on the entire cohort in the trial, the treatment recommendation is for everyone, and may not be the best option for an individual. Medical research is now focusing more on providing personalized care for patients, which requires investigating how patient characteristics, including novel biomarkers, modify the effect of current treatment modalities. This is known as heterogeneity of treatment effects. A better understanding of the interaction between treatment and patient-specific prognostic factors will enable practitioners to expand the availability of tailored therapies, with the ultimate goal of improving patient outcomes. The Subpopulation Treatment Effect Pattern Plot (STEPP) approach was developed to allow researchers to investigate the heterogeneity of treatment effects on survival outcomes across values of a (continuously measured) covariate, such as a biomarker measurement. Here, we extend the Subpopulation Treatment Effect Pattern Plot approach to continuous, binary, and count outcomes, which can be easily modeled using generalized linear models. With this extension of Subpopulation Treatment Effect Pattern Plot, these additional types of treatment effects within subpopulations defined with respect to a covariate of interest can be estimated, and the statistical significance of any observed heterogeneity of treatment effect can be assessed using permutation tests. The desirable feature that commonly used models are applied to well-defined patient subgroups to estimate treatment effects is retained in this extension. We describe a simulation study to confirm that the proper Type I error rate is maintained when there is no treatment heterogeneity, and a power study to show that the statistics have

  8. Cervical cancer treatment costs and cost-effectiveness analysis of human papillomavirus vaccination in Vietnam: a PRIME modeling study.

    Science.gov (United States)

    Van Minh, Hoang; My, Nguyen Thi Tuyet; Jit, Mark

    2017-05-15

    Cervical cancer is currently the leading cause of cancer mortality among women in South Vietnam and the second leading cause of cancer mortality in North Vietnam. Human papillomavirus (HPV) vaccination has the potential to substantially decrease this burden. The World Health Organization (WHO) recommends that a cost-effectiveness analysis of HPV vaccination is conducted before nationwide introduction. The Papillomavirus Rapid Interface for Modeling and Economics (PRIME) model was used to evaluate the cost-effectiveness of HPV vaccine introduction. A costing study based on expert panel discussions, interviews and hospital case note reviews was conducted to explore the cost of cervical cancer care. The cost of cervical cancer treatment ranged from US$368 - 11400 depending on the type of hospital and treatment involved. Under Gavi-negotiated prices of US$4.55, HPV vaccination is likely to be very cost-effective with an incremental cost per disability-adjusted life year (DALY) averted in the range US$780 - 1120. However, under list prices for Cervarix and Gardasil in Vietnam, the incremental cost per DALY averted for HPV vaccination can exceed US$8000. HPV vaccine introduction appears to be economically attractive only if Vietnam is able to procure the vaccine at Gavi prices. This highlights the importance of initiating a nationwide vaccination programme while such prices are still available.

  9. Cost-effectiveness analysis of optimal strategy for tumor treatment

    International Nuclear Information System (INIS)

    Pang, Liuyong; Zhao, Zhong; Song, Xinyu

    2016-01-01

    We propose and analyze an antitumor model with combined immunotherapy and chemotherapy. Firstly, we explore the treatment effects of single immunotherapy and single chemotherapy, respectively. Results indicate that neither immunotherapy nor chemotherapy alone are adequate to cure a tumor. Hence, we apply optimal theory to investigate how the combination of immunotherapy and chemotherapy should be implemented, for a certain time period, in order to reduce the number of tumor cells, while minimizing the implementation cost of the treatment strategy. Secondly, we establish the existence of the optimality system and use Pontryagin’s Maximum Principle to characterize the optimal levels of the two treatment measures. Furthermore, we calculate the incremental cost-effectiveness ratios to analyze the cost-effectiveness of all possible combinations of the two treatment measures. Finally, numerical results show that the combination of immunotherapy and chemotherapy is the most cost-effective strategy for tumor treatment, and able to eliminate the entire tumor with size 4.470 × 10"8 in a year.

  10. Negative Effects of Chronic Rapamycin Treatment on Behavior in a Mouse Model of Fragile X Syndrome

    Directory of Open Access Journals (Sweden)

    Rachel M. Saré

    2018-01-01

    Full Text Available Fragile X syndrome (FXS, the most common form of inherited intellectual disability, is also highly associated with autism spectrum disorders (ASD. It is caused by expansion of a CGG repeat sequence on the X chromosome resulting in silencing of the FMR1 gene. This is modeled in the mouse by deletion of Fmr1 (Fmr1 KO. Fmr1 KO mice recapitulate many of the behavioral features of the disorder including seizure susceptibility, hyperactivity, impaired social behavior, sleep problems, and learning and memory deficits. The mammalian target of rapamycin pathway (mTORC1 is upregulated in Fmr1 KO mice and is thought to be important for the pathogenesis of this disorder. We treated Fmr1 KO mice chronically with an mTORC1 inhibitor, rapamycin, to determine if rapamycin treatment could reverse behavioral phenotypes. We performed open field, zero maze, social behavior, sleep, passive avoidance, and audiogenic seizure testing. We found that pS6 was upregulated in Fmr1 KO mice and normalized by rapamycin treatment, but, except for an anxiogenic effect, it did not reverse any of the behavioral phenotypes examined. In fact, rapamycin treatment had an adverse effect on sleep and social behavior in both control and Fmr1 KO mice. These results suggest that targeting the mTOR pathway in FXS is not a good treatment strategy and that other pathways should be considered.

  11. Modeling of the water uptake process for cowpea seeds (vigna unguiculata l.) under common treatment and microwave treatment

    International Nuclear Information System (INIS)

    Demirhan, E.

    2015-01-01

    The water uptake kinetics of cowpea seeds were carried out at two different water absorption treatments - common treatment and microwave treatment - to evaluate the effects of rehydration temperatures and microwave output powers on rehydration. Water uptake of cowpea seeds during soaking in water was studied at various temperatures of 20 - 45 degree C, and at various microwave output powers of 180 - 900 W. As the rehydration temperature and microwave output power increased, the water uptake of cowpea seeds increased and the rehydration time decreased. The Peleg and Richards Models were capable of predicting water uptake of cowpea seeds undergoing common treatment and microwave treatment, respectively. The effective diffusivity values were evaluated by fitting experimental absorption data to Fick second law of diffusion. The effective diffusivity coefficients for cowpea seeds varied from 7.75*10-11 to 1.99*10-10 m2/s and from 2.23*10-9 to 9.78*10-9 m2/s for common treatment and microwave treatment, respectively. (author)

  12. Personalized neuromusculoskeletal modeling to improve treatment of mobility impairments: a perspective from European research sites

    Directory of Open Access Journals (Sweden)

    Fregly Benjamin J

    2012-03-01

    Full Text Available Abstract Mobility impairments due to injury or disease have a significant impact on quality of life. Consequently, development of effective treatments to restore or replace lost function is an important societal challenge. In current clinical practice, a treatment plan is often selected from a standard menu of options rather than customized to the unique characteristics of the patient. Furthermore, the treatment selection process is normally based on subjective clinical experience rather than objective prediction of post-treatment function. The net result is treatment methods that are less effective than desired at restoring lost function. This paper discusses the possible use of personalized neuromusculoskeletal computer models to improve customization, objectivity, and ultimately effectiveness of treatments for mobility impairments. The discussion is based on information gathered from academic and industrial research sites throughout Europe, and both clinical and technical aspects of personalized neuromusculoskeletal modeling are explored. On the clinical front, we discuss the purpose and process of personalized neuromusculoskeletal modeling, the application of personalized models to clinical problems, and gaps in clinical application. On the technical front, we discuss current capabilities of personalized neuromusculoskeletal models along with technical gaps that limit future clinical application. We conclude by summarizing recommendations for future research efforts that would allow personalized neuromusculoskeletal models to make the greatest impact possible on treatment design for mobility impairments.

  13. Measuring the effect of fuel treatments on forest carbon using landscape risk analysis

    Science.gov (United States)

    A.A. Ager; M.A. Finney; A. McMahan; J. Carthcart

    2010-01-01

    Wildfire simulation modelling was used to examine whether fuel reduction treatments can potentially reduce future wildfire emissions and provide carbon benefits. In contrast to previous reports, the current study modelled landscape scale effects of fuel treatments on fire spread and intensity, and used a probabilistic framework to quantify wildfire effects on carbon...

  14. Treatment model of dengue hemorrhagic fever infection in human body

    Science.gov (United States)

    Handayani, D.; Nuraini, N.; Primasari, N.; Wijaya, K. P.

    2014-03-01

    The treatment model of DHF presented in this paper involves the dynamic of five time-dependent compartments, i.e. susceptible, infected, free virus particle, immune cell, and haematocrit level. The treatment model is investigated based on normalization of haematocrit level, which is expressed as intravenous fluid infusion control. We analyze the stability of the disease free equilibrium and the endemic equilibrium. The numerical simulations will explain the dynamic of each compartment in human body. These results show particularly that infected compartment and free virus particle compartment are tend to be vanished in two weeks after the onset of dengue virus. However, these simulation results also show that without the treatment, the haematocrit level will decrease even though not up to the normal level. Therefore the effective haematocrit normalization should be done with the treatment control.

  15. Model for Simulating Fasting Glucose in Type 2 Diabetes and the Effect of Adherence to Treatment

    DEFF Research Database (Denmark)

    Aradóttir, Tinna Björk; Boiroux, Dimitri; Bengtsson, Henrik

    2017-01-01

    trial results where a dose guidance algorithm was used. We investigate sources of variance and through simulations evaluate the contribution of adherence to variance and dose guidance quality. The results suggest that the model for simulation of T2D patients is sufficient for simulating fasting glucose......The primary goal of this paper is to predict fasting glucose levels in type 2 diabetes (T2D) in long-acting insulin treatment. The paper presents a model for simulating insulin-glucose dynamics in T2D patients. The model combines a physiological model of type 1 diabetes (T1D) and an endogenous...... insulin production model in T2D. We include a review of sources of variance in fasting glucose values in long-acting insulin treatment, with respect to dose guidance algorithms. We use the model to simulate fasting glucose levels in T2D long-acting insulin treatment and compare the results with clinical...

  16. Clinical effectiveness and cost-effectiveness of interventions for the treatment of anogenital warts: systematic review and economic evaluation.

    Science.gov (United States)

    Thurgar, Elizabeth; Barton, Samantha; Karner, Charlotta; Edwards, Steven J

    2016-03-01

    Typically occurring on the external genitalia, anogenital warts (AGWs) are benign epithelial skin lesions caused by human papillomavirus infection. AGWs are usually painless but can be unsightly and physically uncomfortable, and affected people might experience psychological distress. The evidence base on the clinical effectiveness and cost-effectiveness of treatments for AGWs is limited. To systematically review the evidence on the clinical effectiveness of medical and surgical treatments for AGWs and to develop an economic model to estimate the cost-effectiveness of the treatments. Electronic databases (MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases and Web of Science) were searched from inception (or January 2000 for Web of Science) to September 2014. Bibliographies of relevant systematic reviews were hand-searched to identify potentially relevant studies. The World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov were searched for ongoing and planned studies. A systematic review of the clinical effectiveness literature was carried out according to standard methods and a mixed-treatment comparison (MTC) undertaken. The model implemented for each outcome was that with the lowest deviance information criterion. A de novo economic model was developed to assess cost-effectiveness from the perspective of the UK NHS. The model structure was informed through a systematic review of the economic literature and in consultation with clinical experts. Effectiveness data were obtained from the MTC. Costs were obtained from the literature and standard UK sources. Of 4232 titles and abstracts screened for inclusion in the review of clinical effectiveness, 60 randomised controlled trials (RCTs) evaluating 19 interventions were included. Analysis by MTC indicated that ablative techniques were typically more effective than topical interventions at completely clearing AGWs at the end of

  17. The Effects of Modeling and Behavior Rehearsal in Assertive Training with Adolescents.

    Science.gov (United States)

    Parr, Gerald D.; Lundquist, Gerald

    The effects of modeling and rehearsal in counseling nonassertive adolescents were examined by randomly assigning subjects (Ss) to one of five treatment groups: modeling plus rehearsal (MR), modeling only (M), rehearsal only (R), placebo control (P), or delayed-treatment control (C). Significant (p < .05) main effects for treatment were found on…

  18. Hepatitis C Treatment Regimens Are Cost-Effective: But Compared With What?

    Science.gov (United States)

    Mattingly, T Joseph; Slejko, Julia F; Mullins, C Daniel

    2017-11-01

    Numerous economic models have been published evaluating treatment of chronic hepatitis C virus (HCV) infection, but none provide a comprehensive comparison among new antiviral agents. Evaluate the cost-effectiveness of all recommended therapies for treatment of genotypes 1 and 4 chronic HCV. Using data from clinical trials, observational analyses, and drug pricing databases, Markov decision models were developed for HCV genotypes 1 and 4 to compare all recommended drugs from the perspective of the third-party payer over a 5-, 10-, and 50-year time horizon. A probabilistic sensitivity analysis (PSA) was conducted by assigning distributions for clinical cure, age entering the model, costs for each health state, and quality-adjusted life years (QALYs) for each health state in a Monte Carlo simulation of 10 000 repetitions of the model. In the lifetime model for genotype 1, effects ranged from 18.08 to 18.40 QALYs and total costs ranged from $88 107 to $184 636. The lifetime model of genotype 4 treatments had a range of effects from 18.23 to 18.43 QALYs and total costs ranging from $87 063 to $127 637. Grazoprevir/elbasvir was the optimal strategy followed by velpatasvir/sofosbuvir as the second-best strategy in most simulations for both genotypes 1 and 4, with drug costs and efficacy of grazoprevir/elbasvir as the primary model drivers. Grazoprevir/elbasvir was cost-effective compared with all strategies for genotypes 1 and 4. Effects for all strategies were similar with cost of drug in the initial year driving the results.

  19. Stochastic modelling to evaluate the economic efficiency of treatment of chronic subclinical mastitis

    OpenAIRE

    Steeneveld, W.; Hogeveen, H.; Borne, van den, B.H.P.; Swinkels, J.M.

    2006-01-01

    Treatment of subclinical mastitis is traditionally no common practice. However, some veterinarians regard treatment of some types of subclinical mastitis to be effective. The goal of this research was to develop a stochastic Monte Carlo simulation model to support decisions around treatment of chronic subclinical mastitis caused by Streptococcus uberis. Factors in the model include, amongst others, the probability of spontaneous cure, probability of the cow becoming clinically diseased, trans...

  20. Effective treatment of steatosis and steatohepatitis by fibroblast growth factor 1 in mouse models of nonalcoholic fatty liver disease.

    Science.gov (United States)

    Liu, Weilin; Struik, Dicky; Nies, Vera J M; Jurdzinski, Angelika; Harkema, Liesbeth; de Bruin, Alain; Verkade, Henkjan J; Downes, Michael; Evans, Ronald M; van Zutphen, Tim; Jonker, Johan W

    2016-02-23

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder and is strongly associated with obesity and type 2 diabetes. Currently, there is no approved pharmacological treatment for this disease, but improvement of insulin resistance using peroxisome proliferator-activated receptor-γ (PPARγ) agonists, such as thiazolidinediones (TZDs), has been shown to reduce steatosis and steatohepatitis effectively and to improve liver function in patients with obesity-related NAFLD. However, this approach is limited by adverse effects of TZDs. Recently, we have identified fibroblast growth factor 1 (FGF1) as a target of nuclear receptor PPARγ in visceral adipose tissue and as a critical factor in adipose remodeling. Because FGF1 is situated downstream of PPARγ, it is likely that therapeutic targeting of the FGF1 pathway will eliminate some of the serious adverse effects associated with TZDs. Here we show that pharmacological administration of recombinant FGF1 (rFGF1) effectively improves hepatic inflammation and damage in leptin-deficient ob/ob mice and in choline-deficient mice, two etiologically different models of NAFLD. Hepatic steatosis was effectively reduced only in ob/ob mice, suggesting that rFGF1 stimulates hepatic lipid catabolism. Potentially adverse effects such as fibrosis or proliferation were not observed in these models. Because the anti-inflammatory effects were observed in both the presence and absence of the antisteatotic effects, our findings further suggest that the anti-inflammatory property of rFGF1 is independent of its effect on lipid catabolism. Our current findings indicate that, in addition to its potent glucose-lowering and insulin-sensitizing effects, rFGF1 could be therapeutically effective in the treatment of NAFLD.

  1. Effectiveness of Relapse Prevention Cognitive-Behavioral Model in Opioid-Dependent Patients Participating in the Methadone Maintenance Treatment in Iran.

    Science.gov (United States)

    Pashaei, Tahereh; Shojaeizadeh, Davoud; Rahimi Foroushani, Abbas; Ghazitabatabae, Mahmoud; Moeeni, Maryam; Rajati, Fatemeh; M Razzaghi, Emran

    2013-08-01

    To evaluate the effectiveness of a relapse prevention cognitive-behavioral model, based on Marlatt treatment approach, in Opioid-dependent patients participating in the Methadone Maintenance Treatment (MMT) in Iran. The study consisted of 92 individuals treated with methadone in Iranian National Center of Addiction Studies (INCAS). Participants were randomized into two groups: educational intervention group (N=46) and control group (N=46). The intervention was comprised of 10 weekly 90 minute sessions, done during a period of 2.5 months based on the most high risk situations determined using Inventory Drug Taking Situation instrument. Relapse was defined as not showing up for MMT, drug use for at least 5 continuous days, and a positive urinary morphine test. While, only 36.4% of the intervention group relapsed into drug use, 63.6% of the control group relapsed. The result of the logistic regressions showed that the odd ratio of the variable of intervention program for the entire follow up period was 0.43 (P<0.01). Further, the odd ratio of this variable in one month, three months, and 195 days after the therapy were 0.48 (P<.03), 0.31 (P<.02), and 0.13 (P<.02) respectively that revealed that on average, the probability of relapse among individuals in the intervention group was lower than patients in control group. Relapse prevention model based on Marlatt treatment approach has an effective role in decreasing relapse rate. This model can be introduced as a complementary therapy in patients treated with methadone maintenance.

  2. Modeling Test and Treatment Strategies for Presymptomatic Alzheimer Disease

    Science.gov (United States)

    Burke, James F.; Langa, Kenneth M.; Hayward, Rodney A.; Albin, Roger L.

    2014-01-01

    Objectives In this study, we developed a model of presymptomatic treatment of Alzheimer disease (AD) after a screening diagnostic evaluation and explored the circumstances required for an AD prevention treatment to produce aggregate net population benefit. Methods Monte Carlo simulation methods were used to estimate outcomes in a simulated population derived from data on AD incidence and mortality. A wide variety of treatment parameters were explored. Net population benefit was estimated in aggregated QALYs. Sensitivity analyses were performed by individually varying the primary parameters. Findings In the base-case scenario, treatment effects were uniformly positive, and net benefits increased with increasing age at screening. A highly efficacious treatment (i.e. relative risk 0.6) modeled in the base-case is estimated to save 20 QALYs per 1000 patients screened and 221 QALYs per 1000 patients treated. Conclusions Highly efficacious presymptomatic screen and treat strategies for AD are likely to produce substantial aggregate population benefits that are likely greater than the benefits of aspirin in primary prevention of moderate risk cardiovascular disease (28 QALYS per 1000 patients treated), even in the context of an imperfect treatment delivery environment. PMID:25474698

  3. The Cost and Cost-Effectiveness of Scaling up Screening and Treatment of Syphilis in Pregnancy: A Model

    Science.gov (United States)

    Kahn, James G.; Jiwani, Aliya; Gomez, Gabriela B.; Hawkes, Sarah J.; Chesson, Harrell W.; Broutet, Nathalie; Kamb, Mary L.; Newman, Lori M.

    2014-01-01

    Background Syphilis in pregnancy imposes a significant global health and economic burden. More than half of cases result in serious adverse events, including infant mortality and infection. The annual global burden from mother-to-child transmission (MTCT) of syphilis is estimated at 3.6 million disability-adjusted life years (DALYs) and $309 million in medical costs. Syphilis screening and treatment is simple, effective, and affordable, yet, worldwide, most pregnant women do not receive these services. We assessed cost-effectiveness of scaling-up syphilis screening and treatment in existing antenatal care (ANC) programs in various programmatic, epidemiologic, and economic contexts. Methods and Findings We modeled the cost, health impact, and cost-effectiveness of expanded syphilis screening and treatment in ANC, compared to current services, for 1,000,000 pregnancies per year over four years. We defined eight generic country scenarios by systematically varying three factors: current maternal syphilis testing and treatment coverage, syphilis prevalence in pregnant women, and the cost of healthcare. We calculated program and net costs, DALYs averted, and net costs per DALY averted over four years in each scenario. Program costs are estimated at $4,142,287 – $8,235,796 per million pregnant women (2010 USD). Net costs, adjusted for averted medical care and current services, range from net savings of $12,261,250 to net costs of $1,736,807. The program averts an estimated 5,754 – 93,484 DALYs, yielding net savings in four scenarios, and a cost per DALY averted of $24 – $111 in the four scenarios with net costs. Results were robust in sensitivity analyses. Conclusions Eliminating MTCT of syphilis through expanded screening and treatment in ANC is likely to be highly cost-effective by WHO-defined thresholds in a wide range of settings. Countries with high prevalence, low current service coverage, and high healthcare cost would benefit most. Future analyses can be

  4. Network meta-analysis of disconnected networks: How dangerous are random baseline treatment effects?

    Science.gov (United States)

    Béliveau, Audrey; Goring, Sarah; Platt, Robert W; Gustafson, Paul

    2017-12-01

    In network meta-analysis, the use of fixed baseline treatment effects (a priori independent) in a contrast-based approach is regularly preferred to the use of random baseline treatment effects (a priori dependent). That is because, often, there is not a need to model baseline treatment effects, which carry the risk of model misspecification. However, in disconnected networks, fixed baseline treatment effects do not work (unless extra assumptions are made), as there is not enough information in the data to update the prior distribution on the contrasts between disconnected treatments. In this paper, we investigate to what extent the use of random baseline treatment effects is dangerous in disconnected networks. We take 2 publicly available datasets of connected networks and disconnect them in multiple ways. We then compare the results of treatment comparisons obtained from a Bayesian contrast-based analysis of each disconnected network using random normally distributed and exchangeable baseline treatment effects to those obtained from a Bayesian contrast-based analysis of their initial connected network using fixed baseline treatment effects. For the 2 datasets considered, we found that the use of random baseline treatment effects in disconnected networks was appropriate. Because those datasets were not cherry-picked, there should be other disconnected networks that would benefit from being analyzed using random baseline treatment effects. However, there is also a risk for the normality and exchangeability assumption to be inappropriate in other datasets even though we have not observed this situation in our case study. We provide code, so other datasets can be investigated. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Stochastic modelling to evaluate the economic efficiency of treatment of chronic subclinical mastitis

    NARCIS (Netherlands)

    Steeneveld, W.; Hogeveen, H.; Borne, van den B.H.P.; Swinkels, J.M.

    2006-01-01

    Treatment of subclinical mastitis is traditionally no common practice. However, some veterinarians regard treatment of some types of subclinical mastitis to be effective. The goal of this research was to develop a stochastic Monte Carlo simulation model to support decisions around treatment of

  6. Hyperbolastic modeling of tumor growth with a combined treatment of iodoacetate and dimethylsulphoxide

    International Nuclear Information System (INIS)

    Eby, Wayne M; Tabatabai, Mohammad A; Bursac, Zoran

    2010-01-01

    An understanding of growth dynamics of tumors is important in understanding progression of cancer and designing appropriate treatment strategies. We perform a comparative study of the hyperbolastic growth models with the Weibull and Gompertz models, which are prevalently used in the field of tumor growth. The hyperbolastic growth models H1, H2, and H3 are applied to growth of solid Ehrlich carcinoma under several different treatments. These are compared with results from Gompertz and Weibull models for the combined treatment. The growth dynamics of the solid Ehrlich carcinoma with the combined treatment are studied using models H1, H2, and H3, and the models are highly accurate in representing the growth. The growth dynamics are also compared with the untreated tumor, the tumor treated with only iodoacetate, and the tumor treated with only dimethylsulfoxide, and the combined treatment. The hyperbolastic models prove to be effective in representing and analyzing the growth dynamics of the solid Ehrlich carcinoma. These models are more precise than Gompertz and Weibull and show less error for this data set. The precision of H3 allows for its use in a comparative analysis of tumor growth rates between the various treatments

  7. Hanging drop cultures of human testis and testis cancer samples: a model used to investigate activin treatment effects in a preserved niche.

    Science.gov (United States)

    Jørgensen, A; Young, J; Nielsen, J E; Joensen, U N; Toft, B G; Rajpert-De Meyts, E; Loveland, K L

    2014-05-13

    Testicular germ cell tumours of young adults, seminoma or non-seminomas, are preceded by a pre-invasive precursor, carcinoma in situ (CIS), understood to arise through differentiation arrest of embryonic germ cells. Knowledge about the malignant transformation of germ cells is currently limited by the lack of experimental models. The aim of this study was to establish an experimental tissue culture model to maintain normal and malignant germ cells within their niche and allow investigation of treatment effects. Human testis and testis cancer specimens from orchidectomies were cultured in 'hanging drops' and effects of activin A and follistatin treatment were investigated in seminoma cultures. Testis fragments with normal spermatogenesis or CIS cells were cultured for 14 days with sustained proliferation of germ cells and CIS cells and without increased apoptosis. Seminoma cultures survived 7 days, with proliferating cells detectable during the first 5 days. Activin A treatment significantly reduced KIT transcript and protein levels in seminoma cultures, thereby demonstrating a specific treatment response. Hanging drop cultures of human testis and testis cancer samples can be employed to delineate mechanisms governing growth of normal, CIS and tumorigenic germ cells retained within their niche.

  8. An investigation of an open-access model for scaling up methadone maintenance treatment.

    Science.gov (United States)

    Madden, Lynn M; Farnum, Scott O; Eggert, Kathryn F; Quanbeck, Andrew R; Freeman, Robert M; Ball, Samuel A; Schottenfeld, Richard S; Shi, Julia M; Savage, Mary Ellen; Barry, Declan T

    2018-02-17

    To examine retrospectively patient and programmatic outcomes following the development and implementation of an 'open-access' model in which prospective patients were enrolled rapidly in methadone maintenance treatment, irrespective of ability to pay, and provided real-time access to multiple voluntary treatment options. Medical and administrative records were abstracted to compare data for 1 year before and 9 years after initiating the implementation of an open-access treatment model in May 2007. Methadone maintenance treatment center in Connecticut, USA. Individuals with opioid use disorder entering treatment between July 2006 and June 2015. In June 2015, 64% (n = 2594) of the sample were men and 80% (n = 3133) reported that they were white. The Network for the Improvement of Addiction Treatment-informed open-access treatment model uses process improvement strategies to improve treatment access and capacity. Census, waiting time, retention, non-medical opioid use, patient mortality and financial sustainability (net income and state-block grants as proportions of revenue). In the 9 years following the initial implementation of the open-access model, patient census increased by 183% from 1431 to 4051, and average waiting-time days decreased from 21 to 0.3 (same day) without apparent deleterious effects on rates of retention, non-medical opioid use or mortality. Between fiscal years (FY) 06 and FY 15, net operating margin rose from 2 to 10%, while state-block grant revenues declined 14% and the proportion of total revenue from state-block grant revenue decreased from 49 to 24%. An open-access model for rapid enrolment of people with opioid use disorder in methadone treatment appears to improve treatment access, capacity, and financial sustainability without evidence of deleterious effects on treatment outcomes. © 2018 Society for the Study of Addiction.

  9. Desensitization and Modeling Treatments of Spider Fear Using Two Types of Scenes

    Science.gov (United States)

    Denney, Douglas R.; Sullivan, Bernard J.

    1976-01-01

    Three types of therapy were combined with two types of scenes. Spider-phobic subjects were assigned to one of the six treatment conditions or to an untreated control group. In general, (a) Desensitization and modeling therapies were equally effective; (b) modeling alone was more effective than mere exposure to the phobic object. (Author)

  10. Effective treatment strategies against Ebola virus

    Directory of Open Access Journals (Sweden)

    Amina Yaqoob

    2015-08-01

    Full Text Available Ebola virus (EBOV, a member of order Mononegavirales is most famous for causing the endemics of hemorrhagic fever in different countries of the world. Various effective treatment for EBOV are available presently but different clinical trials and experimental studies on animal models are ongoing for this purpose. Results from different studies showed that selective vaccines and therapeutic drugs have potential to interfere the viral life events within host cell in order to inhibit its replication. Various pre-clinical trials in this regard are proved successful on non-human primates (NHPs and found to be significant in inhibiting EBOV infections. It is the need of hour to develop effective vaccines against Ebola virus to combat this problem as soon as possible. The present article is a brief review on potential treatment strategies against Ebola virus.

  11. Evaluation of treatment effects by ranking

    DEFF Research Database (Denmark)

    Halekoh, U; Kristensen, K

    2008-01-01

    In crop experiments measurements are often made by a judge evaluating the crops' conditions after treatment. In the present paper an analysis is proposed for experiments where plots of crops treated differently are mutually ranked. In the experimental layout the crops are treated on consecutive...... plots usually placed side by side in one or more rows. In the proposed method a judge ranks several neighbouring plots, say three, by ranking them from best to worst. For the next observation the judge moves on by no more than two plots, such that up to two plots will be re-evaluated again...... in a comparison with the new plot(s). Data from studies using this set-up were analysed by a Thurstonian random utility model, which assumed that the judge's rankings were obtained by comparing latent continuous utilities or treatment effects. For the latent utilities a variance component model was considered...

  12. Phenomenological modelling of second cancer incidence for radiation treatment planning

    International Nuclear Information System (INIS)

    Pfaffenberger, Asja; Oelfke, Uwe; Schneider, Uwe; Poppe, Bjoern

    2009-01-01

    It is still an unanswered question whether a relatively low dose of radiation to a large volume or a higher dose to a small volume produces the higher cancer incidence. This is of interest in view of modalities like IMRT or rotation therapy where high conformity to the target volume is achieved at the cost of a large volume of normal tissue exposed to radiation. Knowledge of the shape of the dose response for radiation-induced cancer is essential to answer the question of what risk of second cancer incidence is implied by which treatment modality. This study therefore models the dose response for radiation-induced second cancer after radiation therapy of which the exact mechanisms are still unknown. A second cancer risk estimation tool for treatment planning is presented which has the potential to be used for comparison of different treatment modalities, and risk is estimated on a voxel basis for different organs in two case studies. The presented phenomenological model summarises the impact of microscopic biological processes into effective parameters of mutation and cell sterilisation. In contrast to other models, the effective radiosensitivities of mutated and non-mutated cells are allowed to differ. Based on the number of mutated cells present after irradiation, the model is then linked to macroscopic incidence by summarising model parameters and modifying factors into natural cancer incidence and the dose response in the lower-dose region. It was found that all principal dose-response functions discussed in the literature can be derived from the model. However, from the investigation and due to scarcity of adequate data, rather vague statements about likelihood of dose-response functions can be made than a definite decision for one response. Based on the predicted model parameters, the linear response can probably be rejected using the dynamics described, but both a flattening response and a decrease appear likely, depending strongly on the effective cell

  13. Using Dirichlet Processes for Modeling Heterogeneous Treatment Effects across Sites

    Science.gov (United States)

    Miratrix, Luke; Feller, Avi; Pillai, Natesh; Pati, Debdeep

    2016-01-01

    Modeling the distribution of site level effects is an important problem, but it is also an incredibly difficult one. Current methods rely on distributional assumptions in multilevel models for estimation. There it is hoped that the partial pooling of site level estimates with overall estimates, designed to take into account individual variation as…

  14. Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment

    DEFF Research Database (Denmark)

    Larsen, Marianne H; Mikkelsen, Jens D; Hay-Schmidt, Anders

    2010-01-01

    Chronic unpredictable stress (CUS) is a widely used animal model of depression. The present study was undertaken to investigate behavioral, physiological and molecular effects of CUS and/or chronic antidepressant treatment (venlafaxine or imipramine) in the same set of animals. Anhedonia, a core ...

  15. Effects of non-ablative fractional erbium glass laser treatment on gene regulation in human three-dimensional skin models.

    Science.gov (United States)

    Amann, Philipp M; Marquardt, Yvonne; Steiner, Timm; Hölzle, Frank; Skazik-Voogt, Claudia; Heise, Ruth; Baron, Jens M

    2016-04-01

    Clinical experiences with non-ablative fractional erbium glass laser therapy have demonstrated promising results for dermal remodelling and for the indications of striae, surgical scars and acne scars. So far, molecular effects on human skin following treatment with these laser systems have not been elucidated. Our aim was to investigate laser-induced effects on skin morphology and to analyse molecular effects on gene regulation. Therefore, human three-dimensional (3D) organotypic skin models were irradiated with non-ablative fractional erbium glass laser systems enabling qRT-PCR, microarray and histological studies at same and different time points. A decreased mRNA expression of matrix metalloproteinases (MMPs) 3 and 9 was observed 3 days after treatment. MMP3 also remained downregulated on protein level, whereas the expression of other MMPs like MMP9 was recovered or even upregulated 5 days after irradiation. Inflammatory gene regulatory responses measured by the expression of chemokine (C-X-C motif) ligands (CXCL1, 2, 5, 6) and interleukin expression (IL8) were predominantly reduced. Epidermal differentiation markers such as loricrin, filaggrin-1 and filaggrin-2 were upregulated by both tested laser optics, indicating a potential epidermal involvement. These effects were also shown on protein level in the immunofluorescence analysis. This novel standardised laser-treated human 3D skin model proves useful for monitoring time-dependent ex vivo effects of various laser systems on gene expression and human skin morphology. Our study reveals erbium glass laser-induced regulations of MMP and interleukin expression. We speculate that these alterations on gene expression level could play a role for dermal remodelling, anti-inflammatory effects and increased epidermal differentiation. Our finding may have implications for further understanding of the molecular mechanism of erbium glass laser-induced effects on human skin.

  16. Evaluation of treatment response in depression studies using a Bayesian parametric cure rate model.

    Science.gov (United States)

    Santen, Gijs; Danhof, Meindert; Della Pasqua, Oscar

    2008-10-01

    Efficacy trials with antidepressant drugs often fail to show significant treatment effect even though efficacious treatments are investigated. This failure can, amongst other factors, be attributed to the lack of sensitivity of the statistical method as well as of the endpoints to pharmacological activity. For regulatory purposes the most widely used efficacy endpoint is still the mean change in HAM-D score at the end of the study, despite evidence from literature showing that the HAM-D scale might not be a sensitive tool to assess drug effect and that changes from baseline at the end of treatment may not reflect the extent of response. In the current study, we evaluate the prospect of applying a Bayesian parametric cure rate model (CRM) to analyse antidepressant effect in efficacy trials with paroxetine. The model is based on a survival approach, which allows for a fraction of surviving patients indefinitely after completion of treatment. Data was extracted from GlaxoSmithKline's clinical databases. Response was defined as a 50% change from baseline HAM-D at any assessment time after start of therapy. Survival times were described by a log-normal distribution and drug effect was parameterised as a covariate on the fraction of non-responders. The model was able to fit the data from different studies accurately and results show that response to treatment does not lag for two weeks, as is mythically believed. In conclusion, we demonstrate how parameterisation of a survival model can be used to characterise treatment response in depression trials. The method contrasts with the long-established snapshot on changes from baseline, as it incorporates the time course of response throughout treatment.

  17. Decision analytic cost-effectiveness model to compare prostate cryotherapy to androgen deprivation therapy for treatment of radiation recurrent prostate cancer

    Science.gov (United States)

    Boyd, Kathleen A; Jones, Rob J; Paul, Jim; Birrell, Fiona; Briggs, Andrew H; Leung, Hing Y

    2015-01-01

    Objective To determine the cost-effectiveness of salvage cryotherapy (SC) in men with radiation recurrent prostate cancer (RRPC). Design Cost-utility analysis using decision analytic modelling by a Markov model. Setting and methods Compared SC and androgen deprivation therapy (ADT) in a cohort of patients with RRPC (biopsy proven local recurrence, no evidence of metastatic disease). A literature review captured published data to inform the decision model, and resource use data were from the Scottish Prostate Cryotherapy Service. The model was run in monthly cycles for RRPC men, mean age of 70 years. The model was run over the patient lifetime, to assess changes in patient health states and the associated quality of life, survival and cost impacts. Results are reported in terms of the discounted incremental costs and discounted incremental quality-adjusted life years (QALYs) gained between the 2 alternative interventions. Probabilistic sensitivity analysis used a 10 000 iteration Monte Carlo simulation. Results SC has a high upfront treatment cost, but delays the ongoing monthly cost of ADT. SC is the dominant strategy over the patient lifetime; it is more effective with an incremental 0.56 QALY gain (95% CI 0.28 to 0.87), and less costly with a reduced lifetime cost of £29 719 (€37 619) (95% CI −51 985 to −9243). For a ceiling ratio of £30 000, SC has a 100% probability to be cost-effective. The cost neutral point was at 3.5 years, when the upfront cost of SC (plus any subsequent cumulative cost of side effects and ADT) equates the cumulative cost in the ADT arm. Limitations of our model may arise from its insensitivity to parameter or structural uncertainty. Conclusions The platform for SC versus ADT cost-effective analysis can be employed to evaluate other treatment modalities or strategies in RRPC. SC is the dominant strategy, costing less over a patient's lifetime with improvements in QALYs. Trial registration number This economic analysis

  18. [AIT (Adolescent Identity Treatment) - an Integrative Treatment Model for the Treatment of Personality Disorders].

    Science.gov (United States)

    Schlüter-Müller, Susanne

    2017-07-01

    AIT (Adolescent Identity Treatment) - an Integrative Treatment Model for the Treatment of Personality Disorders Personality disorders are patterns of maladaptive personality traits that have an impact on the individual throughout the life span. Borderline Personality Disorder (BPD) is a very severe, but treatable mental disorder. Identity disturbance is seen as the central construct for detecting severe personality pathology - and, most notably, borderline personality disorder - in adults and adolescents. Crises in the development of identity usually resolve into a normal and consolidated identity with flexible and adaptive functioning whereas identity diffusion is viewed as a lack of integration of the concept of the self and significant others. It is seen as the basis for subsequent personality pathology, including that of borderline personality disorder. Although BPD has its onset in adolescence and emerging adulthood the diagnosis is often delayed. In most cases, specific treatment is only offered late in the course of the disorder and to relatively few individuals. Adolescent Identity Treatment (AIT) is a treatment model that focuses on identity pathology as the core characteristic of personality disorders. This model integrates specific techniques for the treatment of adolescent personality pathology on the background of object-relation theories and modified elements of Transference-Focused Psychotherapy. Moreover, psychoeducation, a behavior-oriented homeplan and intensive family work is part of AIT.

  19. Modelling the cost-effectiveness of mass screening and treatment for reducing Plasmodium falciparum malaria burden

    Directory of Open Access Journals (Sweden)

    Crowell Valerie

    2013-01-01

    Full Text Available Abstract Background Past experience and modelling suggest that, in most cases, mass treatment strategies are not likely to succeed in interrupting Plasmodium falciparum malaria transmission. However, this does not preclude their use to reduce disease burden. Mass screening and treatment (MSAT is preferred to mass drug administration (MDA, as the latter involves massive over-use of drugs. This paper reports simulations of the incremental cost-effectiveness of well-conducted MSAT campaigns as a strategy for P. falciparum malaria disease-burden reduction in settings with varying receptivity (ability of the combined vector population in a setting to transmit disease and access to case management. Methods MSAT incremental cost-effectiveness ratios (ICERs were estimated in different sub-Saharan African settings using simulation models of the dynamics of malaria and a literature-based MSAT cost estimate. Imported infections were simulated at a rate of two per 1,000 population per annum. These estimates were compared to the ICERs of scaling up case management or insecticide-treated net (ITN coverage in each baseline health system, in the absence of MSAT. Results MSAT averted most episodes, and resulted in the lowest ICERs, in settings with a moderate level of disease burden. At a low pre-intervention entomological inoculation rate (EIR of two infectious bites per adult per annum (IBPAPA MSAT was never more cost-effective than scaling up ITNs or case management coverage. However, at pre-intervention entomological inoculation rates (EIRs of 20 and 50 IBPAPA and ITN coverage levels of 40 or 60%, respectively, the ICER of MSAT was similar to that of scaling up ITN coverage further. Conclusions In all the transmission settings considered, achieving a minimal level of ITN coverage is a “best buy”. At low transmission, MSAT probably is not worth considering. Instead, MSAT may be suitable at medium to high levels of transmission and at moderate ITN coverage

  20. A model-based cost-effectiveness analysis of osteoporosis screening and treatment strategy for postmenopausal Japanese women.

    Science.gov (United States)

    Yoshimura, M; Moriwaki, K; Noto, S; Takiguchi, T

    2017-02-01

    Although an osteoporosis screening program has been implemented as a health promotion project in Japan, its cost-effectiveness has yet to be elucidated fully. We performed a cost-effectiveness analysis and found that osteoporosis screening and treatment would be cost-effective for Japanese women over 60 years. The purpose of this study was to estimate the cost-effectiveness of osteoporosis screening and drug therapy in the Japanese healthcare system for postmenopausal women with no history of fracture. A patient-level state transition model was developed to predict the outcomes of Japanese women with no previous fracture. Lifetime costs and quality-adjusted life years (QALYs) were estimated for women who receive osteoporosis screening and alendronate therapy for 5 years and those who do not receive the screening and treatments. The incremental cost-effectiveness ratio (ICER) of the screening option compared with the no screening option was estimated. Sensitivity analyses were performed to examine the influence of parameter uncertainty on the base case results. The ICERs of osteoporosis screening and treatments for Japanese women aged 50-54, 55-59, 60-64, 65-69, 70-74, and 75-79 years were estimated to be $89,242, $64,010, $40,596, $27,697, $17,027, and $9771 per QALY gained, respectively. Deterministic sensitivity analyses showed that several parameters such as the disutility due to vertebral fracture had a significant influence on the base case results. Applying a willingness to pay of $50,000 per QALY gained, the probability that the screening option became cost-effectiveness estimated to 50.9, 56.3, 59.1, and 64.7 % for women aged 60-64, 65-69, 70-74, and 75-79 years, respectively. Scenario analyses showed that the ICER for women aged 55-59 years with at least one clinical risk factor was below $50,000 per QALY. In conclusion, dual energy X-ray absorptiometry (DXA) screening and alendronate therapy for osteoporosis would be cost-effective for

  1. Mediation and moderation of treatment effects in randomised controlled trials of complex interventions.

    Science.gov (United States)

    Emsley, Richard; Dunn, Graham; White, Ian R

    2010-06-01

    Complex intervention trials should be able to answer both pragmatic and explanatory questions in order to test the theories motivating the intervention and help understand the underlying nature of the clinical problem being tested. Key to this is the estimation of direct effects of treatment and indirect effects acting through intermediate variables which are measured post-randomisation. Using psychological treatment trials as an example of complex interventions, we review statistical methods which crucially evaluate both direct and indirect effects in the presence of hidden confounding between mediator and outcome. We review the historical literature on mediation and moderation of treatment effects. We introduce two methods from within the existing causal inference literature, principal stratification and structural mean models, and demonstrate how these can be applied in a mediation context before discussing approaches and assumptions necessary for attaining identifiability of key parameters of the basic causal model. Assuming that there is modification by baseline covariates of the effect of treatment (i.e. randomisation) on the mediator (i.e. covariate by treatment interactions), but no direct effect on the outcome of these treatment by covariate interactions leads to the use of instrumental variable methods. We describe how moderation can occur through post-randomisation variables, and extend the principal stratification approach to multiple group methods with explanatory models nested within the principal strata. We illustrate the new methodology with motivating examples of randomised trials from the mental health literature.

  2. Evaluating the effect of smoking cessation treatment on a complex dynamical system.

    Science.gov (United States)

    Bekiroglu, Korkut; Russell, Michael A; Lagoa, Constantino M; Lanza, Stephanie T; Piper, Megan E

    2017-11-01

    To understand the dynamic relations among tobacco withdrawal symptoms to inform the development of effective smoking cessation treatments. Dynamical system models from control engineering are introduced and utilized to evaluate complex treatment effects. We demonstrate how dynamical models can be used to examine how distinct withdrawal-related processes are related over time and how treatment influences these relations. Intensive longitudinal data from a randomized placebo-controlled smoking cessation trial (N=1504) are used to estimate a dynamical model of withdrawal-related processes including momentary craving, negative affect, quitting self-efficacy, and cessation fatigue for each of six treatment conditions (nicotine patch, nicotine lozenge, bupropion, patch + lozenge, bupropion + lozenge, and placebo). Estimation and simulation results show that (1) withdrawal measurements are interrelated over time, (2) nicotine patch + nicotine lozenge showed reduced cessation fatigue and enhanced self-efficacy in the long-term while bupropion + nicotine lozenge was more effective at reducing negative affect and craving, and (3) although nicotine patch + nicotine lozenge had a better initial effect on cessation fatigue and self-efficacy, nicotine lozenge had a stronger effect on negative affect and nicotine patch had a stronger impact on craving. This approach can be used to provide new evidence illustrating (a) the total impact of treatment conditions (via steady state values) and (b) the total initial impact (via rate of initial change values) on smoking-related outcomes for separate treatment conditions, noting that the conditions that produce the largest change may be different than the conditions that produce the fastest change. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Multistrain models predict sequential multidrug treatment strategies to result in less antimicrobial resistance than combination treatment

    DEFF Research Database (Denmark)

    Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo

    2016-01-01

    generated by a mathematical model of the competitive growth of multiple strains of Escherichia coli.Results: Simulation studies showed that sequential use of tetracycline and ampicillin reduced the level of double resistance, when compared to the combination treatment. The effect of the cycling frequency...... frequency did not play a role in suppressing the growth of resistant strains, but the specific order of the two antimicrobials did. Predictions made from the study could be used to redesign multidrug treatment strategies not only for intramuscular treatment in pigs, but also for other dosing routes.......Background: Combination treatment is increasingly used to fight infections caused by bacteria resistant to two or more antimicrobials. While multiple studies have evaluated treatment strategies to minimize the emergence of resistant strains for single antimicrobial treatment, fewer studies have...

  4. Alternate day treatment and late effects: The concept of an effective dose per fraction

    International Nuclear Information System (INIS)

    Courdi, A.; Hery, M.; Gabillat, J.M.

    1990-01-01

    Although most institutions treat all fields each day, some radiotherapists continue to adopt an alternate day schedule. The resulting daily variations of the dose per fraction in laterally located targets have been analyzed using the linear-quadratic model. Patients with breast carcinoma treated with definitive radiotherapy in 1974-1975 with one field a day were studied. An effective dose per fraction was derived, with a value higher than the average dose per fraction received by the reference point. The greater the fluctuations between the doses per fraction on successive days, the higher the effective dose per fraction. The corresponding cell survival due to alternate treatment as compared to survival with daily treatment depends on the alpha/beta ratio. For a late effect with low alpha/beta ratio, an alternate treatment may lead to almost 10-fold increase in cell kill in these lateral targets such as those responsible for subcutaneous sclerosis as compared to daily treatment of all fields with the same total dose. Taking the average effective dose per fraction in our series, the increase in cell kill was 4-fold. Acute effects would suffer less damage due to alternate treatment because of a high alpha/beta ratio. Treatment on an alternate schedule should be restricted to palliative radiotherapy

  5. [The model program of psycho-social treatment and staff training].

    Science.gov (United States)

    Ikebuchi, Emi

    2012-01-01

    The model program of psycho-social treatment and staff training were reported in this issue. The mission of model program is supporting recovery of persons with mental illness and their family as well as empowering their hope and sense of values. The personal support specialists belonging to multi-disciplinary team have responsibility to support life-long process of recovery across hospitalization, out-patients clinic, day treatment, and outreach service. The shared value of multi-disciplinary team (the community life supporting team) is recovery so that the team renders self directive life, various alternatives of their lives, and peer group with models of recovery to persons with mental illness. There should be several technologies which are used in the team such as engagement, psycho-education, cognitive-behavior therapy, care-management, cooperating with other resources. The responsibility, assessment and evaluation techniques, guarantee of opportunities for training, and auditing system of the team and process of treatment are important factors to educate team staff. Raising effective multi-disciplinary team requires existence of a mentor or good model near the team.

  6. Mental health treatment teams and leadership: a systems model.

    Science.gov (United States)

    Yank, G R; Barber, J W; Spradlin, W W

    1994-10-01

    Mental health treatment teams are living systems at the group level and comprise key productive subsystems of organizations providing mental health care. Effective treatment teams, like effective organizations, are anticipatory systems that contain subsystems that model and predict future system and environmental conditions and enable responses that increase system viability. A systems analysis of treatment teams highlights their potential instability due to their tendencies to regress toward dysfunctional partial systems and their active maintenance in nonequilibrium steady states with their organizational and external environments. Team subsystems are analyzed from the viewpoints of system processes and also with regard to individuals and their roles. Boundary processes are central to effective team functioning, assure constancy of team membership, and regulate the team's interfaces with its parent agency and with the external environment. Various causes and forms of disturbed information processing within hierarchical organizations are examined, and their effects at the treatment team level are discussed. The conclusion of the discussion focuses on team leadership and how leadership expands upon the concept of the decider subsystem to include role and personal factors to the team's leaders, and functions that are anticipatory and integrative in nature. Effective leaders must set appropriate thresholds for feedback regulation processes, and balance several pairs of seemingly opposing forces, including homeostasis and development, role differentiation and role overlap, and personal accountability and empowerment of others.

  7. Random effects models in clinical research

    NARCIS (Netherlands)

    Cleophas, T. J.; Zwinderman, A. H.

    2008-01-01

    BACKGROUND: In clinical trials a fixed effects research model assumes that the patients selected for a specific treatment have the same true quantitative effect and that the differences observed are residual error. If, however, we have reasons to believe that certain patients respond differently

  8. Direct and Indirect Effects of Tofacitinib on Treatment Satisfaction in Patients with Ulcerative Colitis.

    Science.gov (United States)

    Panés, Julian; Su, Chinyu; Bushmakin, Andrew G; Cappelleri, Joseph C; Healey, Paul

    2016-11-01

    This mediation modelling analysis evaluated direct and indirect effects of tofacitinib, an oral, small molecule Janus kinase inhibitor under investigation for ulcerative colitis, on patient treatment satisfaction. Data from an 8-week randomized Phase 2 trial [NCT00787202] in adults with moderate-to-severe, active ulcerative colitis receiving twice-daily tofacitinib 0.5-15mg [n=146] or placebo [n=48] were analysed in patient-reported [n=149] and clinician-reported [n=170] outcomes-based mediation models. Binary predictor variable: Treatment [pooled active treatment vs placebo]. Eventual dependent variable: Week 8 patient treatment satisfaction [measured on a five-point Likert scale]. Mediators of treatment effect on satisfaction: Week 8 Inflammatory Bowel Disease Questionnaire domains [Bowel Symptoms, Emotional Health, Social Function and Systemic Symptoms] and Mayo scale domains [Stool Frequency, Rectal Bleeding, Physician's Global Assessment and Endoscopic Disease Activity] for patient-reported and clinician-reported models, respectively. Overall tofacitinib indirect effect on satisfaction via Inflammatory Bowel Disease Questionnaire domains was 40.5% [ptofacitinib effect on satisfaction, 32.4% [p=0.05] was indirectly mediated via Bowel Symptoms; and 30.0% [p=0.04] via Stool Frequency. In total, 59.5% [ptofacitinib's effect on satisfaction was unrelated to Inflammatory Bowel Disease Questionnaire and Mayo scale domains in the patient-reported and clinician-reported models, respectively. Bowel function is an important factor for patient treatment satisfaction with tofacitinib. Treatment effect on patient satisfaction was almost completely mediated via improvement in Mayo scale domains. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  9. Effect of human milk as a treatment for dry eye syndrome in a mouse model.

    Science.gov (United States)

    Diego, Jose L; Bidikov, Luke; Pedler, Michelle G; Kennedy, Jeffrey B; Quiroz-Mercado, Hugo; Gregory, Darren G; Petrash, J Mark; McCourt, Emily A

    Dry eye syndrome (DES) affects millions of people worldwide. Homeopathic remedies to treat a wide variety of ocular diseases have previously been documented in the literature, but little systematic work has been performed to validate the remedies' efficacy using accepted laboratory models of disease. The purpose of this study was to evaluate the efficacy of human milk and nopal cactus (prickly pear), two widely used homeopathic remedies, as agents to reduce pathological markers of DES. The previously described benzalkonium chloride (BAK) dry eye mouse model was used to study the efficacy of human milk and nopal cactus (prickly pear). BAK (0.2%) was applied to the mouse ocular surface twice daily to induce dry eye pathology. Fluorescein staining was used to verify that the animals had characteristic signs of DES. After induction of DES, the animals were treated with human milk (whole and fat-reduced), nopal, nopal extract derivatives, or cyclosporine four times daily for 7 days. Punctate staining and preservation of corneal epithelial thickness, measured histologically at the end of treatment, were used as indices of therapeutic efficacy. Treatment with BAK reduced the mean corneal epithelial thickness from 36.77±0.64 μm in the control mice to 21.29±3.2 μm. Reduction in corneal epithelial thickness was largely prevented by administration of whole milk (33.2±2.5 μm) or fat-reduced milk (36.1±1.58 μm), outcomes that were similar to treatment with cyclosporine (38.52±2.47 μm), a standard in current dry eye therapy. In contrast, crude or filtered nopal extracts were ineffective at preventing BAK-induced loss of corneal epithelial thickness (24.76±1.78 μm and 27.99±2.75 μm, respectively), as were solvents used in the extraction of nopal materials (26.53±1.46 μm for ethyl acetate, 21.59±5.87 μm for methanol). Epithelial damage, as reflected in the punctate scores, decreased over 4 days of treatment with whole and fat-reduced milk but continued to

  10. Effects of tailored neck-shoulder pain treatment based on a decision model guided by clinical assessments and standardized functional tests. A study protocol of a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Björklund Martin

    2012-05-01

    Full Text Available Abstract Background A major problem with rehabilitation interventions for neck pain is that the condition may have multiple causes, thus a single treatment approach is seldom efficient. The present study protocol outlines a single blinded randomised controlled trial evaluating the effect of tailored treatment for neck-shoulder pain. The treatment is based on a decision model guided by standardized clinical assessment and functional tests with cut-off values. Our main hypothesis is that the tailored treatment has better short, intermediate and long-term effects than either non-tailored treatment or treatment-as-usual (TAU on pain and function. We sub-sequentially hypothesize that tailored and non-tailored treatment both have better effect than TAU. Methods/Design 120 working women with minimum six weeks of nonspecific neck-shoulder pain aged 20–65, are allocated by minimisation with the factors age, duration of pain, pain intensity and disability in to the groups tailored treatment (T, non-tailored treatment (NT or treatment-as-usual (TAU. Treatment is given to the groups T and NT for 11 weeks (27 sessions evenly distributed. An extensive presentation of the tests and treatment decision model is provided. The main treatment components are manual therapy, cranio-cervical flexion exercise and strength training, EMG-biofeedback training, treatment for cervicogenic headache, neck motor control training. A decision algorithm based on the baseline assessment determines the treatment components given to each participant of T- and NT-groups. Primary outcome measures are physical functioning (Neck Disability Index and average pain intensity last week (Numeric Rating Scale. Secondary outcomes are general improvement (Patient Global Impression of Change scale, symptoms (Profile Fitness Mapping neck questionnaire, capacity to work in the last 6 weeks (quality and quantity and pressure pain threshold of m. trapezius. Primary and secondary outcomes will

  11. Effect of monopolar radiofrequency treatment over soft-tissue fillers in an animal model: part 2.

    Science.gov (United States)

    Shumaker, Peter R; England, Laura J; Dover, Jeffrey S; Ross, E Victor; Harford, Robert; Derienzo, Damian; Bogle, Melissa; Uebelhoer, Nathan; Jacoby, Mark; Pope, Karl

    2006-03-01

    Monopolar radiofrequency (RF) treatment is used by physicians to heat skin and promote tissue tightening and contouring. Cosmetic fillers are used to soften deep facial lines and wrinkles. Patients who have had dermal fillers implanted may also benefit from or are candidates for monopolar RF skin tightening. This study examined the effect of RF treatment on various dermal filler substances. This is the second part of a two-part study. A juvenile farm pig was injected with dermal fillers including cross-linked human collagen (Cosmoplast), polylactic acid (PLA) (Sculptra), liquid injectable silicone (Silikon 1000), calcium hydroxylapatite (CaHA) (Radiesse), and hyaluronic acid (Restylane). Skin injected with dermal fillers was RF-treated using a 1.5-cm2 treatment tip and treatment levels typically used in the clinical setting. Fillers were examined histologically 5 days, 2 weeks, or 1 month after treatment. Histological specimens were scored for inflammatory response, foreign body response, and fibrosis in order to assess the effect of treatment on early filler processes, such as inflammation and encapsulation. Each filler substance produced a characteristic inflammatory response. No immediate thermal effect of RF treatment was observed histologically. RF treatment resulted in statistically significant increases in the inflammatory, foreign body, and fibrotic responses associated with the filler substances. Monopolar RF treatment levels that are typically used in the clinical setting were employed in this animal study. RF treatment resulted in measurable and statistically significant histological changes associated with the various filler materials. Additional clinical and histological studies are required to determine the optimal timing of monopolar RF treatment and filler placement for maximal potential aesthetic outcome. 2006 Wiley-Liss, Inc.

  12. A Distributive Model of Treatment Acceptability

    Science.gov (United States)

    Carter, Stacy L.

    2008-01-01

    A model of treatment acceptability is proposed that distributes overall treatment acceptability into three separate categories of influence. The categories are comprised of societal influences, consultant influences, and influences associated with consumers of treatments. Each of these categories are defined and their inter-relationships within…

  13. Intensive treatment models and coercion

    DEFF Research Database (Denmark)

    Ohlenschlaeger, Johan; Thorup, Anne; Petersen, Lone

    2007-01-01

    and on client satisfaction. Integrated Treatment had fewer bed-days, more patients living in non-supervised accommodation, and better score on quality of life. No differences were found as to the use of coercion. This study adds to the evidence that intensified treatment models are superior to standard...

  14. Cost-Effectiveness of Competing Treatment Strategies for Clostridium difficile Infection: A Systematic Review.

    Science.gov (United States)

    Le, Phuc; Nghiem, Van T; Mullen, Patricia Dolan; Deshpande, Abhishek

    2018-04-01

    BACKGROUND Clostridium difficile infection (CDI) presents a substantial economic burden and is associated with significant morbidity. While multiple treatment strategies have been evaluated, a cost-effective management strategy remains unclear. OBJECTIVE We conducted a systematic review to assess cost-effectiveness analyses of CDI treatment and to summarize key issues for clinicians and policy makers to consider. METHODS We searched PubMed and 5 other databases from inception to August 2016. These searches were not limited by study design or language of publication. Two reviewers independently screened the literature, abstracted data, and assessed methodological quality using the Drummond and Jefferson checklist. We extracted data on study characteristics, type of CDI, treatment characteristics, and model structure and inputs. RESULTS We included 14 studies, and 13 of these were from high-income countries. More than 90% of these studies were deemed moderate-to-high or high quality. Overall, 6 studies used a decision-tree model and 7 studies used a Markov model. Cost of therapy, time horizon, treatment cure rates, and recurrence rates were common influential factors in the study results. For initial CDI, fidaxomicin was a more cost-effective therapy than metronidazole or vancomycin in 2 of 3 studies. For severe initial CDI, 2 of 3 studies found fidaxomicin to be the most cost-effective therapy. For recurrent CDI, fidaxomicin was cost-effective in 3 of 5 studies, while fecal microbiota transplantation (FMT) by colonoscopy was consistently cost-effective in 4 of 4 studies. CONCLUSIONS The cost-effectiveness of fidaxomicin compared with other pharmacologic therapies was not definitive for either initial or recurrent CDI. Despite its high cost, FMT by colonoscopy may be a cost-effective therapy for recurrent CDI. A consensus on model design and assumptions are necessary for future comparison of CDI treatment. Infect Control Hosp Epidemiol 2018;39:412-424.

  15. A Danish cost-effectiveness model of escitalopram in comparison with citalopram and venlafaxine as first-line treatments for major depressive disorder in primary care

    DEFF Research Database (Denmark)

    Sørensen, Jan; Stage, Kurt B; Damsbo, Niels

    2007-01-01

    The objective of this study was to model the cost-effectiveness of escitalopram in comparison with generic citalopram and venlafaxine in primary care treatment of major depressive disorder (baseline scores 22-40 on the Montgomery-Asberg Depression Rating Scale, MADRS) in Denmark. A three-path dec...... clinical benefit and cost-savings, and similar in cost-effectiveness to venlafaxine.......The objective of this study was to model the cost-effectiveness of escitalopram in comparison with generic citalopram and venlafaxine in primary care treatment of major depressive disorder (baseline scores 22-40 on the Montgomery-Asberg Depression Rating Scale, MADRS) in Denmark. A three......, ad-hoc survey and expert opinion. Main outcome measures were remission defined as MADRS costs. Analyses were conducted from healthcare system and societal perspectives. The human capital approach was used to estimate societal cost of lost productivity. Costs were reported...

  16. Pavement Pre- and Post-Treatment Performance Models Using LTPP Data

    OpenAIRE

    Lu, Pan; Tolliver, Denver

    2012-01-01

    This paper determines that pavement performance in International Roughness Index (IRI) is affected by exogenous interventions such as pavement age, precipitation level, freeze-thaw level, and lower level preservation maintenance strategies. An exponential function of pavement age was used to represent pavement IRI performance curves. Moreover, this paper demonstrates a method which calculates short-term post-pavement performance models from maintenance effect models and pre-treatment performa...

  17. Obesity and Surgical Treatment – A Cost-Effectiveness Assessment for Sweden

    Directory of Open Access Journals (Sweden)

    Sixten Borg

    2014-07-01

    Full Text Available Background:The rising trend in the prevalence of obesity has during the past decades become a major public health concern in many countries, as obesity may lead to comorbidities and death. A frequent used marker for obesity is the Body Mass Index (BMI. The cost of treatment for obesity related diseases has become a heavy burden on national health care budget in many countries. While diet and exercise are the cornerstones of weight management, pharmaco­therapy is often needed to achieve and maintain desired weight loss.  In some cases of extreme obesity, bariatric surgery may be recommended. It is expected to increase by 50% in Sweden.Objective: The overall objective was to develop a cost-effectiveness model using the best available evidence to assess the cost-effectiveness of gastric bypass (GBP surgical treatments for obesity in adult patients, in comparison with conventional treatment (CT, in Sweden from a healthcare perspective. With the model we also seeked to identify the lower cut-off point using BMI criteria, for the surgical intervention to be cost-effective. Methods:A micro-simulation model with an underlying Markov methodology was developed, that simulates individual patients. It simulates the outcomes of the patients in terms of treatment costs, life years, and quality adjusted life years (QALY over his/her remaining lifetime. The costs are presented in SEK in the year 2006 price level (1 SEK ≈ 0.11 EUR ≈ 0.14 USD.Results: We estimated that the incremental cost per QALY gained will not exceed SEK 33,000 per QALY in patients with BMI < 35. In patients with BMI > 35 kg/m2, gastric bypass surgery has lower costs compared to conventional treatment. Conclusion: Gastric bypass surgery is a cost-effective intervention compared to conventional treatment consisting of watchful waiting, diet and exercise.

  18. Modeling cost-effectiveness and health gains of a "universal" versus "prioritized" hepatitis C virus treatment policy in a real-life cohort.

    Science.gov (United States)

    Kondili, Loreta A; Romano, Federica; Rolli, Francesca Romana; Ruggeri, Matteo; Rosato, Stefano; Brunetto, Maurizia Rossana; Zignego, Anna Linda; Ciancio, Alessia; Di Leo, Alfredo; Raimondo, Giovanni; Ferrari, Carlo; Taliani, Gloria; Borgia, Guglielmo; Santantonio, Teresa Antonia; Blanc, Pierluigi; Gaeta, Giovanni Battista; Gasbarrini, Antonio; Chessa, Luchino; Erne, Elke Maria; Villa, Erica; Ieluzzi, Donatella; Russo, Francesco Paolo; Andreone, Pietro; Vinci, Maria; Coppola, Carmine; Chemello, Liliana; Madonia, Salvatore; Verucchi, Gabriella; Persico, Marcello; Zuin, Massimo; Puoti, Massimo; Alberti, Alfredo; Nardone, Gerardo; Massari, Marco; Montalto, Giuseppe; Foti, Giuseppe; Rumi, Maria Grazia; Quaranta, Maria Giovanna; Cicchetti, Americo; Craxì, Antonio; Vella, Stefano

    2017-12-01

    We evaluated the cost-effectiveness of two alternative direct-acting antiviral (DAA) treatment policies in a real-life cohort of hepatitis C virus-infected patients: policy 1, "universal," treat all patients, regardless of fibrosis stage; policy 2, treat only "prioritized" patients, delay treatment of the remaining patients until reaching stage F3. A liver disease progression Markov model, which used a lifetime horizon and health care system perspective, was applied to the PITER cohort (representative of Italian hepatitis C virus-infected patients in care). Specifically, 8,125 patients naive to DAA treatment, without clinical, sociodemographic, or insurance restrictions, were used to evaluate the policies' cost-effectiveness. The patients' age and fibrosis stage, assumed DAA treatment cost of €15,000/patient, and the Italian liver disease costs were used to evaluate quality-adjusted life-years (QALY) and incremental cost-effectiveness ratios (ICER) of policy 1 versus policy 2. To generalize the results, a European scenario analysis was performed, resampling the study population, using the mean European country-specific health states costs and mean treatment cost of €30,000. For the Italian base-case analysis, the cost-effective ICER obtained using policy 1 was €8,775/QALY. ICERs remained cost-effective in 94%-97% of the 10,000 probabilistic simulations. For the European treatment scenario the ICER obtained using policy 1 was €19,541.75/QALY. ICER was sensitive to variations in DAA costs, in the utility value of patients in fibrosis stages F0-F3 post-sustained virological response, and in the transition probabilities from F0 to F3. The ICERs decrease with decreasing DAA prices, becoming cost-saving for the base price (€15,000) discounts of at least 75% applied in patients with F0-F2 fibrosis. Extending hepatitis C virus treatment to patients in any fibrosis stage improves health outcomes and is cost-effective; cost-effectiveness significantly increases

  19. Selecting Effective Treatments: A Comprehensive, Systematic Guide to Treating Mental Disorders. Revised Edition.

    Science.gov (United States)

    Seligman, Linda

    This book presents an overview of the major types of mental disorders, accompanied by treatment models that are structured, comprehensive, grounded in research, and likely to be effective. Chapter topics are: (1) "Introduction to Effective Treatment Planning"; (2) "Mental Disorders in Infants, Children, and Adolescents"; (3) "Situationally…

  20. Modeling fuels and fire effects in 3D: Model description and applications

    Science.gov (United States)

    Francois Pimont; Russell Parsons; Eric Rigolot; Francois de Coligny; Jean-Luc Dupuy; Philippe Dreyfus; Rodman R. Linn

    2016-01-01

    Scientists and managers critically need ways to assess how fuel treatments alter fire behavior, yet few tools currently exist for this purpose.We present a spatially-explicit-fuel-modeling system, FuelManager, which models fuels, vegetation growth, fire behavior (using a physics-based model, FIRETEC), and fire effects. FuelManager's flexible approach facilitates...

  1. Analysis of a Heroin Epidemic Model with Saturated Treatment Function

    Directory of Open Access Journals (Sweden)

    Isaac Mwangi Wangari

    2017-01-01

    Full Text Available A mathematical model is developed that examines how heroin addiction spreads in society. The model is formulated to take into account the treatment of heroin users by incorporating a realistic functional form that “saturates” representing the limited availability of treatment. Bifurcation analysis reveals that the model has an intrinsic backward bifurcation whenever the saturation parameter is larger than a fixed threshold. We are particularly interested in studying the model’s global stability. In the absence of backward bifurcations, Lyapunov functions can often be found and used to prove global stability. However, in the presence of backward bifurcations, such Lyapunov functions may not exist or may be difficult to construct. We make use of the geometric approach to global stability to derive a condition that ensures that the system is globally asymptotically stable. Numerical simulations are also presented to give a more complete representation of the model dynamics. Sensitivity analysis performed by Latin hypercube sampling (LHS suggests that the effective contact rate in the population, the relapse rate of heroin users undergoing treatment, and the extent of saturation of heroin users are mechanisms fuelling heroin epidemic proliferation.

  2. The effectiveness of the Minnesota Model approach in the treatment of adolescent drug abusers.

    Science.gov (United States)

    Winters, K C; Stinchfield, R D; Opland, E; Weller, C; Latimer, W W

    2000-04-01

    The treatment outcome of drug-abusing adolescents treated with a 12-Step approach. The study compares drug use outcome data at 6 and 12 months post-treatment among three groups of adolescents: those who completed treatment, those who did not and those on a waiting list. Also, among treatment completers, residential and outpatient samples were compared on outcome. The treatment site is located in the Minneapolis/St Paul area of Minnesota. Two hundred and forty-five drug clinic-referred adolescents (12-18 years old), all of whom met at least one DSM-III-R substance dependence disorder. One hundred and seventy-nine subjects received either complete or incomplete 12-Step, Minnesota Model treatment and 66 were waiting list subjects. In addition to demographics and clinical background variables, measures included treatment involvement, treatment setting and drug use frequency at intake and follow-up. Absolute and relative outcome analyses indicated that completing treatment was associated with far superior outcome compared to those who did not complete treatment or receive any at all. The percentage of treatment completers who reported either abstinence or a minor lapse for the 12 months following treatment was 53%, compared to 15 and 28% for the incompleter and waiting list groups, respectively. Favorable treatment outcome for drug abuse was about two to three times more likely if treatment was completed. Also, there were no outcome differences between residential and outpatient groups. Alcohol was the most common drug used during the follow-up period, despite cannabis being the preferred drug at intake.

  3. Model-based optimization of G-CSF treatment during cytotoxic chemotherapy.

    Science.gov (United States)

    Schirm, Sibylle; Engel, Christoph; Loibl, Sibylle; Loeffler, Markus; Scholz, Markus

    2018-02-01

    Although G-CSF is widely used to prevent or ameliorate leukopenia during cytotoxic chemotherapies, its optimal use is still under debate and depends on many therapy parameters such as dosing and timing of cytotoxic drugs and G-CSF, G-CSF pharmaceuticals used and individual risk factors of patients. We integrate available biological knowledge and clinical data regarding cell kinetics of bone marrow granulopoiesis, the cytotoxic effects of chemotherapy and pharmacokinetics and pharmacodynamics of G-CSF applications (filgrastim or pegfilgrastim) into a comprehensive model. The model explains leukocyte time courses of more than 70 therapy scenarios comprising 10 different cytotoxic drugs. It is applied to develop optimized G-CSF schedules for a variety of clinical scenarios. Clinical trial results showed validity of model predictions regarding alternative G-CSF schedules. We propose modifications of G-CSF treatment for the chemotherapies 'BEACOPP escalated' (Hodgkin's disease), 'ETC' (breast cancer), and risk-adapted schedules for 'CHOP-14' (aggressive non-Hodgkin's lymphoma in elderly patients). We conclude that we established a model of human granulopoiesis under chemotherapy which allows predictions of yet untested G-CSF schedules, comparisons between them, and optimization of filgrastim and pegfilgrastim treatment. As a general rule of thumb, G-CSF treatment should not be started too early and patients could profit from filgrastim treatment continued until the end of the chemotherapy cycle.

  4. Modelling the Ozone-Based Treatments for Inactivation of Microorganisms

    Directory of Open Access Journals (Sweden)

    Agnieszka Joanna Brodowska

    2017-10-01

    Full Text Available The paper presents the development of a model for ozone treatment in a dynamic bed of different microorganisms (Bacillus subtilis, B. cereus, B. pumilus, Escherichia coli, Pseudomonas fluorescens, Aspergillus niger, Eupenicillium cinnamopurpureum on a heterogeneous matrix (juniper berries, cardamom seeds initially treated with numerous ozone doses during various contact times was studied. Taking into account various microorganism susceptibility to ozone, it was of great importance to develop a sufficiently effective ozone dose to preserve food products using different strains based on the microbial model. For this purpose, we have chosen the Weibull model to describe the survival curves of different microorganisms. Based on the results of microorganism survival modelling after ozone treatment and considering the least susceptible strains to ozone, we selected the critical ones. Among tested strains, those from genus Bacillus were recognized as the most critical strains. In particular, B. subtilis and B. pumilus possessed the highest resistance to ozone treatment because the time needed to achieve the lowest level of its survival was the longest (up to 17.04 min and 16.89 min for B. pumilus reduction on juniper berry and cardamom seed matrix, respectively. Ozone treatment allow inactivate microorganisms to achieving lower survival rates by ozone dose (20.0 g O3/m3 O2, with a flow rate of 0.4 L/min and contact time (up to 20 min. The results demonstrated that a linear correlation between parameters p and k in Weibull distribution, providing an opportunity to calculate a fitted equation of the process.

  5. Modelling the Ozone-Based Treatments for Inactivation of Microorganisms

    Science.gov (United States)

    Brodowska, Agnieszka Joanna; Nowak, Agnieszka; Kondratiuk-Janyska, Alina; Piątkowski, Marcin; Śmigielski, Krzysztof

    2017-01-01

    The paper presents the development of a model for ozone treatment in a dynamic bed of different microorganisms (Bacillus subtilis, B. cereus, B. pumilus, Escherichia coli, Pseudomonas fluorescens, Aspergillus niger, Eupenicillium cinnamopurpureum) on a heterogeneous matrix (juniper berries, cardamom seeds) initially treated with numerous ozone doses during various contact times was studied. Taking into account various microorganism susceptibility to ozone, it was of great importance to develop a sufficiently effective ozone dose to preserve food products using different strains based on the microbial model. For this purpose, we have chosen the Weibull model to describe the survival curves of different microorganisms. Based on the results of microorganism survival modelling after ozone treatment and considering the least susceptible strains to ozone, we selected the critical ones. Among tested strains, those from genus Bacillus were recognized as the most critical strains. In particular, B. subtilis and B. pumilus possessed the highest resistance to ozone treatment because the time needed to achieve the lowest level of its survival was the longest (up to 17.04 min and 16.89 min for B. pumilus reduction on juniper berry and cardamom seed matrix, respectively). Ozone treatment allow inactivate microorganisms to achieving lower survival rates by ozone dose (20.0 g O3/m3 O2, with a flow rate of 0.4 L/min) and contact time (up to 20 min). The results demonstrated that a linear correlation between parameters p and k in Weibull distribution, providing an opportunity to calculate a fitted equation of the process. PMID:28991199

  6. Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats

    OpenAIRE

    Polonio, Igor Bastos; Acencio, Milena Marques Pagliareli; Pazetti, Rogério; Almeida, Francine Maria de; Silva, Bárbara Soares da; Pereira, Karina Aparecida Bonifácio; Souza, Rogério

    2014-01-01

    We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and...

  7. A simple empirical model for the clarification-thickening process in wastewater treatment plants.

    Science.gov (United States)

    Zhang, Y K; Wang, H C; Qi, L; Liu, G H; He, Z J; Fan, H T

    2015-01-01

    In wastewater treatment plants (WWTPs), activated sludge is thickened in secondary settling tanks and recycled into the biological reactor to maintain enough biomass for wastewater treatment. Accurately estimating the activated sludge concentration in the lower portion of the secondary clarifiers is of great importance for evaluating and controlling the sludge recycled ratio, ensuring smooth and efficient operation of the WWTP. By dividing the overall activated sludge-thickening curve into a hindered zone and a compression zone, an empirical model describing activated sludge thickening in the compression zone was obtained by empirical regression. This empirical model was developed through experiments conducted using sludge from five WWTPs, and validated by the measured data from a sixth WWTP, which fit the model well (R² = 0.98, p settling was also developed. Finally, the effects of denitrification and addition of a polymer were also analysed because of their effect on sludge thickening, which can be useful for WWTP operation, e.g., improving wastewater treatment or the proper use of the polymer.

  8. Modeling Hydrogen Generation Rates in the Hanford Waste Treatment and Immobilization Plant

    Energy Technology Data Exchange (ETDEWEB)

    Camaioni, Donald M.; Bryan, Samuel A.; Hallen, Richard T.; Sherwood, David J.; Stock, Leon M.

    2004-03-29

    This presentation describes a project in which Hanford Site and Environmental Management Science Program investigators addressed issues concerning hydrogen generation rates in the Hanford waste treatment and immobilization plant. The hydrogen generation rates of radioactive wastes must be estimated to provide for safe operations. While an existing model satisfactorily predicts rates for quiescent wastes in Hanford underground storage tanks, pretreatment operations will alter the conditions and chemical composition of these wastes. Review of the treatment process flowsheet identified specific issues requiring study to ascertain whether the model would provide conservative values for waste streams in the plant. These include effects of adding hydroxide ion, alpha radiolysis, saturation with air (oxygen) from pulse-jet mixing, treatment with potassium permanganate, organic compounds from degraded ion exchange resins and addition of glass-former chemicals. The effects were systematically investigated through literature review, technical analyses and experimental work.

  9. A Biomathematical Model of Pneumococcal Lung Infection and Antibiotic Treatment in Mice.

    Science.gov (United States)

    Schirm, Sibylle; Ahnert, Peter; Wienhold, Sandra; Mueller-Redetzky, Holger; Nouailles-Kursar, Geraldine; Loeffler, Markus; Witzenrath, Martin; Scholz, Markus

    2016-01-01

    Pneumonia is considered to be one of the leading causes of death worldwide. The outcome depends on both, proper antibiotic treatment and the effectivity of the immune response of the host. However, due to the complexity of the immunologic cascade initiated during infection, the latter cannot be predicted easily. We construct a biomathematical model of the murine immune response during infection with pneumococcus aiming at predicting the outcome of antibiotic treatment. The model consists of a number of non-linear ordinary differential equations describing dynamics of pneumococcal population, the inflammatory cytokine IL-6, neutrophils and macrophages fighting the infection and destruction of alveolar tissue due to pneumococcus. Equations were derived by translating known biological mechanisms and assuming certain response kinetics. Antibiotic therapy is modelled by a transient depletion of bacteria. Unknown model parameters were determined by fitting the predictions of the model to data sets derived from mice experiments of pneumococcal lung infection with and without antibiotic treatment. Time series of pneumococcal population, debris, neutrophils, activated epithelial cells, macrophages, monocytes and IL-6 serum concentrations were available for this purpose. The antibiotics Ampicillin and Moxifloxacin were considered. Parameter fittings resulted in a good agreement of model and data for all experimental scenarios. Identifiability of parameters is also estimated. The model can be used to predict the performance of alternative schedules of antibiotic treatment. We conclude that we established a biomathematical model of pneumococcal lung infection in mice allowing predictions regarding the outcome of different schedules of antibiotic treatment. We aim at translating the model to the human situation in the near future.

  10. Estimating the effect of a rare time-dependent treatment on the recurrent event rate.

    Science.gov (United States)

    Smith, Abigail R; Zhu, Danting; Goodrich, Nathan P; Merion, Robert M; Schaubel, Douglas E

    2018-05-30

    In many observational studies, the objective is to estimate the effect of treatment or state-change on the recurrent event rate. If treatment is assigned after the start of follow-up, traditional methods (eg, adjustment for baseline-only covariates or fully conditional adjustment for time-dependent covariates) may give biased results. We propose a two-stage modeling approach using the method of sequential stratification to accurately estimate the effect of a time-dependent treatment on the recurrent event rate. At the first stage, we estimate the pretreatment recurrent event trajectory using a proportional rates model censored at the time of treatment. Prognostic scores are estimated from the linear predictor of this model and used to match treated patients to as yet untreated controls based on prognostic score at the time of treatment for the index patient. The final model is stratified on matched sets and compares the posttreatment recurrent event rate to the recurrent event rate of the matched controls. We demonstrate through simulation that bias due to dependent censoring is negligible, provided the treatment frequency is low, and we investigate a threshold at which correction for dependent censoring is needed. The method is applied to liver transplant (LT), where we estimate the effect of development of post-LT End Stage Renal Disease (ESRD) on rate of days hospitalized. Copyright © 2018 John Wiley & Sons, Ltd.

  11. Effects of naloxone distribution alone or in combination with addiction treatment with or without pre-exposure prophylaxis for HIV prevention in people who inject drugs: a cost-effectiveness modelling study.

    Science.gov (United States)

    Uyei, Jennifer; Fiellin, David A; Buchelli, Marianne; Rodriguez-Santana, Ramon; Braithwaite, R Scott

    2017-03-01

    In the USA, an epidemic of opioid overdose deaths is occurring, many of which are from heroin. Combining naloxone distribution with linkage to addiction treatment or pre-exposure prophylaxis (PrEP) for HIV prevention through syringe service programmes has the potential to save lives and be cost-effective. We estimated the outcomes and cost-effectiveness of five alternative strategies: no additional intervention, naloxone distribution, naloxone distribution plus linkage to addiction treatment, naloxone distribution plus PrEP, and naloxone distribution plus linkage to addiction treatment and PrEP. We developed a decision analytical Markov model to simulate opioid overdose, HIV incidence, overdose-related deaths, and HIV-related deaths in people who inject drugs in Connecticut, USA. Model input parameters were derived from published sources. We compared each strategy with no intervention, as well as simultaneously considering all strategies. Sensitivity analysis was done for all variables. Linkage to addiction treatment was referral to an opioid treatment programme for methadone. Endpoints were survival, life expectancy, quality-adjusted life-years (QALYs), number and percentage of overdose deaths averted, number of HIV-related deaths averted, total costs (in 2015 US$) associated with each strategy, and incremental cost per QALY gained. In the base-case analysis, compared with no additional intervention, the naloxone distribution strategy yielded an incremental cost-effectiveness ratio (ICER) of $323 per QALY, and naloxone distribution plus linkage to addiction treatment was cost saving compared with no additional intervention (greater effectiveness and less expensive). The most efficient strategies (ie, those conferring the greatest health benefit for a particular budget) were naloxone distribution combined with linkage to addiction treatment (cost saving), and naloxone distribution combined with PrEP and linkage to addiction treatment (ICER $95 337 per QALY) at a

  12. The effectiveness of stuttering treatments in Germany.

    Science.gov (United States)

    Euler, Harald A; Lange, Benjamin P; Schroeder, Sascha; Neumann, Katrin

    2014-03-01

    Persons who stutter (PWS) should be referred to the most effective treatments available, locally or regionally. A prospective comparison of the effects of the most common stuttering treatments in Germany is not available. Therefore, a retrospective evaluation by clients of stuttering treatments was carried out. The five most common German stuttering treatments (231 single treatment cases) were rated as to their perceived effectiveness, using a structured questionnaire, by 88 PWS recruited through various sources. The participants had received between 1 and 7 treatments for stuttering. Two stuttering treatments (stuttering modification, fluency shaping) showed favorable and three treatments (breathing therapy, hypnosis, unspecified logopedic treatment) showed unsatisfactory effectiveness ratings. The effectiveness ratings of stuttering modification and fluency shaping did not differ significantly. The three other treatments were equally ineffective. The differences between the effective and ineffective treatments were of large effect sizes. The typical therapy biography begins in childhood with an unspecified logopedic treatment administered extensively in single and individual sessions. Available comparisons showed intensive or interval treatments to be superior to extensive treatments, and group treatments to be superior to single client treatments. The stuttering treatment most often prescribed in Germany, namely a weekly session of individual treatment by a speech-language pathologist, usually with an assorted package of mostly unknown components, is of limited effectiveness. Better effectiveness can be expected from fluency shaping or stuttering modification approaches, preferably with an intensive time schedule and with group sessions. Readers will be able to: (a) discuss the five most prevalent stuttering treatments in Germany; (b) summarize the effectiveness of these treatments; and (c) describe structural treatment components that seem to be preferable

  13. Costs and effectiveness of fingolimod versus alemtuzumab in the treatment of highly active relapsing-remitting multiple sclerosis in the UK: re-treatment, discount, and disutility.

    Science.gov (United States)

    Montgomery, Stephen M; Kusel, Jeanette; Nicholas, Richard; Adlard, Nicholas

    2017-09-01

    Patients with relapsing-remitting multiple sclerosis (RRMS) treated with disease modifying therapies (DMTs) who continue to experience disease activity may be considered for escalation therapies such as fingolimod, or may be considered for alemtuzumab. Previous economic modeling used Markov models; applying one alternative technique, discrete event simulation (DES) modeling, allows re-treatment and long-term adverse events (AEs) to be included in the analysis. A DES was adapted to model relapse-triggered re-treatment with alemtuzumab and the effect of including ongoing quality-adjusted life year (QALY) decrements for AEs that extend beyond previous 1-year Markov cycles. As the price to the NHS of fingolimod in the UK is unknown, due to a confidential patient access scheme (PAS), a variety of possible discounts were tested. The interaction of re-treatment assumptions for alemtuzumab with the possible discounts for fingolimod was tested to determine which DMT resulted in lower lifetime costs. The lifetime QALY results were derived from modeled treatment effect and short- and long-term AEs. Most permutations of fingolimod PAS discount and alemtuzumab re-treatment rate resulted in fingolimod being less costly than alemtuzumab. As the percentage of patients who are re-treated with alemtuzumab due to experiencing a relapse approaches 100% of those who relapse whilst on treatment, the discount required for fingolimod to be less costly drops below 5%. Consideration of treatment effect alone found alemtuzumab generated 0.2 more QALYs/patient; the inclusion of AEs up to a duration of 1 year reduced this advantage to only 0.14 QALYs/patient. Modeling AEs with a lifetime QALY decrement found that both DMTs generated very similar QALYs with the difference only 0.04 QALYs/patient. When the model captured alemtuzumab re-treatment and long-term AE decrements, it was found that fingolimod is cost-effective compared to alemtuzumab, assuming application of only a modest level of

  14. HIV Treatment and Prevention: A Simple Model to Determine Optimal Investment.

    Science.gov (United States)

    Juusola, Jessie L; Brandeau, Margaret L

    2016-04-01

    To create a simple model to help public health decision makers determine how to best invest limited resources in HIV treatment scale-up and prevention. A linear model was developed for determining the optimal mix of investment in HIV treatment and prevention, given a fixed budget. The model incorporates estimates of secondary health benefits accruing from HIV treatment and prevention and allows for diseconomies of scale in program costs and subadditive benefits from concurrent program implementation. Data sources were published literature. The target population was individuals infected with HIV or at risk of acquiring it. Illustrative examples of interventions include preexposure prophylaxis (PrEP), community-based education (CBE), and antiretroviral therapy (ART) for men who have sex with men (MSM) in the US. Outcome measures were incremental cost, quality-adjusted life-years gained, and HIV infections averted. Base case analysis indicated that it is optimal to invest in ART before PrEP and to invest in CBE before scaling up ART. Diseconomies of scale reduced the optimal investment level. Subadditivity of benefits did not affect the optimal allocation for relatively low implementation levels. The sensitivity analysis indicated that investment in ART before PrEP was optimal in all scenarios tested. Investment in ART before CBE became optimal when CBE reduced risky behavior by 4% or less. Limitations of the study are that dynamic effects are approximated with a static model. Our model provides a simple yet accurate means of determining optimal investment in HIV prevention and treatment. For MSM in the US, HIV control funds should be prioritized on inexpensive, effective programs like CBE, then on ART scale-up, with only minimal investment in PrEP. © The Author(s) 2015.

  15. Parameter trajectory analysis to identify treatment effects of pharmacological interventions.

    Directory of Open Access Journals (Sweden)

    Christian A Tiemann

    Full Text Available The field of medical systems biology aims to advance understanding of molecular mechanisms that drive disease progression and to translate this knowledge into therapies to effectively treat diseases. A challenging task is the investigation of long-term effects of a (pharmacological treatment, to establish its applicability and to identify potential side effects. We present a new modeling approach, called Analysis of Dynamic Adaptations in Parameter Trajectories (ADAPT, to analyze the long-term effects of a pharmacological intervention. A concept of time-dependent evolution of model parameters is introduced to study the dynamics of molecular adaptations. The progression of these adaptations is predicted by identifying necessary dynamic changes in the model parameters to describe the transition between experimental data obtained during different stages of the treatment. The trajectories provide insight in the affected underlying biological systems and identify the molecular events that should be studied in more detail to unravel the mechanistic basis of treatment outcome. Modulating effects caused by interactions with the proteome and transcriptome levels, which are often less well understood, can be captured by the time-dependent descriptions of the parameters. ADAPT was employed to identify metabolic adaptations induced upon pharmacological activation of the liver X receptor (LXR, a potential drug target to treat or prevent atherosclerosis. The trajectories were investigated to study the cascade of adaptations. This provided a counter-intuitive insight concerning the function of scavenger receptor class B1 (SR-B1, a receptor that facilitates the hepatic uptake of cholesterol. Although activation of LXR promotes cholesterol efflux and -excretion, our computational analysis showed that the hepatic capacity to clear cholesterol was reduced upon prolonged treatment. This prediction was confirmed experimentally by immunoblotting measurements of SR-B1

  16. A model of nonparticipation in alcohol treatment programs.

    Science.gov (United States)

    Burton, T L; Williamson, D L

    1997-01-01

    Why do the vast majority of those who suffer harm from drinking fail to obtain treatment? Based on a review of research literature and educational and treatment program materials, a model of nonparticipation in treatment is proposed whereby particular population groups are separated out according to whether or not they exhibit specified characteristics related to both harm from drinking and attitudes towards treatment. Eleven groups have been identified in the model, each of which has different reasons for failing to seek and/or obtain treatment. It is suggested that differing educational program messages should be sent to each group. While the model does not purport to be wholly inclusive of all nonparticipation, it offers a basis for addressing the variety of disparate groups that suffer harm from drinking but do not obtain treatment.

  17. Optimal treatment interruptions control of TB transmission model

    Science.gov (United States)

    Nainggolan, Jonner; Suparwati, Titik; Kawuwung, Westy B.

    2018-03-01

    A tuberculosis model which incorporates treatment interruptions of infectives is established. Optimal control of individuals infected with active TB is given in the model. It is obtained that the control reproduction numbers is smaller than the reproduction number, this means treatment controls could optimize the decrease in the spread of active TB. For this model, controls on treatment of infection individuals to reduce the actively infected individual populations, by application the Pontryagins Maximum Principle for optimal control. The result further emphasized the importance of controlling disease relapse in reducing the number of actively infected and treatment interruptions individuals with tuberculosis.

  18. Preclinical validation of electrochemotherapy as an effective treatment for brain tumors

    DEFF Research Database (Denmark)

    Agerholm-Larsen, Birgit; Iversen, Helle K; Ibsen, Per

    2011-01-01

    treatment. Bleomycin was injected intracranially into male rats inoculated with rat glia-derived tumor cells 2 weeks before the application of the electrical field (32 pulses, 100 V, 0.1 ms, and 1 Hz). In this model, where presence of tumor was confirmed by magnetic resonance imaging (MRI) before treatment...... to the treated area, which MRI and histology showed to contain a fluid-filled cavity. In a long-range survival study, treatment side effects seemed to be minimal, with normal rat behavior observed after electrochemotherapy. Our findings suggest that electrochemotherapy may offer a safe and effective new tool...

  19. Effects of Modeling and Desensitation in Reducing Dentist Phobia

    Science.gov (United States)

    Shaw, David W.; Thoresen, Carl E.

    1974-01-01

    Many persons avoid dentists and dental work. The present study explored the effects of systematic desensitization and social-modeling treatments with placebo and assessment control groups. Modeling was more effective than desensitization as shown by the number of subjects who went to a dentist. (Author)

  20. Heroin epidemics, treatment and ODE modelling.

    Science.gov (United States)

    White, Emma; Comiskey, Catherine

    2007-07-01

    The UN [United Nations Office on Drugs and Crime (UNODC): World Drug Report, 2005, vol. 1: Analysis. UNODC, 2005.], EU [European Monitoring Centre for Drugs and Drug Addiction (EMCDDA): Annual Report, 2005.http://annualreport.emcdda.eu.int/en/home-en.html.] and WHO [World Health Organisation (WHO): Biregional Strategy for Harm Reduction, 2005-2009. HIV and Injecting Drug Use. WHO, 2005.] have consistently highlighted in recent years the ongoing and persistent nature of opiate and particularly heroin use on a global scale. While this is a global phenomenon, authors have emphasised the significant impact such an epidemic has on individual lives and on society. National prevalence studies have indicated the scale of the problem, but the drug-using career, typically consisting of initiation, habitual use, a treatment-relapse cycle and eventual recovery, is not well understood. This paper presents one of the first ODE models of opiate addiction, based on the principles of mathematical epidemiology. The aim of this model is to identify parameters of interest for further study, with a view to informing and assisting policy-makers in targeting prevention and treatment resources for maximum effectiveness. An epidemic threshold value, R(0), is proposed for the drug-using career. Sensitivity analysis is performed on R(0) and it is then used to examine the stability of the system. A condition under which a backward bifurcation may exist is found, as are conditions that permit the existence of one or more endemic equilibria. A key result arising from this model is that prevention is indeed better than cure.

  1. Differential effects of repeated low dose treatment with the cannabinoid agonist WIN 55,212-2 in experimental models of bone cancer pain and neuropathic pain

    DEFF Research Database (Denmark)

    Hald, Andreas; Ding, Ming; Egerod, Kristoffer Lihme

    2008-01-01

    Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment with can......Pain due to bone malignancies is one of the most difficult types of cancer pain to fully control and may further decrease the patients' quality of life. Animal models of chronic pain conditions resulting from peripheral inflammatory reactions or nerve injuries are responsive to treatment...... with cannabinoid agonists. However, the use of cannabinoid agonists in humans may be hampered by CNS related side effects and development of tolerance. In the present study, we investigated the effect of repeated low dose administration of the synthetic cannabinoid agonist WIN 55,212-2 on bone cancer pain...... and neuropathic pain in mice. In addition, we investigated the development of CNS related side effects and tolerance. We found that 0.5 mg/kg/day for 18 days reduced pain related behavior and expression of spinal glial fibrillary acidic protein in the bone cancer pain model but not in the neuropathic pain model...

  2. Effectiveness of an intensive multidisciplinary headache treatment program.

    Science.gov (United States)

    Gunreben-Stempfle, Birgit; Griessinger, Norbert; Lang, Eberhard; Muehlhans, Barbara; Sittl, Reinhard; Ulrich, Kathrin

    2009-07-01

    To investigate if the effectiveness of a 96-hour multidisciplinary headache treatment program exceeds the effectiveness of a 20-hour program and primary care. When dealing with chronic back pain, low-intensity multidisciplinary treatment yields no significantly better results than standard care and monodisciplinary therapy; however, high-intensity treatment does. For multidisciplinary headache treatment, such comparisons are not yet available. In a previous study undertaken by our Pain Center, the outcome of a minimal multidisciplinary intervention model (20-hour) did not exceed primary care. Forty-two patients suffering from frequent headaches (20 +/- 9 headache days/month; range: 8-30) were treated and evaluated in a 96-hour group program. The results were compared with the outcomes of the previous study. Subjects who had undergone either the 20-hour multidisciplinary program or the primary care were used as historical control groups. A significant reduction in migraine days (P tension-type headache days (P tension-type headache days (P = .016), and frequency of migraine attacks (P = .016). In comparison with the 20-hour multidisciplinary program, the 96-hour program showed significantly better effects only in the reduction of migraine days (P = .037) and depression score (P = .003). The responder-rates (> or =50% improvement) in the 96-hour program were significantly higher than in the 20-hour program (migraine days, P = .008; tension-type headache days, P = .044) and primary care (migraine days, P = .007; tension-type headache days, P = .003; tension-type headache intensity, P = .037). The effect sizes were small to medium in the 96-hour program. Particularly with the reduction of migraine symptomatology, the 96-hour program performed better than the 20-hour program, which produced only negligible or small effects. Intensive multidisciplinary headache treatment is highly effective for patients with chronic headaches. Furthermore, migraine symptomatology

  3. Emerging from Depression: Treatment of Adolescent Depression Using the Major Treatment Models of Adult Depression.

    Science.gov (United States)

    Long, Kathleen M.

    Noting that adolescents who commit suicide are often clinically depressed, this paper examines various approaches in the treatment of depression. Major treatment models of adult depression, which can be directly applied to the treatment of the depressed adolescent, are described. Major treatment models and selected research studies are reviewed in…

  4. Cost-effectiveness analysis of treatments for premenstrual dysphoric disorder.

    Science.gov (United States)

    Rendas-Baum, Regina; Yang, Min; Gricar, Joseph; Wallenstein, Gene V

    2010-01-01

    Premenstrual syndrome (PMS) is reported to affect between 13% and 31% of women. Between 3% and 8% of women are reported to meet criteria for the more severe form of PMS, premenstrual dysphoric disorder (PMDD). Although PMDD has received increased attention in recent years, the cost effectiveness of treatments for PMDD remains unknown. To evaluate the cost effectiveness of the four medications with a US FDA-approved indication for PMDD: fluoxetine, sertraline, paroxetine and drospirenone plus ethinyl estradiol (DRSP/EE). A decision-analytic model was used to evaluate both direct costs (medication and physician visits) and clinical outcomes (treatment success, failure and discontinuation). Medication costs were based on average wholesale prices of branded products; physician visit costs were obtained from a claims database study of PMDD patients and the Agency for Healthcare Research and Quality. Clinical outcome probabilities were derived from published clinical trials in PMDD. The incremental cost-effectiveness ratio (ICER) was calculated using the difference in costs and percentage of successfully treated patients at 6 months. Deterministic and probabilistic sensitivity analyses were used to assess the impact of uncertainty in parameter estimates. Threshold values where a change in the cost-effective strategy occurred were identified using a net benefit framework. Starting therapy with DRSP/EE dominated both sertraline and paroxetine, but not fluoxetine. The estimated ICER of initiating treatment with fluoxetine relative to DRSP/EE was $US4385 per treatment success (year 2007 values). Cost-effectiveness acceptability curves revealed that for ceiling ratios>or=$US3450 per treatment success, fluoxetine had the highest probability (>or=0.37) of being the most cost-effective treatment, relative to the other options. The cost-effectiveness acceptability frontier further indicated that DRSP/EE remained the option with the highest expected net monetary benefit for

  5. Identifying treatment effect heterogeneity in clinical trials using subpopulations of events: STEPP.

    Science.gov (United States)

    Lazar, Ann A; Bonetti, Marco; Cole, Bernard F; Yip, Wai-Ki; Gelber, Richard D

    2016-04-01

    the subpopulation treatment effect pattern plot analysis. We introduce methodology designed to improve stability of the subpopulation treatment effect pattern plot analysis and generalize O-E methodology to the competing risks setting. Simulation studies were designed to assess the type I error rate of the tests for a variety of treatment effect measures, including subdistribution hazard ratio based on O-E estimation. This subpopulation treatment effect pattern plot methodology and standard regression modeling were used to evaluate heterogeneity of Ki-67 in the Breast International Group 1-98 randomized clinical trial. We introduce methodology that generalizes O-E methodology to the competing risks setting and that improves stability of the STEPP analysis by pre-specifying the number of events across subpopulations while controlling the type I error rate. The subpopulation treatment effect pattern plot analysis of the Breast International Group 1-98 randomized clinical trial showed that patients with high Ki-67 percentages may benefit most from letrozole, while heterogeneity was not detected using standard regression modeling. The STEPP methodology can be used to study complex patterns of treatment effect heterogeneity, as illustrated in the Breast International Group 1-98 randomized clinical trial. For the subpopulation treatment effect pattern plot analysis, we recommend a minimum of 20 events within each subpopulation. © The Author(s) 2015.

  6. Processing Technology Selection for Municipal Sewage Treatment Based on a Multi-Objective Decision Model under Uncertainty.

    Science.gov (United States)

    Chen, Xudong; Xu, Zhongwen; Yao, Liming; Ma, Ning

    2018-03-05

    This study considers the two factors of environmental protection and economic benefits to address municipal sewage treatment. Based on considerations regarding the sewage treatment plant construction site, processing technology, capital investment, operation costs, water pollutant emissions, water quality and other indicators, we establish a general multi-objective decision model for optimizing municipal sewage treatment plant construction. Using the construction of a sewage treatment plant in a suburb of Chengdu as an example, this paper tests the general model of multi-objective decision-making for the sewage treatment plant construction by implementing a genetic algorithm. The results show the applicability and effectiveness of the multi-objective decision model for the sewage treatment plant. This paper provides decision and technical support for the optimization of municipal sewage treatment.

  7. Mathematical modeling identifies optimum lapatinib dosing schedules for the treatment of glioblastoma patients.

    Directory of Open Access Journals (Sweden)

    Shayna Stein

    2018-01-01

    Full Text Available Human primary glioblastomas (GBM often harbor mutations within the epidermal growth factor receptor (EGFR. Treatment of EGFR-mutant GBM cell lines with the EGFR/HER2 tyrosine kinase inhibitor lapatinib can effectively induce cell death in these models. However, EGFR inhibitors have shown little efficacy in the clinic, partly because of inappropriate dosing. Here, we developed a computational approach to model the in vitro cellular dynamics of the EGFR-mutant cell line SF268 in response to different lapatinib concentrations and dosing schedules. We then used this approach to identify an effective treatment strategy within the clinical toxicity limits of lapatinib, and developed a partial differential equation modeling approach to study the in vivo GBM treatment response by taking into account the heterogeneous and diffusive nature of the disease. Despite the inability of lapatinib to induce tumor regressions with a continuous daily schedule, our modeling approach consistently predicts that continuous dosing remains the best clinically feasible strategy for slowing down tumor growth and lowering overall tumor burden, compared to pulsatile schedules currently known to be tolerated, even when considering drug resistance, reduced lapatinib tumor concentrations due to the blood brain barrier, and the phenotypic switch from proliferative to migratory cell phenotypes that occurs in hypoxic microenvironments. Our mathematical modeling and statistical analysis platform provides a rational method for comparing treatment schedules in search for optimal dosing strategies for glioblastoma and other cancer types.

  8. A Danish cost-effectiveness model of escitalopram in comparison with citalopram and venlafaxine as first-line treatments for major depressive disorder in primary care.

    Science.gov (United States)

    Sørensen, Jan; Stage, Kurt B; Damsbo, Niels; Le Lay, Agathe; Hemels, Michiel E

    2007-01-01

    The objective of this study was to model the cost-effectiveness of escitalopram in comparison with generic citalopram and venlafaxine in primary care treatment of major depressive disorder (baseline scores 22-40 on the Montgomery-Asberg Depression Rating Scale, MADRS) in Denmark. A three-path decision analytic model with a 6-month horizon was used. All patients started at the primary care path and were referred to outpatient or inpatient secondary care in the case of insufficient response to treatment. Model inputs included drug-specific probabilities derived from systematic literature review, ad-hoc survey and expert opinion. Main outcome measures were remission defined as MADRS escitalopram (64.1%) than citalopram (58.9%). From both perspectives, the total expected cost per successfully treated patient was lower for escitalopram (DKK 22,323 healthcare, DKK 72,399 societal) than for citalopram (DKK 25,778 healthcare, DKK 87,786 societal). Remission rates and costs were similar for escitalopram and venlafaxine. Robustness of the findings was verified in multivariate sensitivity analyses. For patients in primary care, escitalopram appears to be a cost-effective alternative to (generic) citalopram, with greater clinical benefit and cost-savings, and similar in cost-effectiveness to venlafaxine.

  9. Neural network models for biological waste-gas treatment systems.

    Science.gov (United States)

    Rene, Eldon R; Estefanía López, M; Veiga, María C; Kennes, Christian

    2011-12-15

    This paper outlines the procedure for developing artificial neural network (ANN) based models for three bioreactor configurations used for waste-gas treatment. The three bioreactor configurations chosen for this modelling work were: biofilter (BF), continuous stirred tank bioreactor (CSTB) and monolith bioreactor (MB). Using styrene as the model pollutant, this paper also serves as a general database of information pertaining to the bioreactor operation and important factors affecting gas-phase styrene removal in these biological systems. Biological waste-gas treatment systems are considered to be both advantageous and economically effective in treating a stream of polluted air containing low to moderate concentrations of the target contaminant, over a rather wide range of gas-flow rates. The bioreactors were inoculated with the fungus Sporothrix variecibatus, and their performances were evaluated at different empty bed residence times (EBRT), and at different inlet styrene concentrations (C(i)). The experimental data from these bioreactors were modelled to predict the bioreactors performance in terms of their removal efficiency (RE, %), by adequate training and testing of a three-layered back propagation neural network (input layer-hidden layer-output layer). Two models (BIOF1 and BIOF2) were developed for the BF with different combinations of easily measurable BF parameters as the inputs, that is concentration (gm(-3)), unit flow (h(-1)) and pressure drop (cm of H(2)O). The model developed for the CSTB used two inputs (concentration and unit flow), while the model for the MB had three inputs (concentration, G/L (gas/liquid) ratio, and pressure drop). Sensitivity analysis in the form of absolute average sensitivity (AAS) was performed for all the developed ANN models to ascertain the importance of the different input parameters, and to assess their direct effect on the bioreactors performance. The performance of the models was estimated by the regression

  10. Fluctuations induced extinction and stochastic resonance effect in a model of tumor growth with periodic treatment

    Energy Technology Data Exchange (ETDEWEB)

    Li Dongxi, E-mail: lidongxi@mail.nwpu.edu.c [Department of Applied Mathematics, Northwestern Polytechnical University, Xi' an 710072 (China); Xu Wei; Guo, Yongfeng; Xu Yong [Department of Applied Mathematics, Northwestern Polytechnical University, Xi' an 710072 (China)

    2011-01-31

    We investigate a stochastic model of tumor growth derived from the catalytic Michaelis-Menten reaction with positional and environmental fluctuations under subthreshold periodic treatment. Firstly, the influences of environmental fluctuations on the treatable stage are analyzed numerically. Applying the standard theory of stochastic resonance derived from the two-state approach, we derive the signal-to-noise ratio (SNR) analytically, which is used to measure the stochastic resonance phenomenon. It is found that the weak environmental fluctuations could induce the extinction of tumor cells in the subthreshold periodic treatment. The positional stability is better in favor of the treatment of the tumor cells. Besides, the appropriate and feasible treatment intensity and the treatment cycle should be highlighted considered in the treatment of tumor cells.

  11. Fluctuations induced extinction and stochastic resonance effect in a model of tumor growth with periodic treatment

    International Nuclear Information System (INIS)

    Li Dongxi; Xu Wei; Guo, Yongfeng; Xu Yong

    2011-01-01

    We investigate a stochastic model of tumor growth derived from the catalytic Michaelis-Menten reaction with positional and environmental fluctuations under subthreshold periodic treatment. Firstly, the influences of environmental fluctuations on the treatable stage are analyzed numerically. Applying the standard theory of stochastic resonance derived from the two-state approach, we derive the signal-to-noise ratio (SNR) analytically, which is used to measure the stochastic resonance phenomenon. It is found that the weak environmental fluctuations could induce the extinction of tumor cells in the subthreshold periodic treatment. The positional stability is better in favor of the treatment of the tumor cells. Besides, the appropriate and feasible treatment intensity and the treatment cycle should be highlighted considered in the treatment of tumor cells.

  12. Design and implementation of a combined observational and interventional study: Trends of prevalence, awareness, treatment and control hypertension and the effect of expanded chronic care model on control, treatment and self-care

    Directory of Open Access Journals (Sweden)

    Maryam Eghbali-Babadi

    2017-10-01

    Full Text Available BACKGROUND: Lack of information about hypertension leads to failure in detection, treatment and reduced estimation of this disease effects. So, a comprehensive study, named trends of prevalence, awareness, treatment and control hypertension among the adults in Isfahan, Iran (2001-2016 and evaluation of the effect of expanded chronic care model (ECCM on control, treatment and self-care, has been designed. This study explains the aspects of design and methods of its implementation. METHODS: This study was conducted in four stages in 2014-2016. In the 1st­ stage, valid questionnaires were made to assess knowledge, attitude and practice, and self-care. In the 2nd stage, the status of prevalence, awareness, treatment and control and hypertension risk factors was assessed. In the 3rd­ stage, a two-group clinical trial was conducted to evaluate the effectiveness of ECCM on hypertensive patients and their families. In the 4th­ stage, the results of hypertension prevalence and its risk factors in adults in 2016 were compared with two other studies undertaken in 2001 and 2007. RESULTS: To develop the questionnaire, face and content validity, internal and external reliability, and construct validity were examined. Prevalence, awareness, treatment and control of hypertension and risk factors among 2107 adult individuals were determined in Isfahan. In a clinical trial, 216 hypertensive patients were randomly assigned into intervention and control groups. Finally, a sample size of 8073 people was used to determine and compare the 15-year-old trend of hypertension and its affecting factors. CONCLUSION: It is obvious that the final findings of this study will play a key role in health and research policy and provide a suitable model for implementing appropriate interventional measures at the provincial and national levels. 

  13. Methodology for Designing Models Predicting Success of Infertility Treatment

    OpenAIRE

    Alireza Zarinara; Mohammad Mahdi Akhondi; Hojjat Zeraati; Koorsh Kamali; Kazem Mohammad

    2016-01-01

    Abstract Background: The prediction models for infertility treatment success have presented since 25 years ago. There are scientific principles for designing and applying the prediction models that is also used to predict the success rate of infertility treatment. The purpose of this study is to provide basic principles for designing the model to predic infertility treatment success. Materials and Methods: In this paper, the principles for developing predictive models are explained and...

  14. Effect of patient's life expectancy on the cost-effectiveness of treatment for ocular hypertension.

    Science.gov (United States)

    Kymes, Steven M; Plotzke, Michael R; Kass, Michael A; Boland, Michael V; Gordon, Mae O

    2010-05-01

    To assess the influence of expected life span on the cost-effectiveness of treating ocular hypertension to prevent primary open-angle glaucoma. We used a Markov simulation model to estimate the cost and benefit of ocular hypertension treatment over a person's remaining life. We examined the influence of age on the cost-effectiveness decision in 2 ways: (1) by evaluating specific age cohorts to assess the influence of age at the initiation of treatment; and (2) by evaluating the influence of a specific life span. At a willingness to pay $50,000/quality-adjusted life year to $100,000/quality-adjusted life year, treatment of people with a 2% or greater annual risk of developing glaucoma was cost-effective for people aged 45 years with a life expectancy of at least 18 remaining years. However, to be cost-effective, a person aged 55 years must have a life expectancy of 21 remaining years and someone aged 65 years must have a life expectancy of 23 remaining years. A person with ocular hypertension must have a life expectancy of at least 18 remaining years to justify treatment at a threshold of a 2% or greater annual risk of developing glaucoma. Persons at higher levels of risk require a life expectancy of 7 to 10 additional years to justify treatment.

  15. Preventing relapse after incentivized choice treatment: A laboratory model.

    Science.gov (United States)

    Bouton, Mark E; Thrailkill, Eric A; Bergeria, Cecilia L; Davis, Danielle R

    2017-08-01

    Two experiments with rats examined relapse of an operant behavior that occurred after the behavior was suppressed by reinforcing (incentivizing) an alternative behavior. In the first phase, a target response (R1) was reinforced. In a treatment phase, R1 was still reinforced, but a new response (R2) was introduced and associated with a larger reinforcer. As in human contingency management treatments, incentivizing R2 this way was effective at suppressing R1. However, when R2's reinforcement was discontinued, there was a robust and immediate relapse to R1. Experiment 1 found that the strength of R1 during relapse testing was not different from that seen in a no treatment control. Experiment 2 found that relapse could nevertheless be reduced by presenting reinforcers not contingent on responding during the test. Either the reinforcer for R1 or the reinforcer for R2 (which were qualitatively different types of food pellets) were effective. The experiments introduce a laboratory method for studying relapse and how to prevent it after contingency management treatments, and suggest at least one treatment that discourages relapse. The incentivized choice paradigm differs from other models of relapse of operant behavior (e.g., resurgence, renewal, reinstatement) in that it does not focus on the return of behaviors that are inhibited by extinction. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. HIV models for treatment interruption: Adaptation and comparison

    Science.gov (United States)

    Hillmann, Andreas; Crane, Martin; Ruskin, Heather J.

    2017-10-01

    In recent years, Antiretroviral Therapy (ART) has become commonplace for treating HIV infections, although a cure remains elusive, given reservoirs of replicating latently-infected cells, which are resistant to normal treatment regimes. Treatment interruptions, whether ad hoc or structured, are known to cause a rapid increase in viral production to detectable levels, but numerous clinical trials remain inconclusive on the dangers inherent in this resurgence. In consequence, interest in examining interruption strategies has recently been rekindled. This overview considers modelling approaches, which have been used to explore the issue of treatment interruption. We highlight their purpose and the formalisms employed and examine ways in which clinical data have been used. Implementation of selected models is demonstrated, illustrative examples provided and model performance compared for these cases. Possible extensions to bottom-up modelling techniques for treatment interruptions are briefly discussed.

  17. Adolescent Atomoxetine Treatment in a Rodent Model of ADHD: Effects on Cocaine Self-Administration and Dopamine Transporters in Frontostriatal Regions

    Science.gov (United States)

    Somkuwar, Sucharita S; Jordan, Chloe J; Kantak, Kathleen M; Dwoskin, Linda P

    2013-01-01

    Cocaine abuse and attention deficit/hyperactivity disorder (ADHD) are often comorbid. Preclinical research indicates that medial prefrontal (mPFC) and orbitofrontal (OFC) cortices are important neural substrates for both disorders. Using the spontaneously hypertensive rat (SHR) model of ADHD, we reported that adolescent treatment with the stimulant methylphenidate, a dopamine (DAT) and norepinephrine (NET) transporter inhibitor, enhanced cocaine self-administration during adulthood, and was associated with increased DAT function in mPFC. This study investigates the effects of atomoxetine ((R)-N-methyl-γ-(2-methylphenoxy)-benzenepropanamine hydrochloride) treatment, a selective NET inhibitor, during adolescence on cocaine self-administration and on DAT function and cell-surface expression in mPFC and OFC during adulthood. SHR acquired cocaine self-administration faster than Wistar–Kyoto and Wistar. Across cocaine doses, SHR earned more cocaine infusions and had higher progressive-ratio breakpoints than Wistar–Kyoto and Wistar, demonstrating that the SHR phenotype models comorbid ADHD and cocaine abuse. Prior atomoxetine treatment did not augment cocaine self-administration in SHR, but acquisition was enhanced in Wistar–Kyoto. No strain differences were found for DAT kinetic parameters or cellular localization in the vehicle controls. Atomoxetine did not alter DAT kinetic parameters or localization in SHR mPFC. Rather, atomoxetine decreased Vmax and DAT cell surface expression in SHR OFC, indicating that inhibition of NET by atomoxetine treatment during adolescence indirectly reduced DAT function and trafficking to the cell surface in OFC, specifically in the ADHD model. Thus, atomoxetine, unlike methylphenidate, does not enhance vulnerability to cocaine abuse in SHR and may represent an important alternative for teens with ADHD when drug addiction is a concern. PMID:23822950

  18. Processing Technology Selection for Municipal Sewage Treatment Based on a Multi-Objective Decision Model under Uncertainty

    Directory of Open Access Journals (Sweden)

    Xudong Chen

    2018-03-01

    Full Text Available This study considers the two factors of environmental protection and economic benefits to address municipal sewage treatment. Based on considerations regarding the sewage treatment plant construction site, processing technology, capital investment, operation costs, water pollutant emissions, water quality and other indicators, we establish a general multi-objective decision model for optimizing municipal sewage treatment plant construction. Using the construction of a sewage treatment plant in a suburb of Chengdu as an example, this paper tests the general model of multi-objective decision-making for the sewage treatment plant construction by implementing a genetic algorithm. The results show the applicability and effectiveness of the multi-objective decision model for the sewage treatment plant. This paper provides decision and technical support for the optimization of municipal sewage treatment.

  19. Benchmarking biological nutrient removal in wastewater treatment plants: influence of mathematical model assumptions

    DEFF Research Database (Denmark)

    Flores-Alsina, Xavier; Gernaey, Krist V.; Jeppsson, Ulf

    2012-01-01

    This paper examines the effect of different model assumptions when describing biological nutrient removal (BNR) by the activated sludge models (ASM) 1, 2d & 3. The performance of a nitrogen removal (WWTP1) and a combined nitrogen and phosphorus removal (WWTP2) benchmark wastewater treatment plant...

  20. [Effects in the adherence treatment and psychological adjustment after the disclosure of HIV/AIDS diagnosis with the "DIRE" clinical model in Colombian children under 17].

    Science.gov (United States)

    Trejos, Ana María; Reyes, Lizeth; Bahamon, Marly Johana; Alarcón, Yolima; Gaviria, Gladys

    2015-08-01

    A study in five Colombian cities in 2006, confirms the findings of other international studies: the majority of HIV-positive children not know their diagnosis, caregivers are reluctant to give this information because they believe that the news will cause emotional distress to the child becoming primary purpose of this study to validate a model of revelation. We implemented a clinical model, referred to as: "DIRE" that hypothetically had normalizing effects on psychological adjustment and adherence to antiretroviral treatment of HIV seropositive children, using a quasi-experimental design. Test were administered (questionnaire to assess patterns of disclosure and non-disclosure of the diagnosis of VIH/SIDA on children in health professionals and participants caregivers, Family Apgar, EuroQol EQ- 5D, MOS Social Support Survey Questionnaire Information treatment for VIH/SIDA and child Symptom Checklist CBCL/6-18 adapted to Latinos) before and after implementation of the model to 31 children (n: 31), 30 caregivers (n: 30) and 41 health professionals. Data processing was performed using the Statistical Package for the Social Science version 21 by applying parametric tests (Friedman) and nonparametric (t Student). No significant differences in adherence to treatment (p=0.392), in the psychological adjustment were found positive significant differences at follow-ups compared to baseline 2 weeks (p: 0.001), 3 months (p: 0.000) and 6 months (p: 0.000). The clinical model demonstrated effectiveness in normalizing of psychological adjustment and maintaining treatment compliance. The process also generated confidence in caregivers and health professionals in this difficult task.

  1. Iatrogenic Effects of Group Treatment on Adolescents with Conduct and Substance Use Problems: A Review of the Literature and a Presentation of a Model

    OpenAIRE

    Macgowan, Mark J.; Wagner, Eric F.

    2005-01-01

    Group therapy is the most popular approach in the treatment of adolescent substance use problems. Recently, concerns have mounted about possible iatrogenic effects of group therapy based on studies on adolescents with conduct disorder. This paper reviews three possible contributors to response to group treatment among adolescents, and proposes a model of the relations among these variables, specifically in regard to how they independently and interactively contribute to outcomes among youth w...

  2. Artificial neural network modelling of a large-scale wastewater treatment plant operation.

    Science.gov (United States)

    Güçlü, Dünyamin; Dursun, Sükrü

    2010-11-01

    Artificial Neural Networks (ANNs), a method of artificial intelligence method, provide effective predictive models for complex processes. Three independent ANN models trained with back-propagation algorithm were developed to predict effluent chemical oxygen demand (COD), suspended solids (SS) and aeration tank mixed liquor suspended solids (MLSS) concentrations of the Ankara central wastewater treatment plant. The appropriate architecture of ANN models was determined through several steps of training and testing of the models. ANN models yielded satisfactory predictions. Results of the root mean square error, mean absolute error and mean absolute percentage error were 3.23, 2.41 mg/L and 5.03% for COD; 1.59, 1.21 mg/L and 17.10% for SS; 52.51, 44.91 mg/L and 3.77% for MLSS, respectively, indicating that the developed model could be efficiently used. The results overall also confirm that ANN modelling approach may have a great implementation potential for simulation, precise performance prediction and process control of wastewater treatment plants.

  3. An Integrated, Multidimensional Treatment Model for Individuals Living with HIV, Mental Illness, and Substance Abuse

    Science.gov (United States)

    Bouis, Stephanie; Reif, Susan; Whetten, Kathryn; Scovil, Janet; Murray, Andrea; Swartz, Marvin

    2007-01-01

    The challenge of providing effective treatment services for the growing population of HIV-positive individuals who are also dually diagnosed with substance use and mental disorders has only recently been recognized as an important public health concern affecting both HIV treatment and prevention. This article describes a treatment model that was…

  4. Cost-effectiveness analysis of treatment alternatives for beef bulls with preputial prolapse.

    Science.gov (United States)

    Kasari, T R; McGrann, J M; Hooper, R N

    1997-10-01

    To develop an economic model for comparing cost-effectiveness of medical and surgical treatment versus replacement of beef bulls with preputial prolapse. Economic analysis. Estimates determined from medical records of bulls treated for preputial prolapse at our hospital and from information about treatment of bulls published elsewhere. Annual depreciation cost for treatment (ADC(T)) and replacement (ADC(R)) were calculated. Total investment for an injured bull equaled the sum of salvage value, maintenance cost, and expected cost of the treatment option under consideration. Total investment for a replacement bull was purchase price. Net present value of cost was calculated for each year of bull use. Sensitivity analyses were constructed to determine the value that would warrant treatment of an injured bull. The decision to treat was indicated when ADC(T) was less than ADC(R). In our example, it was more cost-effective for owners to cull an injured bull. The ADC(R) was $97 less than ADC(T) for medical treatment ($365 vs $462) and $280 less than ADC(T) for surgical treatment ($365 vs $645). Likewise, net present value of cost values indicated that it was more cost-effective for owners to cull an injured bull. Sensitivity analysis indicated treatment decisions were justified on the basis of replacement value or planned number of breeding seasons remaining for the bull. The model described here can be used by practitioners to provide an objective basis to guide decision making of owners who seek advice on whether to treat or replace bulls with preputial prolapse.

  5. Modeling and Hemofiltration Treatment of Acute Inflammation

    Directory of Open Access Journals (Sweden)

    Robert S. Parker

    2016-10-01

    Full Text Available The body responds to endotoxins by triggering the acute inflammatory response system to eliminate the threat posed by gram-negative bacteria (endotoxin and restore health. However, an uncontrolled inflammatory response can lead to tissue damage, organ failure, and ultimately death; this is clinically known as sepsis. Mathematical models of acute inflammatory disease have the potential to guide treatment decisions in critically ill patients. In this work, an 8-state (8-D differential equation model of the acute inflammatory response system to endotoxin challenge was developed. Endotoxin challenges at 3 and 12 mg/kg were administered to rats, and dynamic cytokine data for interleukin (IL-6, tumor necrosis factor (TNF, and IL-10 were obtained and used to calibrate the model. Evaluation of competing model structures was performed by analyzing model predictions at 3, 6, and 12 mg/kg endotoxin challenges with respect to experimental data from rats. Subsequently, a model predictive control (MPC algorithm was synthesized to control a hemoadsorption (HA device, a blood purification treatment for acute inflammation. A particle filter (PF algorithm was implemented to estimate the full state vector of the endotoxemic rat based on time series cytokine measurements. Treatment simulations show that: (i the apparent primary mechanism of HA efficacy is white blood cell (WBC capture, with cytokine capture a secondary benefit; and (ii differential filtering of cytokines and WBC does not provide substantial improvement in treatment outcomes vs. existing HA devices.

  6. Poster — Thur Eve — 33: The Influence of a Modeled Treatment Couch on Dose Distributions During IMRT and RapidArc Treatment Delivery

    International Nuclear Information System (INIS)

    Aldosary, Ghada; Nobah, Ahmad; Al-Zorkani, Faisal; Moftah, Belal; Devic, Slobodan

    2014-01-01

    Treatment couches have been known to perturb dose delivery in patients. This effect is most pronounced in techniques such as IMRT and RapidArc. Although modern treatment planning systems (TPS) include data for a “default” treatment couch, actual couches are not manufactured identically. Thus, variations in their Hounsfield Unit (HU) values may exist. This study demonstrates a practical and simple method of acquiring reliable HU data for any treatment couch. We also investigate the effects of both the default and modeled treatment couches on absorbed dose. Experimental verifications show that by neglecting to incorporate the treatment couch in the TPS, dose differences of up to 9.5% and 7.3% were present for 4 MV and 10 MV photon beams, respectively. Furthermore, a clinical study based on a cohort of 20 RapidArc and IMRT (brain, pelvis and abdominal) cases is performed. 2D dose distributions show that without the couch in the planning phase, differences ≤ 4.6% and 5.9% for RapidArc and IMRT cases are present for the same cases that the default couch was added to. Additionally, in comparison to the default couch, employing the modeled couch in the calculation process influences dose distributions by ≤ 2.7% and 8% for RapidArc and IMRT cases, respectively. This result was found to be site specific; where an accurate couch proves to be preferable for IMRT brain plans. As such, adding the couch during dose calculation decreases dose calculation errors, and a precisely modeled treatment couch offers higher dose delivery accuracy for brain treatment using IMRT

  7. Poster — Thur Eve — 33: The Influence of a Modeled Treatment Couch on Dose Distributions During IMRT and RapidArc Treatment Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Aldosary, Ghada [Medical Physics Unit, Montreal General Hospital, McGill University, Montreal, Quebec (Canada); Nobah, Ahmad; Al-Zorkani, Faisal; Moftah, Belal [Biomedical Physics Department, King Faisal Specialist Hospital and Research Center, Riyadh (Saudi Arabia); Devic, Slobodan [Department of Radiation Oncology, Jewish General Hospital, McGill University, Montreal, Quebec (Canada)

    2014-08-15

    Treatment couches have been known to perturb dose delivery in patients. This effect is most pronounced in techniques such as IMRT and RapidArc. Although modern treatment planning systems (TPS) include data for a “default” treatment couch, actual couches are not manufactured identically. Thus, variations in their Hounsfield Unit (HU) values may exist. This study demonstrates a practical and simple method of acquiring reliable HU data for any treatment couch. We also investigate the effects of both the default and modeled treatment couches on absorbed dose. Experimental verifications show that by neglecting to incorporate the treatment couch in the TPS, dose differences of up to 9.5% and 7.3% were present for 4 MV and 10 MV photon beams, respectively. Furthermore, a clinical study based on a cohort of 20 RapidArc and IMRT (brain, pelvis and abdominal) cases is performed. 2D dose distributions show that without the couch in the planning phase, differences ≤ 4.6% and 5.9% for RapidArc and IMRT cases are present for the same cases that the default couch was added to. Additionally, in comparison to the default couch, employing the modeled couch in the calculation process influences dose distributions by ≤ 2.7% and 8% for RapidArc and IMRT cases, respectively. This result was found to be site specific; where an accurate couch proves to be preferable for IMRT brain plans. As such, adding the couch during dose calculation decreases dose calculation errors, and a precisely modeled treatment couch offers higher dose delivery accuracy for brain treatment using IMRT.

  8. Computational models as predictors of HIV treatment outcomes for the Phidisa cohort in South Africa

    Directory of Open Access Journals (Sweden)

    Andrew Revell

    2016-06-01

    Full Text Available Background: Selecting the optimal combination of HIV drugs for an individual in resourcelimited settings is challenging because of the limited availability of drugs and genotyping. Objective: The evaluation as a potential treatment support tool of computational models that predict response to therapy without a genotype, using cases from the Phidisa cohort in South Africa. Methods: Cases from Phidisa of treatment change following failure were identified that had the following data available: baseline CD4 count and viral load, details of failing and previous antiretroviral drugs, drugs in new regimen and time to follow-up. The HIV Resistance Response Database Initiative’s (RDI’s models used these data to predict the probability of a viral load < 50 copies/mL at follow-up. The models were also used to identify effective alternative combinations of three locally available drugs. Results: The models achieved accuracy (area under the receiver–operator characteristic curve of 0.72 when predicting response to therapy, which is less accurate than for an independent global test set (0.80 but at least comparable to that of genotyping with rules-based interpretation. The models were able to identify alternative locally available three-drug regimens that were predicted to be effective in 69% of all cases and 62% of those whose new treatment failed in the clinic. Conclusion: The predictive accuracy of the models for these South African patients together with the results of previous studies suggest that the RDI’s models have the potential to optimise treatment selection and reduce virological failure in different patient populations, without the use of a genotype. Keywords: HIV therapy; mathematical modelling; treatment; genotype

  9. A cost-effectiveness analysis of celecoxib compared with diclofenac in the treatment of pain in osteoarthritis (OA) within the Swedish health system using an adaptation of the NICE OA model.

    Science.gov (United States)

    Brereton, Nicholas; Pennington, Becky; Ekelund, Mats; Akehurst, Ronald

    2014-09-01

    Celecoxib for the treatment of pain resulting from osteoarthritis (OA) was reviewed by the Tandvårds- och läkemedelsförmånsverket-Dental and Pharmaceutical Benefits Board (TLV) in Sweden in late 2010. This study aimed to evaluate the incremental cost-effectiveness ratio (ICER) of celecoxib plus a proton pump inhibitor (PPI) compared to diclofenac plus a PPI in a Swedish setting. The National Institute for Health and Care Excellence (NICE) in the UK developed a health economic model as part of their 2008 assessment of treatments for OA. In this analysis, the model was reconstructed and adapted to a Swedish perspective. Drug costs were updated using the TLV database. Adverse event costs were calculated using the regional price list of Southern Sweden and the standard treatment guidelines from the county council of Stockholm. Costs for treating cardiovascular (CV) events were taken from the Swedish DRG codes and the literature. Over a patient's lifetime treatment with celecoxib plus a PPI was associated with a quality-adjusted life year (QALY) gain of 0.006 per patient when compared to diclofenac plus a PPI. There was an increase in discounted costs of 529 kr per patient, which resulted in an incremental cost-effectiveness ratio (ICER) of 82,313 kr ($12,141). Sensitivity analysis showed that treatment was more cost effective in patients with an increased risk of bleeding or gastrointestinal (GI) complications. The results suggest that celecoxib plus a PPI is a cost effective treatment for OA when compared to diclofenac plus a PPI. Treatment is shown to be more cost effective in Sweden for patients with a high risk of bleeding or GI complications. It was in this population that the TLV gave a positive recommendation. There are known limitations on efficacy in the original NICE model.

  10. Wastewater treatment modelling: dealing with uncertainties

    DEFF Research Database (Denmark)

    Belia, E.; Amerlinck, Y.; Benedetti, L.

    2009-01-01

    This paper serves as a problem statement of the issues surrounding uncertainty in wastewater treatment modelling. The paper proposes a structure for identifying the sources of uncertainty introduced during each step of an engineering project concerned with model-based design or optimisation...

  11. Validation and uncertainty analysis of a pre-treatment 2D dose prediction model

    Science.gov (United States)

    Baeza, Jose A.; Wolfs, Cecile J. A.; Nijsten, Sebastiaan M. J. J. G.; Verhaegen, Frank

    2018-02-01

    Independent verification of complex treatment delivery with megavolt photon beam radiotherapy (RT) has been effectively used to detect and prevent errors. This work presents the validation and uncertainty analysis of a model that predicts 2D portal dose images (PDIs) without a patient or phantom in the beam. The prediction model is based on an exponential point dose model with separable primary and secondary photon fluence components. The model includes a scatter kernel, off-axis ratio map, transmission values and penumbra kernels for beam-delimiting components. These parameters were derived through a model fitting procedure supplied with point dose and dose profile measurements of radiation fields. The model was validated against a treatment planning system (TPS; Eclipse) and radiochromic film measurements for complex clinical scenarios, including volumetric modulated arc therapy (VMAT). Confidence limits on fitted model parameters were calculated based on simulated measurements. A sensitivity analysis was performed to evaluate the effect of the parameter uncertainties on the model output. For the maximum uncertainty, the maximum deviating measurement sets were propagated through the fitting procedure and the model. The overall uncertainty was assessed using all simulated measurements. The validation of the prediction model against the TPS and the film showed a good agreement, with on average 90.8% and 90.5% of pixels passing a (2%,2 mm) global gamma analysis respectively, with a low dose threshold of 10%. The maximum and overall uncertainty of the model is dependent on the type of clinical plan used as input. The results can be used to study the robustness of the model. A model for predicting accurate 2D pre-treatment PDIs in complex RT scenarios can be used clinically and its uncertainties can be taken into account.

  12. Modeling the Effects of Onsite Wastewater Treatment Systems on Nitrate Loads Using SWAT in an Urban Watershed of Metropolitan Atlanta.

    Science.gov (United States)

    Hoghooghi, Nahal; Radcliffe, David E; Habteselassie, Mussie Y; Jeong, Jaehak

    2017-05-01

    Onsite wastewater treatment systems (OWTSs) can be a source of nitrogen (N) pollution in both surface and ground waters. In metropolitan Atlanta, GA, >26% of homes are on OWTSs. In a previous article, we used the Soil Water Assessment Tool to model the effect of OWTSs on stream flow in the Big Haynes Creek Watershed in metropolitan Atlanta. The objective of this study was to estimate the effect of OWTSs, including failing systems, on nitrate as N (NO-N) load in the same watershed. Big Haynes Creek has a drainage area of 44 km with mainly urban land use (67%), and most of the homes use OWTSs. A USGS gauge station where stream flow was measured daily and NO-N concentrations were measured monthly was used as the outlet. The model was simulated for 12 yr. Overall, the model showed satisfactory daily stream flow and NO-N loads with Nash-Sutcliffe coefficients of 0.62 and 0.58 for the calibration period and 0.67 and 0.33 for the validation period at the outlet of the Big Haynes Watershed. Onsite wastewater treatment systems caused an average increase in NO-N load of 23% at the watershed scale and 29% at the outlet of a subbasin with the highest density of OWTSs. Failing OWTSs were estimated to be 1% of the total systems and did not have a large impact on stream flow or NO-N load. The NO-N load was 74% of the total N load in the watershed, indicating the important effect of OWTSs on stream loads in this urban watershed. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

  13. Effects of prolonged treatment with memantine in the MRL model of CNS lupus.

    Science.gov (United States)

    Marcinko, Katarina; Parsons, Tiffany; Lerch, Jason P; Sled, John G; Sakic, Boris

    2012-09-01

    Neuropsychiatric manifestations and brain atrophy of unknown etiology are common and severe complications of systemic lupus erythematosus (SLE). An autoantibody that binds to N-methyl-D-aspartate (NMDA) receptor NR2 has been proposed as a key factor in the etiology of central nervous system (CNS) SLE. This hypothesis was supported by evidence suggesting memantine (MEM), an uncompetitive NMDA receptor antagonist, prevents behavioral dysfunction and brain pathology in healthy mice immunized with a peptide similar to an epitope on the NR2 receptor. Given that SLE is a chronic condition, we presently examine the effects of MEM in MRL/lpr mice, which develop behavioral deficits alongside SLE-like disease. A broad behavioral battery and 7-Tesla MRI were used to examine whether prolonged treatment with MEM (~25 mg/kg b.w. in drinking water) prevents CNS involvement in this spontaneous model of SLE. Although MEM increased novel object exploration in MRL/lpr mice, it did not show other beneficial, substrain-specific effects. Conversely, MEM was detrimental to spontaneous activity in control MRL +/+ mice and had a negative effect on body mass gain. Similarly, MRI revealed comparable increases in the volume of periventricular structures in MEM-treated groups. Sustained exposure to MEM affects body growth, brain morphology, and behavior primarily by pharmacological, and not autoimmunity-dependant mechanisms. Substrain-specific improvement in exploratory behavior of MEM-treated MRL/lpr mice may indicate that the NMDA system is merely a constituent of a complex pathogenenic cascade. However, it was evident that chronic administration of MEM is unable to completely prevent the development of a CNS SLE-like syndrome.

  14. Integrated Specialized Early-Course Psychosis Treatment Services - University Psychiatric Hospital Vrapce Model.

    Science.gov (United States)

    Ostojić, DraŽenka; Čulo, Ilaria; Silić, Ante; Kos, Suzana; Savić, Aleksandar

    2018-06-01

    First episode of psychosis presents a critical period in terms of numerous associated risks, but also possibilities for effective therapeutic interventions. There is a continued focus on early interventions in prodromal states and early course of frank psychosis, aimed at ensuring faster remission, reducing relapses, achieving better long-term functioning, and preventing adverse outcomes linked to untreated psychosis and chronic psychotic disorders. A number of different specialized treatment models and services exist trying to close knowledge gaps and provide clinical interventions to first-episode psychosis (FEP) patients, but there is still no generally accepted standard of care informing our every-day practice. FEP and early-course psychosis specialized treatment model developed in 2004 in University Psychiatric Hospital Vrapce rests on integration of care across different organization units and clinical presentation acuity levels and patient needs (intensive care, FEP inpatient unit, FEP outpatient services including day hospital). Such integration of FEP services allows for flexible entry point on multiple levels, earlier structuring of therapeutic alliance for those requiring inpatient care, reduction of risks associated with FEP, quicker formation of long-term treatment plans, reduction of delay in accessing specialized services, and a more coordinated diagnostic process and recruitment of FEP patient population. Detailed evaluations of outcomes and comparisons with different treatment models are necessary in order to assess strengths and weaknesses of each specific model and inform modifications to current practice models.

  15. Contemporary treatment of sexual dysfunction: reexamining the biopsychosocial model.

    Science.gov (United States)

    Berry, Michael D; Berry, Philip D

    2013-11-01

    The introduction of phosphodiesterase type 5 inhibitors has revolutionized the armamentarium of clinicians in the field of sexual medicine. However, pharmacotherapy as a stand-alone treatment option has been criticized, particularly by psychosocial therapists, as incomplete. Specifically, it is widely argued that drug treatment alone often does not meet the standards of biopsychosocial (BPS) therapy. A literature review was performed to explore the role of the biopsychosocial paradigm in the treatment of sexual dysfunction and outline some of the key challenges and possible shortcomings in the current application of biopsychosocial treatment. Published treatment outcomes of integrative biopsychosocial clinical practice, including medical outcomes, psychological and relational factors, treatment of comorbid conditions, cost of treatment, and treatment efficacy, were investigated. Using Medline, PubMed, and EMBASE databases, a literature search for articles published from January 1, 1980, to March 1, 2013, was performed, examining current approaches to the biopsychosocial model of sexual dysfunction and sexual medicine. Data were reviewed and combined, allowing characterization of current treatment approaches and recommendations for clinical practice and future research. The biopsychosocial model of treatment appears to have an intuitively obvious meaning (i.e., treatment of all three facets of the patient's biological-psychological-social condition). However, research suggests that clear treatment algorithms are still in development. By virtue of the ongoing development of biopsychosocial methods in sexual medicine, new models and research initiatives may be warranted. The evidence identified allows for characterization of some of the current clinical, professional, financial, and systemic challenges to biopsychosocial treatment, with the aim of helping identify possible directions for future research. Implementation of biopsychosocial treatment, though mandated by

  16. Measuring the effect of fuel treatments on forest carbon using landscape risk analysis

    Directory of Open Access Journals (Sweden)

    A. A. Ager

    2010-12-01

    Full Text Available Wildfire simulation modelling was used to examine whether fuel reduction treatments can potentially reduce future wildfire emissions and provide carbon benefits. In contrast to previous reports, the current study modelled landscape scale effects of fuel treatments on fire spread and intensity, and used a probabilistic framework to quantify wildfire effects on carbon pools to account for stochastic wildfire occurrence. The study area was a 68 474 ha watershed located on the Fremont-Winema National Forest in southeastern Oregon, USA. Fuel reduction treatments were simulated on 10% of the watershed (19% of federal forestland. We simulated 30 000 wildfires with random ignition locations under both treated and untreated landscapes to estimate the change in burn probability by flame length class resulting from the treatments. Carbon loss functions were then calculated with the Forest Vegetation Simulator for each stand in the study area to quantify change in carbon as a function of flame length. We then calculated the expected change in carbon from a random ignition and wildfire as the sum of the product of the carbon loss and the burn probabilities by flame length class. The expected carbon difference between the non-treatment and treatment scenarios was then calculated to quantify the effect of fuel treatments. Overall, the results show that the carbon loss from implementing fuel reduction treatments exceeded the expected carbon benefit associated with lowered burn probabilities and reduced fire severity on the treated landscape. Thus, fuel management activities resulted in an expected net loss of carbon immediately after treatment. However, the findings represent a point in time estimate (wildfire immediately after treatments, and a temporal analysis with a probabilistic framework used here is needed to model carbon dynamics over the life cycle of the fuel treatments. Of particular importance is the long-term balance between emissions from the

  17. Measuring the effect of fuel treatments on forest carbon using landscape risk analysis

    Science.gov (United States)

    Ager, A. A.; Finney, M. A.; McMahan, A.; Cathcart, J.

    2010-12-01

    Wildfire simulation modelling was used to examine whether fuel reduction treatments can potentially reduce future wildfire emissions and provide carbon benefits. In contrast to previous reports, the current study modelled landscape scale effects of fuel treatments on fire spread and intensity, and used a probabilistic framework to quantify wildfire effects on carbon pools to account for stochastic wildfire occurrence. The study area was a 68 474 ha watershed located on the Fremont-Winema National Forest in southeastern Oregon, USA. Fuel reduction treatments were simulated on 10% of the watershed (19% of federal forestland). We simulated 30 000 wildfires with random ignition locations under both treated and untreated landscapes to estimate the change in burn probability by flame length class resulting from the treatments. Carbon loss functions were then calculated with the Forest Vegetation Simulator for each stand in the study area to quantify change in carbon as a function of flame length. We then calculated the expected change in carbon from a random ignition and wildfire as the sum of the product of the carbon loss and the burn probabilities by flame length class. The expected carbon difference between the non-treatment and treatment scenarios was then calculated to quantify the effect of fuel treatments. Overall, the results show that the carbon loss from implementing fuel reduction treatments exceeded the expected carbon benefit associated with lowered burn probabilities and reduced fire severity on the treated landscape. Thus, fuel management activities resulted in an expected net loss of carbon immediately after treatment. However, the findings represent a point in time estimate (wildfire immediately after treatments), and a temporal analysis with a probabilistic framework used here is needed to model carbon dynamics over the life cycle of the fuel treatments. Of particular importance is the long-term balance between emissions from the decay of dead trees

  18. Cost-effectiveness of sequenced treatment of rheumatoid arthritis with targeted immune modulators.

    Science.gov (United States)

    Jansen, Jeroen P; Incerti, Devin; Mutebi, Alex; Peneva, Desi; MacEwan, Joanna P; Stolshek, Bradley; Kaur, Primal; Gharaibeh, Mahdi; Strand, Vibeke

    2017-07-01

    To determine the cost-effectiveness of treatment sequences of biologic disease-modifying anti-rheumatic drugs or Janus kinase/STAT pathway inhibitors (collectively referred to as bDMARDs) vs conventional DMARDs (cDMARDs) from the US societal perspective for treatment of patients with moderately to severely active rheumatoid arthritis (RA) with inadequate responses to cDMARDs. An individual patient simulation model was developed that assesses the impact of treatments on disease based on clinical trial data and real-world evidence. Treatment strategies included sequences starting with etanercept, adalimumab, certolizumab, or abatacept. Each of these treatment strategies was compared with cDMARDs. Incremental cost, incremental quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated for each treatment sequence relative to cDMARDs. The cost-effectiveness of each strategy was determined using a US willingness-to-pay (WTP) threshold of $150,000/QALY. For the base-case scenario, bDMARD treatment sequences were associated with greater treatment benefit (i.e. more QALYs), lower lost productivity costs, and greater treatment-related costs than cDMARDs. The expected ICERs for bDMARD sequences ranged from ∼$126,000 to $140,000 per QALY gained, which is below the US-specific WTP. Alternative scenarios examining the effects of homogeneous patients, dose increases, increased costs of hospitalization for severely physically impaired patients, and a lower baseline Health Assessment Questionnaire (HAQ) Disability Index score resulted in similar ICERs. bDMARD treatment sequences are cost-effective from a US societal perspective.

  19. Mouse Models Applied to the Research of Pharmacological Treatments in Asthma.

    Science.gov (United States)

    Marqués-García, Fernando; Marcos-Vadillo, Elena

    2016-01-01

    Models developed for the study of asthma mechanisms can be used to investigate new compounds with pharmacological activity against this disease. The increasing number of compounds requires a preclinical evaluation before starting the application in humans. Preclinical evaluation in animal models reduces the number of clinical trials positively impacting in the cost and in safety. In this chapter, three protocols for the study of drugs are shown: a model to investigate corticoids as a classical treatment of asthma; a protocol to test the effects of retinoic acid (RA) on asthma; and a mouse model to test new therapies in asthma as monoclonal antibodies.

  20. Video self-modeling as a post-treatment fluency recovery strategy for adults.

    Science.gov (United States)

    Harasym, Jessica; Langevin, Marilyn; Kully, Deborah

    2015-06-01

    This multiple-baseline across subjects study investigated the effectiveness of video self-modeling (VSM) in reducing stuttering and bringing about improvements in associated self-report measures. Participants' viewing practices and perceptions of the utility of VSM also were explored. Three adult males who had previously completed speech restructuring treatment viewed VSM recordings twice per week for 6 weeks. Weekly speech data, treatment viewing logs, and pre- and post-treatment self-report measures were obtained. An exit interview also was conducted. Two participants showed a decreasing trend in stuttering frequency. All participants appeared to engage in fewer avoidance behaviors and had less expectations to stutter. All participants perceived that, in different ways, the VSM treatment had benefited them and all participants had unique viewing practices. Given the increasing availability and ease in using portable audio-visual technology, VSM appears to offer an economical and clinically useful tool for clients who are motivated to use the technology to recover fluency. Readers will be able to describe: (a) the tenets of video-self modeling; (b) the main components of video-self modeling as a fluency recovery treatment as used in this study; and (c) speech and self-report outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Describing treatment effects to patients.

    Science.gov (United States)

    Moxey, Annette; O'Connell, Dianne; McGettigan, Patricia; Henry, David

    2003-11-01

    To examine the impact of different presentations of equivalent information (framing) on treatment decisions faced by patients. A systematic review of the published literature was conducted. English language publications allocating participants to different frames were retrieved using electronic and bibliographic searches. Two reviewers examined each article for inclusion, and assessed methodological quality. Study characteristics were tabulated and where possible, relative risks (RR; 95% confidence intervals) were calculated to estimate intervention effects. Thirty-seven articles, yielding 40 experimental studies, were included. Studies examined treatment (N = 24), immunization (N = 5), or health behavior scenarios (N = 11). Overall, active treatments were preferred when outcomes were described in terms of relative rather than absolute risk reductions or number needed to treat. Surgery was preferred to other treatments when treatment efficacy was presented in a positive frame (survival) rather than a negative frame (mortality) (relative risk [RR] = 1.51, 95% confidence interval [CI], 1.39 to 1.64). Framing effects were less obvious for immunization and health behavior scenarios. Those with little interest in the behavior at baseline were influenced by framing, particularly when information was presented as gains. In studies judged to be of good methodological quality and/or examining actual decisions, the framing effect, although still evident, was less convincing compared to the results of all included studies. Framing effects varied with the type of scenario, responder characteristics, scenario manipulations, and study quality. When describing treatment effects to patients, expressing the information in more than one way may present a balanced view to patients and enable them to make informed decisions.

  2. Cost effectiveness of intermittent screening followed by treatment versus intermittent preventive treatment during pregnancy in West Africa

    DEFF Research Database (Denmark)

    Fernandes, Silke; Sicuri, Elisa; Halimatou, Diawara

    2016-01-01

    $/DALY averted. Simulations show that cost-effectiveness of ISTp-AL increases as the efficacy of IPTp-SP decreases, though the specific threshold at which ISTp-AL becomes cost-effective depends on assumptions about the contribution of bed nets to malaria control, bed net coverage and the willingness......-to-pay threshold used.  Conclusions: At SP efficacy levels currently observed in the trial settings it would not be cost-effective to switch from IPTp-SP to ISTp-AL, mainly due to the substantially higher costs of ISTp-AL and limited difference in outcomes. The modelling results indicate thresholds below which IPT......Background: Emergence of high-grade sulfadoxine-pyrimethamine (SP) resistance in parts of Africa has led to growing concerns about the efficacy of intermittent preventive treatment of malaria during pregnancy (IPTp) with SP. The incremental cost-effectiveness of intermittent screening and treatment...

  3. Low-level laser treatment accelerated hair regrowth in a rat model of chemotherapy-induced alopecia (CIA).

    Science.gov (United States)

    Wikramanayake, Tongyu Cao; Villasante, Alexandra C; Mauro, Lucia M; Nouri, Keyvan; Schachner, Lawrence A; Perez, Carmen I; Jimenez, Joaquin J

    2013-05-01

    Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of antineoplastic chemotherapy for which there is no effective interventional approach. A low-level laser (LLL) device, the HairMax LaserComb®, has been cleared by the FDA to treat androgenetic alopecia. Its effects may be extended to other settings; we have demonstrated that LaserComb treatment induced hair regrowth in a mouse model for alopecia areata. In the current study, we tested whether LLL treatment could promote hair regrowth in a rat model for CIA. Chemotherapy agents cyclophosphamide, etoposide, or a combination of cyclophosphamide and doxorubicin were administered in young rats to induce alopecia, with or without LLL treatment. As expected, 7-10 days later, all the rats developed full body alopecia. However, rats receiving laser treatment regrew hair 5 days earlier than rats receiving chemotherapy alone or sham laser treatment (with the laser turned off). The accelerated hair regrowth in laser-treated rats was confirmed by histology. In addition, LLL treatment did not provide local protection to subcutaneously injected Shay chloroleukemic cells. Taken together, our results demonstrated that LLL treatment significantly accelerated hair regrowth after CIA without compromising the efficacy of chemotherapy in our rat model. Our results suggest that LLL should be explored for the treatment of CIA in clinical trials because LLL devices for home use (such as the HairMax LaserComb®) provide a user-friendly and noninvasive approach that could be translated to increased patient compliance and improved efficacy.

  4. The predicted effectiveness of noble metal treatment at the Chinshan boiling water reactor

    International Nuclear Information System (INIS)

    Yeh Tsungkuang; Chu Fang; Chang Ching; Huang Chiashen

    2000-01-01

    The technique of noble metal treatment (NMT) available in a form of noble metal cooling (NMC) or noble metal chemical addition (NMCA), was introduced to enhance effectiveness of hydrogen water chemistry. Since it is technically difficult to gain access to an entire primary heat transport circuit (PHTC) of a BWR and monitor variation on electrochemical corrosion potential (ECP), a question whether the NMC technology is indeed effective for lowering the ECP of every location in a BWR is not still well understood at the moment. Then, computer modeling is so far the best tool to help investigate effectiveness of the NMT along PHCT of the BWR. Here was discussed on how the computer model was calibrated by using measured chemistry data obtained from No. 2 unit (BWR) in the Kuosheng Plant. The effect of noble metal treatment coupled with hydrogen water chemistry has been quantitatively molded, on a base of two different sets of ECD enhancement data. It was predicted that No. 1 unit in the Chinshan could be protected by noble metal treatment with lower [H 2 ] FW . In the case of competitive enhancing factors for the ECDs of oxygen reduction, hydrogen peroxide reduction, and hydrogen oxidation reactions, HWC had always to be present for noble metal treatment to be effective for protecting a reactor. Otherwise, according to a model calculation based upon the results from Kim's work, the ECP might instead be increased due to the enhanced reduction reaction rate of oxygen and hydrogen peroxide, especially in the near core regions. (G.K.)

  5. The Effectiveness of Holistic Multi-dimensional Treatment Model (HMTM in the Treatment of Children with Autism Spectrum Disorder (ASD

    Directory of Open Access Journals (Sweden)

    Maryam Hojati

    2014-04-01

    Full Text Available Introduction: Autism spectrum disorders (ASD belong to the pervasive neurodevelopmental disorders. The prevalence of ASD has increased significantly throughout recent decades, bringing the overall estimated prevalence to 11.3 per 1000 children. ASD is characterized by severe difficulties in reciprocal social interaction, stereotyped patterns of behavior and profound impairments in verbal and nonverbal communication. Materials and Method: In this experimental study, 150 children with ASD, who referred to psychiatry clinics of children in two Mashhad academic Hospitals-Iran, were enrolled. At the first, they divided into 3 groups (N=50 patients in each group. All groups were educated and treated with Holistic Multidimensional Treatment Model (HMTM method but for different periods: one, two, and three years. Data analysis was done using ANOVA and ANCOVA test. Results: 78% of participants were boys. According to the results, 26% of participants after one year treatment, 44% after two years and 52% after three years treatment improved. The participants’ symptoms of behavioral, cognitive and physical function declined in 3 groups significantly (p

  6. Treatment selection in a randomized clinical trial via covariate-specific treatment effect curves.

    Science.gov (United States)

    Ma, Yunbei; Zhou, Xiao-Hua

    2017-02-01

    For time-to-event data in a randomized clinical trial, we proposed two new methods for selecting an optimal treatment for a patient based on the covariate-specific treatment effect curve, which is used to represent the clinical utility of a predictive biomarker. To select an optimal treatment for a patient with a specific biomarker value, we proposed pointwise confidence intervals for each covariate-specific treatment effect curve and the difference between covariate-specific treatment effect curves of two treatments. Furthermore, to select an optimal treatment for a future biomarker-defined subpopulation of patients, we proposed confidence bands for each covariate-specific treatment effect curve and the difference between each pair of covariate-specific treatment effect curve over a fixed interval of biomarker values. We constructed the confidence bands based on a resampling technique. We also conducted simulation studies to evaluate finite-sample properties of the proposed estimation methods. Finally, we illustrated the application of the proposed method in a real-world data set.

  7. Effects of Melittin Treatment in Cholangitis and Biliary Fibrosis in a Model of Xenobiotic-Induced Cholestasis in Mice

    Directory of Open Access Journals (Sweden)

    Kyung-Hyun Kim

    2015-08-01

    Full Text Available Cholangiopathy is a chronic immune-mediated disease of the liver, which is characterized by cholangitis, ductular reaction and biliary-type hepatic fibrosis. There is no proven medical therapy that changes the course of the disease. In previous studies, melittin was known for attenuation of hepatic injury, inflammation and hepatic fibrosis. This study investigated whether melittin provides inhibition on cholangitis and biliary fibrosis in vivo. Feeding 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC to mice is a well-established animal model to study cholangitis and biliary fibrosis. To investigate the effects of melittin on cholangiopathy, mice were fed with a 0.1% DDC-containing diet with or without melittin treatment for four weeks. Liver morphology, serum markers of liver injury, cholestasis markers for inflammation of liver, the degree of ductular reaction and the degree of liver fibrosis were compared between with or without melittin treatment DDC-fed mice. DDC feeding led to increased serum markers of hepatic injury, ductular reaction, induction of pro-inflammatory cytokines and biliary fibrosis. Interestingly, melittin treatment attenuated hepatic function markers, ductular reaction, the reactive phenotype of cholangiocytes and cholangitis and biliary fibrosis. Our data suggest that melittin treatment can be protective against chronic cholestatic disease in DDC-fed mice. Further studies on the anti-inflammatory capacity of melittin are warranted for targeted therapy in cholangiopathy.

  8. TU-G-210-02: TRANS-FUSIMO - An Integrative Approach to Model-Based Treatment Planning of Liver FUS

    Energy Technology Data Exchange (ETDEWEB)

    Preusser, T. [Fraunhofer MEVIS & Jacobs University (Germany)

    2015-06-15

    Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such as the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)

  9. TU-G-210-02: TRANS-FUSIMO - An Integrative Approach to Model-Based Treatment Planning of Liver FUS

    International Nuclear Information System (INIS)

    Preusser, T.

    2015-01-01

    Modeling can play a vital role in predicting, optimizing and analyzing the results of therapeutic ultrasound treatments. Simulating the propagating acoustic beam in various targeted regions of the body allows for the prediction of the resulting power deposition and temperature profiles. In this session we will apply various modeling approaches to breast, abdominal organ and brain treatments. Of particular interest is the effectiveness of procedures for correcting for phase aberrations caused by intervening irregular tissues, such as the skull in transcranial applications or inhomogeneous breast tissues. Also described are methods to compensate for motion in targeted abdominal organs such as the liver or kidney. Douglas Christensen – Modeling for Breast and Brain HIFU Treatment Planning Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Tobias Preusser – TRANS-FUSIMO – An Integrative Approach to Model-Based Treatment Planning of Liver FUS Learning Objectives: Understand the role of acoustic beam modeling for predicting the effectiveness of therapeutic ultrasound treatments. Apply acoustic modeling to specific breast, liver, kidney and transcranial anatomies. Determine how to obtain appropriate acoustic modeling parameters from clinical images. Understand the separate role of absorption and scattering in energy delivery to tissues. See how organ motion can be compensated for in ultrasound therapies. Compare simulated data with clinical temperature measurements in transcranial applications. Supported by NIH R01 HL172787 and R01 EB013433 (DC); EU Seventh Framework Programme (FP7/2007-2013) under 270186 (FUSIMO) and 611889 (TRANS-FUSIMO)(TP); and P01 CA159992, GE, FUSF and InSightec (UV)

  10. Modeling pathogenesis and treatment response in childhood absence epilepsy.

    Science.gov (United States)

    Knox, Andrew T; Glauser, Tracy; Tenney, Jeffrey; Lytton, William W; Holland, Katherine

    2018-01-01

    Childhood absence epilepsy (CAE) is a genetic generalized epilepsy syndrome with polygenic inheritance, with genes for γ-aminobutyric acid (GABA) receptors and T-type calcium channels implicated in the disorder. Previous studies of T-type calcium channel electrophysiology have shown genetic changes and medications have multiple effects. The aim of this study was to use an established thalamocortical computer model to determine how T-type calcium channels work in concert with cortical excitability to contribute to pathogenesis and treatment response in CAE. The model is comprised of cortical pyramidal, cortical inhibitory, thalamocortical relay, and thalamic reticular single-compartment neurons, implemented with Hodgkin-Huxley model ion channels and connected by AMPA, GABA A , and GABA B synapses. Network behavior was simulated for different combinations of T-type calcium channel conductance, inactivation time, steady state activation/inactivation shift, and cortical GABA A conductance. Decreasing cortical GABA A conductance and increasing T-type calcium channel conductance converted spindle to spike and wave oscillations; smaller changes were required if both were changed in concert. In contrast, left shift of steady state voltage activation/inactivation did not lead to spike and wave oscillations, whereas right shift reduced network propensity for oscillations of any type. These results provide a window into mechanisms underlying polygenic inheritance in CAE, as well as a mechanism for treatment effects and failures mediated by these channels. Although the model is a simplification of the human thalamocortical network, it serves as a useful starting point for predicting the implications of ion channel electrophysiology in polygenic epilepsy such as CAE. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  11. Ecotoxicological effects extrapolation models

    Energy Technology Data Exchange (ETDEWEB)

    Suter, G.W. II

    1996-09-01

    One of the central problems of ecological risk assessment is modeling the relationship between test endpoints (numerical summaries of the results of toxicity tests) and assessment endpoints (formal expressions of the properties of the environment that are to be protected). For example, one may wish to estimate the reduction in species richness of fishes in a stream reach exposed to an effluent and have only a fathead minnow 96 hr LC50 as an effects metric. The problem is to extrapolate from what is known (the fathead minnow LC50) to what matters to the decision maker, the loss of fish species. Models used for this purpose may be termed Effects Extrapolation Models (EEMs) or Activity-Activity Relationships (AARs), by analogy to Structure-Activity Relationships (SARs). These models have been previously reviewed in Ch. 7 and 9 of and by an OECD workshop. This paper updates those reviews and attempts to further clarify the issues involved in the development and use of EEMs. Although there is some overlap, this paper does not repeat those reviews and the reader is referred to the previous reviews for a more complete historical perspective, and for treatment of additional extrapolation issues.

  12. Treatments for compulsive buying: A systematic review of the quality, effectiveness and progression of the outcome evidence.

    Science.gov (United States)

    Hague, Ben; Hall, Jo; Kellett, Stephen

    2016-09-01

    Background and aims This review appraises the progression and status of the evidence base for the treatment of compulsive buying disorder (CBD), in order to highlight what currently works and to prompt useful future research. Methods Online databases ISI Web of Knowledge, PsycINFO, and PubMed via Ovid were searched at two time points. Two quality checklists and an established model of therapy evaluation (hourglass model) evaluated the quality and progression of both psychotherapy and pharmacotherapy treatments for CBD. Uncontrolled effect sizes were calculated and meta-regression analyses were performed regarding treatment duration. Results A total of 29 articles met the inclusion criteria, which were divided into psychotherapy (n = 17) and pharmacotherapy treatments (n = 12). Of the 29 studies, only 5 studies have been tested under conditions of high methodological quality. Both forms of treatment had been evaluated in a haphazard manner across the stages of the hourglass model. Although large effects were demonstrated for group psychotherapy and pharmacotherapy, such evidence of effectiveness was undermined by poor study quality and risk of publication bias. Long-term CBD treatment was associated with improved outcome with pharmacotherapy, but not when delivering psychotherapy. Discussion Group psychotherapy currently appears the most promising treatment option for CBD. Poor methodological control and sporadic evaluation of specific treatments have slowed the generation of a convincing evidence base for CBD treatment. Defining the active ingredients of effective CBD treatment is a key research goal.

  13. [Study on relationship of dose-effect and time-effect of APA microencapsulated bovine chromaffin cells on pain treatment].

    Science.gov (United States)

    Hui, Jianfeng; Li, Tao; Du, Zhi; Song, Jichang

    2011-12-01

    This study was to investigate the relationship of dose-effect and time-effect of Alginate-Polylysine-Alginate (APA) microencapsulated bovine chromaffin cells on the treatment of pain model rats. Using a rat model of painful peripheral neuropathy, the antinociceptive effects of APA microencapsulated bovine cells transplanted into the subarachnoid space was evaluated by cold allodynia test and hot hyperalgesia test. Compared with control group, the withdrawal difference with cell number 50 thousands groups, 100 thousands groups and 200 thousands groups was reduced (P APA microencapsulated bovine chromaffin cells which were transplanted to treat pain model rats, and the effective antinociception remained longer than 12 weeks.

  14. Cost-effectiveness analysis of anidulafungin for the treatment of candidaemia and other forms of invasive candidiasis.

    Science.gov (United States)

    Auzinger, Georg; Playford, E Geoffrey; Graham, Christopher N; Knox, Hediyyih N; Weinstein, David; Kantecki, Michal; Schlamm, Haran; Charbonneau, Claudie

    2015-10-26

    Candidaemia and other forms of invasive candidiasis (C/IC) in the intensive care unit are challenging conditions that are associated with high rates of mortality. New guidelines from the European Society for Clinical Microbiology and Infectious Diseases strongly recommend echinocandins for the first-line treatment of C/IC. Here, a cost-effectiveness model was developed from the United Kingdom perspective to examine the costs and outcomes of antifungal treatment for C/IC based on the European Society for Clinical Microbiology and Infectious Diseases guidelines. Costs and treatment outcomes with the echinocandin anidulafungin were compared with those for caspofungin, micafungin and fluconazole. The model included non-neutropenic patients aged ≥16 years with confirmed C/IC who were receiving intravenous first-line treatment. Patients were categorised as either a clinical success or failure (patients with persistent/breakthrough infection); successfully treated patients switched to oral therapy, while patients categorised as clinical failures switched to a different antifungal class. Other inputs were all-cause mortality at 6 weeks, costs of treatment-related adverse events and other medical resource utilisation costs. Resource use was derived from the published literature and from discussion with clinical experts. Drug-acquisition/administration costs were taken from standard United Kingdom costing sources. The model indicated that first-line anidulafungin could be considered cost-effective versus fluconazole (incremental cost-effectiveness ratio £813 per life-year gained) for the treatment of C/IC. Anidulafungin was cost-saving versus caspofungin and micafungin due to lower total costs and a higher rate of survival combined with a higher probability of clinical success. European Society for Clinical Microbiology and Infectious Diseases guidelines recommend echinocandins for the first-line treatment of C/IC; our model indicated that anidulafungin marries clinical

  15. Improving treatment outcome assessment in a mouse tuberculosis model.

    Science.gov (United States)

    Mourik, Bas C; Svensson, Robin J; de Knegt, Gerjo J; Bax, Hannelore I; Verbon, Annelies; Simonsson, Ulrika S H; de Steenwinkel, Jurriaan E M

    2018-04-09

    Preclinical treatment outcome evaluation of tuberculosis (TB) occurs primarily in mice. Current designs compare relapse rates of different regimens at selected time points, but lack information about the correlation between treatment length and treatment outcome, which is required to efficiently estimate a regimens' treatment-shortening potential. Therefore we developed a new approach. BALB/c mice were infected with a Mycobacterium tuberculosis Beijing genotype strain and were treated with rifapentine-pyrazinamide-isoniazid-ethambutol (R p ZHE), rifampicin-pyrazinamide-moxifloxacin-ethambutol (RZME) or rifampicin-pyrazinamide-moxifloxacin-isoniazid (RZMH). Treatment outcome was assessed in n = 3 mice after 9 different treatment lengths between 2-6 months. Next, we created a mathematical model that best fitted the observational data and used this for inter-regimen comparison. The observed data were best described by a sigmoidal E max model in favor over linear or conventional E max models. Estimating regimen-specific parameters showed significantly higher curative potentials for RZME and R p ZHE compared to RZMH. In conclusion, we provide a new design for treatment outcome evaluation in a mouse TB model, which (i) provides accurate tools for assessment of the relationship between treatment length and predicted cure, (ii) allows for efficient comparison between regimens and (iii) adheres to the reduction and refinement principles of laboratory animal use.

  16. Study on the toxic side effect of 131I-17-AAG treatment in ovarian cancer-bearing nude mice

    International Nuclear Information System (INIS)

    Gao Wen

    2007-01-01

    Objective: To investigate the toixc side effect on bone marrow and hepatic function of 131 I-17-allylamino-17-demethoxy geldanamycin ( 131 I-17 AAG) treatment for ovarian-cancer-bearing nude mice models. Methods: Ovarian-cancer- bearing nude mice models (n=40) were prepared with cancer cell inoculation. 131 I labelled 17 AAG originally prepared in this laboratory was used intravenously for treatment at a single dose of 3 mCi in 20 models and the remain 20 models were used as controls. Rontine bllod examination (CBC, Hgb, platalet) and liver function test (ALT, AST, ALP and r-GT) were performed in these models at lwk and 2wk after treatment. Results: CBC and Hgb in the treated models were not much different from those in controls at 2wk with the exception of a higher platalet count (P 0.05). Conclusion: Toxic side-effect of 131 I-17-AAG treatment on hematologyical and hepatic function in the models was rather mild and there was a tendency toward recovery at 2wk after treatment. (authors)

  17. Comparative Cost-Effectiveness of Conservative or Intensive Blood Pressure Treatment Guidelines in Adults Aged 35-74 Years: The Cardiovascular Disease Policy Model.

    Science.gov (United States)

    Moise, Nathalie; Huang, Chen; Rodgers, Anthony; Kohli-Lynch, Ciaran N; Tzong, Keane Y; Coxson, Pamela G; Bibbins-Domingo, Kirsten; Goldman, Lee; Moran, Andrew E

    2016-07-01

    The population health effect and cost-effectiveness of implementing intensive blood pressure goals in high-cardiovascular disease (CVD) risk adults have not been described. Using the CVD Policy Model, CVD events, treatment costs, quality-adjusted life years, and drug and monitoring costs were simulated over 2016 to 2026 for hypertensive patients aged 35 to 74 years. We projected the effectiveness and costs of hypertension treatment according to the 2003 Joint National Committee (JNC)-7 or 2014 JNC8 guidelines, and then for adults aged ≥50 years, we assessed the cost-effectiveness of adding an intensive goal of systolic blood pressure cost-effectiveness ratios cost-effective. JNC7 strategies treat more patients and are more costly to implement compared with JNC8 strategies. Adding intensive systolic blood pressure goals for high-risk patients prevents an estimated 43 000 and 35 000 annual CVD events incremental to JNC8 and JNC7, respectively. Intensive strategies save costs in men and are cost-effective in women compared with JNC8 alone. At a willingness-to-pay threshold of $50 000 per quality-adjusted life years gained, JNC8+intensive had the highest probability of cost-effectiveness in women (82%) and JNC7+intensive the highest probability of cost-effectiveness in men (100%). Assuming higher drug and monitoring costs, adding intensive goals for high-risk patients remained consistently cost-effective in men, but not always in women. Among patients aged 35 to 74 years, adding intensive blood pressure goals for high-risk groups to current national hypertension treatment guidelines prevents additional CVD deaths while saving costs provided that medication costs are controlled. © 2016 American Heart Association, Inc.

  18. Patient specific actual size 3D printed models for patient education in glioma treatment: first experiences.

    Science.gov (United States)

    van de Belt, Tom H; Nijmeijer, Hugo; Grim, David; Engelen, Lucien Jlpg; Vreeken, Rinaldo; van Gelder, Marleen Mmj; Laan, Mark Ter

    2018-06-02

    Cancer patients need high quality information about the disease stage, treatment options and side effects. High quality information can also improve health literacy, shared decision-making and satisfaction. We created patient-specific 3D models of tumours including surrounding functional areas, and assessed what patients with glioma actually value (or fear) about these models when they are used to educate them about the relation between their tumour and specific brain parts, the surgical procedure, and risks. We carried out an explorative study with adult glioma patients, who underwent functional MRI and DTi as part of the pre-operative work-up. All participants received an actual size 3D model, printed based on fMRI and DTi imaging. Semi-structured interviews were held to identify facilitators and barriers for using the model, and perceived effects. A model was successfully created for all 11 participants. A total of 18 facilitators and 8 barriers were identified. The model improved patients' understanding about their situation, that it was easier to ask questions to their neurosurgeon based on their model and that it supported their decision about the preferred treatment. A perceived barrier for using the 3D model was that it could be emotionally confronting, particularly in an early phase of the disease process. Positive effects were related to psychological domains including coping, learning effects and communication. Patient-specific 3D models are promising and simple tools that could help patients with glioma to better understand their situation, treatment options and risks. They have the potential to improve shared decision-making. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Pharmacodynamic model of interleukin-21 effects on red blood cells in cynomolgus monkeys

    DEFF Research Database (Denmark)

    Overgaard, Rune Viig; Karlsson, M.; Ingwersen, S.H.

    2007-01-01

    of treatment. The present analysis investigates the observed pharmacodynamics effects on red blood cells following various treatment schedules of human IL-21 administrated to cynomolgus monkeys. These effects are described by a novel non-linear mixed-effects model that enabled separation of drug effects......Interleukin-21 (IL-21) is a novel cytokine that is currently under clinical investigations as a potential anti-cancer agent. Like many other anti-cancer agents, including other interleukins, IL-21 is seen to produce a broad range of biological effects that may be related to both efficacy and safety...... and sampling effects, the latter believed to be due partly to blood loss and partly to stress induced haemolysis in connection with blood sampling. Two different studies with a total of 9 different treatment groups of cynomolgus monkeys were used for model development. In conclusion, the model describes the IL...

  20. Understanding placebo, nocebo, and iatrogenic treatment effects.

    Science.gov (United States)

    Bootzin, Richard R; Bailey, Elaine T

    2005-07-01

    Placebo and nonplacebo treatments have both positive and negative effects on patient outcomes. To better understand the patterning of treatment effects, three specific interventions will be discussed that are reported to produce more harm than benefit: critical incident stress debriefing, group therapy for adolescents with conduct disorders, and psychotherapy for dissociative identity disorder. In each case, there is an interaction between mechanisms thought to underlie both placebo and specific treatment effects. Mechanisms hypothesized to underlie placebo and nocebo effects include patient expectancy, self-focused attention to symptoms, motivation to change, and sociocultural role-enactment cues. In the three treatments discussed, specific mechanisms interact with nonspecific mechanisms to produce iatrogenic effects. To advance knowledge, it is important both to specify the theory of treatment and its expected outcomes and to put the theory to test. Only with attention to the empirical findings from programmatic research of specific and nonspecific effects and their interaction is it possible to improve the outcomes of treatment beyond the status quo.

  1. Treatment Model in Children with Speech Disorders and Its Therapeutic Efficiency

    Directory of Open Access Journals (Sweden)

    Barberena, Luciana

    2014-05-01

    Full Text Available Introduction Speech articulation disorders affect the intelligibility of speech. Studies on therapeutic models show the effectiveness of the communication treatment. Objective To analyze the progress achieved by treatment with the ABAB—Withdrawal and Multiple Probes Model in children with different degrees of phonological disorders. Methods The diagnosis of speech articulation disorder was determined by speech and hearing evaluation and complementary tests. The subjects of this research were eight children, with the average age of 5:5. The children were distributed into four groups according to the degrees of the phonological disorders, based on the percentage of correct consonants, as follows: severe, moderate to severe, mild to moderate, and mild. The phonological treatment applied was the ABAB—Withdrawal and Multiple Probes Model. The development of the therapy by generalization was observed through the comparison between the two analyses: contrastive and distinctive features at the moment of evaluation and reevaluation. Results The following types of generalization were found: to the items not used in the treatment (other words, to another position in the word, within a sound class, to other classes of sounds, and to another syllable structure. Conclusion The different types of generalization studied showed the expansion of production and proper use of therapy-trained targets in other contexts or untrained environments. Therefore, the analysis of the generalizations proved to be an important criterion to measure the therapeutic efficacy.

  2. Cost-effectiveness of renal denervation therapy for the treatment of resistant hypertension in The Netherlands.

    Science.gov (United States)

    Henry, Thea L; De Brouwer, Bonnie F E; Van Keep, Marjolijn M L; Blankestijn, Peter J; Bots, Michiel L; Koffijberg, Hendrik

    2015-01-01

    Safety and efficacy data for catheter-based renal denervation (RDN) in the treatment of resistant hypertension have been used to estimate the cost-effectiveness of this approach. However, there are no Dutch-specific analyses. This study examined the cost-effectiveness of RDN from the perspective of the healthcare payer in The Netherlands. A previously constructed Markov state-transition model was adapted and updated with costs and utilities relevant to the Dutch setting. The cost-effectiveness of RDN was compared with standard of care (SoC) for patients with resistant hypertension. The efficacy of RDN treatment was modeled as a reduction in the risk of cardiovascular events associated with a lower systolic blood pressure (SBP). Treatment with RDN compared to SoC gave an incremental quality-adjusted life year (QALY) gain of 0.89 at an additional cost of €1315 over a patient's lifetime, resulting in a base case incremental cost-effectiveness ratio (ICER) of €1474. Deterministic and probabilistic sensitivity analyses (PSA) showed that treatment with RDN therapy was cost-effective at conventional willingness-to-pay thresholds (€10,000-80,000/QALY). RDN is a cost-effective intervention for patients with resistant hypertension in The Netherlands.

  3. Application of Statistical Model in Wastewater Treatment Process Modeling Using Data Analysis

    Directory of Open Access Journals (Sweden)

    Alireza Raygan Shirazinezhad

    2015-06-01

    Full Text Available Background: Wastewater treatment includes very complex and interrelated physical, chemical and biological processes which using data analysis techniques can be rigorously modeled by a non-complex mathematical calculation models. Materials and Methods: In this study, data on wastewater treatment processes from water and wastewater company of Kohgiluyeh and Boyer Ahmad were used. A total of 3306 data for COD, TSS, PH and turbidity were collected, then analyzed by SPSS-16 software (descriptive statistics and data analysis IBM SPSS Modeler 14.2, through 9 algorithm. Results: According to the results on logistic regression algorithms, neural networks, Bayesian networks, discriminant analysis, decision tree C5, tree C & R, CHAID, QUEST and SVM had accuracy precision of 90.16, 94.17, 81.37, 70.48, 97.89, 96.56, 96.46, 96.84 and 88.92, respectively. Discussion and conclusion: The C5 algorithm as the best and most applicable algorithms for modeling of wastewater treatment processes were chosen carefully with accuracy of 97.899 and the most influential variables in this model were PH, COD, TSS and turbidity.

  4. Nonparametric Bounds and Sensitivity Analysis of Treatment Effects

    Science.gov (United States)

    Richardson, Amy; Hudgens, Michael G.; Gilbert, Peter B.; Fine, Jason P.

    2015-01-01

    This paper considers conducting inference about the effect of a treatment (or exposure) on an outcome of interest. In the ideal setting where treatment is assigned randomly, under certain assumptions the treatment effect is identifiable from the observable data and inference is straightforward. However, in other settings such as observational studies or randomized trials with noncompliance, the treatment effect is no longer identifiable without relying on untestable assumptions. Nonetheless, the observable data often do provide some information about the effect of treatment, that is, the parameter of interest is partially identifiable. Two approaches are often employed in this setting: (i) bounds are derived for the treatment effect under minimal assumptions, or (ii) additional untestable assumptions are invoked that render the treatment effect identifiable and then sensitivity analysis is conducted to assess how inference about the treatment effect changes as the untestable assumptions are varied. Approaches (i) and (ii) are considered in various settings, including assessing principal strata effects, direct and indirect effects and effects of time-varying exposures. Methods for drawing formal inference about partially identified parameters are also discussed. PMID:25663743

  5. Analytical incorporation of fractionation effects in probabilistic treatment planning for intensity-modulated proton therapy.

    Science.gov (United States)

    Wahl, Niklas; Hennig, Philipp; Wieser, Hans-Peter; Bangert, Mark

    2018-04-01

    We show that it is possible to explicitly incorporate fractionation effects into closed-form probabilistic treatment plan analysis and optimization for intensity-modulated proton therapy with analytical probabilistic modeling (APM). We study the impact of different fractionation schemes on the dosimetric uncertainty induced by random and systematic sources of range and setup uncertainty for treatment plans that were optimized with and without consideration of the number of treatment fractions. The APM framework is capable of handling arbitrarily correlated uncertainty models including systematic and random errors in the context of fractionation. On this basis, we construct an analytical dose variance computation pipeline that explicitly considers the number of treatment fractions for uncertainty quantitation and minimization during treatment planning. We evaluate the variance computation model in comparison to random sampling of 100 treatments for conventional and probabilistic treatment plans under different fractionation schemes (1, 5, 30 fractions) for an intracranial, a paraspinal and a prostate case. The impact of neglecting the fractionation scheme during treatment planning is investigated by applying treatment plans that were generated with probabilistic optimization for 1 fraction in a higher number of fractions and comparing them to the probabilistic plans optimized under explicit consideration of the number of fractions. APM enables the construction of an analytical variance computation model for dose uncertainty considering fractionation at negligible computational overhead. It is computationally feasible (a) to simultaneously perform a robustness analysis for all possible fraction numbers and (b) to perform a probabilistic treatment plan optimization for a specific fraction number. The incorporation of fractionation assumptions for robustness analysis exposes a dose to uncertainty trade-off, i.e., the dose in the organs at risk is increased for a

  6. A semi-analytical model of biological effectiveness for treatment planning in light ion radiotherapy

    Czech Academy of Sciences Publication Activity Database

    Kundrát, Pavel

    2007-01-01

    Roč. 34, č. 6 (2007), s. 2654-2654 ISSN 0094-2405. [AAPM Annual Meeting. Minneapolis, 22.07.2007-26.07.2007] R&D Projects: GA ČR GA202/05/2728 Institutional research plan: CEZ:AV0Z10100502 Keywords : treatment planning * light-ion therapy * radiobiological models Subject RIV: BF - Elementary Particles and High Energy Physics Impact factor: 3.198, year: 2007

  7. Effects of Sildenafil Citrate and Heparin Treatments on Placental Cell Morphology in a Murine Model of Pregnancy Loss.

    Science.gov (United States)

    Luna, Rayana Leal; Vasconcelos, Anne Gabrielle; Nunes, Ana Karolina Santana; de Oliveira, Wilma Helena; Barbosa, Karla Patricia de Sousa; Peixoto, Christina Alves

    2016-01-01

    Lipopolysaccharide (LPS) injections during pregnancy are well established as models for pregnancy complications, including fetal growth restriction (FGR), thrombophilia, preterm labor and abortion. Indeed, inflammation, as induced by LPS injection has been described as a pivotal factor in cases of miscarriage related to placental tissue damage. The phosphodiesterase-5 inhibitor sildenafil (Viagra®) is currently used to treat FGR cases in women, while low-molecular weight heparin (Fragmin®) is a standard treatment for recurrent miscarriage (RM). However, the pathways and cellular dynamics involved in RM are not completely understood. The aim of this study was to evaluate the protective effect of sildenafil and dalteparin in a mouse model of LPS-induced abortion. Histopathology, ultrastructural analysis and immunofluorescence for P-selectin were studied in two different placental cell types: trophoblast cells and labyrinth endothelial cells. Treatment with sildenafil either alone or in combination with heparin showed the best response against LPS-induced injury during pregnancy. In conclusion, our results support the use of these drugs as future therapeutic agents that may protect the placenta against inflammatory injury in RM events. Analyses of the ultrastructure and placental immunophysiology are important to understand the mechanism underlying RM. These findings may spark future studies and aid in the development of new therapies in cases of RM. © 2016 S. Karger AG, Basel.

  8. Gold nanoclusters-assisted delivery of NGF siRNA for effective treatment of pancreatic cancer

    Science.gov (United States)

    Lei, Yifeng; Tang, Lixue; Xie, Yangzhouyun; Xianyu, Yunlei; Zhang, Lingmin; Wang, Peng; Hamada, Yoh; Jiang, Kai; Zheng, Wenfu; Jiang, Xingyu

    2017-01-01

    Pancreatic cancer is one of the deadliest human cancers, whose progression is highly dependent on the nervous microenvironment. The suppression of gene expression of nerve growth factor (NGF) may have great potential in pancreatic cancer treatment. Here we show that gold nanocluster-assisted delivery of siRNA of NGF (GNC–siRNA) allows efficient NGF gene silencing and pancreatic cancer treatment. The GNC–siRNA complex increases the stability of siRNA in serum, prolongs the circulation lifetime of siRNA in blood and enhances the cellular uptake and tumour accumulation of siRNA. The GNC–siRNA complex potently downregulates the NGF expression in Panc-1 cells and in pancreatic tumours, and effectively inhibits the tumour progression in three pancreatic tumour models (subcutaneous model, orthotopic model and patient-derived xenograft model) without adverse effects. Our study constitutes a straightforward but effective approach to inhibit pancreatic cancer via NGF knockdown, suggesting a promising therapeutic direction for pancreatic cancer. PMID:28440296

  9. Treatment Effect on Recidivism for Juveniles Who Have Sexually Offended: a Multilevel Meta-Analysis.

    Science.gov (United States)

    Ter Beek, Ellis; Spruit, Anouk; Kuiper, Chris H Z; van der Rijken, Rachel E A; Hendriks, Jan; Stams, Geert Jan J M

    2018-04-01

    The current study investigated the effect on recidivism of treatment aimed at juveniles who have sexually offended. It also assessed the potential moderating effect of type of recidivism, and several treatment, participant and study characteristics. In total, 14 published and unpublished primary studies, making use of a comparison group and reporting on official recidivism rates, were included in a multilevel meta-analysis. This resulted in the use of 77 effect sizes, and 1726 participants. A three-level meta-analytic model was used to calculate the combined effect sizes (Cohens d) and to perform moderator analyses. Study quality was assessed with the EPHPP Quality Assessment Tool for Quantitative Studies. A moderate effect size was found (d = 0.37), indicating that the treatment groups achieved an estimated relative reduction in recidivism of 20.5% as compared to comparison groups. However, after controlling for publication bias, a significant treatment effect was no longer found. Type of recidivism did not moderate the effect of treatment, indicating that treatment groups were equally effective for all types of recidivism. Also, no moderating effects of participant or treatment characteristics were found. Regarding study characteristics, a shorter follow up time showed a trend for larger effect sizes, and the effect size calculation based on proportions yielded larger effect sizes than calculation via mean frequency of offending. Implications for future research and clinical practice are discussed.

  10. Cost-effectiveness of hepatitis C treatment using generic direct-acting antivirals available in India.

    Directory of Open Access Journals (Sweden)

    Rakesh Aggarwal

    Full Text Available Availability of directly-acting antivirals (DAAs has changed the treatment landscape of hepatitis C virus (HCV infection. The high price of DAAs has restricted their use in several countries. However, in some countries such as India, generic DAAs are available at much cheaper price. This study examined whether generic DAAs could be cost-saving and how long it would take for the treatment to become cost-saving/effective.A previously-validated, mathematical model was adapted to the HCV-infected population in India to compare the outcomes of no treatment versus treatment with DAAs. Model parameters were estimated from published studies. Cost-effectiveness of HCV treatment using available DAAs was calculated, using a payer's perspective. We estimated quality-adjusted life years (QALYs, disability-adjusted life years (DALYs, total costs, and incremental cost-effectiveness ratio of DAAs versus no treatment. One-way and probabilistic sensitivity analyses were conducted.Compared with no treatment, the use of generic DAAs in Indian HCV patients would increase the life expectancy by 8.02 years, increase QALYs by 3.89, avert 19.07 DALYs, and reduce the lifetime healthcare costs by $1,309 per-person treated. Treatment became cost-effective within 2 years, and cost-saving within 10 years of its initiation overall and within 5 years in persons with cirrhosis. Treating 10,000 HCV-infected persons could prevent 3400-3850 decompensated cirrhosis, 1800-2500 HCC, and 4000-4550 liver-related deaths. The results were sensitive to the costs of DAAs, pre- and post-treatment diagnostic tests and management of cirrhosis, and quality of life after sustained virologic response.Treatment with generic DAAs available in India will improve patient outcomes, provide a good value for money within 2 years, and be ultimately cost-saving. Therefore, in this and similar settings, HCV treatment should be a priority from a public health as well an economic perspective.

  11. Gender effects on treatment response to interferon-beta in multiple sclerosis

    DEFF Research Database (Denmark)

    Magyari, M; Koch-Henriksen, N; Laursen, B

    2014-01-01

    BACKGROUND: Gender appears to play a role in incidence and disease course of multiple sclerosis (MS). OBJECTIVE: The objective was to determine whether male and female patients with MS respond differently to interferon-beta treatment in terms of reduction in relapse rates. METHODS: We included all....... Patients served as their own controls, and relapse rates were compared between NAb-negative and NAb-positive periods. RESULTS: NAbs significantly abrogated the interferon-beta treatment efficacy in both genders. The all-over women:men relapse rate ratio irrespective of NAb status was 1.47 (95%CI; 1.......28-1.68). In a generalized linear Poisson models analysis with relapse counts as response variable, the main effects NAbs, sex, age at treatment start and number of relapses in 2 years before treatment start were strongly significant, but the effect of NAbs on relapse rates did not differ significantly between men and women...

  12. Treatment planning for heavy ion radiotherapy: calculation and optimization of biologically effective dose

    International Nuclear Information System (INIS)

    Kraemer, M.; Scholz, M.

    2000-09-01

    We describe a novel approach to treatment planning for heavy ion radiotherapy based on the local effect model (LEM) which allows to calculate the biologically effective dose not only for the target region but for the entire irradiation volume. LEM is ideally suited to be used as an integral part of treatment planning code systems for active dose shaping devices like the GSI raster scan system. Thus, it has been incorporated into our standard treatment planning system for ion therapy (TRiP). Single intensity modulated fields can be optimized with respect to homogeneous biologically effective dose. The relative biological effectiveness (RBE) is calculated separately for each voxel of the patient CT. Our radiobiologically oriented code system is in use since 1995 for the planning of irradiation experiments with cell cultures and animals such as rats and minipigs. Since 1997 it is in regular and successful use for patient treatment planning. (orig.)

  13. Maximizing cost-effectiveness by adjusting treatment strategy according to glaucoma severity

    Science.gov (United States)

    Guedes, Ricardo Augusto Paletta; Guedes, Vanessa Maria Paletta; Gomes, Carlos Eduardo de Mello; Chaoubah, Alfredo

    2016-01-01

    Abstract Background: The aim of this study is to determine the most cost-effective strategy for the treatment of primary open-angle glaucoma (POAG) in Brazil, from the payer's perspective (Brazilian Public Health System) in the setting of the Glaucoma Referral Centers. Methods: Study design was a cost-effectiveness analysis of different treatment strategies for POAG. We developed 3 Markov models (one for each glaucoma stage: early, moderate and advanced), using a hypothetical cohort of POAG patients, from the perspective of the Brazilian Public Health System (SUS) and a horizon of the average life expectancy of the Brazilian population. Different strategies were tested according to disease severity. For early glaucoma, we compared observation, laser and medications. For moderate glaucoma, medications, laser and surgery. For advanced glaucoma, medications and surgery. Main outcome measures were ICER (incremental cost-effectiveness ratio), medical direct costs and QALY (quality-adjusted life year). Results: In early glaucoma, both laser and medical treatment were cost-effective (ICERs of initial laser and initial medical treatment over observation only, were R$ 2,811.39/QALY and R$ 3,450.47/QALY). Compared to observation strategy, the two alternatives have provided significant gains in quality of life. In moderate glaucoma population, medical treatment presented the highest costs among treatment strategies. Both laser and surgery were highly cost-effective in this group. For advanced glaucoma, both tested strategies were cost-effective. Starting age had a great impact on results in all studied groups. Initiating glaucoma therapy using laser or surgery were more cost-effective, the younger the patient. Conclusion: All tested treatment strategies for glaucoma provided real gains in quality of life and were cost-effective. However, according to the disease severity, not all strategies provided the same cost-effectiveness profile. Based on our findings, there should be a

  14. Process modeling for the Integrated Nonthermal Treatment System (INTS) study

    Energy Technology Data Exchange (ETDEWEB)

    Brown, B.W.

    1997-04-01

    This report describes the process modeling done in support of the Integrated Nonthermal Treatment System (INTS) study. This study was performed to supplement the Integrated Thermal Treatment System (ITTS) study and comprises five conceptual treatment systems that treat DOE contract-handled mixed low-level wastes (MLLW) at temperatures of less than 350{degrees}F. ASPEN PLUS, a chemical process simulator, was used to model the systems. Nonthermal treatment systems were developed as part of the INTS study and include sufficient processing steps to treat the entire inventory of MLLW. The final result of the modeling is a process flowsheet with a detailed mass and energy balance. In contrast to the ITTS study, which modeled only the main treatment system, the INTS study modeled each of the various processing steps with ASPEN PLUS, release 9.1-1. Trace constituents, such as radionuclides and minor pollutant species, were not included in the calculations.

  15. Refinement of the basic treatment equivalent model to reflect radiotherapy treatment throughput using Australasian data

    International Nuclear Information System (INIS)

    Delaney, G.; Gebski, V.; Sydney University, NSW; Lunn, A.D.; Open University, Milton Keynes,; Oxford University, Oxford,; Lunn, M.; Oxford University, Oxford,

    1999-01-01

    The present study aims to develop a more sensitive basic treatment equivalent (BTE) model that still measures linear accelerator throughput and considers some of the shortcomings of the previous model. All radiation oncology departments in Australia and New Zealand were invited to participate. Departments were asked to time with a stopwatch all episodes of radiotherapy treatment over a 4-week period. Data collected for each treatment fraction included treatment intent, tumour site, patient age, Eastern Cooperative Oncology Group (ECOG) performance status, number of fields used, number of wedges used, number of junctions, number of shielding blocks used, whether the treatment was the first fraction, the use of general anaesthesia and whether port films or electronic portal imaging was used. Twenty-six departments of radiation oncology (70%) participated in this trial. A total of 7929 fractions of treatment, administered to 2424 patients, were timed. The factors found to most significantly impact on treatment duration on multivariate analysis were the type of fraction (first fraction was longer than subsequent fractions), type of beam (electrons were quicker than photons, which were quicker than mixed), number of fields, number of shields, number of junctions, number of port films and performance status (ECOG 2). The age of the patient, number of compensators and the sex of the patient were not significant. The relationships between factors were assessed, and models of measuring linear accelerator throughput which consider complexity corrections were derived. It is possible to show that linear accelerator throughput is poorly measured by just considering numbers of patients or fields treated per unit time; and that other factors that impact on treatment duration must be considered. A more sensitive model of patient throughput is suggested; but even when a large number of factors are considered, some insensitivity still remains in the model. Copyright (1999) Blackwell

  16. Histopathologic and metabolic effect of ursodeoxycholic acid treatment on PCOS rat model.

    Science.gov (United States)

    Gozukara, Ilay; Dokuyucu, Recep; Özgür, Tümay; Özcan, Oguzhan; Pınar, Neslihan; Kurt, Raziye Keskin; Kucur, Suna Kabil; Dolapçı, Kenan

    2016-06-01

    The aim of this study was to determine the effect of ursodeoxycholic acid (UDCA) treatment on a polycystic ovary syndrome (PCOS) rat model. Thirty-two female Wistar-Albino rats were randomly divided into four groups as follows - group 1: sham group (n: 8), group 2: letrozole-induced PCOS group (n: 8), group 3: letrozole-induced PCOS plus metformin-treated (500 mg/kg) group (n: 8) and group 4: letrozole-induced PCOS plus UDCA (150 mg/kg)-treated group (n: 8). Histopathologic examination of the ovaries, circulating estrone (E1), estradiol (E2), testosterone, androstenedione, glucose, insulin and lipid profiles were evaluated. Histopathologic examination results revealed that groups 3 and 4 had significantly lower cystic and atretic follicles compared to group 2. Besides, group 4 had significantly higher antral follicles than group 2 (8.5 ± 2.9 versus 5.4 ± 1.1; p: 0.001). Furthermore, total testosterone (4.9 ± 2.8 versus 8.8 ± 2.9; p= 0.004) and insulin levels were significantly lower in group 4 compared to group 2 (1.7 ± 0.08 versus 2.1 ± 0.5; p = 0.02). However, lipid parameters, E1, E2, glucose and HOMA-IR were comparable between the groups. Our study results demonstrated that UDCA therapy improves ovarian morphology and decreases total testosterone and insulin levels.

  17. New framework for standardized notation in wastewater treatment modelling

    DEFF Research Database (Denmark)

    Corominas, L.; Rieger, L.; Takacs, I.

    2010-01-01

    Many unit process models are available in the field of wastewater treatment. All of these models use their own notation, causing problems for documentation, implementation and connection of different models (using different sets of state variables). The main goal of this paper is to propose a new...... is a framework that can be used in whole plant modelling, which consists of different fields such as activated sludge, anaerobic digestion, sidestream treatment, membrane bioreactors, metabolic approaches, fate of micropollutants and biofilm processes. The main objective of this consensus building paper...... notational framework which allows unique and systematic naming of state variables and parameters of biokinetic models in the wastewater treatment field. The symbols are based on one main letter that gives a general description of the state variable or parameter and several subscript levels that provide...

  18. Cost-effectiveness of treatments reducing coronary heart disease mortality in Ireland, 2000 to 2010.

    LENUS (Irish Health Repository)

    Bennett, Kathleen

    2009-01-01

    OBJECTIVE: Coronary heart disease (CHD) is associated with a large burden of disease in Ireland and is responsible for more than 6000 deaths annually. This study examined the cost-effectiveness of specific CHD treatments in Ireland. METHODS: Irish epidemiological data on patient numbers and median survival in specific groups, plus the uptake, effectiveness, and costs of specific interventions, all stratified by age and sex, were incorporated into a previously validated CHD mortality model, the IMPACT model. This model calculates the number of life-years gained (LYGs) by specific cardiology interventions to generate incremental cost-effectiveness ratios (ICERs) per LYG for each intervention. RESULTS: In 2000, medical and surgical treatments together prevented or postponed approximately 1885 CHD deaths in patients aged 25 to 84 years, and thus generated approximately 14,505 extra life-years (minimum 7270, maximum 22,475). In general, all the cardiac interventions investigated were highly cost-effective in the Irish setting. Aspirin, beta-blockers, ACE inhibitors, spironolactone, and warfarin for specific conditions were the most cost-effective interventions (< euro 3000\\/LYG), followed by the statins for secondary prevention (< euro 6500\\/LYG). Revascularization for chronic angina and primary angioplasty for myocardial infarction, although still cost-effective, had the highest ICER (between euro 12,000 and euro 20,000\\/LYG). CONCLUSIONS: Using a comprehensive standardized methodology, cost-effectiveness ratios in this study clearly favored simple medical treatments for myocardial infarction, secondary prevention, angina, and heart failure.

  19. A treatment model for craving identification and management.

    Science.gov (United States)

    Stalcup, S Alex; Christian, Darrell; Stalcup, Janice; Brown, Michelle; Galloway, Gantt P

    2006-06-01

    This article presents an addiction treatment model based on craving identification and management (CIM). Craving is broadly defined as the desire to use alcohol or other drugs; it increases the likelihood of use of these substances. In the CIM Model treatment interventions are referenced to craving, i.e., helping clients to identify their craving level and equipping them with strategies to avoid use. Four causes of craving are identified: (1) environmental cues (triggers): exposure to people, places, and things associated with prior drug-using experiences may cause immediate and overwhelming craving; (2) stress: addicted persons experience stress as craving; (3) mental illness; and (4) drug withdrawal: symptoms of both mental illness and withdrawal lead to craving if clients associate use with relief of these symptoms. The CIM Model incorporates four service delivery elements: Relapse Prevention Workshop, individual counseling, medical/psychiatric services, and screening for ongoing drug use. At its core, the CIM Model asks clients to be aware of craving, analyze its causes, and, based on those causes, implement specific strategies to prevent and manage craving. The CIM Model combines several treatment components, including control of exposure to environmental cues, establishment of a daily schedule, the use of behaviors that dissipate craving (tools), and treatment (with medications when appropriate) of mental health and withdrawal symptoms. The CIM Model is a client-derived approach to achieving and maintaining sobriety based on a process of analyzing craving and managing it with an individualized program of recovery activities.

  20. Modelling malaria treatment practices in Bangladesh using spatial statistics

    Directory of Open Access Journals (Sweden)

    Haque Ubydul

    2012-03-01

    Full Text Available Abstract Background Malaria treatment-seeking practices vary worldwide and Bangladesh is no exception. Individuals from 88 villages in Rajasthali were asked about their treatment-seeking practices. A portion of these households preferred malaria treatment from the National Control Programme, but still a large number of households continued to use drug vendors and approximately one fourth of the individuals surveyed relied exclusively on non-control programme treatments. The risks of low-control programme usage include incomplete malaria treatment, possible misuse of anti-malarial drugs, and an increased potential for drug resistance. Methods The spatial patterns of treatment-seeking practices were first examined using hot-spot analysis (Local Getis-Ord Gi statistic and then modelled using regression. Ordinary least squares (OLS regression identified key factors explaining more than 80% of the variation in control programme and vendor treatment preferences. Geographically weighted regression (GWR was then used to assess where each factor was a strong predictor of treatment-seeking preferences. Results Several factors including tribal affiliation, housing materials, household densities, education levels, and proximity to the regional urban centre, were found to be effective predictors of malaria treatment-seeking preferences. The predictive strength of each of these factors, however, varied across the study area. While education, for example, was a strong predictor in some villages, it was less important for predicting treatment-seeking outcomes in other villages. Conclusion Understanding where each factor is a strong predictor of treatment-seeking outcomes may help in planning targeted interventions aimed at increasing control programme usage. Suggested strategies include providing additional training for the Building Resources across Communities (BRAC health workers, implementing educational programmes, and addressing economic factors.

  1. An Integrated Model for Identifying Linkages Between the Management of Fuel Treatments, Fire and Ecosystem Services

    Science.gov (United States)

    Bart, R. R.; Anderson, S.; Moritz, M.; Plantinga, A.; Tague, C.

    2015-12-01

    Vegetation fuel treatments (e.g. thinning, prescribed burning) are a frequent tool for managing fire-prone landscapes. However, predicting how fuel treatments may affect future wildfire risk and associated ecosystem services, such as forest water availability and streamflow, remains a challenge. This challenge is in part due to the large range of conditions under which fuel treatments may be implemented, as response is likely to vary with species type, rates of vegetation regrowth, meteorological conditions and physiographic properties of the treated site. It is also due to insufficient understanding of how social factors such as political pressure, public demands and economic constraints affect fuel management decisions. To examine the feedbacks between ecological and social dimensions of fuel treatments, we present an integrated model that links a biophysical model that simulates vegetation and hydrology (RHESSys), a fire spread model (WMFire) and an empirical fuel treatment model that accounts for agency decision-making. We use this model to investigate how management decisions affect landscape fuel loads, which in turn affect fire severity and ecosystem services, which feedback to management decisions on fuel treatments. We hypothesize that this latter effect will be driven by salience theory, which predicts that fuel treatments are more likely to occur following major wildfire events. The integrated model provides a flexible framework for answering novel questions about fuel treatments that span social and ecological domains, areas that have previously been treated separately.

  2. Effects of gypenosides on anxiety disorders in MPTP-lesioned mouse model of Parkinson's disease.

    Science.gov (United States)

    Shin, Keon Sung; Zhao, Ting Ting; Choi, Hyun Sook; Hwang, Bang Yeon; Lee, Chong Kil; Lee, Myung Koo

    2014-06-03

    Ethanol extract (GP-EX) of Gynostemma pentaphyllum (GP) ameliorates chronic stress-induced anxiety in mice. The present study investigated the effects of gypenoside-enriched components (GPS), GP-EX and water extract of GP (GP-WX) on MPTP lesion-induced affective disorders in C57BL/6 mice. GPS (50mg/kg) and GP-EX (50mg/kg) for 21 day-treatment period improved the symptom of anxiety disorders in the MPTP-lesioned mouse model of PD with or without L-DOPA treatment, which was examined by the elevated plus-maze and marble burying tests. In these states, treatments with GPS (50mg/kg) and GP-EX (50mg/kg) significantly increased the brain levels of dopamine and serotonin in the MPTP-lesioned mouse model of PD with or without l-DOPA treatment. In addition, treatments with GPS (50mg/kg) and GP-EX (50mg/kg) showed protective effects on dopaminergic neurons in MPTP-lesioned mouse model of PD with or without L-DOPA treatment. In contrast, GPS (30 mg/kg) and GP-WX (50mg/kg) showed anxiolytic effects in the same animal models, but it was not significant. These results suggest that GPS (50mg/kg) and GP-EX (50mg/kg) showed anxiolytic effects on affective disorders and protective effects on dopaminergic neurons by modulating the brain levels of dopamine and serotonin in the MPTP-lesioned mouse model of PD with or without l-DOPA treatment. Clinical trials of GPS and GP-EX need to be conducted further so as to develop adjuvant therapeutic agents for PD patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Sexually transmitted infections screening at HIV treatment centers for MSM can be cost-effective

    NARCIS (Netherlands)

    Vriend, Henrike J.; Lugnér, Anna K.; Xiridou, Maria; Van Der Loeff, Maarten F. Schim; Prins, Maria; De Vries, Henry J.C.; Geerlings, Suzanne E.; Prins, Jan M.; Rijnders, Bart J.A.; Van Veen, Maaike G.; Fennema, Johannes S.A.; Postma, Maarten J.; Van Der Sande, Marianne A.B.

    2013-01-01

    Objective:To estimate the cost-effectiveness of anorectal chlamydia screening among men who have sex with men (MSM) in care at HIV treatment centers. Design:Transmission model combined with economic analysis over a 20-year period. Setting and participants:MSM in care at HIV treatment centers.

  4. A mathematical model for long-term effect of diethylcarbamazine-albendazole mass drug administration on lymphatic filariasis

    Science.gov (United States)

    Tasman, H.; Supali, T.; Supriatna, A. K.; Nuraini, N.; Soewono, E.

    2015-03-01

    In this paper we discuss a mathematical model for the transmission of lymphatic filariasis disease. The human population is divided into susceptible, latent, acute and chronic subpopulations. Treatment is carried out within the scheme of mass drug administration (MDA) by giving the diethylcarbamazine (DEC) and albendazole (ALB) to all individuals. In the model, we assume that the treatments have direct killing effect to microfilariae, increase of immune-mediated effect. The treated individuals are assumed to remain susceptible to the disease. This is due to the fact that the treatment is only partially effective against macrofilaria. Simulations of the model reveals that DEC-ALB treatment does give significant reduction of acute and chronic compartments at the end of the treatment period and slow down the growth after the treatment before eventually tend to the endemic state. It showed that repeated treatment during MDA is effective to decrease the transmission. This suggests that terminating MDA program after a long period of its application may still effective in controlling the disease.

  5. Learning Effective Treatment Pathways for Type-2 Diabetes from a clinical data warehouse.

    Science.gov (United States)

    Vashisht, Rohit; Jung, Ken; Shah, Nigam

    2016-01-01

    Treatment guidelines for management of type-2 diabetes mellitus (T2DM) are controversial because existing evidence from randomized clinical trials do not address many important clinical questions. Data from Electronic Medical Records (EMRs) has been used to profile first line therapy choices, but this work did not elucidate the factors underlying deviations from current treatment guidelines and the relative efficacy of different treatment options. We have used data from the Stanford Hospital to attempt to address these issues. Clinical features associated with the initial choice of treatment were effectively re-discovered using a machine learning approach. In addition, the efficacies of first and second line treatments were evaluated using Cox proportional hazard models for control of Hemoglobin A 1c . Factors such as acute kidney disorder and liver disorder were predictive of first line therapy choices. Sitagliptin was the most effective second-line therapy, and as effective as metformin as a first line therapy.

  6. Modeling the cost-effectiveness of ilaprazole versus omeprazole for the treatment of newly diagnosed duodenal ulcer patients in China.

    Science.gov (United States)

    Xuan, J W; Song, R L; Xu, G X; Lu, W Q; Lu, Y J; Liu, Z

    2016-11-01

    To evaluate the cost-effectiveness of 10 mg ilaprazole once-daily vs 20 mg omeprazole once-daily to treat newly-diagnosed duodenal ulcer patients in China. A decision tree model was constructed and the treatment impact was projected up to 1 year. The CYP2C19 polymorphism distribution in the Chinese population, the respective cure rates in the CYP2C19 genotype sub-groups, the impact of Duodenal Ulcer (DU) on utility value and drug-related side-effect data were obtained from the literature. The total costs of medications were calculated to estimate the treatment costs based on current drug retail prices in China. Expert surveys were conducted when published data were not available. Probabilistic sensitivity analysis was performed to gauge the robustness of the results. Ilaprazole, when compared with omeprazole, achieved a better overall clinical efficacy. For the overall population, ilaprazole achieved an incremental cost effectiveness ratio (ICER) of ¥132 056 per QALY gained. This is less than the WHO recommended threshold of 3-times the average GDP per capita in China (2014). Furthermore, sub-group analysis showed that ilaprazole is cost-effective in every province in CYP2C19 hetEM patients and in the most developed provinces in CYP2C19 homEM patients. Probabilistic sensitivity analysis suggests that the results are robust with 97% probability that ilaprozole is considered cost-effective when a threshold of 3-times China's average GDP per capita is considered. This study didn't have the data of ilaprazole combined with Hp eradication therapy. Caution should be taken when extrapolating these findings to DU patients with an Hp eradication therapy. The cost-effectiveness analysis results demonstrated that ilaprazole would be considered a cost-effective therapy, compared with omeprazole, in Chinese DU patients based on the efficacy projections in various CYP2C19 polymorphism types.

  7. Modeling Patient Treatment With Medical Records: An Abstraction Hierarchy to Understand User Competencies and Needs.

    Science.gov (United States)

    St-Maurice, Justin D; Burns, Catherine M

    2017-07-28

    Health care is a complex sociotechnical system. Patient treatment is evolving and needs to incorporate the use of technology and new patient-centered treatment paradigms. Cognitive work analysis (CWA) is an effective framework for understanding complex systems, and work domain analysis (WDA) is useful for understanding complex ecologies. Although previous applications of CWA have described patient treatment, due to their scope of work patients were previously characterized as biomedical machines, rather than patient actors involved in their own care. An abstraction hierarchy that characterizes patients as beings with complex social values and priorities is needed. This can help better understand treatment in a modern approach to care. The purpose of this study was to perform a WDA to represent the treatment of patients with medical records. The methods to develop this model included the analysis of written texts and collaboration with subject matter experts. Our WDA represents the ecology through its functional purposes, abstract functions, generalized functions, physical functions, and physical forms. Compared with other work domain models, this model is able to articulate the nuanced balance between medical treatment, patient education, and limited health care resources. Concepts in the analysis were similar to the modeling choices of other WDAs but combined them in as a comprehensive, systematic, and contextual overview. The model is helpful to understand user competencies and needs. Future models could be developed to model the patient's domain and enable the exploration of the shared decision-making (SDM) paradigm. Our work domain model links treatment goals, decision-making constraints, and task workflows. This model can be used by system developers who would like to use ecological interface design (EID) to improve systems. Our hierarchy is the first in a future set that could explore new treatment paradigms. Future hierarchies could model the patient as a

  8. Optimization model for the design of distributed wastewater treatment networks

    Directory of Open Access Journals (Sweden)

    Ibrić Nidret

    2012-01-01

    Full Text Available In this paper we address the synthesis problem of distributed wastewater networks using mathematical programming approach based on the superstructure optimization. We present a generalized superstructure and optimization model for the design of the distributed wastewater treatment networks. The superstructure includes splitters, treatment units, mixers, with all feasible interconnections including water recirculation. Based on the superstructure the optimization model is presented. The optimization model is given as a nonlinear programming (NLP problem where the objective function can be defined to minimize the total amount of wastewater treated in treatment operations or to minimize the total treatment costs. The NLP model is extended to a mixed integer nonlinear programming (MINLP problem where binary variables are used for the selection of the wastewater treatment technologies. The bounds for all flowrates and concentrations in the wastewater network are specified as general equations. The proposed models are solved using the global optimization solvers (BARON and LINDOGlobal. The application of the proposed models is illustrated on the two wastewater network problems of different complexity. First one is formulated as the NLP and the second one as the MINLP. For the second one the parametric and structural optimization is performed at the same time where optimal flowrates, concentrations as well as optimal technologies for the wastewater treatment are selected. Using the proposed model both problems are solved to global optimality.

  9. Using Multisite Experiments to Study Cross-Site Variation in Treatment Effects: A Hybrid Approach with Fixed Intercepts and A Random Treatment Coefficient

    Science.gov (United States)

    Bloom, Howard S.; Raudenbush, Stephen W.; Weiss, Michael J.; Porter, Kristin

    2017-01-01

    The present article considers a fundamental question in evaluation research: "By how much do program effects vary across sites?" The article first presents a theoretical model of cross-site impact variation and a related estimation model with a random treatment coefficient and fixed site-specific intercepts. This approach eliminates…

  10. A novel design for randomized immuno-oncology clinical trials with potentially delayed treatment effects

    Directory of Open Access Journals (Sweden)

    Pei He

    2015-10-01

    Full Text Available The semi-parametric proportional hazards model is widely adopted in randomized clinical trials with time-to-event outcomes, and the log-rank test is frequently used to detect a potential treatment effect. Immuno-oncology therapies pose unique challenges to the design of a trial as the treatment effect may be delayed, which violates the proportional hazards assumption, and the log-rank test has been shown to markedly lose power under the non-proportional hazards setting. A novel design and analysis approach for immuno-oncology trials is proposed through a piecewise treatment effect function, which is capable of detecting a potentially delayed treatment effect. The number of events required for the trial will be determined to ensure sufficient power for both the overall log-rank test without a delayed effect and the test beyond the delayed period when such a delay exists. The existence of a treatment delay is determined by a likelihood ratio test with resampling. Numerical results show that the proposed design adequately controls the Type I error rate, has a minimal loss in power under the proportional hazards setting and is markedly more powerful than the log-rank test with a delayed treatment effect.

  11. Differential effectiveness of placebo treatments

    DEFF Research Database (Denmark)

    Meissner, Karin; Fässler, Margrit; Rücker, Gerta

    2013-01-01

    IMPORTANCE When analyzing results of randomized clinical trials, the treatment with the greatest specific effect compared with its placebo control is considered to be the most effective one. Although systematic variations of improvements in placebo control groups would have important implications...... relevant sources through February 2012 and contacted the authors to identify randomized clinical trials on the prophylaxis of migraine with an observation period of at least 8 weeks after randomization that compared an experimental treatment with a placebo control group. We calculated pooled random-effects...... and sham surgery are associated with higher responder ratios than oral pharmacological placebos. Clinicians who treat patients with migraine should be aware that a relevant part of the overall effect they observe in practice might be due to nonspecific effects and that the size of such effects might differ...

  12. Dynamic Computational Model of Symptomatic Bacteremia to Inform Bacterial Separation Treatment Requirements.

    Directory of Open Access Journals (Sweden)

    Sinead E Miller

    Full Text Available The rise of multi-drug resistance has decreased the effectiveness of antibiotics, which has led to increased mortality rates associated with symptomatic bacteremia, or bacterial sepsis. To combat decreasing antibiotic effectiveness, extracorporeal bacterial separation approaches have been proposed to capture and separate bacteria from blood. However, bacteremia is dynamic and involves host-pathogen interactions across various anatomical sites. We developed a mathematical model that quantitatively describes the kinetics of pathogenesis and progression of symptomatic bacteremia under various conditions, including bacterial separation therapy, to better understand disease mechanisms and quantitatively assess the biological impact of bacterial separation therapy. Model validity was tested against experimental data from published studies. This is the first multi-compartment model of symptomatic bacteremia in mammals that includes extracorporeal bacterial separation and antibiotic treatment, separately and in combination. The addition of an extracorporeal bacterial separation circuit reduced the predicted time of total bacteria clearance from the blood of an immunocompromised rodent by 49%, compared to antibiotic treatment alone. Implementation of bacterial separation therapy resulted in predicted multi-drug resistant bacterial clearance from the blood of a human in 97% less time than antibiotic treatment alone. The model also proposes a quantitative correlation between time-dependent bacterial load among tissues and bacteremia severity, analogous to the well-known 'area under the curve' for characterization of drug efficacy. The engineering-based mathematical model developed may be useful for informing the design of extracorporeal bacterial separation devices. This work enables the quantitative identification of the characteristics required of an extracorporeal bacteria separation device to provide biological benefit. These devices will potentially

  13. Regulatory odour model development: Survey of modelling tools and datasets with focus on building effects

    DEFF Research Database (Denmark)

    Olesen, H. R.; Løfstrøm, P.; Berkowicz, R.

    dispersion models for estimating local concentration levels in general. However, the report focuses on some particular issues, which are relevant for subsequent work on odour due to animal production. An issue of primary concern is the effect that buildings (stables) have on flow and dispersion. The handling...... of building effects is a complicated problem, and a major part of the report is devoted to the treatment of building effects in dispersion models......A project within the framework of a larger research programme, Action Plan for the Aquatic Environment III (VMP III) aims towards improving an atmospheric dispersion model (OML). The OML model is used for regulatory applications in Denmark, and it is the candidate model to be used also in future...

  14. Modeling and analyzing the effects of heat treatment on the characteristics of magnesium alloy joint welded by the tungsten-arc inert gas welding

    International Nuclear Information System (INIS)

    Tsai, Te-Chang; Chou, Chih-Chung; Tsai, Deng-Maw; Chiang, Ko-Ta

    2011-01-01

    Highlights: → The mathematical model was provided to study the effect of heat treatment on the magnesium alloy welded joint. → The solution strengthening effect of β-phase Mg 17 Al 12 gain promotes the strengthening matrix and ductility of hcp-α-phase Mg. → The average size and proportion of α-phase Mg grain decreases with the increase of the tempering time and temperature. → An increase in the high value of tempering temperature and tempering time leads to increase the maximum tensile strength. → The values of the elongation increases with increasing in both the value of tempering temperature and tempering time. -- Abstract: The objective of this paper is to present the mathematical models for modeling and analysis of the effects of heat treatment on the characteristics of magnesium alloy joint welded by the tungsten-arc inert gas (TIG) welding. The process of heat treatment adopts the tempering process with varying processing parameters, including tempering temperature and tempering time. The microstructure and mechanical properties of the welded joint are considered in the characteristic evaluation and explored by experiment. An experimental plan of the face-centered central composite design (CCD) based on the response surface methodology (RSM) has been employed to carry out the experimental study. The results of analysis of variance (ANOVA) and comparisons of experimental data show that the mathematical models of the value of the maximum tensile strength and elongation are fairly well fitted with the experimental values with a 95% confidence interval. In the tempering process, the microstructure of welded joint in the weld bead displays two main microstructures of hcp-α-phase Mg and bcc-β-phase Mg 17 Al 12 . Results show that the average size and proportion of α-phase Mg grains decreases with the increase of the tempering time and temperature. But, the increase of the tempering time and temperature promote increasing the average size and

  15. Cost-effectiveness of treatment strategies for BRAF-mutated metastatic melanoma.

    Directory of Open Access Journals (Sweden)

    Patti Curl

    Full Text Available Genetically-targeted therapies are both promising and costly advances in the field of oncology. Several treatments for metastatic melanoma with a mutation in the BRAF gene have been approved. They extend life but are more expensive than the previous standard of care (dacarbazine. Vemurafenib, the first drug in this class, costs $13,000 per month ($207,000 for a patient with median survival. Patients failing vemurafenib are often given ipilimumab, an immunomodulator, at $150,000 per course. Assessment of cost-effectiveness is a valuable tool to help navigate the transition toward targeted cancer therapy.We performed a cost-utility analysis to compare three strategies for patients with BRAF+ metastatic melanoma using a deterministic expected-value decision tree model to calculate the present value of lifetime costs and quality-adjusted life years (QALYs for each strategy. We performed sensitivity analyses on all variables.In the base case, the incremental cost-effectiveness ratio (ICER for vemurafenib compared with dacarbazine was $353,993 per QALY gained (0.42 QALYs added, $156,831 added. The ICER for vemurafenib followed by ipilimumab compared with vemurafenib alone was $158,139. In sensitivity analysis, treatment cost had the largest influence on results: the ICER for vemurafenib versus dacarbazine dropped to $100,000 per QALY gained with a treatment cost of $3600 per month.The cost per QALY gained for treatment of BRAF+ metastatic melanoma with vemurafenib alone or in combination exceeds widely-cited thresholds for cost-effectiveness. These strategies may become cost-effective with lower drug prices or confirmation of a durable response without continued treatment.

  16. Out of Warburg effect: An effective cancer treatment targeting the tumor specific metabolism and dysregulated pH.

    Science.gov (United States)

    Schwartz, Laurent; Seyfried, Thomas; Alfarouk, Khalid O; Da Veiga Moreira, Jorgelindo; Fais, Stefano

    2017-04-01

    As stated by Otto Warburg nearly a century ago, cancer is a metabolic disease, a fermentation caused by malfunctioning mitochondria, resulting in increased anabolism and decreased catabolism. Treatment should, therefore, aim at restoring the energy yield. To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase catabolism, the oxidative phosphorylation should be restored. Treatment with a combination of α-lipoic acid and hydroxycitrate has been shown to be effective in multiple animal models. This treatment, in combination with conventional chemotherapy, has yielded extremely encouraging results in glioblastoma, brain metastasis and lung cancer. Randomized trials are necessary to confirm these preliminary data. The major limitation is the fact that the combination of α-lipoic acid and hydroxycitrate can only be effective if the mitochondria are still present and/or functional. That may not be the case in the most aggressive tumors. The increased intracellular alkalosis is a strong mitogenic signal, which bypasses most inhibitory signals. Concomitant correction of this alkalosis may be a very effective treatment in case of mitochondrial failure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Evaluation and comparison of models and modelling tools simulating nitrogen processes in treatment wetlands

    DEFF Research Database (Denmark)

    Edelfeldt, Stina; Fritzson, Peter

    2008-01-01

    with Modelica 2.1 (Wiley-IEEE Press, USA, 2004).] and an associated tool. The differences and similarities between the MathModelica Model Editor and three other ecological modelling tools have also been evaluated. The results show that the models can well be modelled and simulated in the MathModelica Model...... Editor, and that nitrogen decrease in a constructed treatment wetland should be described and simulated using the Nitrification/Denitrification model as this model has the highest overall quality score and provides a more variable environment.......In this paper, two ecological models of nitrogen processes in treatment wetlands have been evaluated and compared. These models were implemented, simulated, and visualized using the Modelica modelling and simulation language [P. Fritzson, Principles of Object-Oriented Modelling and Simulation...

  18. Bioeconomic modeling of lactational antimicrobial treatment of new bovine subclinical intramammary infections caused by contagious pathogens

    NARCIS (Netherlands)

    Borne, van den B.H.P.; Halasa, T.; Schaik, van G.; Hogeveen, H.; Nielen, M.

    2010-01-01

    This study determined the direct and indirect epidemiologic and economic effects of lactational treatment of new bovine subclinical intramammary infections (IMI) caused by contagious pathogens using an existing bioeconomic model. The dynamic and stochastic model simulated the dynamics of

  19. A marginal structural model to estimate the causal effect of antidepressant medication treatment on viral suppression among homeless and marginally housed persons with HIV.

    Science.gov (United States)

    Tsai, Alexander C; Weiser, Sheri D; Petersen, Maya L; Ragland, Kathleen; Kushel, Margot B; Bangsberg, David R

    2010-12-01

    Depression strongly predicts nonadherence to human immunodeficiency virus (HIV) antiretroviral therapy, and adherence is essential to maintaining viral suppression. This suggests that pharmacologic treatment of depression may improve virologic outcomes. However, previous longitudinal observational analyses have inadequately adjusted for time-varying confounding by depression severity, which could yield biased estimates of treatment effect. Application of marginal structural modeling to longitudinal observation data can, under certain assumptions, approximate the findings of a randomized controlled trial. To determine whether antidepressant medication treatment increases the probability of HIV viral suppression. Community-based prospective cohort study with assessments conducted every 3 months. Community-based research field site in San Francisco, California. One hundred fifty-eight homeless and marginally housed persons with HIV who met baseline immunologic (CD4+ T-lymphocyte count, 13) inclusion criteria, observed from April 2002 through August 2007. Probability of achieving viral suppression to less than 50 copies/mL. Secondary outcomes of interest were probability of being on an antiretroviral therapy regimen, 7-day self-reported percentage adherence to antiretroviral therapy, and probability of reporting complete (100%) adherence. Marginal structural models estimated a 2.03 greater odds of achieving viral suppression (95% confidence interval [CI], 1.15-3.58; P = .02) resulting from antidepressant medication treatment. In addition, antidepressant medication use increased the probability of antiretroviral uptake (weighted odds ratio, 3.87; 95% CI, 1.98-7.58; P effect is likely attributable to improved adherence to a continuum of HIV care, including increased uptake and adherence to antiretroviral therapy.

  20. Utility and translatability of mathematical modeling, cell culture and small and large animal models in magnetic nanoparticle hyperthermia cancer treatment research

    Science.gov (United States)

    Hoopes, P. J.; Petryk, Alicia A.; Misra, Adwiteeya; Kastner, Elliot J.; Pearce, John A.; Ryan, Thomas P.

    2015-03-01

    For more than 50 years, hyperthermia-based cancer researchers have utilized mathematical models, cell culture studies and animal models to better understand, develop and validate potential new treatments. It has been, and remains, unclear how and to what degree these research techniques depend on, complement and, ultimately, translate accurately to a successful clinical treatment. In the past, when mathematical models have not proven accurate in a clinical treatment situation, the initiating quantitative scientists (engineers, mathematicians and physicists) have tended to believe the biomedical parameters provided to them were inaccurately determined or reported. In a similar manner, experienced biomedical scientists often tend to question the value of mathematical models and cell culture results since those data typically lack the level of biologic and medical variability and complexity that are essential to accurately study and predict complex diseases and subsequent treatments. Such quantitative and biomedical interdependence, variability, diversity and promise have never been greater than they are within magnetic nanoparticle hyperthermia cancer treatment. The use of hyperthermia to treat cancer is well studied and has utilized numerous delivery techniques, including microwaves, radio frequency, focused ultrasound, induction heating, infrared radiation, warmed perfusion liquids (combined with chemotherapy), and, recently, metallic nanoparticles (NP) activated by near infrared radiation (NIR) and alternating magnetic field (AMF) based platforms. The goal of this paper is to use proven concepts and current research to address the potential pathobiology, modeling and quantification of the effects of treatment as pertaining to the similarities and differences in energy delivered by known external delivery techniques and iron oxide nanoparticles.

  1. Is aggressive treatment of traumatic brain injury cost-effective?

    Science.gov (United States)

    Whitmore, Robert G; Thawani, Jayesh P; Grady, M Sean; Levine, Joshua M; Sanborn, Matthew R; Stein, Sherman C

    2012-05-01

    The object of this study was to determine whether aggressive treatment of severe traumatic brain injury (TBI), including invasive intracranial monitoring and decompressive craniectomy, is cost-effective. A decision-analytical model was created to compare costs, outcomes, and cost-effectiveness of 3 strategies for treating a patient with severe TBI. The aggressive-care approach is compared with "routine care," in which Brain Trauma Foundation guidelines are not followed. A "comfort care" category, in which a single day in the ICU is followed by routine floor care, is included for comparison only. Probabilities of each treatment resulting in various Glasgow Outcome Scale (GOS) scores were obtained from the literature. The GOS scores were converted to quality-adjusted life years (QALYs), based on expected longevity and calculated quality of life associated with each GOS category. Estimated direct (acute and long-term medical care) and indirect (loss of productivity) costs were calculated from the perspective of society. Sensitivity analyses employed a 2D Monte Carlo simulation of 1000 trials, each with 1000 patients. The model was also used to estimate these values for patients 40, 60, and 80 years of age. For the average 20-year-old, aggressive care yields 11.7 (± 1.6 [SD]) QALYs, compared with routine care (10.0 ± 1.5 QALYs). This difference is highly significant (p care remains significantly better at all ages. When all costs are considered, aggressive care is also significantly less costly than routine care ($1,264,000 ± $118,000 vs $1,361,000 ± $107,000) for the average 20-year-old. Aggressive care remains significantly less costly until age 80, at which age it costs more than routine care. However, even in the 80-year-old, aggressive care is likely the more cost-effective approach. Comfort care is associated with poorer outcomes at all ages and with higher costs for all groups except 80-year-olds. When all the costs of severe TBI are considered, aggressive

  2. The effectiveness of the anti-CD11d treatment is reduced in rat models of spinal cord injury that produce significant levels of intraspinal hemorrhage.

    Science.gov (United States)

    Geremia, N M; Hryciw, T; Bao, F; Streijger, F; Okon, E; Lee, J H T; Weaver, L C; Dekaban, G A; Kwon, B K; Brown, A

    2017-09-01

    We have previously reported that administration of a CD11d monoclonal antibody (mAb) improves recovery in a clip-compression model of SCI. In this model the CD11d mAb reduces the infiltration of activated leukocytes into the injured spinal cord (as indicated by reduced intraspinal MPO). However not all anti-inflammatory strategies have reported beneficial results, suggesting that success of the CD11d mAb treatment may depend on the type or severity of the injury. We therefore tested the CD11d mAb treatment in a rat hemi-contusion model of cervical SCI. In contrast to its effects in the clip-compression model, the CD11d mAb treatment did not improve forelimb function nor did it significantly reduce MPO levels in the hemi-contused cord. To determine if the disparate results using the CD11d mAb were due to the biomechanical nature of the cord injury (compression SCI versus contusion SCI) or to the spinal level of the injury (12th thoracic level versus cervical) we further evaluated the CD11d mAb treatment after a T12 contusion SCI. In contrast to the T12 clip compression SCI, the CD11d mAb treatment did not improve locomotor recovery or significantly reduce MPO levels after T12 contusion SCI. Lesion analyses revealed increased levels of hemorrhage after contusion SCI compared to clip-compression SCI. SCI that is accompanied by increased intraspinal hemorrhage would be predicted to be refractory to the CD11d mAb therapy as this approach targets leukocyte diapedesis through the intact vasculature. These results suggest that the disparate results of the anti-CD11d treatment in contusion and clip-compression models of SCI are due to the different pathophysiological mechanisms that dominate these two types of spinal cord injuries. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  3. Global stability of two models with incomplete treatment for tuberculosis

    International Nuclear Information System (INIS)

    Yang Yali; Li Jianquan; Ma Zhien; Liu Luju

    2010-01-01

    Research highlights: → Two tuberculosis models with incomplete treatment. → Intuitive epidemiological interpretations for the basic reproduction numbers. → Global dynamics of the two models. → Strategies to control the spread of tuberculosis. - Abstract: Two tuberculosis (TB) models with incomplete treatment are investigated. It is assumed that the treated individuals may enter either the latent compartment due to the remainder of Mycobacterium tuberculosis or the infectious compartment due to the treatment failure. The first model is a simple one with treatment failure reflecting the current TB treatment fact in most countries with high tuberculosis incidence. The second model refines the simple one by dividing the latent compartment into slow and fast two kinds of progresses. This improvement can be used to describe the case that the latent TB individuals have been infected with some other chronic diseases (such as HIV and diabetes) which may weaken the immunity of infected individuals and shorten the latent period of TB. Both of the two models assume mass action incidence and exponential distributions of transfers between different compartments. The basic reproduction numbers of the two models are derived and their intuitive epidemiological interpretations are given. The global dynamics of two models are all proved by using Liapunov functions. At last, some strategies to control the spread of tuberculosis are discussed.

  4. The cost-effectiveness of IVF in the UK: a comparison of three gonadotrophin treatments.

    Science.gov (United States)

    Sykes, D; Out, H J; Palmer, S J; van Loon, J

    2001-12-01

    The objective of this study was to evaluate the cost-effectiveness of women undergoing IVF treatment with recombinant FSH (rFSH) in comparison with highly purified urinary FSH (uFSH-HP) and human menopausal gonadotrophins (HMG). A decision-analytic model was used to estimate cost-effectiveness ratios for 'the average cost per ongoing pregnancy' and 'incremental cost per additional pregnancy' for women entering into IVF treatment for a maximum of three cycles. The model was constructed based on a previously published large prospective randomized clinical trial comparing rFSH and uFSH-HP. Where necessary, these data were augmented with a combination of expert opinion, evidence from the literature and observational data relating to the management and cost of IVF treatment in the UK. The cost of rFSH, uFSH-HP and HMG were obtained from National Health Service list prices in the UK. The model predicted a cumulative pregnancy rate after three cycles of 57.1% for rFSH and 44.4% for both uFSH-HP and HMG. The cost of IVF treatment was 5135 pounds sterling for rFSH, 4806 pounds sterling for uFSH-HP and 4202 pounds sterling for HMG. When assessed in association with outcomes, the average cost per ongoing pregnancy was more favourable with rFSH (8992 pounds sterling) than with either uFSH-HP (10 834 pounds sterling) or HMG (9472 pounds sterling). The incremental cost per additional pregnancy was 2583 pounds sterling using rFSH instead of uFSH-HP and 7321 pounds sterling using rFSH instead of HMG. These results were robust to changes in the baseline assumptions of the model. rFSH is a cost-effective treatment strategy in ovulation induction prior to IVF.

  5. SU-E-T-272: Direct Verification of a Treatment Planning System Megavoltage Linac Beam Photon Spectra Models, and Analysis of the Effects On Patient Plans

    Energy Technology Data Exchange (ETDEWEB)

    Leheta, D; Shvydka, D; Parsai, E [University of Toledo Medical Center, Toledo, OH (United States)

    2015-06-15

    Purpose: For the photon dose calculation Philips Pinnacle Treatment Planning System (TPS) uses collapsed cone convolution algorithm, which relies on energy spectrum of the beam in computing the scatter component. The spectrum is modeled based on Linac’s standard commissioning data and typically is not independently verified. We explored a methodology of using transmission measurements in combination with regularization data processing to unfold Linac spectra. The measured spectra were compared to those modeled by the TPS, and the effect on patient plans was evaluated. Methods: Transmission measurements were conducted in narrow-beam geometry using a standard Farmer ionization chamber. Two attenuating materials and two build -up caps, having different atomic numbers, served to enhance discrimination between absorption of low and high-energy portions of the spectra, thus improving the accuracy of the results. The data was analyzed using a regularization technique implemented through spreadsheet-based calculations. Results: The unfolded spectra were found to deviate from the TPS beam models. The effect of such deviations on treatment planning was evaluated for patient plans through dose distribution calculations with either TPS modeled or measured energy spectra. The differences were reviewed through comparison of isodose distributions, and quantified based on maximum dose values for critical structures. While in most cases no drastic differences in the calculated doses were observed, plans with deviations of 4 to 8% in the maximum dose values for critical structures were discovered. The anatomical sites with large scatter contributions are the most vulnerable to inaccuracies in the modeled spectrum. Conclusion: An independent check of the TPS model spectrum is highly desirable and should be included as part of commissioning of a new Linac. The effect is particularly important for dose calculations in high heterogeneity regions. The developed approach makes

  6. A Mathematical Model to Investigate the Long-Term Effects of the Lymphatic Filariasis Medical Treatment in Jati Sampurna, West Java

    Directory of Open Access Journals (Sweden)

    A.K. Supriatna

    2009-03-01

    Full Text Available In this paper we discuss a mathematical model for the transmission of Lymphatic Filariasis disease in Jati Sampurna, West Java Indonesia. The model assumes that acute infected humans are infectious and treatment is given to a certain number of acute infected humans found from screening process. The treated acute individuals are assumed to be remain susceptible to the disease. The model is analyzed and it is found a condition for the existence and stability of the endemic equilibrium. A well known rule of thumb in epidemiological model, that is, the endemic equilibrium exists and stable if the basic reproduction number is greater than one, is shown. Moreover, it is also shown that if the level of screening n is sufficiently large, current medical treatment strategy will be able to reduce the long-term level of incidences. However, in practice it is not realistic and cannot eliminate the disease, in terms of reducing the basic reproduction number. The reproduction number can be reduced by giving additional treatments, such as reducing the biting rate and mosquito's density. This suggests that there should be a combination of treatment to eliminate the disease.

  7. MATHEMATICAL MODELING OF HEATING RATE PRODUCT AT HIGH HEAT TREATMENT

    Directory of Open Access Journals (Sweden)

    M. M. Akhmedova

    2014-01-01

    Full Text Available Methods of computing and mathematical modeling are all widely used in the study of various heat exchange processes that provide the ability to study the dynamics of the processes, as well as to conduct a reasonable search for the optimal technological parameters of heat treatment.This work is devoted to the identification of correlations among the factors that have the greatest effect on the rate of heating of the product at hightemperature heat sterilization in a stream of hot air, which are chosen as the temperature difference (between the most and least warming up points and speed cans during heat sterilization.As a result of the experimental data warming of the central and peripheral layers compote of apples in a 3 liter pot at high-temperature heat treatment in a stream of hot air obtained by the regression equation in the form of a seconddegree polynomial, taking into account the effects of pair interaction of these parameters. 

  8. Treatment efficacy in a soman-poisoned guinea pig model: added value of physostigmine?

    NARCIS (Netherlands)

    Joosen, M.J.A.; Smit, A.B.; van Helden, H.P.

    2011-01-01

    Current treatment of organophosphate poisoning is insufficient, and survivors may suffer from long-lasting adverse effects, such as cognitive deficits and sleep-wake disturbances. In the present study, we aimed at developing a guinea pig model to investigate the benefits of immediate and delayed

  9. Treatment efficacy in a soman-poisoned guinea pig model: Added value of physostigmine?

    NARCIS (Netherlands)

    Joosen, M.J.A.; Smit, A.B.; Helden, H.P.M. van

    2011-01-01

    Current treatment of organophosphate poisoning is insufficient, and survivors may suffer from long-lasting adverse effects, such as cognitive deficits and sleep-wake disturbances. In the present study, we aimed at developing a guinea pig model to investigate the benefits of immediate and delayed

  10. An integrated treatment model for dual diagnosis of psychosis and addiction.

    Science.gov (United States)

    Minkoff, K

    1989-10-01

    A model that integrates the treatment of patients with a dual diagnosis of psychosis and addiction has been developed on a general hospital psychiatric unit. The model emphasizes the parallels between the standard biopsychosocial illness-and-rehabilitation model for treatment of serious psychiatric disorders and the 12-step disease-and-recovery model of Alcoholics Anonymous for treatment of addiction. Dual-diagnosis patients are viewed as having two primary, chronic, biologic mental illnesses, each requiring specific treatment to stabilize acute symptoms and engage the patient in a recovery process. An integrated treatment program is described, as are the steps taken to alleviate psychiatric clinicians' concerns about patient involvement in AA and addiction clinicians' discomfort with patients' use of medication.

  11. Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma.

    Science.gov (United States)

    Sagar, Seil; Morgan, Mary E; Chen, Si; Vos, Arjan P; Garssen, Johan; van Bergenhenegouwen, Jeroen; Boon, Louis; Georgiou, Niki A; Kraneveld, Aletta D; Folkerts, Gert

    2014-04-16

    Asthma is estimated to affect as many as 300 million people worldwide and its incidence and prevalence are rapidly increasing throughout the world, especially in children and within developing countries. Recently, there has been a growing interest in the use of potentially beneficial bacteria for allergic diseases. This study is aimed at exploring the therapeutic effects of long-term treatment with two different beneficial bacterial strains (Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1) and a glucocorticoid (budesonide), as a reference treatment, on inflammatory response in a murine model for chronic allergic asthma. To mimic the chronic disease in asthmatic patients, we used the murine ovalbumin-induced asthma model combined with prolonged allergen exposure. Airway function; pulmonary airway inflammation; airway remodelling, mRNA expression of pattern recognition receptors, Th-specific cytokines and transcription factors in lung tissue; mast cell degranulation; in vitro T cell activation; and expression of Foxp3 in blood Th cells were examined. Lactobacillus rhamnosus reduced lung resistance to a similar extent as budesonide treatment in chronically asthmatic mice. Pulmonary airway inflammation, mast cell degranulation, T cell activation and airway remodelling were suppressed by all treatments. Beneficial bacteria and budesonide differentially modulated the expression of toll-like receptors (TLRs), nod-like receptors (NLRs), cytokines and T cell transcription factors. Bifidobacterium breve induced regulatory T cell responses in the airways by increasing Il10 and Foxp3 transcription in lung tissue as well as systemic by augmenting the mean fluorescence intensity of Foxp3 in blood CD4+ T cells. These findings show that Bifidobacterium breve M-16 V and Lactobacillus rhamnosus NutRes1 have strong anti-inflammatory properties that are comparable to budesonide and therefore may be beneficial in the treatment of chronic asthma.

  12. Differential effects of acute amphetamine and phencyclidine treatment and withdrawal from repeated amphetamine or phencyclidine treatment on social interaction and social memory in rats.

    Science.gov (United States)

    Li, Ming; He, Wei; Munro, Rebecca

    2012-06-01

    Although animal models based on amphetamine (AMPH) or phencyclidine (PCP) treatment have been used extensively to study the neurobiological and behavioral characteristics of schizophrenia, there are conflicting reports regarding their validity in modeling the negative symptoms and cognitive deficits of schizophrenia. The present study examined how acute AMPH or PCP treatment (Experiment 1) and withdrawal from repeated AMPH treatment (Experiment 2) or PCP treatment (Experiment 3) affects social behavior and social recognition memory in male Sprague-Dawley rats. Each subject was tested on two consecutive days. On the first day, the rats were tested four times (5 min/each) at 10-min intervals with the same partner rat (termed "AAAA" day). One day later, the rats were tested with the previous partner in the first three sessions and with a new partner rat in the final session (termed "AAAB" day). The results show that acute AMPH treatment (1.5 mg/kg, sc) significantly reduced the time spent on social interaction, but did not affect social recognition on the first day. Acute AMPH only disrupted social recognition on the second day of drug testing. In contrast, acute PCP treatment (2.0 mg/kg, sc) had no effect on time spent on social interaction, but did significantly disrupt social recognition on both days. Withdrawal from repeated AMPH (3.0 mg/kg/day for 7 days, ip) or PCP (5.0 mg/kg/twice daily for 7 days, ip) treatment did not affect social interaction or social recognition, indicating a lack of long-term detrimental effect of repeated AMPH or PCP treatment. These results suggest that acute AMPH treatment at a low dose (1.5 mg/kg) may be useful in modeling social withdrawal symptoms of schizophrenia, whereas acute PCP treatment at a similar dose range (2.0 mg/kg) may be useful in modeling the social cognitive deficit of schizophrenia. © 2012 The Institute of Psychology, Chinese Academy of Sciences and Blackwell Publishing Asia Pty Ltd.

  13. Uncertainties in model-based outcome predictions for treatment planning

    International Nuclear Information System (INIS)

    Deasy, Joseph O.; Chao, K.S. Clifford; Markman, Jerry

    2001-01-01

    Purpose: Model-based treatment-plan-specific outcome predictions (such as normal tissue complication probability [NTCP] or the relative reduction in salivary function) are typically presented without reference to underlying uncertainties. We provide a method to assess the reliability of treatment-plan-specific dose-volume outcome model predictions. Methods and Materials: A practical method is proposed for evaluating model prediction based on the original input data together with bootstrap-based estimates of parameter uncertainties. The general framework is applicable to continuous variable predictions (e.g., prediction of long-term salivary function) and dichotomous variable predictions (e.g., tumor control probability [TCP] or NTCP). Using bootstrap resampling, a histogram of the likelihood of alternative parameter values is generated. For a given patient and treatment plan we generate a histogram of alternative model results by computing the model predicted outcome for each parameter set in the bootstrap list. Residual uncertainty ('noise') is accounted for by adding a random component to the computed outcome values. The residual noise distribution is estimated from the original fit between model predictions and patient data. Results: The method is demonstrated using a continuous-endpoint model to predict long-term salivary function for head-and-neck cancer patients. Histograms represent the probabilities for the level of posttreatment salivary function based on the input clinical data, the salivary function model, and the three-dimensional dose distribution. For some patients there is significant uncertainty in the prediction of xerostomia, whereas for other patients the predictions are expected to be more reliable. In contrast, TCP and NTCP endpoints are dichotomous, and parameter uncertainties should be folded directly into the estimated probabilities, thereby improving the accuracy of the estimates. Using bootstrap parameter estimates, competing treatment

  14. Coping with Cosmetic Effects of Cancer Treatment

    Science.gov (United States)

    ... Search English Español Coping With Cosmetic Effects of Cancer Treatment KidsHealth / For Parents / Coping With Cosmetic Effects of Cancer Treatment What's in this article? Hair Loss Skin Problems ...

  15. Overview of climate information needs for ecological effects models

    Energy Technology Data Exchange (ETDEWEB)

    Peer, R.L.

    1990-01-01

    Atmospheric scientists engaged in climate change research require a basic understanding of how ecological effects models incorporate climate. The report provides an overview of existing ecological models that might be used to model climate change effects on vegetation. Some agricultural models and statistical methods are also discussed. The weather input data requirements, weather simulation methods, and other model characteristics relevant to climate change research are described for a selected number of models. The ecological models are classified as biome, ecosystem, or tree models; the ecosystem models are further subdivided into species dynamics or process models. In general, ecological modelers have had to rely on readily available meteorological data such as temperature and rainfall. Although models are becoming more sophisticated in their treatment of weather and require more kinds of data (such as wind, solar radiation, or potential evapotranspiration), modelers are still hampered by a lack of data for many applications. Future directions of ecological effects models and the climate variables that will be required by the models are discussed.

  16. Siblings' Perceptions of Differential Treatment, Fairness, and Jealousy and Adolescent Adjustment: A Moderated Indirect Effects Model.

    Science.gov (United States)

    Loeser, Meghan K; Whiteman, Shawn D; McHale, Susan M

    2016-08-01

    Youth's perception of parents' differential treatment (PDT) are associated with maladjustment during adolescence. Although the direct relations between PDT and youth's maladjustment have been well established, the mechanisms underlying these associations remain unclear. We addressed this gap by examining whether sibling jealousy accounted for the links between PDT and youth's depressive symptoms, self-worth, and risky behaviors. Additionally, we examined whether youth's perceptions of fairness regarding their treatment as well as the gender constellation of the dyad moderated these indirect relations (i.e., moderated-indirect effects). Participants were first- and second-born adolescent siblings ( M = 15.96, SD = .72 years for older siblings, M = 13.48, SD = 1.02 years for younger siblings) and their parents from 197 working and middle class European American families. Data were collected via home interviews. A series of Conditional Process Analyses revealed significant indirect effects of PDT through sibling jealousy to all three adjustment outcomes. Furthermore, perceptions of fairness moderated the relations between PDT and jealousy, such that the indirect effects were only significant at low (-1 SD ) and average levels of fairness. At high levels of fairness (+1 SD ) there was no association between PDT, jealousy, and youth adjustment. Taken together, results indicate that youth and parents would benefit from engaging in clear communication regarding the reasoning for the occurrence of differential treatment, likely maximizing youth and parent perceptions of that treatment as being fair, and in turn mitigating sibling jealousy and maladjustment.

  17. Siblings’ Perceptions of Differential Treatment, Fairness, and Jealousy and Adolescent Adjustment: A Moderated Indirect Effects Model

    Science.gov (United States)

    Loeser, Meghan K.; Whiteman, Shawn D.; McHale, Susan M.

    2016-01-01

    Youth's perception of parents’ differential treatment (PDT) are associated with maladjustment during adolescence. Although the direct relations between PDT and youth's maladjustment have been well established, the mechanisms underlying these associations remain unclear. We addressed this gap by examining whether sibling jealousy accounted for the links between PDT and youth's depressive symptoms, self-worth, and risky behaviors. Additionally, we examined whether youth's perceptions of fairness regarding their treatment as well as the gender constellation of the dyad moderated these indirect relations (i.e., moderated-indirect effects). Participants were first- and second-born adolescent siblings (M = 15.96, SD = .72 years for older siblings, M = 13.48, SD = 1.02 years for younger siblings) and their parents from 197 working and middle class European American families. Data were collected via home interviews. A series of Conditional Process Analyses revealed significant indirect effects of PDT through sibling jealousy to all three adjustment outcomes. Furthermore, perceptions of fairness moderated the relations between PDT and jealousy, such that the indirect effects were only significant at low (−1 SD) and average levels of fairness. At high levels of fairness (+1 SD) there was no association between PDT, jealousy, and youth adjustment. Taken together, results indicate that youth and parents would benefit from engaging in clear communication regarding the reasoning for the occurrence of differential treatment, likely maximizing youth and parent perceptions of that treatment as being fair, and in turn mitigating sibling jealousy and maladjustment. PMID:27867295

  18. Sufficient conditions for optimality for a mathematical model of drug treatment with pharmacodynamics

    Directory of Open Access Journals (Sweden)

    Maciej Leszczyński

    2017-01-01

    Full Text Available We consider an optimal control problem for a general mathematical model of drug treatment with a single agent. The control represents the concentration of the agent and its effect (pharmacodynamics is modelled by a Hill function (i.e., Michaelis-Menten type kinetics. The aim is to minimize a cost functional consisting of a weighted average related to the state of the system (both at the end and during a fixed therapy horizon and to the total amount of drugs given. The latter is an indirect measure for the side effects of treatment. It is shown that optimal controls are continuous functions of time that change between full or no dose segments with connecting pieces that take values in the interior of the control set. Sufficient conditions for the strong local optimality of an extremal controlled trajectory in terms of the existence of a solution to a piecewise defined Riccati differential equation are given.

  19. A systematic review of cost-effectiveness studies of prevention and treatment for eating disorders.

    Science.gov (United States)

    Le, Long Khanh-Dao; Hay, Phillipa; Mihalopoulos, Cathrine

    2018-04-01

    Eating disorders are serious mental disorders and are associated with substantial economic and social burden. The aim of this study is to undertake a systematic review of the cost-effectiveness studies of both preventive and treatment interventions for eating disorder. Electronic databases (including the Cochrane Controlled Trial Register, MEDLINE, PsycINFO, Academic Search Complete, Global Health, CINAHL complete, Health Business Elite, Econlit, Health Policy Reference Center and ERIC) were searched for published cost-effectiveness studies of eating disorder prevention and treatment including papers published up to January 2017. The quality of studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. In all, 13 studies met the review inclusion criteria as full cost-effectiveness studies and 8 were published since 2011. The studies included three modelled and one trial-based study focused on prevention, two trial-based and one modelled study for anorexia nervosa treatment and three trial-based studies for bulimia nervosa treatment. The remaining studies targeted binge-eating disorder or non-specific eating disorder treatment. The average percent of CHEERS checklist items reported was 71% (standard deviation 21%). Eating disorder interventions were mainly cost-saving or more effective and more costly compared to comparators; however, some results did not reach statistical significance. In the two studies that achieved 100% CHEERS checklist, one study reported that a cognitive dissonance intervention might be cost-effective for prevention of anorexia nervosa and bulimia nervosa with a 90% participation rate and the second study supported lisdexamfetamine to be cost-effective in the treatment of binge-eating disorder. Insufficient evidence for long-term cost-effectiveness (e.g. over 2 years) was found. Cost-effectiveness studies in eating disorder appear to be increasing in number over the last 6 years. Findings

  20. Clinical effectiveness and cost-effectiveness of pegvisomant for the treatment of acromegaly: a systematic review and economic evaluation

    Directory of Open Access Journals (Sweden)

    Connock Martin J

    2009-10-01

    Full Text Available Abstract Background Acromegaly, an orphan disease usually caused by a benign pituitary tumour, is characterised by hyper-secretion of growth hormone (GH and insulin-like growth factor I (IGF-1. It is associated with reduced life expectancy, cardiovascular problems, a variety of insidiously progressing detrimental symptoms and metabolic malfunction. Treatments include surgery, radiotherapy and pharmacotherapy. Pegvisomant (PEG is a genetically engineered GH analogue licensed as a third or fourth line option when other treatments have failed to normalise IGF-1 levels. Methods Evidence about effectiveness and cost-effectiveness of PEG was systematically reviewed. Data were extracted from published studies and used for a narrative synthesis of evidence. A decision analytical economic model was identified and modified to assess the cost-effectiveness of PEG. Results One RCT and 17 non-randomised studies were reviewed for effectiveness. PEG substantially reduced and rapidly normalised IGF-1 levels in the majority of patients, approximately doubled GH levels, and improved some of the signs and symptoms of the disease. Tumour size was unaffected at least in the short term. PEG had a generally safe adverse event profile but a few patients were withdrawn from treatment because of raised liver enzymes. An economic model was identified and adapted to estimate the lower limit for the cost-effectiveness of PEG treatment versus standard care. Over a 20 year time horizon the incremental cost-effectiveness ratio was £81,000/QALY and £212,000/LYG. To reduce this to £30K/QALY would require a reduction in drug cost by about one third. Conclusion PEG is highly effective for improving patients' IGF-1 level. Signs and symptoms of disease improve but evidence is lacking about long term effects on improved signs and symptoms of disease, quality of life, patient compliance and safety. Economic evaluation indicated that if current standards (UK for determining cost-effectiveness

  1. Integrated modeling of ozonation for optimization of drinking water treatment

    NARCIS (Netherlands)

    van der Helm, A.W.C.

    2007-01-01

    Drinking water treatment plants automation becomes more sophisticated, more on-line monitoring systems become available and integration of modeling environments with control systems becomes easier. This gives possibilities for model-based optimization. In operation of drinking water treatment

  2. Long-Term Treatment with Liraglutide, a Glucagon-Like Peptide-1 (GLP-1 Receptor Agonist, Has No Effect on β-Amyloid Plaque Load in Two Transgenic APP/PS1 Mouse Models of Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Henrik H Hansen

    Full Text Available One of the major histopathological hallmarks of Alzheimer's disease (AD is cerebral deposits of extracellular β-amyloid peptides. Preclinical studies have pointed to glucagon-like peptide 1 (GLP-1 receptors as a potential novel target in the treatment of AD. GLP-1 receptor agonists, including exendin-4 and liraglutide, have been shown to promote plaque-lowering and mnemonic effects of in a number of experimental models of AD. Transgenic mouse models carrying genetic mutations of amyloid protein precursor (APP and presenilin-1 (PS1 are commonly used to assess the pharmacodynamics of potential amyloidosis-lowering and pro-cognitive compounds. In this study, effects of long-term liraglutide treatment were therefore determined in two double APP/PS1 transgenic mouse models of Alzheimer's disease carrying different clinical APP/PS1 mutations, i.e. the 'London' (hAPPLon/PS1A246E and 'Swedish' mutation variant (hAPPSwe/PS1ΔE9 of APP, with co-expression of distinct PS1 variants. Liraglutide was administered in 5 month-old hAPPLon/PS1A246E mice for 3 months (100 or 500 ng/kg/day, s.c., or 7 month-old hAPPSwe/PS1ΔE9 mice for 5 months (500 ng/kg/day, s.c.. In both models, regional plaque load was quantified throughout the brain using stereological methods. Vehicle-dosed hAPPSwe/PS1ΔE9 mice exhibited considerably higher cerebral plaque load than hAPPLon/PS1A246E control mice. Compared to vehicle-dosed transgenic controls, liraglutide treatment had no effect on the plaque levels in hAPPLon/PS1A246E and hAPPSwe/PS1ΔE9 mice. In conclusion, long-term liraglutide treatment exhibited no effect on cerebral plaque load in two transgenic mouse models of low- and high-grade amyloidosis, which suggests differential sensitivity to long-term liraglutide treatment in various transgenic mouse models mimicking distinct pathological hallmarks of AD.

  3. Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats.

    Science.gov (United States)

    Polonio, Igor Bastos; Acencio, Milena Marques Pagliareli; Pazetti, Rogério; Almeida, Francine Maria de; Silva, Bárbara Soares da; Pereira, Karina Aparecida Bonifácio; Souza, Rogério

    2014-01-01

    We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and IL-1 levels in lung fragments. The number of cases of RVH was significantly higher in the monocrotaline group than in the lodenafil and control groups, as were mPAP and IL-1 levels. We conclude that lodenafil can prevent monocrotaline-induced PH, RVH, and inflammation.

  4. Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats*

    Science.gov (United States)

    Polonio, Igor Bastos; Acencio, Milena Marques Pagliareli; Pazetti, Rogério; de Almeida, Francine Maria; da Silva, Bárbara Soares; Pereira, Karina Aparecida Bonifácio; Souza, Rogério

    2014-01-01

    We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH). Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model); and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days) Mean pulmonary artery pressure (mPAP) was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH) and IL-1 levels in lung fragments. The number of cases of RVH was significantly higher in the monocrotaline group than in the lodenafil and control groups, as were mPAP and IL-1 levels. We conclude that lodenafil can prevent monocrotaline-induced PH, RVH, and inflammation. PMID:25210965

  5. Thermo-mechanical modeling of laser treatment on titanium cold-spray coatings

    Science.gov (United States)

    Paradiso, V.; Rubino, F.; Tucci, F.; Astarita, A.; Carlone, P.

    2018-05-01

    Titanium coatings are very attractive to several industrial fields, especially aeronautics, due to the enhanced corrosion resistance and wear properties as well as improved compatibility with carbon fiber reinforced plastic (CFRP) materials. Cold sprayed titanium coatings, among the others deposition processes, are finding a widespread use in high performance applications, whereas post-deposition treatments are often used to modify the microstructure of the cold-sprayed layer. Laser treatments allow one to noticeably increase the superficial properties of titanium coatings when the process parameters are properly set. On the other hand, the high heat input required to melt titanium particles may result in excessive temperature increase even in the substrate. This paper introduces a thermo-mechanical model to simulate the laser treatment effects on a cold sprayed titanium coating as well as the aluminium substrate. The proposed thermo-mechanical finite element model considers the transient temperature field due to the laser source and applied boundary conditions using them as input loads for the subsequent stress-strain analysis. Numerical outcomes highlighted the relevance of thermal gradients and thermally induced stresses and strains in promoting the damage of the coating.

  6. Modelling the relationship between antiretroviral treatment and HIV ...

    African Journals Online (AJOL)

    This paper shows how two publicly available epidemiological modelling packages, namely the Spectrum AIDS Impact Model and the ASSA2003 AIDS and Demographic Model, predict very different impacts from rolling out highly active antiretroviral treatment (HAART) on new HIV infections. Using South Africa as a case ...

  7. Structural Models Describing Placebo Treatment Effects in Schizophrenia and Other Neuropsychiatric Disorders

    NARCIS (Netherlands)

    Reddy, Venkatesh Pilla; Kozielska, Magdalena; Johnson, Martin; Vermeulen, An; de Greef, Rik; Liu, Jing; Groothuis, Geny M. M.; Danhof, Meindert; Proost, Johannes H.

    2011-01-01

    Large variation in placebo response within and among clinical trials can substantially affect conclusions about the efficacy of new medications in psychiatry. Developing a robust placebo model to describe the placebo response is important to facilitate quantification of drug effects, and eventually

  8. A novel brain trauma model in the mouse : effects of dexamethasone treatment

    NARCIS (Netherlands)

    Hortobágyi, Tibor; Hortobagyi, S; Gorlach, C; Harkany, T; Benbyo, Z; Gorogh, T; Nagel, W; Wahl, M

    2000-01-01

    We describe a novel methodological approach for inducing cold lesion in the mouse as a model of human cortical contusion trauma. To validate its reproducibility and reliability, dexamethasone (Dxm) was repeatedly applied to demonstrate possible antioedematous drug effects. Following tho induction of

  9. Fertility effects of cancer treatment.

    Science.gov (United States)

    Marsden, Donald E; Hacker, Neville

    2003-01-01

    Cancer sufferers are a subfertile group, and most treatments have the potential to adversely affect gonadal function. As cancer treatment becomes more effective and survival rates improve there are more cancer survivors in the reproductive age group for whom parenting is an important consideration. This article outlines the effects on fertility of cancer treatments and techniques to minimise the risk of infertility. The overall prospects for younger cancer sufferers to either retain their fertility or have genetic offspring is now better than ever before, due to advances in assisted reproductive technology, the appropriate use of fertility sparing surgery and other techniques to reduce the toxicity of therapy on the reproductive organs. These advances raise new moral and ethical concerns that must be considered before advising cancer sufferers of the options for preserving reproductive capacity.

  10. Elementary microscopic treatment of the effect of static disorder on superconductivity

    International Nuclear Information System (INIS)

    Wiecko, Cristina

    1988-01-01

    Dividing explicitely both phonon and electrons in extended and localized excitations, the effect of static disorder on superconductivity is derived by standard treatment. Main increase is obtained from localized levels above ε F which are paired by local phonon modes, in agreement with a previous model derived in mean-field approximation. (Author)

  11. [Cost-effectiveness analysis of etanercept compared with other biologic therapies in the treatment of rheumatoid arthritis].

    Science.gov (United States)

    Salinas-Escudero, Guillermo; Vargas-Valencia, Juan; García-García, Erika Gabriela; Munciño-Ortega, Emilio; Galindo-Suárez, Rosa María

    2013-01-01

    to conduct cost-effectiveness analysis of etanercept compared with other biologic therapies in the treatment of moderate or severe rheumatoid arthritis in patients with previous unresponse to immune selective anti-inflammatory derivatives failure. a pharmacoeconomic model based on decision analysis to assess the clinical outcome after giving etanercept, infliximab, adalimumab or tocilizumab to treat moderate or severe rheumatoid arthritis was employed. Effectiveness of medications was assessed with improvement rates of 20 % or 70 % of the parameters established by the American College of Rheumatology (ACR 20 and ACR 70). the model showed that etanercept had the most effective therapeutic response rate: 79.7 % for ACR 20 and 31.4 % for ACR 70, compared with the response to other treatments. Also, etanercept had the lowest cost ($149,629.10 per patient) and had the most cost-effective average ($187,740.40 for clinical success for ACR 20 and $476,525.80 for clinical success for ACR 70) than the other biologic therapies. we demonstrated that treatment with etanercept is more effective and less expensive compared to the other drugs, thus making it more efficient therapeutic option both in terms of means and incremental cost-effectiveness ratios for the treatment of rheumatoid arthritis.

  12. An ecological vegetation-activated sludge process (V-ASP) for decentralized wastewater treatment: system development, treatment performance, and mathematical modeling.

    Science.gov (United States)

    Yuan, Jiajia; Dong, Wenyi; Sun, Feiyun; Li, Pu; Zhao, Ke

    2016-05-01

    An environment-friendly decentralized wastewater treatment process that is comprised of activated sludge process (ASP) and wetland vegetation, named as vegetation-activated sludge process (V-ASP), was developed for decentralized wastewater treatment. The long-term experimental results evidenced that the vegetation sequencing batch reactor (V-SBR) process had consistently stable higher removal efficiencies of organic substances and nutrients from domestic wastewater compared with traditional sequencing batch reactor (SBR). The vegetation allocated into V-SBR system could not only remove nutrients through its vegetation transpiration ratio but also provide great surface area for microorganism activity enhancement. This high vegetation transpiration ratio enhanced nutrients removal effectiveness from wastewater mainly by flux enhancement, oxygen and substrate transportation acceleration, and vegetation respiration stimulation. A mathematical model based on ASM2d was successfully established by involving the specific function of vegetation to simulate system performance. The simulation results on the influence of operational parameters on V-ASP treatment effectiveness demonstrated that V-SBR had a high resistance to seasonal temperature fluctuations and influent loading shocking.

  13. Interpretable inference on the mixed effect model with the Box-Cox transformation.

    Science.gov (United States)

    Maruo, K; Yamaguchi, Y; Noma, H; Gosho, M

    2017-07-10

    We derived results for inference on parameters of the marginal model of the mixed effect model with the Box-Cox transformation based on the asymptotic theory approach. We also provided a robust variance estimator of the maximum likelihood estimator of the parameters of this model in consideration of the model misspecifications. Using these results, we developed an inference procedure for the difference of the model median between treatment groups at the specified occasion in the context of mixed effects models for repeated measures analysis for randomized clinical trials, which provided interpretable estimates of the treatment effect. From simulation studies, it was shown that our proposed method controlled type I error of the statistical test for the model median difference in almost all the situations and had moderate or high performance for power compared with the existing methods. We illustrated our method with cluster of differentiation 4 (CD4) data in an AIDS clinical trial, where the interpretability of the analysis results based on our proposed method is demonstrated. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  14. Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China.

    Science.gov (United States)

    Ke, Weixia; Zhang, Chi; Liu, Li; Gao, Yanhui; Yao, Zhenjiang; Ye, Xiaohua; Zhou, Shudong; Yang, Yi

    2016-11-01

    Tenofovir disoproxil fumarate (TDF) is newly available for treatment of chronic hepatitis B patients in China. To date, no study has been conducted to examine the cost-effectiveness of this treatment. The aim of this study was to estimate the cost-effectiveness of TDF versus four oral nucleos(t)ide analogs [lamivudine (LAM), adefovir (ADV), telbivudine (LdT), and entecavir (ETV)] and from a pharmacoeconomic perspective to assess current drug pricing for TDF. Based on Chinese healthcare perspectives, a Markov model was applied to simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for five different monotherapy strategies. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: directly using ETV + ADV) were separately considered for treatment of patients refractory to monotherapy. Model parameters (including disease transition, cost, and utility) were obtained from previous Chinese population studies. Both branded and generic drugs were separately analyzed. Study model uncertainties were assessed by one-way and probabilistic sensitivity analyses. Two-way sensitivity analysis was used to explore uncertainties between efficacy and price of TDF. In the base-case analysis, the lowest lifetime cost and the best cost-effectiveness ratio were obtained by ETV, which was considered the reference treatment. LAM, ADV, and LdT treatments had significantly greater costs and lower efficacies. Compared to ETV, TDF was more effective but also more expensive. The incremental cost-effectiveness ratios of TDF versus ETV were much higher than the willing-to-pay threshold of $20,466 US dollars (USD) per QALY gained (3 × gross domestic product per capita of China, 2014). TDF would be the most cost-effective strategy if the annual cost did not exceed $2260 USD and $1600 USD for branded and generic drugs, respectively. For Chinese chronic hepatitis B patients, ETV is still the most cost-effective

  15. Comparison of acute effect of systemic versus intravitreal infliximab treatment in an experimental model of endotoxin-induced uveitis.

    Science.gov (United States)

    Yuksel, Erdem; Hasanreisoglu, Berati; Yuksel, Nilay; Yilmaz, Guldal; Ercin, Ugur; Bilgihan, Ayse

    2014-02-01

    In this study, we investigated the efficacy of systemic and intravitreal (IV) infliximab treatments and compared these 2 different treatment modalities in an experimental model of endotoxin-induced uveitis (EIU). Twenty-four white New Zealand rabbits were equally divided into 4 groups. Group 1 received IV injection of lipopolysaccharide (LPS), group 2 received IV injections of LPS and saline, group 3 received IV LPS and IV 2 mg/0.1 cc infliximab, and group 4 received IV LPS and 5 mg/kg intravenous infliximab. Inflammation was determined with objective and subjective tests. The subjective test was clinical determination of uveitis, the objective tests were determination of protein concentrations and tumor necrosis factor alpha (TNF-α) levels and histopathology. Clinical examination score was lower in group 3 and group 4 (4±0.6 and 3.5±1.6, respectively) when compared with group 1 (P=0.02; P=0.04, respectively) and group 2. In group 3 and 4, the aqueous and vitreous protein and TNF-α concentration measured significantly lower than group 1 and 2. In histopathologic examination, there was no statistically significant difference between group 1, 2, and 3 (3.5±0.5, 3.6±0.5, 3.6±0.5, respectively). However, the lowest histopathologic inflammation was determined in group 4 (2.5±0.5) (compared with group 1 and group 3, respectively; P=0.03; P=0.014). In a rabbit model of experimental EIU, intravenous administration of infliximab was more effective than IV route in an acute period.

  16. Fuel treatment effectiveness in forests of the upper Atlantic Coastal Plain—an evaluation at two spatial scales

    Science.gov (United States)

    Roger D. Ottmar; Susan J. Prichard

    2012-01-01

    Fuel treatment effectiveness in Southern forests has been demonstrated using fire behavior modeling and observations of reduced wildfire area and tree damage. However, assessments of treatment effectiveness may be improved with a more rigorous accounting of the fuel characteristics. We present two case studies to introduce a relatively new approach to characterizing...

  17. Power analysis to detect treatment effects in longitudinal clinical trials for Alzheimer's disease.

    Science.gov (United States)

    Huang, Zhiyue; Muniz-Terrera, Graciela; Tom, Brian D M

    2017-09-01

    Assessing cognitive and functional changes at the early stage of Alzheimer's disease (AD) and detecting treatment effects in clinical trials for early AD are challenging. Under the assumption that transformed versions of the Mini-Mental State Examination, the Clinical Dementia Rating Scale-Sum of Boxes, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale tests'/components' scores are from a multivariate linear mixed-effects model, we calculated the sample sizes required to detect treatment effects on the annual rates of change in these three components in clinical trials for participants with mild cognitive impairment. Our results suggest that a large number of participants would be required to detect a clinically meaningful treatment effect in a population with preclinical or prodromal Alzheimer's disease. We found that the transformed Mini-Mental State Examination is more sensitive for detecting treatment effects in early AD than the transformed Clinical Dementia Rating Scale-Sum of Boxes and Alzheimer's Disease Assessment Scale-Cognitive Subscale. The use of optimal weights to construct powerful test statistics or sensitive composite scores/endpoints can reduce the required sample sizes needed for clinical trials. Consideration of the multivariate/joint distribution of components' scores rather than the distribution of a single composite score when designing clinical trials can lead to an increase in power and reduced sample sizes for detecting treatment effects in clinical trials for early AD.

  18. A systematic review of the cost and cost effectiveness of treatment for multidrug-resistant tuberculosis.

    Science.gov (United States)

    Fitzpatrick, Christopher; Floyd, Katherine

    2012-01-01

    Around 0.4 million cases of multidrug-resistant tuberculosis (MDR-TB) occur each year. Only a small fraction of these cases are treated according to international guidelines. Evidence relevant to decisions about whether to scale-up treatment for MDR-TB includes cost and cost-effectiveness data. Up to 2010, no systematic review of this evidence has been available. Our objective was to conduct a systematic review of the cost and cost effectiveness of treatment for MDR-TB and synthesize the available data. We searched for papers published or prepared for publication in peer-review journals and grey literature using search terms in five languages: English, French, Portuguese, Russian and Spanish. From an initial set of 420 studies, four were included, from Peru, the Philippines, Estonia and Tomsk Oblast in the Russian Federation. Results on costs, effectiveness and cost effectiveness were extracted. Assessment of the quality of each economic evaluation was guided by two existing checklists around which there is broad consensus. Costs were adjusted to a common year of value (2005) to remove distortions caused by inflation, and calculated in two common currencies: $US and international dollars (I$), to standardize for purchasing power parity. Data from the four identified studies were then synthesized using probabilistic sensitivity analysis, to appraise the likely cost and cost effectiveness of MDR-TB treatment in other settings, relative to WHO benchmarks for assessing whether or not an intervention is cost effective. Best estimates are provided as means, with 5th and 95th percentiles of the distributions. The cost per patient for MDR-TB treatment in Estonia, Peru, the Philippines and Tomsk was $US10 880, $US2423, $US3613 and $US14 657, respectively. Best estimates of the cost per disability-adjusted life-year (DALY) averted were $US598 (I$960), $US163 (I$291), $US143 (I$255) and $US745 (I$1059), respectively. The main influences on costs were (i) the model of care

  19. Computational model to simulate the interplay effect in dynamic IMRT delivery

    International Nuclear Information System (INIS)

    Yoganathan, S A; Maria Das, K J; Kumar, Shaleen

    2014-01-01

    The purpose of this study was to develop and experimentally verify a patient specific model for simulating the interplay effect in a DMLC based IMRT delivery. A computational model was developed using MATLAB program to incorporate the interplay effect in a 2D beams eye view fluence of dynamic IMRT fields. To simulate interplay effect, the model requires two inputs: IMRT field (DMLC file with dose rate and MU) and the patient specific respiratory motion. The interplay between the DMLC leaf motion and target was simulated for three lung patients. The target trajectory data was acquired using RPM system during the treatment simulation. The model was verified experimentally for the same patients using Imatrix 2D array device placed over QUASAR motion platform in CL2100 linac. The simulated fluences and measured fluences were compared with the TPS generated static fluence (no motion) using an in-house developed gamma evaluation program (2%/2mm). The simulated results were well within agreement with the measured. Comparison of the simulated and measured fluences with the TPS static fluence resulted 55.3% and 58.5% pixels passed the gamma criteria. A patient specific model was developed and validated for simulating the interplay effect in the dynamic IMRT delivery. This model can be clinically used to quantify the dosimetric uncertainty due to the interplay effect prior to the treatment delivery.

  20. Bioeconomic modeling of lactational antimicrobial treatment of new bovine subclinical intramammary infections caused by contagious pathogens

    DEFF Research Database (Denmark)

    Van den Borne, B. H. P.; Hisham Beshara Halasa, Tariq; Van Schaik, G.

    2010-01-01

    This study determined the direct and indirect epidemiologic and economic effects of lactational treatment of new bovine subclinical intramammary infections (IMI) caused by contagious pathogens using an existing bioeconomic model. The dynamic and stochastic model simulated the dynamics...... of uncured cows after 2 mo of infection. Model behavior was observed for variation in parameter input values. Compared with no lactational intervention, lactational intervention of new subclinical IMI resulted in fewer clinical flare ups, less transmission within the herd, and much lower combined total....... Changing the probability of cure resulted in a nonlinear change in the cumulative incidence of IMI cases and associated costs. Lactational treatment was able to prevent IMI epidemics in dairy herds at high transmission rates of Strep. uberis, Strep. dysgalactiae, and E. coli. Lactational treatment did...

  1. Financing and cost-effectiveness analysis of public-private partnerships: provision of tuberculosis treatment in South Africa

    Directory of Open Access Journals (Sweden)

    Kumaranayake Lilani

    2006-06-01

    Full Text Available Abstract Background Public-private partnerships (PPP could be effective in scaling up services. We estimated cost and cost-effectiveness of different PPP arrangements in the provision of tuberculosis (TB treatment, and the financing required for the different models from the perspective of the provincial TB programme, provider, and the patient. Methods Two different models of TB provider partnerships are evaluated, relative to sole public provision: public-private workplace (PWP and public-private non-government (PNP. Cost and effectiveness data were collected at six sites providing directly observed treatment (DOT. Effectiveness for a 12-month cohort of new sputum positive patients was measured using cure and treatment success rates. Provider and patient costs were estimated, and analysed according to sources of financing. Cost-effectiveness is estimated from the perspective of the provider, patient and society in terms of the cost per TB case cured and cost per case successfully treated. Results Cost per case cured was significantly lower in PNP (US $354–446, and comparable between PWP (US $788–979 and public sites (US $700–1000. PPP models could significantly reduce costs to the patient by 64–100%. Relative to pure public sector provision and financing, expansion of PPPs could reduce government financing required per TB patient treated from $609–690 to $130–139 in PNP and $36–46 in PWP. Conclusion There is a strong economic case for expanding PPP in TB treatment and potentially for other types of health services. Where PPPs are tailored to target groups and supported by the public sector, scaling up of effective services could occur at much lower cost than solely relying on public sector models.

  2. Treatment with escitalopram but not desipramine decreases escape latency times in a learned helplessness model using juvenile rats.

    Science.gov (United States)

    Reed, Abbey L; Anderson, Jeffrey C; Bylund, David B; Petty, Frederick; El Refaey, Hesham; Happe, H Kevin

    2009-08-01

    The pharmacological treatment of depression in children and adolescents is different from that of adults due to the lack of efficacy of certain antidepressants in the pediatric age group. Our current understanding of why these differences occur is very limited. To develop more effective treatments, a juvenile animal model of depression was tested to validate it as a possible model to specifically study pediatric depression. Procedures for use with juvenile rats at postnatal day (PND) 21 and 28 were adapted from the adult learned helplessness model in which, 24 h after exposure to inescapable stress, animals are unable to remove themselves from an easily escapable stressor. Rats were treated for 7 days with either the selective serotonin reuptake inhibitor escitalopram at 10 mg/kg or the tricyclic antidepressant desipramine at 3, 10, or 15 mg/kg to determine if treatment could decrease escape latency times. Escitalopram treatment was effective at decreasing escape latency times in all ages tested. Desipramine treatment did not decrease escape latency times for PND 21 rats, but did decrease times for PND 28 and adult animals. The learned helplessness model with PND 21 rats predicts the efficacy of escitalopram and the lack of efficacy of desipramine seen in the treatment of pediatric depression. These findings suggest that the use of PND 21 rats in a modified learned helplessness procedure may be a valuable model of human pediatric depression that can predict pediatric antidepressant efficacy and be used to study antidepressant mechanisms involved in pediatric depression.

  3. Computer modeling of lung cancer diagnosis-to-treatment process.

    Science.gov (United States)

    Ju, Feng; Lee, Hyo Kyung; Osarogiagbon, Raymond U; Yu, Xinhua; Faris, Nick; Li, Jingshan

    2015-08-01

    We introduce an example of a rigorous, quantitative method for quality improvement in lung cancer care-delivery. Computer process modeling methods are introduced for lung cancer diagnosis, staging and treatment selection process. Two types of process modeling techniques, discrete event simulation (DES) and analytical models, are briefly reviewed. Recent developments in DES are outlined and the necessary data and procedures to develop a DES model for lung cancer diagnosis, leading up to surgical treatment process are summarized. The analytical models include both Markov chain model and closed formulas. The Markov chain models with its application in healthcare are introduced and the approach to derive a lung cancer diagnosis process model is presented. Similarly, the procedure to derive closed formulas evaluating the diagnosis process performance is outlined. Finally, the pros and cons of these methods are discussed.

  4. Effectiveness of propanolol for treatment of infantile haemangioma

    DEFF Research Database (Denmark)

    Andersen, Ida Gillberg; Rechnitzer, Catherine; Charabi, Birgitte

    2014-01-01

    : This study was retrospective and based on a review of children treated for IH with propranolol from the 2010-2012 period at Rigshospitalet. RESULTS: Overall, propranolol was effective in all but one child (97%). The majority of the children (84%) were treated with an initial dose of 1 mg/kg/day, which...... was considered sufficient in most cases (71%). Children who started treatment before five months of age had a significantly better response than children who started treatment at a later age. No relation was found between location of IH and the effect of treatment. There were only few and mild side effects....... CONCLUSION: Propranolol is effective in the treatment of IH and it has only few and mild side effects. In most cases, a low dose of 1 mg/kg/day was sufficient. Early initiation of treatment is recommended as the response to treatment was better in younger children and because early initiation helps prevent...

  5. Cost-effectiveness analysis of treatments for vertebral compression fractures.

    Science.gov (United States)

    Edidin, Avram A; Ong, Kevin L; Lau, Edmund; Schmier, Jordana K; Kemner, Jason E; Kurtz, Steven M

    2012-07-01

    Vertebral compression fractures (VCFs) can be treated by nonsurgical management or by minimally invasive surgical treatment including vertebroplasty and balloon kyphoplasty. The purpose of the present study was to characterize the cost to Medicare for treating VCF-diagnosed patients by nonsurgical management, vertebroplasty, or kyphoplasty. We hypothesized that surgical treatments for VCFs using vertebroplasty or kyphoplasty would be a cost-effective alternative to nonsurgical management for the Medicare patient population. Cost per life-year gained for VCF patients in the US Medicare population was compared between operated (kyphoplasty and vertebroplasty) and non-operated patients and between kyphoplasty and vertebroplasty patients, all as a function of patient age and gender. Life expectancy was estimated using a parametric Weibull survival model (adjusted for comorbidities) for 858 978 VCF patients in the 100% Medicare dataset (2005-2008). Median payer costs were identified for each treatment group for up to 3 years following VCF diagnosis, based on 67 018 VCF patients in the 5% Medicare dataset (2005-2008). A discount rate of 3% was used for the base case in the cost-effectiveness analysis, with 0% and 5% discount rates used in sensitivity analyses. After accounting for the differences in median costs and using a discount rate of 3%, the cost per life-year gained for kyphoplasty and vertebroplasty patients ranged from $US1863 to $US6687 and from $US2452 to $US13 543, respectively, compared with non-operated patients. The cost per life-year gained for kyphoplasty compared with vertebroplasty ranged from -$US4878 (cost saving) to $US2763. Among patients for whom surgical treatment was indicated, kyphoplasty was found to be cost effective, and perhaps even cost saving, compared with vertebroplasty. Even for the oldest patients (85 years of age and older), both interventions would be considered cost effective in terms of cost per life-year gained.

  6. Biological effective dose evaluation in gynaecological brachytherapy: LDR and HDR treatments, dependence on radiobiological parameters, and treatment optimisation.

    Science.gov (United States)

    Bianchi, C; Botta, F; Conte, L; Vanoli, P; Cerizza, L

    2008-10-01

    This study was undertaken to compare the biological efficacy of different high-dose-rate (HDR) and low-dose-rate (LDR) treatments of gynaecological lesions, to identify the causes of possible nonuniformity and to optimise treatment through customised calculation. The study considered 110 patients treated between 2001 and 2006 with external beam radiation therapy and/or brachytherapy with either LDR (afterloader Selectron, (137)Cs) or HDR (afterloader microSelectron Classic, (192)Ir). The treatments were compared in terms of biologically effective dose (BED) to the tumour and to the rectum (linear-quadratic model) by using statistical tests for comparisons between independent samples. The difference between the two treatments was statistically significant in one case only. However, within each technique, we identified considerable nonuniformity in therapeutic efficacy due to differences in fractionation schemes and overall treatment time. To solve this problem, we created a Microsoft Excel spreadsheet allowing calculation of the optimal treatment for each patient: best efficacy (BED(tumour)) without exceeding toxicity threshold (BED(rectum)). The efficacy of a treatment may vary as a result of several factors. Customised radiobiological evaluation is a useful adjunct to clinical evaluation in planning equivalent treatments that satisfy all dosimetric constraints.

  7. Effects of stigma on Chinese women's attitudes towards seeking treatment for urinary incontinence.

    Science.gov (United States)

    Wang, Cuili; Li, Jingjing; Wan, Xiaojuan; Wang, Xiaojuan; Kane, Robert L; Wang, Kefang

    2015-04-01

    To examine whether and how stigma influences attitudes towards seeking treatment for urinary incontinence, and whether its effect varies by symptom severity. Urinary incontinence is prevalent among women, but few seek treatment. Negative attitudes towards urinary incontinence treatment inhibit from seeking care. Urinary incontinence is a stigmatised attribute. However, the relationship between stigma and attitudes towards seeking treatment for urinary incontinence has not been well understood. This was a cross-sectional community-based study. We enrolled a sample of 305 women aged 40-65 years with stress urinary incontinence from three communities in a Chinese city between May-October in 2011. Data were collected on socio-demographic characteristics, urinary incontinence symptoms, stigma and attitudes towards seeking treatment for urinary incontinence using a self-reported questionnaire. Effects of stigma were analysed using path analysis. Attitudes towards seeking treatment for urinary incontinence were generally negative. For the total sample, all the stigma domains of social rejection, social isolation and internalised shame had direct negative effects on treatment-seeking attitudes. The public stigma domain of social rejection also indirectly affected treatment-seeking attitudes through increasing social isolation, as well as through increasing social isolation and then internalised shame. The final model accounted for 28% of the variance of treatment-seeking attitudes. Symptom severity influenced the strength of paths: the effect of internalised shame was higher in women with more severe urinary incontinence. Stigma enhances the formation of negative attitudes towards seeking treatment for urinary incontinence; public stigma affects treatment-seeking attitudes through internalisation of social messages. Stigma reduction may help incontinent women to form positive treatment-seeking attitudes and engage them in treatment. Interventions should specifically target

  8. Cost-effectiveness analysis of universal noninvasive testing for post-treatment confirmation of Helicobacter pylori eradication and the impact of patient adherence.

    Science.gov (United States)

    Boklage, Susan H; Mangel, Allen W; Ramamohan, Varun; Mladsi, Deirdre; Wang, Tao

    2016-01-01

    The treatment failure rate for Helicobacter pylori eradication therapy is ~20% due to poor patient compliance and increased antibiotic resistance. This analysis assessed the cost-effectiveness of universal post-treatment testing to confirm eradication of H. pylori infection in adults. Decision-analytic models evaluated the cost-effectiveness of universal post-treatment testing (urea breath test [UBT] or monoclonal fecal antigen test [mFAT]) vs no testing (Model 1), and UBT vs mFAT after adjusting for patient adherence to testing (Model 2) in adults who previously received first-line antimicrobial therapy. Patients testing positive received second-line quadruple therapy; no further action was taken for those testing negative or with no testing (Model 1) or for those nonadherent to testing (Model 2). In addition to testing costs, excess lifetime costs and reduced quality-adjusted life-years (QALYs) due to continuing H. pylori infection were considered in the model. Expected total costs per patient were higher for post-treatment testing (UBT: US$325.76; mFAT: US$242.12) vs no testing (US$182.41) in Model 1 and for UBT (US$336.75) vs mFAT (US$326.24) in Model 2. Expected QALYs gained per patient were 0.71 and 0.72 for UBT and mFAT, respectively, vs no testing (Model 1), and the same was 0.37 for UBT vs mFAT (Model 2). The estimated incremental costs per QALY gained for post-treatment testing vs no testing were US$82.90-US$202.45 and, after adjusting for adherence, US$28.13 for UBT vs mFAT. Universal post-treatment testing was found to be cost-effective for confirming eradication of H. pylori infection following first-line therapy. Better adherence to UBT relative to mFAT was the key to its cost-effectiveness.

  9. The cost-effectiveness of an intensive treatment protocol for severe dyslexia in children.

    Science.gov (United States)

    Hakkaart-van Roijen, Leona; Goettsch, Wim G; Ekkebus, Michel; Gerretsen, Patty; Stolk, Elly A

    2011-08-01

    Studies of interventions for dyslexia have focused entirely on outcomes related to literacy. In this study, we considered a broader picture assessing improved quality of life compared with costs. A model served as a tool to compare costs and effects of treatment according to a new protocol and care as usual. Quality of life was measured and valued by proxies using a general quality-of-life instrument (EQ-5D). We considered medical cost and non-medical cost (e.g. remedial teaching). The model computed cost per successful treatment and cost per quality adjusted life year (QALY) in time. About 75% of the total costs was related to diagnostic tests to distinguish between children with severe dyslexia and children who have reading difficulties for other reasons. The costs per successful treatment of severe dyslexia were €36 366. Successful treatment showed a quality-of-life gain of about 11%. At primary school, the average cost per QALY for severe dyslexia amounted to €58 647. In the long term, the cost per QALY decreased to €26 386 at secondary school and €17 663 thereafter. The results of this study provide evidence that treatment of severe dyslexia is cost-effective when the investigated protocol is followed. Copyright © 2011 John Wiley & Sons, Ltd.

  10. The Effect of Interface Treatment on Ceramic Performance and Modeling Dyneema Subjected to Ballistic Impact

    Science.gov (United States)

    2018-01-23

    Mechanical Engineering Division January 26, 2018 Professor KT Ramesh JHU/HEMI Project Director Johns Hopkins University 3400 N. Charles...Sincerely, Timothy J. Holmquist Institute Engineer ...Director Record Copy B (Contracts) Engineering Dynamics Department The Effect of Interface Treatment on Ceramic Performance and

  11. The use of mathematical models in teaching wastewater treatment engineering

    DEFF Research Database (Denmark)

    Morgenroth, Eberhard Friedrich; Arvin, Erik; Vanrolleghem, P.

    2002-01-01

    Mathematical modeling of wastewater treatment processes has become increasingly popular in recent years. To prepare students for their future careers, environmental engineering education should provide students with sufficient background and experiences to understand and apply mathematical models...... efficiently and responsibly. Approaches for introducing mathematical modeling into courses on wastewater treatment engineering are discussed depending on the learning objectives, level of the course and the time available....

  12. Treatment-seeking behaviour in low- and middle-income countries estimated using a Bayesian model

    Directory of Open Access Journals (Sweden)

    Victor A. Alegana

    2017-04-01

    Full Text Available Abstract Background Seeking treatment in formal healthcare for uncomplicated infections is vital to combating disease in low- and middle-income countries (LMICs. Healthcare treatment-seeking behaviour varies within and between communities and is modified by socio-economic, demographic, and physical factors. As a result, it remains a challenge to quantify healthcare treatment-seeking behaviour using a metric that is comparable across communities. Here, we present an application for transforming individual categorical responses (actions related to fever to a continuous probabilistic estimate of fever treatment for one country in Sub-Saharan Africa (SSA. Methods Using nationally representative household survey data from the 2013 Demographic and Health Survey (DHS in Namibia, individual-level responses (n = 1138 were linked to theoretical estimates of travel time to the nearest public or private health facility. Bayesian Item Response Theory (IRT models were fitted via Markov Chain Monte Carlo (MCMC simulation to estimate parameters related to fever treatment and estimate probability of treatment for children under five years. Different models were implemented to evaluate computational needs and the effect of including predictor variables such as rurality. The mean treatment rates were then estimated at regional level. Results Modelling results suggested probability of fever treatment was highest in regions with relatively high incidence of malaria historically. The minimum predicted threshold probability of seeking treatment was 0.3 (model 1: 0.340; 95% CI 0.155–0.597, suggesting that even in populations at large distances from facilities, there was still a 30% chance of an individual seeking treatment for fever. The agreement between correctly predicted probability of treatment at individual level based on a subset of data (n = 247 was high (AUC = 0.978, with a sensitivity of 96.7% and a specificity of 75.3%. Conclusion We have shown

  13. The effect of advanced treatment of sewage effluents on metal speciation and (bio)availability.

    Science.gov (United States)

    Peters, A; Merrington, G; Leverett, D; Ellor, B; Lofts, S; Gravell, A

    2014-02-01

    The bioavailability of metals can be strongly influenced by dissolved organic carbon (DOC). Wastewater treatment effluents add considerable quantities of DOC and metals to receiving waters, and as effluent controls become more stringent advanced effluent treatments may be needed. We assessed the effects of two types of advanced treatment processes on metal availability in wastewater effluents. Trace metal availability was assessed using diffuse gradients in thin films and predicted through speciation modelling. The results show little difference in metal availability post-advanced treatment. EDTA-like compounds are important metal complexants in the effluents.

  14. The cost-effectiveness of radiofrequency catheter ablation as first-line treatment for paroxysmal atrial fibrillation

    DEFF Research Database (Denmark)

    Aronsson, Mattias; Walfridsson, Håkan; Janzon, Magnus

    2014-01-01

    AIM: The aim of this prospective substudy was to estimate the cost-effectiveness of treating paroxysmal atrial fibrillation (AF) with radiofrequency catheter ablation (RFA) compared with antiarrhythmic drugs (AADs) as first-line treatment. METHODS AND RESULTS: A decision-analytic Markov model......, based on MANTRA-PAF (Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation) study data, was developed to study long-term effects and costs of RFA compared with AADs as first-line treatment. Positive clinical effects were found in the overall population, a gain...... of an average 0.06 quality-adjusted life years (QALYs) to an incremental cost of €3033, resulting in an incremental cost-effectiveness ratio of €50 570/QALY. However, the result of the subgroup analyses showed that RFA was less costly and more effective in younger patients. This implied an incremental cost-effectiveness...

  15. Effect of annealing treatments on normal state resistivity of YBa 2 ...

    African Journals Online (AJOL)

    Samples of YBa2(Cu1-xTix)3Oy superconductor with x=0.00 , 0.01, 0.03 have been prepared by solide state reaction method. The effect of annealing treatments on normal electrical resistivity has been done using the bipolaron model. The results of this study show the increase of localized charge when the dopant content ...

  16. Kinetic modeling of Nernst effect in magnetized hohlraums

    OpenAIRE

    Joglekar, A. S.; Ridgers, Christopher Paul; Kingham, R J; Thomas, A. G. R.

    2016-01-01

    We present nanosecond time-scale Vlasov-Fokker-Planck-Maxwell modeling of magnetized plasma transport and dynamics in a hohlraum with an applied external magnetic field, under conditions similar to recent experiments. Self-consistent modeling of the kinetic electron momentum equation allows for a complete treatment of the heat flow equation and Ohm's law, including Nernst advection of magnetic fields. In addition to showing the prevalence of nonlocal behavior, we demonstrate that effects such...

  17. Clinical effectiveness and cost-effectiveness of treatments for patients with chronic pain.

    Science.gov (United States)

    Turk, Dennis C

    2002-01-01

    Chronic pain is a prevalent and costly problem. This review addresses the question of the clinical effectiveness and cost-effectiveness of the most common treatments for patients with chronic pain. Representative published studies that evaluate the clinical effectiveness of pharmacological treatments, conservative (standard) care, surgery, spinal cord stimulators, implantable drug delivery systems (IDDSs), and pain rehabilitation programs (PRPs) are examined and compared. The cost-effectiveness of these treatment approaches is also considered. Outcome criteria including pain reduction, medication use, health care consumption, functional activities, and closure of disability compensation cases are examined. In addition to clinical effectiveness, the cost-effectiveness of PRPs, conservative care, surgery, spinal cord stimulators, and IDDSs are compared using costs to return a treated patient to work to illustrate the relative expenses for each of these treatments. There are limitations to the success of all the available treatments. The author urges caution in interpreting the results, particularly in comparisons between treatments and across studies, because there are broad differences in the pain syndromes and inclusion criteria used, the drug dosages, comparability of treatments, the definition of "chronic" used, the outcome criteria selected to determine success, and societal differences. None of the currently available treatments eliminates pain for the majority of patients. Pain rehabilitation programs provide comparable reduction in pain to alternative pain treatment modalities, but with significantly better outcomes for medication use, health care utilization, functional activities, return to work, closure of disability claims, and with substantially fewer iatrogenic consequences and adverse events. Surgery, spinal cord stimulators, and IDDSs appear to have substantial benefits on some outcome criteria for carefully selected patients. These modalities are

  18. Treatment of Amblyopia Using Personalized Dosing Strategies: Statistical Modelling and Clinical Implementation.

    Science.gov (United States)

    Wallace, Michael P; Stewart, Catherine E; Moseley, Merrick J; Stephens, David A; Fielder, Alistair R

    2016-12-01

    To generate a statistical model for personalizing a patient's occlusion therapy regimen. Statistical modelling was undertaken on a combined data set of the Monitored Occlusion Treatment of Amblyopia Study (MOTAS) and the Randomized Occlusion Treatment of Amblyopia Study (ROTAS). This exercise permits the calculation of future patients' total effective dose (TED)-that predicted to achieve their best attainable visual acuity. Daily patching regimens (hours/day) can be calculated from the TED. Occlusion data for 149 study participants with amblyopia (anisometropic in 50, strabismic in 43, and mixed in 56) were analyzed. Median time to best observed visual acuity was 63 days (25% and 75% quartiles; 28 and 91 days). Median visual acuity in the amblyopic eye at start of occlusion was 0.40 logMAR (quartiles 0.22 and 0.68 logMAR) and at end of occlusion was 0.12 (quartiles 0.025 and 0.32 logMAR). Median lower and upper estimates of TED were 120 hours (quartiles 34 and 242 hours), and 176 hours (quartiles 84 and 316 hours). The data suggest a piecewise linear relationship (P = 0.008) between patching dose-rate (hours/day) and TED with a single breakpoint estimated at 2.16 (standard error 0.51) hours/day, suggesting doses below 2.16 hours/day are less effective. We introduce the concept of TED of occlusion. Predictors for TED are visual acuity deficit, amblyopia type, and age at start of occlusion therapy. Dose-rates prescribed within the model range from 2.5 to 12 hours/day and can be revised dynamically throughout treatment in response to recorded patient compliance: a personalized dosing strategy.

  19. Lodenafil treatment in the monocrotaline model of pulmonary hypertension in rats

    Directory of Open Access Journals (Sweden)

    Igor Bastos Polonio

    2014-08-01

    Full Text Available We assessed the effects of lodenafil on hemodynamics and inflammation in the rat model of monocrotaline-induced pulmonary hypertension (PH. Thirty male Sprague-Dawley rats were randomly divided into three groups: control; monocrotaline (experimental model; and lodenafil (experimental model followed by lodenafil treatment, p.o., 5 mg/kg daily for 28 days Mean pulmonary artery pressure (mPAP was obtained by right heart catheterization. We investigated right ventricular hypertrophy (RVH and IL-1 levels in lung fragments. The number of cases of RVH was significantly higher in the monocrotaline group than in the lodenafil and control groups, as were mPAP and IL-1 levels. We conclude that lodenafil can prevent monocrotaline-induced PH, RVH, and inflammation.

  20. A rationale and model for addressing tobacco dependence in substance abuse treatment

    Directory of Open Access Journals (Sweden)

    Richter Kimber P

    2006-08-01

    Full Text Available Abstract Most persons in drug treatment smoke cigarettes. Until drug treatment facilities systematically treat their patients' tobacco use, millions will flow through the drug treatment system, overcome their primary drug of abuse, but die prematurely from tobacco-related illnesses. This paper reviews the literature on the health benefits of quitting smoking for drug treatment patients, whether smoking causes relapse to other drug or alcohol abuse, the treatment of tobacco dependence, and good and bad times for quitting smoking among drug treatment patients. It also presents a conceptual model and recommendations for treating tobacco in substance abuse treatment, and provides references to internet and paper-copy tools and information for treating tobacco dependence. At present, research on tobacco treatment in drug treatment is in its infancy. Although few drug treatment programs currently offer formal services, many more will likely begin to treat nicotine dependence as external forces and patient demand for these services increases. In the absence of clear guidelines and attention to quality of care, drug treatment programs may adopt smoking cessation services based on cost, convenience, or selection criteria other than efficacy. Because research in this field is relatively new, substance abuse treatment professionals should adhere to the standards of care for the general population, but be prepared to update their practices with emerging interventions that have proven to be effective for patients in drug treatment.

  1. Effect of Cordyceps sinensis on the Treatment of Experimental Autoimmune Encephalomyelitis: A Pilot Study on Mice Model

    Directory of Open Access Journals (Sweden)

    Shan-Shan Zhong

    2017-01-01

    Conclusions: Our preliminary study demonstrated that CS efficiently alleviated EAE severity and EAE-related pathology damage and decreased the number of Th1s in the periphery, indicating its effectiveness in the treatment of murine EAE. Thus, our findings strongly support the therapeutic potential of this agent as a new traditional Chinese medicine approach in MS treatment.

  2. Chronic treatment with antipsychotics in rats as a model for antipsychotic-induced weight gain in human

    DEFF Research Database (Denmark)

    Pouzet, B; Mow, T; Kreilgaard, Mads

    2003-01-01

    compounds in an animal model of weight gain. With the aim of evaluating whether the rat can be used as a model for antipsychotic-induced weight gain, we have investigated the effect of chronic treatment (3 weeks) with one antipsychotic drug inducing weight gain in clinic (olanzapine) and one antipsychotic...

  3. Mathematical model for HIV spreads control program with ART treatment

    Science.gov (United States)

    Maimunah; Aldila, Dipo

    2018-03-01

    In this article, using a deterministic approach in a seven-dimensional nonlinear ordinary differential equation, we establish a mathematical model for the spread of HIV with an ART treatment intervention. In a simplified model, when no ART treatment is implemented, disease-free and the endemic equilibrium points were established analytically along with the basic reproduction number. The local stability criteria of disease-free equilibrium and the existing criteria of endemic equilibrium were analyzed. We find that endemic equilibrium exists when the basic reproduction number is larger than one. From the sensitivity analysis of the basic reproduction number of the complete model (with ART treatment), we find that the increased number of infected humans who follow the ART treatment program will reduce the basic reproduction number. We simulate this result also in the numerical experiment of the autonomous system to show how treatment intervention impacts the reduction of the infected population during the intervention time period.

  4. Effect of antibiotic treatment on fat absorption in mice with cystic fibrosis

    NARCIS (Netherlands)

    Wouthuyzen-Bakker, Marjan; Bijvelds, Marcel J. C.; de Jonge, Hugo R.; De Lisle, Robert C.; Burgerhof, Johannes G. M.; Verkade, Henkjan J.

    INTRODUCTION: Improving fat absorption remains a challenge in cystic fibrosis (CF). Antibiotics (AB) treatment has been shown to improve body weight in CF mice. The mechanism may include improvement in fat absorption. We aimed to determine the effect of AB on fat absorption in two CF mouse models.

  5. The neuroprotective effect of hyperbaric oxygen treatment on laser-induced retinal damage in rats

    Science.gov (United States)

    Vishnevskia-Dai, Victoria; Belokopytov, Mark; Dubinsky, Galina; Nachum, Gal; Avni, Isaac; Belkin, Michael; Rosner, Mordechai

    2005-04-01

    Retinal damage induced by mechanical trauma, ischemia or laser photocoagulation increases considerably by secondary degeneration processes. The spread of damage may be ameliorated by neuroprotection that is aimed at reducing the extent of the secondary degeneration and promote healing processes. Hyperbaric oxygen (HBO) treatment consists of inspiration of oxygen at higher than one absolute atmospheric pressure. Improved neural function was observed in patients with acute brain trauma or ischemia treated with HBO. This study was designed to evaluate the neuroprotective effect of hyperbaric oxygen (HBO) on laser induced retinal damage in a rat model. Standard argon laser lesions were created in 25 pigmented rats divided into three groups: Ten rats were treated immediately after the irradiation with HBO three times during the first 24 hr followed by 12 consecutive daily treatments. Five rats received a shorter treatment regimen of 10 consecutive HBO treatments. The control group (10 rats) underwent the laser damage with no additional treatment. The retinal lesions were evaluated 20 days after the injury. All outcome measures were improved by the longer HBO treatment (Ptreatment was less effective, showing an increase only in nuclei density at the central area of lesion (Pretinal damage in a rat model. In the range of HBO exposures studied, longer exposure provides more neuroprotection. These results encourage further evaluation of the potential therapeutic use of hyperbaric oxygen in diseases and injuries of the retina.

  6. Effect of wastewater treatment on bio-kinetics of dissolved oxygen in Ravi river

    International Nuclear Information System (INIS)

    Haider, H.; Ali, W.

    2010-01-01

    Waste management studies are usually done using calibrated and verified water quality models. Ravi River located in Lahore, Pakistan is receiving untreated wastewater from number of out falls and . Surfaced rains and thus model calibration and verification are done using the data under the prevailing conditions. The water quality objectives can only be met with wastewater treatment wherein the model rate coefficients may change. The objective of this paper is to study the changes that may occur in these coefficients as a result of wastewater treatment. For this purpose, long-term BOD analyses have been carried out using river water and wastewater after different degrees of treatment. A laboratory scale biological reactor was used to study the effect of biological treatment on rate coefficients at 3, 6 and 10 days detention times. The study results show that CBOD biokinetic rate coefficient (K) reduces significantly from 0.25 day/sup -1/ for raw waste water to 0.1 day for the wastewater treatment for 3 days detention time in the biological reactor. Further reductions in the value of K to 0.07 day/sup -1 and 0.05 day/sup -1/ occurred for a treatment level corresponding to 6 and 10 days detention times, respectively. The NBOD rate coefficient (K/sub n/ was found to be 0.08 day/sup -1/ for 3 days detention time and 0.06 day/sup -1/ after treatment in the biological reactor at 6 and 10 days detention times. (author)

  7. Modeling the role of information and limited optimal treatment on disease prevalence.

    Science.gov (United States)

    Kumar, Anuj; Srivastava, Prashant K; Takeuchi, Yasuhiro

    2017-02-07

    Disease outbreaks induce behavioural changes in healthy individuals to avoid contracting infection. We first propose a compartmental model which accounts for the effect of individual's behavioural response due to information of the disease prevalence. It is assumed that the information is growing as a function of infective population density that saturates at higher density of infective population and depends on active educational and social programmes. Model analysis has been performed and the global stability of equilibrium points is established. Further, choosing the treatment (a pharmaceutical intervention) and the effect of information (a non-pharmaceutical intervention) as controls, an optimal control problem is formulated to minimize the cost and disease fatality. In the cost functional, the nonlinear effect of controls is accounted. Analytical characterization of optimal control paths is done with the help of Pontryagin's Maximum Principle. Numerical findings suggest that if only control via information is used, it is effective and economical for early phase of disease spread whereas treatment works well for long term control except for initial phase. Furthermore, we observe that the effect of information induced behavioural response plays a crucial role in the absence of pharmaceutical control. Moreover, comprehensive use of both the control interventions is more effective than any single applied control policy and it reduces the number of infective individuals and minimizes the economic cost generated from disease burden and applied controls. Thus, the combined effect of both the control policies is found more economical during the entire epidemic period whereas the implementation of a single policy is not found economically viable. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Effect of marital status on duration of treatment for mental illness

    Directory of Open Access Journals (Sweden)

    Margaret J. Penning

    2012-01-01

    Full Text Available There is a well-established link between marital status and mental health, but previous research has produced mixed results about the reasons for this relationship. Some studies propose that marriage provides protection from stressors and increases personal coping abilities (the causation perspective, whereas other studies argue that marriage markets “weed out” individuals predisposed to illness (the selection perspective. This article addresses the causation-versus-selection debate by examining the effect of marital status on duration of treatment for mental illness. The empirical analysis uses longitudinal data and GEE models to estimate group-level differences in duration of treatment. The results suggest that marriage does not appear to confer a health advantage in terms of duration of treatment. However, the study demonstrates that the never-married experience longer treatment time than the married, divorced, and widowed.

  9. Effect of marital status on duration of treatment for mental illness

    Directory of Open Access Journals (Sweden)

    Zheng Wu

    2012-07-01

    Full Text Available There is a well-established link between marital status and mental health, but previous research has produced mixed results about the reasons for this relationship. Some studies propose that marriage provides protection from stressors and increases personal coping abilities (the causation perspective, whereas other studies argue that marriage markets “weed out” individuals predisposed to illness (the selection perspective. This article addresses the causation-versus-selection debate by examining the effect of marital status on duration of treatment for mental illness. The empirical analysis uses longitudinal data and GEE models to estimate group-level differences in duration of treatment. The results suggest that marriage does not appear to confer a health advantage in terms of duration of treatment. However, the study demonstrates that the never-married experience longer treatment time than the married, divorced, and widowed.

  10. Scattering effects on the performance of carbon nanotube field effect transistor in a compact model

    Science.gov (United States)

    Hamieh, S. D.; Desgreys, P.; Naviner, J. F.

    2010-01-01

    Carbon nanotube field-effect transistors (CNTFET) are being extensively studied as possible successors to CMOS. Device simulators have been developed to estimate their performance in sub-10-nm and device structures have been fabricated. In this work, a new compact model of single-walled semiconducting CNTFET is proposed implementing the calculation of energy conduction sub-band minima and the treatment of scattering effects through energy shift in CNTFET. The developed model has been used to simulate I-V characteristics using VHDL-AMS simulator.

  11. New Gravity Wave Treatments for GISS Climate Models

    Science.gov (United States)

    Geller, Marvin A.; Zhou, Tiehan; Ruedy, Reto; Aleinov, Igor; Nazarenko, Larissa; Tausnev, Nikolai L.; Sun, Shan; Kelley, Maxwell; Cheng, Ye

    2011-01-01

    Previous versions of GISS climate models have either used formulations of Rayleigh drag to represent unresolved gravity wave interactions with the model-resolved flow or have included a rather complicated treatment of unresolved gravity waves that, while being climate interactive, involved the specification of a relatively large number of parameters that were not well constrained by observations and also was computationally very expensive. Here, the authors introduce a relatively simple and computationally efficient specification of unresolved orographic and nonorographic gravity waves and their interaction with the resolved flow. Comparisons of the GISS model winds and temperatures with no gravity wave parameterization; with only orographic gravity wave parameterization; and with both orographic and nonorographic gravity wave parameterizations are shown to illustrate how the zonal mean winds and temperatures converge toward observations. The authors also show that the specifications of orographic and nonorographic gravity waves must be different in the Northern and Southern Hemispheres. Then results are presented where the nonorographic gravity wave sources are specified to represent sources from convection in the intertropical convergence zone and spontaneous emission from jet imbalances. Finally, a strategy to include these effects in a climate-dependent manner is suggested.

  12. Analytical modelling for ultrasonic surface mechanical attrition treatment

    Directory of Open Access Journals (Sweden)

    Guan-Rong Huang

    2015-07-01

    Full Text Available The grain refinement, gradient structure, fatigue limit, hardness, and tensile strength of metallic materials can be effectively enhanced by ultrasonic surface mechanical attrition treatment (SMAT, however, never before has SMAT been treated with rigorous analytical modelling such as the connection among the input energy and power and resultant temperature of metallic materials subjected to SMAT. Therefore, a systematic SMAT model is actually needed. In this article, we have calculated the averaged speed, duration time of a cycle, kinetic energy and kinetic energy loss of flying balls in SMAT for structural metallic materials. The connection among the quantities such as the frequency and amplitude of attrition ultrasonic vibration motor, the diameter, mass and density of balls, the sample mass, and the height of chamber have been considered and modelled in details. And we have introduced the one-dimensional heat equation with heat source within uniform-distributed depth in estimating the temperature distribution and heat energy of sample. In this approach, there exists a condition for the frequency of flying balls reaching a steady speed. With these known quantities, we can estimate the strain rate, hardness, and grain size of sample.

  13. Attenuation of food allergy symptoms following treatment with human milk oligosaccharides in a mouse model.

    Science.gov (United States)

    Castillo-Courtade, L; Han, S; Lee, S; Mian, F M; Buck, R; Forsythe, P

    2015-09-01

    The prebiotic nature of human milk oligosaccharides (HMOs) and increasing evidence of direct immunomodulatory effects of these sugars suggest that they may have some therapeutic potential in allergy. Here, we assess the effect of two HMOs, 2'-fucosyllactose and 6'-sialyllactose, on symptomatology and immune responses in an ovalbumin-sensitized mouse model of food allergy. The effects of oral treatment with 2'-fucosyllactose and 6'-sialyllactose on anaphylactic symptoms induced by oral ovalbumin (OVA) challenge in sensitized mice were investigated. Mast cell functions in response to oral HMO treatment were also measured in the passive cutaneous anaphylaxis model, and direct effects on IgE-mediated degranulation of mast cells were assessed. Daily oral treatment with 2'-fucosyllactose or 6'-sialyllactose attenuated food allergy symptoms including diarrhea and hypothermia. Treatment with HMOs also suppressed antigen-induced increases in mouse mast cell protease-1 in serum and mast cell numbers in the intestine. These effects were associated with increases in the CD4(+) CD25(+) IL-10(+) cell populations in the Peyer's patches and mesenteric lymph nodes, while 6'-sialyllactose also induced increased IL-10 and decreased TNF production in antigen-stimulated splenocytes. Both 2'-fucosyllactose and 6'-sialyllactose reduced the passive cutaneous anaphylaxis response, but only 6'-sialyllactose directly inhibited mast cell degranulation in vitro, at high concentrations. Our results suggest that 2'-fucosyllactose and 6'-sialyllactose reduce the symptoms of food allergy through induction of IL-10(+) T regulatory cells and indirect stabilization of mast cells. Thus, human milk oligosaccharides may have therapeutic potential in allergic disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Combination sclerostin antibody and zoledronic acid treatment outperforms either treatment alone in a mouse model of osteogenesis imperfecta.

    Science.gov (United States)

    Little, David G; Peacock, Lauren; Mikulec, Kathy; Kneissel, Michaela; Kramer, Ina; Cheng, Tegan L; Schindeler, Aaron; Munns, Craig

    2017-08-01

    In this study, we examined the therapeutic potential of anti-Sclerostin Antibody (Scl-Ab) and bisphosphonate treatments for the bone fragility disorder Osteogenesis Imperfecta (OI). Mice with the Amish OI mutation (Col1a2 G610C mice) and control wild type littermates (WT) were treated from week 5 to week 9 of life with (1) saline (control), (2) zoledronic acid given 0.025mg/kg s.c. weekly (ZA), (3) Scl-Ab given 50mg/kg IV weekly (Scl-Ab), or (4) a combination of both (Scl-Ab/ZA). Functional outcomes were prioritized and included bone mineral density (BMD), bone microarchitecture, long bone bending strength, and vertebral compression strength. By dual-energy absorptiometry, Scl-Ab treatment alone had no effect on tibial BMD, while ZA and Scl-Ab/ZA significantly enhanced BMD by week 4 (+16% and +27% respectively, P<0.05). Scl-Ab/ZA treatment also led to increases in cortical thickness and tissue mineral density, and restored the tibial 4-point bending strength to that of control WT mice. In the spine, all treatments increased compression strength over controls, but only the combined group reached the strength of WT controls. Scl-Ab showed greater anabolic effects in the trabecular bone than in cortical bone. In summary, the Scl-Ab/ZA intervention was superior to either treatment alone in this OI mouse model, however further studies are required to establish its efficacy in other preclinical and clinical scenarios. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  15. Stability and bifurcation analysis of an SIR epidemic model with logistic growth and saturated treatment

    International Nuclear Information System (INIS)

    Li, Jinhui; Teng, Zhidong; Wang, Guangqing; Zhang, Long; Hu, Cheng

    2017-01-01

    In this paper, we introduce the saturated treatment and logistic growth rate into an SIR epidemic model with bilinear incidence. The treatment function is assumed to be a continuously differential function which describes the effect of delayed treatment when the medical condition is limited and the number of infected individuals is large enough. Sufficient conditions for the existence and local stability of the disease-free and positive equilibria are established. And the existence of the stable limit cycles also is obtained. Moreover, by using the theory of bifurcations, it is shown that the model exhibits backward bifurcation, Hopf bifurcation and Bogdanov–Takens bifurcations. Finally, the numerical examples are given to illustrate the theoretical results and obtain some additional interesting phenomena, involving double stable periodic solutions and stable limit cycles.

  16. Effectiveness of the Treatment Readiness and Induction Program for increasing adolescent motivation for change.

    Science.gov (United States)

    Becan, Jennifer E; Knight, Danica K; Crawley, Rachel D; Joe, George W; Flynn, Patrick M

    2015-03-01

    Success in substance abuse treatment is improved by problem recognition, desire to seek help, and readiness to engage in treatment, all of which are important aspects of motivation. Interventions that facilitate these at treatment induction for adolescents are especially needed. The purpose of this study is to assess the effectiveness of TRIP (Treatment Readiness and Induction Program) in promoting treatment motivation. Data represent 519 adolescents from 6 residential programs who completed assessments at treatment intake (time 1) and 35 days after admission (time 2). The design consisted of a comparison sample (n=281) that had enrolled in treatment prior to implementation of TRIP (standard operating practice) and a sample of clients that had entered treatment after TRIP began and received standard operating practice enhanced by TRIP (n=238). Repeated measures ANCOVAs were conducted using each time 2 motivation scale as a dependent measure. Motivation scales were conceptualized as representing sequential stages of change. LISREL was used to test a structural model involving TRIP participation, gender, drug use severity, juvenile justice involvement, age, race-ethnicity, prior treatment, and urgency as predictors of the stages of treatment motivation. Compared to standard practice, adolescents receiving TRIP demonstrated greater gains in problem recognition, even after controlling for the other variables in the model. The model fit was adequate, with TRIP directly affecting problem recognition and indirectly affecting later stages of change (desire for help and treatment readiness). Future studies should examine which specific components of TRIP affect change in motivation. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. A South African public-private partnership HIV treatment model: viability and success factors.

    Science.gov (United States)

    Igumbor, Jude; Pascoe, Sophie; Rajap, Shuabe; Townsend, Wendy; Sargent, John; Darkoh, Ernest

    2014-01-01

    The increasing number of people requiring HIV treatment in South Africa calls for efficient use of its human resources for health in order to ensure optimum treatment coverage and outcomes. This paper describes an innovative public-private partnership model which uses private sector doctors to treat public sector patients and ascertains the model's ability to maintain treatment outcomes over time. The study used a retrospective design based on the electronic records of patients who were down-referred from government hospitals to selected private general medical practitioners (GPs) between November 2005 and October 2012. In total, 2535 unique patient records from 40 GPs were reviewed. The survival functions for mortality and attrition were calculated. Cumulative incidence of mortality for different time cohorts (defined by year of treatment initiation) was also established. The median number of patients per GP was 143 (IQR: 66-246). At the time of down-referral to private GPs, 13.8% of the patients had CD4 count private sector based programme can be effectively and efficiently used to either target specific health concerns, key populations or serve as a stop-gap measure to meet urgent health needs.

  18. Cost-effectiveness of seven IVF strategies: results of a Markov decision-analytic model.

    Science.gov (United States)

    Fiddelers, Audrey A A; Dirksen, Carmen D; Dumoulin, John C M; van Montfoort, Aafke P A; Land, Jolande A; Janssen, J Marij; Evers, Johannes L H; Severens, Johan L

    2009-07-01

    A selective switch to elective single embryo transfer (eSET) in IVF has been suggested to prevent complications of fertility treatment for both mother and infants. We compared seven IVF strategies concerning their cost-effectiveness using a Markov model. The model was based on a three IVF-attempts time horizon and a societal perspective using real world strategies and data, comparing seven IVF strategies, concerning costs, live births and incremental cost-effectiveness ratios (ICERs). In order to increase pregnancy probability, one cycle of eSET + one cycle of standard treatment policy [STP, i.e. eSET in patients IVF treatment, combining several transfer policies was not cost-effective. A choice has to be made between three cycles of eSET, STP or DET. It depends, however, on society's willingness to pay which strategy is to be preferred from a cost-effectiveness point of view.

  19. Hippocampal Proteome of Rats Subjected to the Li-Pilocarpine Epilepsy Model and the Effect of Carisbamate Treatment

    Directory of Open Access Journals (Sweden)

    José Eduardo Marques-Carneiro

    2017-07-01

    Full Text Available In adult rats, the administration of lithium–pilocarpine (LiPilo reproduces most clinical and neuropathological features of human temporal lobe epilepsy (TLE. Carisbamate (CRS possesses the property of modifying epileptogenesis in this model. Indeed, about 50% of rats subjected to LiPilo status epilepticus (SE develop non-convulsive seizures (NCS instead of motor seizures when treated with CRS. However, the mechanisms underlying these effects remain unknown. The aim of this study was to perform a proteomic analysis in the hippocampus of rats receiving LiPilo and developing motor seizures or NCS following CRS treatment. Fifteen adult male Sprague–Dawley rats were used. SE was induced by LiPilo injection. CRS treatment was initiated at 1 h and 9 h after SE onset and maintained for 7 days, twice daily. Four groups were studied after video-EEG control of the occurrence of motor seizures: a control group receiving saline (CT n = 3 and three groups that underwent SE: rats treated with diazepam (DZP n = 4, rats treated with CRS displaying NCS (CRS-NCS n = 4 or motor seizures (CRS-TLE n = 4. Proteomic analysis was conducted by 2D-SDS-PAGE. Twenty-four proteins were found altered. In the CRS-NCS group, proteins related to glycolysis and ATP synthesis were down-regulated while proteins associated with pyruvate catabolism were up-regulated. Moreover, among the other proteins differentially expressed, we found proteins related to inflammatory processes, protein folding, tissue regeneration, response to oxidative stress, gene expression, biogenesis of synaptic vesicles, signal transduction, axonal transport, microtubule formation, cell survival, and neuronal plasticity. Our results suggest a global reduction of glycolysis and cellular energy production that might affect brain excitability. In addition, CRS seems to modulate proteins related to many other pathways that could significantly participate in the epileptogenesis-modifying effect observed.

  20. The effects of modeling instruction on high school physics academic achievement

    Science.gov (United States)

    Wright, Tiffanie L.

    The purpose of this study was to explore whether Modeling Instruction, compared to traditional lecturing, is an effective instructional method to promote academic achievement in selected high school physics classes at a rural middle Tennessee high school. This study used an ex post facto , quasi-experimental research methodology. The independent variables in this study were the instructional methods of teaching. The treatment variable was Modeling Instruction and the control variable was traditional lecture instruction. The Treatment Group consisted of participants in Physical World Concepts who received Modeling Instruction. The Control Group consisted of participants in Physical Science who received traditional lecture instruction. The dependent variable was gains scores on the Force Concepts Inventory (FCI). The participants for this study were 133 students each in both the Treatment and Control Groups (n = 266), who attended a public, high school in rural middle Tennessee. The participants were administered the Force Concepts Inventory (FCI) prior to being taught the mechanics of physics. The FCI data were entered into the computer-based Statistical Package for the Social Science (SPSS). Two independent samples t-tests were conducted to answer the research questions. There was a statistically significant difference between the treatment and control groups concerning the instructional method. Modeling Instructional methods were found to be effective in increasing the academic achievement of students in high school physics. There was no statistically significant difference between FCI gains scores for gender. Gender was found to have no effect on the academic achievement of students in high school physics classes. However, even though there was not a statistically significant difference, female students' gains scores were higher than male students' gains scores when Modeling Instructional methods of teaching were used. Based on these findings, it is recommended

  1. Mathematical Modelling and Analysis of the Tumor Treatment Regimens with Pulsed Immunotherapy and Chemotherapy.

    Science.gov (United States)

    Pang, Liuyong; Shen, Lin; Zhao, Zhong

    2016-01-01

    To begin with, in this paper, single immunotherapy, single chemotherapy, and mixed treatment are discussed, and sufficient conditions under which tumor cells will be eliminated ultimately are obtained. We analyze the impacts of the least effective concentration and the half-life of the drug on therapeutic results and then find that increasing the least effective concentration or extending the half-life of the drug can achieve better therapeutic effects. In addition, since most types of tumors are resistant to common chemotherapy drugs, we consider the impact of drug resistance on therapeutic results and propose a new mathematical model to explain the cause of the chemotherapeutic failure using single drug. Based on this, in the end, we explore the therapeutic effects of two-drug combination chemotherapy, as well as mixed immunotherapy with combination chemotherapy. Numerical simulations indicate that combination chemotherapy is very effective in controlling tumor growth. In comparison, mixed immunotherapy with combination chemotherapy can achieve a better treatment effect.

  2. Quality of data computational models and telemedicine treatment effects

    NARCIS (Netherlands)

    Larburu Rubio, Nekane; Widya, I.A.; Bults, Richard G.A.; Hermens, Hermanus J.

    2014-01-01

    Clinical decision-support functions of telemedicine systems use patient's monitored clinical data to support treatment of outpatients. However, the quality of monitored clinical data may vary due to performance variations of technological resources inside a deployed telemedicine system. This paper

  3. Oral Mucosa Model for Electrochemotherapy Treatment of Dog Mouth Cancer: Ex Vivo, In Silico, and In Vivo Experiments.

    Science.gov (United States)

    Suzuki, Daniela O H; Berkenbrock, José A; Frederico, Marisa J S; Silva, Fátima R M B; Rangel, Marcelo M M

    2018-03-01

    Electrochemotherapy (EQT) is a local cancer treatment well established to cutaneous and subcutaneous tumors. Electric fields are applied to biological tissue in order to improve membrane permeability for cytotoxic drugs. This phenomenon is called electroporation or electropermeabilization. Studies have reported that tissue conductivity is electric field dependent. Electroporation numerical models of biological tissues are essential in treatment planning. Tumors of the mouth are very common in dogs. Inadequate EQT treatment of oral tumor may be caused by significant anatomic variations between dogs and tumor position. Numerical models of oral mucosa and tumor allow the treatment planning and optimization of electrodes for each patient. In this work, oral mucosa conductivity during electroporation was characterized by measuring applied voltage and current of ex vivo rats. This electroporation model was used with a spontaneous canine oral melanoma. The model outcomes of oral tumor EQT is applied in different parts of the oral cavity including near bones and the hard palate. The numerical modeling for treatment planning will help the development of new electrodes and increase the EQT effectiveness. © 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  4. Adding smoking to the Fardal model of cost-effectiveness for the life-time treatment of periodontal diseases.

    Science.gov (United States)

    Fardal, Øystein; Grytten, Jostein; Martin, John; Ellingsen, Stig; Fardal, Patrick; Heasman, Peter; Linden, Gerard J

    2018-05-16

    Little is known about the financial costs that smoking adds to the life-time treatment of periodontal disease. The total life-time cost of periodontal treatment was modelled using data from private periodontal practice. The costs of initial and supportive therapy, re-treatment and tooth replacements (with bridgework or implants) were identified using average dental charges from the American Dental Association survey. Smoking costs at $6 and $10 for 20 cigarettes were compared to the costs of life-time periodontal treatment for stable and unstable compliant patients. Smoking added 8.8% to the financial cost of the life-time cost of periodontal therapy in stable maintenance patients, 40.1% in patients who needed one extra maintenance visit and 71.4% in patients who needed two extra maintenance visits per year in addition to added re-treatment. The cost of smoking far exceeded the cost of periodontal treatment; For patients who smoked 10 to 40 cigarettes per day at the cost of $6 or $10 a pack, the cost of smoking exceeded the cost of life-time periodontal treatment by between 2.7 and 17.9 times. Smoking 40 cigarettes at $10 a packet for 3.4 years would pay for the entire life-time cost of periodontal treatment. Smoking adds considerable extra financial costs to the life-time treatment of periodontal diseases. The cost of smoking itself exceeds the cost of periodontal therapy. This article is protected by copyright. All rights reserved. © 2018 American Academy of Periodontology.

  5. Process modeling for the Integrated Thermal Treatment System (ITTS) study

    Energy Technology Data Exchange (ETDEWEB)

    Liebelt, K.H.; Brown, B.W.; Quapp, W.J.

    1995-09-01

    This report describes the process modeling done in support of the integrated thermal treatment system (ITTS) study, Phases 1 and 2. ITTS consists of an integrated systems engineering approach for uniform comparison of widely varying thermal treatment technologies proposed for treatment of the contact-handled mixed low-level wastes (MLLW) currently stored in the U.S. Department of Energy complex. In the overall study, 19 systems were evaluated. Preconceptual designs were developed that included all of the various subsystems necessary for a complete installation, from waste receiving through to primary and secondary stabilization and disposal of the processed wastes. Each system included the necessary auxiliary treatment subsystems so that all of the waste categories in the complex were fully processed. The objective of the modeling task was to perform mass and energy balances of the major material components in each system. Modeling of trace materials, such as pollutants and radioactive isotopes, were beyond the present scope. The modeling of the main and secondary thermal treatment, air pollution control, and metal melting subsystems was done using the ASPEN PLUS process simulation code, Version 9.1-3. These results were combined with calculations for the remainder of the subsystems to achieve the final results, which included offgas volumes, and mass and volume waste reduction ratios.

  6. Process modeling for the Integrated Thermal Treatment System (ITTS) study

    International Nuclear Information System (INIS)

    Liebelt, K.H.; Brown, B.W.; Quapp, W.J.

    1995-09-01

    This report describes the process modeling done in support of the integrated thermal treatment system (ITTS) study, Phases 1 and 2. ITTS consists of an integrated systems engineering approach for uniform comparison of widely varying thermal treatment technologies proposed for treatment of the contact-handled mixed low-level wastes (MLLW) currently stored in the U.S. Department of Energy complex. In the overall study, 19 systems were evaluated. Preconceptual designs were developed that included all of the various subsystems necessary for a complete installation, from waste receiving through to primary and secondary stabilization and disposal of the processed wastes. Each system included the necessary auxiliary treatment subsystems so that all of the waste categories in the complex were fully processed. The objective of the modeling task was to perform mass and energy balances of the major material components in each system. Modeling of trace materials, such as pollutants and radioactive isotopes, were beyond the present scope. The modeling of the main and secondary thermal treatment, air pollution control, and metal melting subsystems was done using the ASPEN PLUS process simulation code, Version 9.1-3. These results were combined with calculations for the remainder of the subsystems to achieve the final results, which included offgas volumes, and mass and volume waste reduction ratios

  7. Natural treatment system models for wastewater management: a study from Hyderabad, India.

    Science.gov (United States)

    Sonkamble, Sahebrao; Wajihuddin, Md; Jampani, Mahesh; Sarah, S; Somvanshi, V K; Ahmed, Shakeel; Amerasinghe, Priyanie; Boisson, Alexandre

    2018-01-01

    Wastewater generated on a global scale has become a significant source of water resources which necessitates appropriate management strategies. However, the complexities associated with wastewater are lack of economically viable treatment systems, especially in low- and middle-income countries. While many types of treatment systems are needed to serve the various local issues, we propose natural treatment systems (NTS) such as natural wetlands that are eco-friendly, cost-effective, and can be jointly driven by public bodies and communities. In order for it to be part of wastewater management, this study explores the NTS potential for removal of pollutants, cost-effectiveness, and reuse options for the 1.20 million m 3 /day of wastewater generated in Hyderabad, India. The pilot study includes hydro-geophysical characterization of natural wetland to determine pollutant removal efficiency and its effective utilization for treated wastewater in the peri-urban habitat. The results show the removal of organic content (76-78%), nutrients (77-97%), and microbes (99.5-99.9%) from the wetland-treated wastewater and its suitability for agriculture applications. Furthermore, the wetland efficiency integrated with engineered interventions led to the development of NTS models with different application scenarios: (i) constructed wetlands, (ii) minimized community wetlands, and (iii) single outlet system, suitable for urban, peri-urban and rural areas, respectively.

  8. A discrete event modelling framework for simulation of long-term outcomes of sequential treatment strategies for ankylosing spondylitis

    NARCIS (Netherlands)

    A. Tran-Duy (An); A. Boonen (Annelies); M.A.F.J. van de Laar (Mart); A. Franke (Andre); J.L. Severens (Hans)

    2011-01-01

    textabstractObjective: To develop a modelling framework which can simulate long-term quality of life, societal costs and cost-effectiveness as affected by sequential drug treatment strategies for ankylosing spondylitis (AS). Methods: Discrete event simulation paradigm was selected for model

  9. A discrete event modelling framework for simulation of long-term outcomes of sequential treatment strategies for ankylosing spondylitis

    NARCIS (Netherlands)

    Tran-Duy, A.; Boonen, A.; Laar, M.A.F.J.; Franke, A.C.; Severens, J.L.

    2011-01-01

    Objective To develop a modelling framework which can simulate long-term quality of life, societal costs and cost-effectiveness as affected by sequential drug treatment strategies for ankylosing spondylitis (AS). Methods Discrete event simulation paradigm was selected for model development. Drug

  10. Effectiveness of cryotherapy treatment for cervical intraepithelial neoplasia.

    Science.gov (United States)

    Luciani, Silvana; Gonzales, Miguel; Munoz, Sergio; Jeronimo, Jose; Robles, Sylvia

    2008-05-01

    To assess the effectiveness of cryotherapy treatment delivered by general practitioners in primary care settings, as part of a screen-and-treat approach for cervical cancer prevention. Women aged between 25 and 49 years residing in San Martin, Peru, who were positive on visual inspection screening were treated, if eligible, with cryotherapy following biopsy. At 12 months post cryotherapy treatment the participants were evaluated for treatment effectiveness and examined by visual inspection and Papanicolaou test and, if positive, referred to a gynecologist for colposcopy and biopsy. Cryotherapy treatment was performed for 1398 women; of these, 531 (38%) had a histology result of cervical intraepithelial neoplasia (CIN). Cryotherapy effectively cured CIN in 418 (88%) women, including 49 (70%) women with a baseline diagnosis of CIN 3. Cryotherapy is an effective treatment for cervical precancerous lesions; it can easily be administered by general practitioners in primary care settings following visual inspection screening.

  11. Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment.

    Directory of Open Access Journals (Sweden)

    Smita Nayak

    Full Text Available Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women.Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA, and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through $800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs; and incremental cost-effectiveness ratios (ICERs in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed.Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days. When assuming alendronate costs of $400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from $714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of $50,000/QALY at all alendronate costs evaluated.Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost

  12. Treatment of Murine Tumor Models of Breast Adenocarcinoma by Continuous Dual-Frequency Ultrasound

    Directory of Open Access Journals (Sweden)

    Amir Hoshang Barati

    2009-03-01

    Full Text Available Introduction: Acoustic transient cavitation is the primary mechanism of sonochemical reaction and has potential use for tumor treatment. In this study, the in vivo anti-tumor effect of simultaneous dual-frequency ultrasound at low-level intensity (ISATA < 6 W/cm2 was investigated in a spontaneous murine model of breast adenocarcinoma in Balb/c mice. Materials and Methods: Forty tumor bearing mice were divided into four groups (10 in each group. The treated groups received 15 or 30 minutes of combined dual-frequency ultrasound in continuous mode (1 MHzcon + 150 kHzcon respectively. The control and the sham groups contained the untreated mice. The tumor growth delay parameters including tumor volume, relative tumor volume, T5 and T2 (the needed time for each tumor to reach 5 and 2 times the initial tumor volume, respectively, survival period and percent of tumor growth inhibition ratio were measured on different days after treatment. Results: The results showed that the 30 min treatment was effective in tumor growth delay and percent of tumor growth inhibitory ratio compared to the sham and the control groups. The tumor volume growth and relative volume of tumors in the same treated group showed an anti-tumor effect relative to the sham and the control groups. There was a significant difference in tumor volume growth between this 30 min treatment group and the sham group 12 days after treatment (p-value

  13. A Neutrophil Phenotype Model for Extracorporeal Treatment of Sepsis.

    Directory of Open Access Journals (Sweden)

    Alexander D Malkin

    2015-10-01

    Full Text Available Neutrophils play a central role in eliminating bacterial pathogens, but may also contribute to end-organ damage in sepsis. Interleukin-8 (IL-8, a key modulator of neutrophil function, signals through neutrophil specific surface receptors CXCR-1 and CXCR-2. In this study a mechanistic computational model was used to evaluate and deploy an extracorporeal sepsis treatment which modulates CXCR-1/2 levels. First, a simplified mechanistic computational model of IL-8 mediated activation of CXCR-1/2 receptors was developed, containing 16 ODEs and 43 parameters. Receptor level dynamics and systemic parameters were coupled with multiple neutrophil phenotypes to generate dynamic populations of activated neutrophils which reduce pathogen load, and/or primed neutrophils which cause adverse tissue damage when misdirected. The mathematical model was calibrated using experimental data from baboons administered a two-hour infusion of E coli and followed for a maximum of 28 days. Ensembles of parameters were generated using a Bayesian parallel tempering approach to produce model fits that could recreate experimental outcomes. Stepwise logistic regression identified seven model parameters as key determinants of mortality. Sensitivity analysis showed that parameters controlling the level of killer cell neutrophils affected the overall systemic damage of individuals. To evaluate rescue strategies and provide probabilistic predictions of their impact on mortality, time of onset, duration, and capture efficacy of an extracorporeal device that modulated neutrophil phenotype were explored. Our findings suggest that interventions aiming to modulate phenotypic composition are time sensitive. When introduced between 3-6 hours of infection for a 72 hour duration, the survivor population increased from 31% to 40-80%. Treatment efficacy quickly diminishes if not introduced within 15 hours of infection. Significant harm is possible with treatment durations ranging from 5

  14. Probabilistic application of a fugacity model to predict triclosan fate during wastewater treatment.

    Science.gov (United States)

    Bock, Michael; Lyndall, Jennifer; Barber, Timothy; Fuchsman, Phyllis; Perruchon, Elyse; Capdevielle, Marie

    2010-07-01

    The fate and partitioning of the antimicrobial compound, triclosan, in wastewater treatment plants (WWTPs) is evaluated using a probabilistic fugacity model to predict the range of triclosan concentrations in effluent and secondary biosolids. The WWTP model predicts 84% to 92% triclosan removal, which is within the range of measured removal efficiencies (typically 70% to 98%). Triclosan is predominantly removed by sorption and subsequent settling of organic particulates during primary treatment and by aerobic biodegradation during secondary treatment. Median modeled removal efficiency due to sorption is 40% for all treatment phases and 31% in the primary treatment phase. Median modeled removal efficiency due to biodegradation is 48% for all treatment phases and 44% in the secondary treatment phase. Important factors contributing to variation in predicted triclosan concentrations in effluent and biosolids include influent concentrations, solids concentrations in settling tanks, and factors related to solids retention time. Measured triclosan concentrations in biosolids and non-United States (US) effluent are consistent with model predictions. However, median concentrations in US effluent are over-predicted with this model, suggesting that differences in some aspect of treatment practices not incorporated in the model (e.g., disinfection methods) may affect triclosan removal from effluent. Model applications include predicting changes in environmental loadings associated with new triclosan applications and supporting risk analyses for biosolids-amended land and effluent receiving waters. (c) 2010 SETAC.

  15. Effectiveness of a Barge-Based Ballast Water Treatment System for Multi-Terminal Ports

    Directory of Open Access Journals (Sweden)

    Lovro Maglić

    2015-10-01

    Full Text Available The paper presents outcomes of the discrete event simulation of the ballast water management in a multi-terminal port. The simulation includes ship’s manoeuvring, cargo and ballast operations and a barge-based ballast water treatment system operating within all terminal areas. The barge-based ballast water treatment system is used by ships unable to use their own equipment, not equipped with an appropriate ballast treatment system or non-compliant with the Ballast Water Management (BWM Convention 2004 for whatever reason. The main goal is to estimate the productivity and cost effectiveness of such systems as an option to support ships not able to comply with the BWM Convention, once it enters into force. The model was built and tested in Arena simulation software. Process parameters are based on real traffic data for the port of Rijeka. The results indicate that barge-based ballast treatment facility will be heavily underutilized, and that such systems are cost-effective only in ports where large volumes of ballast water need to be delivered to shore treatment systems.

  16. Telemedicine diabetes consultations are cost-effective, and effects on essential diabetes treatment parameters are similar to conventional treatment

    DEFF Research Database (Denmark)

    Levin, Klaus; Madsen, Jette R; Petersen, Inge

    2013-01-01

    been offered expert diabetes care using teleconsultations. This article describes the impact of the telemedicine solution on essential diabetes treatment parameters, patient satisfaction, and cost-effectiveness. METHODS: Telemedicine consultations were conducted with the patient and nurse specialist...... in transportation time (7 h). Reductions in traveling costs and saved working days were the most important factors in making the telemedicine set-up economically efficient. CONCLUSION: Telemedicine consultation for remote outpatient diabetes control is feasible, and the interdisciplinary interventions achieved high...... treatment quality results in essential diabetes treatment parameters. In addition, the telemedicine set-up was associated with improved cost-effectiveness and patient satisfaction....

  17. Three-dimensional Monte Carlo model of pulsed-laser treatment of cutaneous vascular lesions

    Science.gov (United States)

    Milanič, Matija; Majaron, Boris

    2011-12-01

    We present a three-dimensional Monte Carlo model of optical transport in skin with a novel approach to treatment of side boundaries of the volume of interest. This represents an effective way to overcome the inherent limitations of ``escape'' and ``mirror'' boundary conditions and enables high-resolution modeling of skin inclusions with complex geometries and arbitrary irradiation patterns. The optical model correctly reproduces measured values of diffuse reflectance for normal skin. When coupled with a sophisticated model of thermal transport and tissue coagulation kinetics, it also reproduces realistic values of radiant exposure thresholds for epidermal injury and for photocoagulation of port wine stain blood vessels in various skin phototypes, with or without application of cryogen spray cooling.

  18. Towards a framework for treatment effectiveness in schizophrenia

    Directory of Open Access Journals (Sweden)

    Juckel G

    2014-09-01

    Full Text Available Georg Juckel,1 Andrea de Bartolomeis,2 Philip Gorwood,3 Sergey Mosolov,4 Luca Pani,5 Alessandro Rossi,6 Julio Sanjuan7 1Department of Psychiatry, LWL-University Hospital, Ruhr-University Bochum, Bochum, Germany; 2Laboratory of Molecular Psychiatry and Unit of Treatment Resistant Psychosis, University School of Medicine of Naples Federico II, Napoli, Italy; 3Groupe Hospitalier Sainte-Anne (CMME, Paris-Descartes University, Paris, France; 4Moscow Research Institute of Psychiatry, Moscow, Russia; 5Institute of Translational Pharmacology, Italian National Research Council, Rome, Italy; 6Università de L’Aquila, L’Aquila, Italy; 7Clinic Hospital, Spanish Mental Health Network (CIBERSAM, University of Valencia, Valencia, Spain Introduction: Prompt administration of antipsychotic treatment that is adhered to is essential for the optimal treatment of schizophrenia. Many patients have benefited from the advent of second-generation antipsychotics, which can offer good symptomatic control with reduced incidence of extrapyramidal symptoms, although with higher risk of metabolic side effects. It is unsurprising that accounts as to whether first- and second-generation antipsychotics differ in their efficacy vary, since treatment effectiveness is a broad notion and difficult to define. Objectives: Numerous factors may be used to gauge treatment effectiveness and, while it has largely been defined in terms of improvements in four domains (symptoms of disease, treatment burden, disease burden, and health and wellness, the real-world clinical utility of this consensus is unclear. Therefore, this article aims to provide a framework that can aid psychiatrists in making assessments about treatment effectiveness. Methods and results: A panel of 12 psychiatrists and psychopharmacologists convened to develop and propose an accessible and globally-applicable framework for assessing the effectiveness of antipsychotic treatments in patients with schizophrenia

  19. Mixed waste treatment model: Basis and analysis

    International Nuclear Information System (INIS)

    Palmer, B.A.

    1995-09-01

    The Department of Energy's Programmatic Environmental Impact Statement (PEIS) required treatment system capacities for risk and cost calculation. Los Alamos was tasked with providing these capacities to the PEIS team. This involved understanding the Department of Energy (DOE) Complex waste, making the necessary changes to correct for problems, categorizing the waste for treatment, and determining the treatment system requirements. The treatment system requirements depended on the incoming waste, which varied for each PEIS case. The treatment system requirements also depended on the type of treatment that was desired. Because different groups contributing to the PEIS needed specific types of results, we provided the treatment system requirements in a variety of forms. In total, some 40 data files were created for the TRU cases, and for the MLLW case, there were 105 separate data files. Each data file represents one treatment case consisting of the selected waste from various sites, a selected treatment system, and the reporting requirements for such a case. The treatment system requirements in their most basic form are the treatment process rates for unit operations in the desired treatment system, based on a 10-year working life and 20-year accumulation of the waste. These results were reported in cubic meters and for the MLLW case, in kilograms as well. The treatment system model consisted of unit operations that are linked together. Each unit operation's function depended on the input waste streams, waste matrix, and contaminants. Each unit operation outputs one or more waste streams whose matrix, contaminants, and volume/mass may have changed as a result of the treatment. These output streams are then routed to the appropriate unit operation for additional treatment until the output waste stream meets the treatment requirements for disposal. The total waste for each unit operation was calculated as well as the waste for each matrix treated by the unit

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

    Science.gov (United States)

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

    2011-05-01

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

  1. Effective physical treatment for chronic low back pain.

    Science.gov (United States)

    Maher, C G

    2004-01-01

    It is now feasible to adopt an evidence-based approach when providing physical treatment for patients with chronic LBP. A summary of the efficacy of a range of physical treatments is provided in Table 1. The evidence-based primary care options are exercise, laser, massage, and spinal manipulation; however, the latter three have small or transient effects that limit their value as therapies for chronic LBP. In contrast, exercise produces large reductions in pain and disability, a feature that suggests that exercise should play a major role in the management of chronic LBP. Physical treatments, such as acupuncture, backschool, hydrotherapy, lumbar supports, magnets, TENS, traction, ultrasound, Pilates therapy, Feldenkrais therapy, Alexander technique, and craniosacral therapy are either of unknown value or ineffective and so should not be considered. Outside of primary care, multidisciplinary treatment or functional restoration is effective; however, the high cost probably means that these programs should be reserved for patients who do not respond to cheaper treatment options for chronic LBP. Although there are now effective treatment options for chronic LBP, it needs to be acknowledged that the problem of chronic LBP is far from solved. Though treatments can provide marked improvements in the patient's condition, the available evidence suggests that the typical chronic LBP patient is left with some residual pain and disability. Developing new, more powerful treatments and refining the current group of known effective treatments is the challenge for the future.

  2. [Cost-effectiveness of Antipsychotics in the Maintenance Treatment of Schizophrenia in Colombia].

    Science.gov (United States)

    Quitian Reyes, Hoover; Arciniegas Barrera, Jair Alberto; Bohórquez Peñaranda, Adriana; Gómez Restrepo, Carlos

    2016-01-01

    Assess the cost-effectiveness of the antipsychotics for treatment of schizophrenia. A five-year Markov model was built form patients with schizophrenia on the stage of maintenance. Costs were taken from the perspective of the Colombian health care system (Sistema General de Seguridad Social en Salud). The effectiveness was measured in years of life under the same maintenance plan. The Markov model indicated clozapine as the as the most cost-effective alternative between the first line antipsychotics and haloperidol is it when comparing other antipsychotics. Clozapine it's the cost-effectiveness strategy among the first line of antipsychotics and haloperidol is it among the other antipsychotics. Strategies prioritizing the use of cost-effective antipsychotics could improve the resources allocation in the Colombian health care system. Copyright © 2014 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  3. Using a Hydrodynamic and Biogeochemical Model to Investigate the Effects of Nutrient Loading from a Wastewater Treatment Plant into Lake Michigan

    Science.gov (United States)

    Khazaei, B.; Bravo, H.; Bootsma, H.

    2017-12-01

    There is clear evidence that excessive nutrient, in particular phosphorus (P), loading into Lake Michigan has produced significant problems, such as algal blooms, hypoxia, and reduced water quality. Addressing those problems requires understanding the transport and fate of P in the lake. The dominance of mixing and dispersion processes on the P transport has been demonstrated, yet recent research has shown the remarkable influence of dreissenid mussels and Cladophora on water clarity and the P budget. Since mussels and Cladophora tend to concentrate near the coastlines, nearshore-offshore P exchange is of a big importance. In this research, a computer model was developed to simulate the P cycle by incorporating the biogeochemical processes relevant to the transport of P into a 3D high-resolution hydrodynamic model. The near-bottom biogeochemical model consists of three linked modules: Cladophora, mussel, and sediment storage modules. The model was applied to the Milwaukee Metropolitan Sewerage District South Shore Wastewater Treatment Plant, between June and October of 2013 and 2015, as a case study. The plant outfall introduces a point source of P into the study domain—the nearshore zone of Lake Michigan adjacent to Milwaukee County. The model was validated against field observations of water temperature, dissolved phosphorus (DP), particulate phosphorus (PP), Cladophora biomass, and P content. The model simulations showed reasonably good agreement with field measurements. Model results showed a) different temporal patterns in 2013 and 2015, b) a larger range of fluctuations in DP than that in PP, and c) that the effects of mussels and Cladophora could explain the differences in patterns and ranges. PP concentrations showed more frequent spikes of concentration in 2013 due to resuspension events during that year because of stronger winds. The model is being applied as a management tool to test scenarios of nutrient loading to determine effluent P limits for the

  4. Adjusting for the Confounding Effects of Treatment Switching—The BREAK-3 Trial: Dabrafenib Versus Dacarbazine

    Science.gov (United States)

    Abrams, Keith R.; Amonkar, Mayur M.; Stapelkamp, Ceilidh; Swann, R. Suzanne

    2015-01-01

    Background. Patients with previously untreated BRAF V600E mutation-positive melanoma in BREAK-3 showed a median overall survival (OS) of 18.2 months for dabrafenib versus 15.6 months for dacarbazine (hazard ratio [HR], 0.76; 95% confidence interval, 0.48–1.21). Because patients receiving dacarbazine were allowed to switch to dabrafenib at disease progression, we attempted to adjust for the confounding effects on OS. Materials and Methods. Rank preserving structural failure time models (RPSFTMs) and the iterative parameter estimation (IPE) algorithm were used. Two analyses, “treatment group” (assumes treatment effect could continue until death) and “on-treatment observed” (assumes treatment effect disappears with discontinuation), were used to test the assumptions around the durability of the treatment effect. Results. A total of 36 of 63 patients (57%) receiving dacarbazine switched to dabrafenib. The adjusted OS HRs ranged from 0.50 to 0.55, depending on the analysis. The RPSFTM and IPE “treatment group” and “on-treatment observed” analyses performed similarly well. Conclusion. RPSFTM and IPE analyses resulted in point estimates for the OS HR that indicate a substantial increase in the treatment effect compared with the unadjusted OS HR of 0.76. The results are uncertain because of the assumptions associated with the adjustment methods. The confidence intervals continued to cross 1.00; thus, the adjusted estimates did not provide statistically significant evidence of a treatment benefit on survival. However, it is clear that a standard intention-to-treat analysis will be confounded in the presence of treatment switching—a reliance on unadjusted analyses could lead to inappropriate practice. Adjustment analyses provide useful additional information on the estimated treatment effects to inform decision making. Implications for Practice: Treatment switching is common in oncology trials, and the implications of this for the interpretation of the

  5. Adjusting for the Confounding Effects of Treatment Switching-The BREAK-3 Trial: Dabrafenib Versus Dacarbazine.

    Science.gov (United States)

    Latimer, Nicholas R; Abrams, Keith R; Amonkar, Mayur M; Stapelkamp, Ceilidh; Swann, R Suzanne

    2015-07-01

    Patients with previously untreated BRAF V600E mutation-positive melanoma in BREAK-3 showed a median overall survival (OS) of 18.2 months for dabrafenib versus 15.6 months for dacarbazine (hazard ratio [HR], 0.76; 95% confidence interval, 0.48-1.21). Because patients receiving dacarbazine were allowed to switch to dabrafenib at disease progression, we attempted to adjust for the confounding effects on OS. Rank preserving structural failure time models (RPSFTMs) and the iterative parameter estimation (IPE) algorithm were used. Two analyses, "treatment group" (assumes treatment effect could continue until death) and "on-treatment observed" (assumes treatment effect disappears with discontinuation), were used to test the assumptions around the durability of the treatment effect. A total of 36 of 63 patients (57%) receiving dacarbazine switched to dabrafenib. The adjusted OS HRs ranged from 0.50 to 0.55, depending on the analysis. The RPSFTM and IPE "treatment group" and "on-treatment observed" analyses performed similarly well. RPSFTM and IPE analyses resulted in point estimates for the OS HR that indicate a substantial increase in the treatment effect compared with the unadjusted OS HR of 0.76. The results are uncertain because of the assumptions associated with the adjustment methods. The confidence intervals continued to cross 1.00; thus, the adjusted estimates did not provide statistically significant evidence of a treatment benefit on survival. However, it is clear that a standard intention-to-treat analysis will be confounded in the presence of treatment switching-a reliance on unadjusted analyses could lead to inappropriate practice. Adjustment analyses provide useful additional information on the estimated treatment effects to inform decision making. Treatment switching is common in oncology trials, and the implications of this for the interpretation of the clinical effectiveness and cost-effectiveness of the novel treatment are important to consider. If

  6. Effect of homeopathic treatment on gene expression in Copenhagen rat tumor tissues.

    Science.gov (United States)

    Thangapazham, Rajesh L; Rajeshkumar, N V; Sharma, Anuj; Warren, Jim; Singh, Anoop K; Ives, John A; Gaddipati, Jaya P; Maheshwari, Radha K; Jonas, Wayne B

    2006-12-01

    Increasing evidence suggests that the inability to undergo apoptosis is an important factor in the development and progression of prostate cancer. Agents that induce apoptosis may inhibit tumor growth and provide therapeutic benefit. In a recent study, the authors found that certain homeopathic treatments produced anticancer effects in an animal model. In this study, the authors examined the immunomodulating and apoptotic effects of these remedies. The authors investigated the effect of a homeopathic treatment regimen containing Conium maculatum, Sabal serrulata, Thuja occidentalis, and a MAT-LyLu Carcinosin nosode on the expression of cytokines and genes that regulate apoptosis. This was assessed in prostate cancer tissues, extracted from animals responsive to these drugs, using ribonuclease protection assay or reverse transcription polymerase chain reaction. There were no significant changes in mRNA levels of the apoptotic genes bax, bcl-2, bcl-x, caspase-1, caspase-2, caspase-3, Fas, FasL, or the cytokines interleukin (IL)-1alpha, IL-1beta, tumor necrosis factor (TNF)-beta, IL-3, IL-4, IL-5, IL-6, IL-10, TNF-alpha, IL-2, and interferon-gamma in prostate tumor and lung metastasis after treatment with homeopathic medicines. This study indicates that treatment with the highly diluted homeopathic remedies does not alter the gene expression in primary prostate tumors or in lung metastasis. The therapeutic effect of homeopathic treatments observed in the in vivo experiments cannot be explained by mechanisms based on distinct alterations in gene expression related to apoptosis or cytokines. Future research should explore subtle modulations in the expression of multiple genes in different biological pathways.

  7. Modeling the growth dynamics of multiple Escherichia coli strains in the pig intestine following intramuscular ampicillin treatment.

    Science.gov (United States)

    Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo; Græsbøll, Kaare; Toft, Nils; Matthews, Louise; Nielsen, Søren Saxmose; Olsen, John Elmerdahl

    2016-09-06

    This study evaluated how dosing regimen for intramuscularly-administered ampicillin, composition of Escherichia coli strains with regard to ampicillin susceptibility, and excretion of bacteria from the intestine affected the level of resistance among Escherichia coli strains in the intestine of nursery pigs. It also examined the dynamics of the composition of bacterial strains during and after the treatment. The growth responses of strains to ampicillin concentrations were determined using in vitro growth curves. Using these results as input data, growth predictions were generated using a mathematical model to simulate the competitive growth of E. coli strains in a pig intestine under specified plasma concentration profiles of ampicillin. In vitro growth results demonstrated that the resistant strains did not carry a fitness cost for their resistance, and that the most susceptible strains were more affected by increasing concentrations of antibiotics that the rest of the strains. The modeling revealed that short treatment duration resulted in lower levels of resistance and that dosing frequency did not substantially influence the growth of resistant strains. Resistance levels were found to be sensitive to the number of competing strains, and this effect was enhanced by longer duration of treatment. High excretion of bacteria from the intestine favored resistant strains over sensitive strains, but at the same time it resulted in a faster return to pre-treatment levels after the treatment ended. When the duration of high excretion was set to be limited to the treatment time (i.e. the treatment was assumed to result in a cure of diarrhea) resistant strains required longer time to reach the previous level. No fitness cost was found to be associated with ampicillin resistance in E. coli. Besides dosing factors, epidemiological factors (such as number of competing strains and bacterial excretion) influenced resistance development and need to be considered further in

  8. Cost-effectiveness analysis evaluating fidaxomicin versus oral vancomycin for the treatment of Clostridium difficile infection in the United States.

    Science.gov (United States)

    Stranges, Paul M; Hutton, David W; Collins, Curtis D

    2013-01-01

    Fidaxomicin is a novel treatment for Clostridium difficile infections (CDIs). This new treatment, however, is associated with a higher acquisition cost compared with alternatives. The objective of this study was to evaluate the cost-effectiveness of fidaxomicin or oral vancomycin for the treatment of CDIs. We performed a cost-utility analysis comparing fidaxomicin with oral vancomycin for the treatment of CDIs in the United States by creating a decision analytic model from the third-party payer perspective. The incremental cost-effectiveness ratio with fidaxomicin compared with oral vancomycin was $67,576/quality-adjusted life-year. A probabilistic Monte Carlo sensitivity analysis showed that fidaxomicin had an 80.2% chance of being cost-effective at a willingness-to-pay threshold of $100,000/quality-adjusted life-year. Fidaxomicin remained cost-effective under all fluctuations of both fidaxomicin and oral vancomycin costs. The decision analytic model was sensitive to variations in clinical cure and recurrence rates. Secondary analyses revealed that fidaxomicin was cost-effective in patients receiving concominant antimicrobials, in patients with mild to moderate CDIs, and when compared with oral metronidazole in patients with mild to moderate disease. Fidaxomicin was dominated by oral vancomycin if CDI was caused by the NAP1/Bl/027 Clostridium difficile strain and was dominant in institutions that did not compound oral vancomycin. Results of our model showed that fidaxomicin may be a more cost-effective option for the treatment of CDIs when compared with oral vancomycin under most scenarios tested. Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  9. Preliminary observations on the effectiveness of levetiracetam in the open adjunctive treatment of refractory bipolar disorder

    NARCIS (Netherlands)

    Post, RM; Altshuler, LL; Frye, MA; Suppes, T; McElroy, SL; Keck, PE; Leverich, GS; Kupka, R; Nolen, WA; Luckenbaugh, DA; Walden, J; Grunze, H

    Objective: Levetiracetam is a recently approved, well-tolerated anticonvulsant with a unique mechanism of action yielding efficacy in treatment-refractory seizure disorders and positive effects in an animal model of mania. Given the effectiveness of a range of other anticonvulsants in bipolar

  10. Somatic mutations in Tradescantia as a model system for studying the effects of the environmental agents

    International Nuclear Information System (INIS)

    Cebulska-Wasilewska, A.

    1986-01-01

    The application of the plant model system for studying the biological effects of ionizing radiation and chemical mutagens is presented. The model system is based on the somatic mutation frequency in stamen hair cells of Tradescantia clones heterosygous for flower color. The interaction of chemical mutagens with radiation in the induction of somatic mutations was investigated. The results demonstrate the synergistic interaction between radiation and chemical mutagens like ethyl methanesulfonate and di-bromoethane. The synergistic effect is clearly manifested after combined treatment with radiation and chemicals. In the low dose region the effect depends on the radiation dose and chemical exposure. Other results show the influence of the fluoride treatment on the radiation effect. The fluoride treatment is likely to alter the DNA double strand breaks repair processes. Additionally the usefulness of the model system for studying the mutagenic effectiveness of the pollution in the ambient air is presented. 148 refs. (author)

  11. Treatment-time-dependence models of early and delayed radiation injury in rat small intestine

    International Nuclear Information System (INIS)

    Denham, James W.; Hauer-Jensen, Martin; Kron, Tomas; Langberg, Carl W.

    2000-01-01

    Background: The present study modeled data from a large series of experiments originally designed to investigate the influence of time, dose, and fractionation on early and late pathologic endpoints in rat small intestine after localized irradiation. The objective was to obtain satisfactory descriptions of the regenerative response to injury together with the possible relationships between early and late endpoints. Methods: Two- and 26-week pathologic radiation injury data in groups of Sprague-Dawley rats irradiated with 27 different fractionation schedules were modeled using the incomplete repair (IR) version of the linear-quadratic model with or without various time correction models. The following time correction models were tested: (1) No time correction; (2) A simple exponential (SE) regenerative response beginning at an arbitrary time after starting treatment; and (3) A bi-exponential response with its commencement linked to accumulated cellular depletion and fraction size (the 'intelligent response model' [INTR]). Goodness of fit of the various models was assessed by correlating the predicted biological effective dose for each dose group with the observed radiation injury score. Results: (1) The incomplete repair model without time correction did not provide a satisfactory description of either the 2- or 26-week data. (2) The models using SE time correction performed better, providing modest descriptions of the data. (3) The INTR model provided reasonable descriptions of both the 2- and 26-week data, confirming a treatment time dependence of both early and late pathological endpoints. (4) The most satisfactory descriptions of the data by the INTR model were obtained when the regenerative response was assumed to cease 2 weeks after irradiation rather than at the end of irradiation. A fraction-size-dependent delay of the regenerative response was also suggested in the best fitting models. (5) Late endpoints were associated with low-fractionation sensitivity

  12. Structural nested mean models for assessing time-varying effect moderation.

    Science.gov (United States)

    Almirall, Daniel; Ten Have, Thomas; Murphy, Susan A

    2010-03-01

    This article considers the problem of assessing causal effect moderation in longitudinal settings in which treatment (or exposure) is time varying and so are the covariates said to moderate its effect. Intermediate causal effects that describe time-varying causal effects of treatment conditional on past covariate history are introduced and considered as part of Robins' structural nested mean model. Two estimators of the intermediate causal effects, and their standard errors, are presented and discussed: The first is a proposed two-stage regression estimator. The second is Robins' G-estimator. The results of a small simulation study that begins to shed light on the small versus large sample performance of the estimators, and on the bias-variance trade-off between the two estimators are presented. The methodology is illustrated using longitudinal data from a depression study.

  13. Oculomotor and neuropsychological effects of antipsychotic treatment for schizophrenia

    Directory of Open Access Journals (Sweden)

    Kristian S. Hill

    2009-04-01

    Full Text Available Cognitive enhancement has become an important target for drug therapies in schizophrenia. Treatment development in this area requires assessment approaches that are sensitive to procognitive effects of antipsychotic and adjunctive treatments. Ideally, new treatments will have translational characteristics for parallel human and animal research. Previous studies of antipsychotic effects on cognition have relied primarily on paper-and-pencil neuropsychological testing. No study has directly compared neurophysiological biomarkers and neuropsychological testing as strategies for assessing cognitive effects of antipsychotic treatment early in the course of schizophrenia. Anti psychotic-naive patients with schizophrenia were tested before treatment with risperidone and again 6 weeks later. Matched healthy participants were tested over a similar time period. Test-retest reliability, effect sizes of within-subject change, and multivariate/univariate analysis of variance were used to compare 3 neurophysiological tests (visually guided saccade, memory-guided saccade, and antisaccade with neuropsychological tests covering 4 cognitive domains (executive function, attention, memory, and manual motor function. While both measurement approaches showed robust neurocognitive impairments in patients prior to risperidone treatment, oculomotor biomarkers were more sensitive to treatment-related effects on neurocognitive function than traditional neuropsychological measures. Further, unlike the pattern of modest generalized cognitive improvement suggested by neuropsychological measures, the oculomotor findings revealed a mixed pattern of beneficial and adverse treatment related effects. These findings warrant further investigation regarding the utility of neurophysiological biomarkers for assessing cognitive outcomes of antipsychotic treatment in clinical trials and in early-phase drug development.

  14. Whole plant based treatment of hypercholesterolemia with Crataegus laevigata in a zebrafish model

    Directory of Open Access Journals (Sweden)

    Littleton Robert M

    2012-07-01

    Full Text Available Abstract Background Consumers are increasingly turning to plant-based complementary and alternative medicines to treat hypercholesterolemia. Many of these treatments are untested and their efficacy is unknown. This multitude of potential remedies necessitates a model system amenable to testing large numbers of organisms that maintains similarity to humans in both mode of drug administration and overall physiology. Here we develop the larval zebrafish (4–30 days post fertilization as a vertebrate model of dietary plant-based treatment of hypercholesterolemia and test the effects of Crataegus laevigata in this model. Methods Larval zebrafish were fed high cholesterol diets infused with fluorescent sterols and phytomedicines. Plants were ground with mortar and pestle into a fine powder before addition to food. Fluorescent sterols were utilized to optically quantify relative difference in intravascular cholesterol levels between groups of fish. We utilized the Zeiss 7-Live Duo high-speed confocal platform in order to both quantify intravascular sterol fluorescence and to capture video of the heart beat for determination of cardiac output. Results In this investigation we developed and utilized a larval zebrafish model to investigate dietary plant-based intervention of the pathophysiology of hypercholesterolemia. We found BODIPY-cholesterol effectively labels diet-introduced intravascular cholesterol levels (P t-test. We also established that zebrafish cardiac output declines as cholesterol dose increases (difference between 0.1% and 8% (w/w high cholesterol diet-treated cardiac output significant at P  Conclusions The results of this study demonstrate that the larval zebrafish has the potential to become a powerful model to test plant based dietary intervention of hypercholesterolemia. Using this model we have shown that hawthorn leaves and flowers have the potential to affect cardiac output as well as intravascular cholesterol levels

  15. Assessing the Effect of Potential Reductions in Non-Hepatic Mortality on the Estimated Cost-Effectiveness of Hepatitis C Treatment in Early Stages of Liver Disease

    Science.gov (United States)

    Chesson, Harrell W.; Spradling, Philip R.; Holmberg, Scott D.

    2018-01-01

    Background Most cost-effectiveness analyses of hepatitis C (HCV) therapy focus on the benefits of reducing liver-related morbidity and mortality. Objectives Our objective was to assess how cost-effectiveness estimates of HCV therapy can vary depending on assumptions regarding the potential impact of HCV therapy on non-hepatic mortality. Methods We adapted a state-transition model to include potential effects of HCV therapy on non-hepatic mortality. We assumed successful treatment could reduce non-hepatic mortality by as little as 0 % to as much as 100 %. Incremental cost-effectiveness ratios were computed comparing immediate treatment versus delayed treatment and comparing immediate treatment versus non-treatment. Results Comparing immediate treatment versus delayed treatment, when we included a 44 % reduction in nonhepatic mortality following successful HCV treatment, the incremental cost per quality-adjusted life year (QALY) gained by HCV treatment fell by 76 % (from US$314,100 to US$76,900) for patients with no fibrosis and by 43 % (from US$62,500 to US$35,800) for patients with moderate fibrosis. Comparing immediate treatment versus non-treatment, assuming a 44 % reduction in non-hepatic mortality following successful HCV treatment, the incremental cost per QALY gained by HCV treatment fell by 64 % (from US$186,700 to US$67,300) for patients with no fibrosis and by 27 % (from US$35,000 to US$25,500) for patients with moderate fibrosis. Conclusion Including reductions in non-hepatic mortality from HCV treatment can have substantial effects on the estimated cost-effectiveness of treatment. PMID:27480538

  16. Methods to model and predict the ViewRay treatment deliveries to aid patient scheduling and treatment planning.

    Science.gov (United States)

    Liu, Shi; Wu, Yu; Wooten, H Omar; Green, Olga; Archer, Brent; Li, Harold; Yang, Deshan

    2016-03-08

    A software tool is developed, given a new treatment plan, to predict treatment delivery time for radiation therapy (RT) treatments of patients on ViewRay magnetic resonance image-guided radiation therapy (MR-IGRT) delivery system. This tool is necessary for managing patient treatment scheduling in our clinic. The predicted treatment delivery time and the assessment of plan complexities could also be useful to aid treatment planning. A patient's total treatment delivery time, not including time required for localization, is modeled as the sum of four components: 1) the treatment initialization time; 2) the total beam-on time; 3) the gantry rotation time; and 4) the multileaf collimator (MLC) motion time. Each of the four components is predicted separately. The total beam-on time can be calculated using both the planned beam-on time and the decay-corrected dose rate. To predict the remain-ing components, we retrospectively analyzed the patient treatment delivery record files. The initialization time is demonstrated to be random since it depends on the final gantry angle of the previous treatment. Based on modeling the relationships between the gantry rotation angles and the corresponding rotation time, linear regression is applied to predict the gantry rotation time. The MLC motion time is calculated using the leaves delay modeling method and the leaf motion speed. A quantitative analysis was performed to understand the correlation between the total treatment time and the plan complexity. The proposed algorithm is able to predict the ViewRay treatment delivery time with the average prediction error 0.22min or 1.82%, and the maximal prediction error 0.89 min or 7.88%. The analysis has shown the correlation between the plan modulation (PM) factor and the total treatment delivery time, as well as the treatment delivery duty cycle. A possibility has been identified to significantly reduce MLC motion time by optimizing the positions of closed MLC pairs. The accuracy of

  17. Effect of treatment duration on pharmacokinetic/pharmacodynamic indices correlating with therapeutic efficacy of ceftazidime in experimental Klebsiella pneumoniae lung infection

    NARCIS (Netherlands)

    I.A.J.M. Bakker-Woudenberg (Irma); M.T. ten Kate (Marian); W.H.F. Goessens (Wil); J.W. Mouton (Johan)

    2006-01-01

    textabstractThe pharmacokinetic/pharmacodynamic (PK/PD) indices that define the therapeutic effect of the betalactam ceftazidime in a rat model of Klebsiella pneumoniae lung infection were investigated in relation to treatment duration and treatment endpoint. Treatment was started 24 h after

  18. Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden.

    Science.gov (United States)

    O'Day, Ken; Meyer, Kellie; Stafkey-Mailey, Dana; Watson, Crystal

    2015-04-01

    To assess the cost-effectiveness of natalizumab vs fingolimod over 2 years in relapsing-remitting multiple sclerosis (RRMS) patients and patients with rapidly evolving severe disease in Sweden. A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from the perspective of the Swedish healthcare system. Modeled 2-year costs in Swedish kronor of treating RRMS patients included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided using data from the AFFIRM and FREEDOMS trials for all patients with RRMS and from post-hoc sub-group analyses for patients with rapidly evolving severe disease. Probabilistic sensitivity analyses were conducted to assess uncertainty. The analysis showed that, in all patients with MS, treatment with fingolimod costs less (440,463 Kr vs 444,324 Kr), but treatment with natalizumab results in more relapses avoided (0.74 vs 0.59), resulting in an incremental cost-effectiveness ratio (ICER) of 25,448 Kr per relapse avoided. In patients with rapidly evolving severe disease, natalizumab dominated fingolimod. Results of the sensitivity analysis demonstrate the robustness of the model results. At a willingness-to-pay (WTP) threshold of 500,000 Kr per relapse avoided, natalizumab is cost-effective in >80% of simulations in both patient populations. Limitations include absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as the primary model outcome, assumption of 100% adherence to MS treatment, and exclusion of adverse event costs in the model. Natalizumab remains a cost-effective treatment option for patients with MS in Sweden. In the RRMS patient population, the incremental cost per relapse avoided is well below a 500,000 Kr WTP threshold per relapse avoided. In the rapidly

  19. Cost-effective treatment for the couple with infertility.

    Science.gov (United States)

    Van Voorhis, B J; Syrop, C H

    2000-12-01

    Although the evaluation of cost-effective approaches to infertility treatment remains in its infancy, several important principles have emerged from the initial studies in this field. Currently, in treating couples with infertility without tubal disease or severe male-factor infertility, the most cost-effective approach is to start with IUI or superovulation-IUI treatments before resorting to IVF procedures. The woman's age and number of sperm present for insemination are significant factors influencing cost-effectiveness. The influence of certain diagnoses on the cost-effectiveness of infertility treatments requires further study. Even when accounting for the costs associated with multiple gestations and premature deliveries, the cost of IVF decreases within the range of other cost-effective medical procedures and decreases to less than the willingness to pay for these procedures. Indeed, for patients with severe tubal disease, IVF has been found to be more cost-effective than surgical repair. The cost-effectiveness of IVF will likely improve as success rates show continued improvements over the course of time. In addition, usefulness of embryo selection and practices to reduce the likelihood of high-order multiple pregnancies, without reductions in pregnancy rates, will significantly impact cost-effectiveness. The exclusion of infertility treatments from insurance plans is unfortunate and accentuates the importance of physicians understanding the economics of infertility treatment with costs that are often passed directly to the patient. The erroneous economic policies and judgments that have led to inequities in access to infertility health care should not be tolerated.

  20. Effects of a non thermal plasma treatment alone or in combination with gemcitabine in a MIA PaCa2-luc orthotopic pancreatic carcinoma model.

    Directory of Open Access Journals (Sweden)

    Laura Brullé

    Full Text Available Pancreatic tumors are the gastrointestinal cancer with the worst prognosis in humans and with a survival rate of 5% at 5 years. Nowadays, no chemotherapy has demonstrated efficacy in terms of survival for this cancer. Previous study focused on the development of a new therapy by non thermal plasma showed significant effects on tumor growth for colorectal carcinoma and glioblastoma. To allow targeted treatment, a fibered plasma (Plasma Gun was developed and its evaluation was performed on an orthotopic mouse model of human pancreatic carcinoma using a MIA PaCa2-luc bioluminescent cell line. The aim of this study was to characterize this pancreatic carcinoma model and to determine the effects of Plasma Gun alone or in combination with gemcitabine. During a 36 days period, quantitative BLI could be used to follow the tumor progression and we demonstrated that plasma gun induced an inhibition of MIA PaCa2-luc cells proliferation in vitro and in vivo and that this effect could be improved by association with gemcitabine possibly thanks to its radiosensitizing properties.

  1. Effects of a non thermal plasma treatment alone or in combination with gemcitabine in a MIA PaCa2-luc orthotopic pancreatic carcinoma model.

    Science.gov (United States)

    Brullé, Laura; Vandamme, Marc; Riès, Delphine; Martel, Eric; Robert, Eric; Lerondel, Stéphanie; Trichet, Valérie; Richard, Serge; Pouvesle, Jean-Michel; Le Pape, Alain

    2012-01-01

    Pancreatic tumors are the gastrointestinal cancer with the worst prognosis in humans and with a survival rate of 5% at 5 years. Nowadays, no chemotherapy has demonstrated efficacy in terms of survival for this cancer. Previous study focused on the development of a new therapy by non thermal plasma showed significant effects on tumor growth for colorectal carcinoma and glioblastoma. To allow targeted treatment, a fibered plasma (Plasma Gun) was developed and its evaluation was performed on an orthotopic mouse model of human pancreatic carcinoma using a MIA PaCa2-luc bioluminescent cell line. The aim of this study was to characterize this pancreatic carcinoma model and to determine the effects of Plasma Gun alone or in combination with gemcitabine. During a 36 days period, quantitative BLI could be used to follow the tumor progression and we demonstrated that plasma gun induced an inhibition of MIA PaCa2-luc cells proliferation in vitro and in vivo and that this effect could be improved by association with gemcitabine possibly thanks to its radiosensitizing properties.

  2. Comparisons of hydrodynamic beam models with kinetic treatments

    International Nuclear Information System (INIS)

    Boyd, J.K.; Mark, J.W.; Sharp, W.M.; Yu, S.S.

    1983-01-01

    Hydrodynamic models have been derived by Mark and Yu and by others to describe energetic self-pinched beams, such as those used in ion-beam fusion. The closure of the Mark-Yu model is obtained with adiabatic assumptions mathematically analogous to those of Chew, Goldberger, and Low for MHD. The other models treated here use an ideal gas closure and a closure by Newcomb based on an expansion in V/sub th//V/sub z/. Features of these hydrodynamic beam models are compared with a kinetic treatment

  3. The intervention research on treatment by Xianchen to rabbits model of chemotherapeutic phlebitis.

    Science.gov (United States)

    Zhang, Jing; Shen, Juan; Yin, Weiwei; Wei, Xiaoyu; Wu, Ligao; Liu, Hao

    2016-08-01

    To develop a chemotherapeutics induced phlebitis and explore the effects of Xianchen on the phlebitis treatment. Forty-eight rabbits were divided into two series. Phlebitis model induced by vincristine was established at each series. The first series had 24 rabbits, which were divided into four groups (6 hours, 12 hours, 18 hours, 24 hours) after vincristine infusion. The grades of phlebitis through visual observation and histopathological examination were observed. The second series had also 24 rabbits. Interventions were performed 12 hours after vincristine infusion. These rabbits were randomly divided into four groups, according to treatment: Hirudoid (bid), Xianchen (daily), Xianchen (tid), Xianchen (five times a day). Four days after intervention, the venous injury through visual observation and histopathological examination were evaluated. Series 1: Phlebitis appeared 12 hours after infusion of vincristine through visual observation. There was a significant difference (pphlebitis appeared early. Xianchen can treat vincristine induced phlebitis, as well as Hirudoid. It is particularly effective in the treatment of edema, and there is a remarkable dose-response relationship.

  4. Multistrain models predict sequential multidrug treatment strategies to result in less antimicrobial resistance than combination treatment

    DEFF Research Database (Denmark)

    Ahmad, Amais; Zachariasen, Camilla; Christiansen, Lasse Engbo

    2016-01-01

    Background: Combination treatment is increasingly used to fight infections caused by bacteria resistant to two or more antimicrobials. While multiple studies have evaluated treatment strategies to minimize the emergence of resistant strains for single antimicrobial treatment, fewer studies have...... the sensitive fraction of the commensal flora.Growth parameters for competing bacterial strains were estimated from the combined in vitro pharmacodynamic effect of two antimicrobials using the relationship between concentration and net bacterial growth rate. Predictions of in vivo bacterial growth were...... (how frequently antibiotics are alternated in a sequential treatment) of the two drugs was dependent upon the order in which the two drugs were used.Conclusion: Sequential treatment was more effective in preventing the growth of resistant strains when compared to the combination treatment. The cycling...

  5. A practical method of modeling a treatment couch using cone-beam computed tomography for intensity-modulated radiation therapy and RapidArc treatment delivery

    Energy Technology Data Exchange (ETDEWEB)

    Aldosary, Ghada, E-mail: ghada.aldosary@mail.mcgill.ca [Medical Physics Unit, McGill University Health Centre, Montreal, Quebec (Canada); Nobah, Ahmad; Al-Zorkani, Faisal [Biomedical Physics Department, King Faisal Specialist Hospital and Research Center, Riyadh (Saudi Arabia); Devic, Slobodan [Department of Radiation Oncology, Jewish General Hospital, McGill University, Montreal, Quebec (Canada); Moftah, Belal [Medical Physics Unit, McGill University Health Centre, Montreal, Quebec (Canada); Biomedical Physics Department, King Faisal Specialist Hospital and Research Center, Riyadh (Saudi Arabia)

    2015-01-01

    The effect of a treatment couch on dose perturbation is not always fully considered in intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). In the course of inverse planning radiotherapy techniques, beam parameter optimization may change in the absence of the couch, causing errors in the calculated dose distributions. Although modern treatment planning systems (TPS) include data for the treatment couch components, they are not manufactured identically. Thus, variations in their Hounsfield unit (HU) values may exist. Moreover, a radiotherapy facility may wish to have a third-party custom tabletop installed that is not included by the TPS vendor. This study demonstrates a practical and simple method of acquiring reliable computed tomography (CT) data for the treatment couch and shows how the absorbed dose calculated with the modeled treatment couch can differ from that with the default treatment couch found in the TPS. We also experimentally verified that neglecting to incorporate the treatment couch completely in the treatment planning process might result in dose differences of up to 9.5% and 7.3% for 4-MV and 10-MV photon beams, respectively. Furthermore, 20 RapidArc and IMRT cases were used to quantify the change in calculated dose distributions caused by using either the default or modeled couch. From 2-dimensional (2D) ionization chamber array measurements, we observed large dose distribution differences between the measurements and calculations when the couch was omitted that varied according to the planning technique and anatomic site. Thus, incorporating the treatment couch in the dose calculation phase of treatment planning significantly decreases dose calculation errors.

  6. An Update on Modifications to Water Treatment Plant Model

    Science.gov (United States)

    Water treatment plant (WTP) model is an EPA tool for informing regulatory options. WTP has a few versions: 1). WTP2.2 can help in regulatory analysis. An updated version (WTP3.0) will allow plant-specific analysis (WTP-ccam) and thus help meet plant-specific treatment objectives...

  7. 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

  8. Cost-effectiveness analysis of universal noninvasive testing for post-treatment confirmation of Helicobacter pylori eradication and the impact of patient adherence

    Directory of Open Access Journals (Sweden)

    Boklage SH

    2016-06-01

    Full Text Available Susan H Boklage,1 Allen W Mangel,2 Varun Ramamohan,2 Deirdre Mladsi,2 Tao Wang1 1Otsuka America Pharmaceutical, Inc, Princeton, NJ, 2RTI Health Solutions, Research Triangle Park, NC, USA Background: The treatment failure rate for Helicobacter pylori eradication therapy is ~20% due to poor patient compliance and increased antibiotic resistance. This analysis assessed the cost-effectiveness of universal post-treatment testing to confirm eradication of H. pylori infection in adults.Methods: Decision-analytic models evaluated the cost-effectiveness of universal post-treatment testing (urea breath test [UBT] or monoclonal fecal antigen test [mFAT] vs no testing (Model 1, and UBT vs mFAT after adjusting for patient adherence to testing (Model 2 in adults who previously received first-line antimicrobial therapy. Patients testing positive received second-line quadruple therapy; no further action was taken for those testing negative or with no testing (Model 1 or for those nonadherent to testing (Model 2. In addition to testing costs, excess lifetime costs and reduced quality-adjusted life-years (QALYs due to continuing H. pylori infection were considered in the model.Results: Expected total costs per patient were higher for post-treatment testing (UBT: US$325.76; mFAT: US$242.12 vs no testing (US$182.41 in Model 1 and for UBT (US$336.75 vs mFAT (US$326.24 in Model 2. Expected QALYs gained per patient were 0.71 and 0.72 for UBT and mFAT, respectively, vs no testing (Model 1, and the same was 0.37 for UBT vs mFAT (Model 2. The estimated incremental costs per QALY gained for post-treatment testing vs no testing were US$82.90–US$202.45 and, after adjusting for adherence, US$28.13 for UBT vs mFAT.Conclusion: Universal post-treatment testing was found to be cost-effective for confirming eradication of H. pylori infection following first-line therapy. Better adherence to UBT relative to mFAT was the key to its cost-effectiveness. Keywords: health

  9. Cost-effectiveness of collaborative care including PST and an antidepressant treatment algorithm for the treatment of major depressive disorder in primary care; a randomised clinical trial

    Directory of Open Access Journals (Sweden)

    Beekman Aartjan TF

    2007-03-01

    Full Text Available Abstract Background Depressive disorder is currently one of the most burdensome disorders worldwide. Evidence-based treatments for depressive disorder are already available, but these are used insufficiently, and with less positive results than possible. Earlier research in the USA has shown good results in the treatment of depressive disorder based on a collaborative care approach with Problem Solving Treatment and an antidepressant treatment algorithm, and research in the UK has also shown good results with Problem Solving Treatment. These treatment strategies may also work very well in the Netherlands too, even though health care systems differ between countries. Methods/design This study is a two-armed randomised clinical trial, with randomization on patient-level. The aim of the trial is to evaluate the treatment of depressive disorder in primary care in the Netherlands by means of an adapted collaborative care framework, including contracting and adherence-improving strategies, combined with Problem Solving Treatment and antidepressant medication according to a treatment algorithm. Forty general practices will be randomised to either the intervention group or the control group. Included will be patients who are diagnosed with moderate to severe depression, based on DSM-IV criteria, and stratified according to comorbid chronic physical illness. Patients in the intervention group will receive treatment based on the collaborative care approach, and patients in the control group will receive care as usual. Baseline measurements and follow up measures (3, 6, 9 and 12 months are assessed using questionnaires and an interview. The primary outcome measure is severity of depressive symptoms, according to the PHQ9. Secondary outcome measures are remission as measured with the PHQ9 and the IDS-SR, and cost-effectiveness measured with the TiC-P, the EQ-5D and the SF-36. Discussion In this study, an American model to enhance care for patients with a

  10. Effects of Cancer Treatment on Fertility (For Parents)

    Science.gov (United States)

    ... Mind Sexual Health Food & Fitness Diseases & Conditions Infections Drugs & Alcohol School & Jobs Sports Expert Answers (Q&A) Staying Safe Videos for Educators Search English Español Effects of Cancer Treatment on Fertility KidsHealth / For Parents / Effects of Cancer Treatment on ...

  11. The hairless guinea-pig as a model for treatment of acute irritation in humans

    DEFF Research Database (Denmark)

    Andersen, F; Hedegaard, K; Fullerton, A

    2006-01-01

    BACKGROUND: The effect of six skin care formulations on experimentally induced acute irritation was studied in hairless guinea-pigs (HLGP) and in human volunteers (HV). The formulations were a basic cream, a carbomer cream and four modifications of the carbomer cream, containing either 10...... and colorimetry. RESULTS: The glycerol cream was the only product showing effects potentially better than no treatment in HV. CONCLUSION: The HLGP was too sensitive an animal model as a predictor for effect in humans. There was no difference in efficacy of the formulations against the two different irritants...

  12. Improved treatment of radiation effects on the skin

    International Nuclear Information System (INIS)

    Wandl, E.O.; Kaercher, K.H.; Wandl-Hainberger, I.

    1985-01-01

    The treatment concept developed by K.H. Kaercher was extended by a therapy using Elasten S cream. In the course of a highvoltage therapy using fast electrons or cobalt-60, interesting aspects in the treatment and progression of the radiation reactions of the skin were established. The dermato-therapeutic principles layed down by K.H. Kaercher with the treatment palette used hitherto, have without doubt invariably proven their value. The exclusive powder treatment, however, may be made more practical by application of the new treatment cream in accordance with the intervals in radiation treatment or as a basic treatment towards the end of therapy. Furthermore it is ideally suited for the care and after-treatment of skin, strained by radiation. It reduces considerably the remaining visible radiation reactions. The treatment with powder and emulsion has for more than 10 years proven effective. After the excellent results of the new cream during radiation treatment, additional positive effects are expected in a long-term trial which will be reported on separately. (orig.) [de

  13. Effects of Quercetin in a Mouse Model of Experimental Dry Eye.

    Science.gov (United States)

    Oh, Ha Na; Kim, Chae Eun; Lee, Ji Hyun; Yang, Jae Wook

    2015-09-01

    To evaluate the effect of treatment with quercetin in a mouse model of dry eye. 0.5% quercetin eye drops were prepared and an experimental dry eye model was induced in NOD.B10.H2(b) mice through desiccation stress. The mice were divided into 3 groups according to the treatment regimen: the DS 10D group (desiccation stress for 10 days), the phosphate buffered saline (PBS) group, and the quercetin group. Tear volumes and corneal irregularity scores were measured at 3, 5, 7, and 10 days after treatment. Hematoxylin and eosin staining, periodic acid-Schiff staining, and immunohistochemistry were performed at the end of the experiment. The quercetin group had increased tear volumes (0.2 ± 0.03 μm, P lacrimal gland than did the PBS group. Topical application of quercetin can help to improve ocular surface disorders of dry eye not only by decreasing the corneal surface irregularity but also by increasing the tear volume and goblet cell density. Moreover, quercetin has the potential for use in eye drops as a treatment for dry eye disease with antiinflammatory effects on the lacrimal functional unit.

  14. Modeling Fuel Treatment Leverage: Encounter Rates, Risk Reduction, and Suppression Cost Impacts

    Directory of Open Access Journals (Sweden)

    Matthew P. Thompson

    2017-11-01

    Full Text Available The primary theme of this study is the cost-effectiveness of fuel treatments at multiple scales of investment. We focused on the nexus of fuel management and suppression response planning, designing spatial fuel treatment strategies to incorporate landscape features that provide control opportunities that are relevant to fire operations. Our analysis explored the frequency and magnitude of fire-treatment encounters, which are critical determinants of treatment efficacy. Additionally, we examined avoided area burned, avoided suppression costs, and avoided damages, and combined all three under the umbrella of leverage to explore multiple dimensions with which to characterize return on investment. We chose the Sierra National Forest, California, USA, as our study site, due to previous work providing relevant data and analytical products, and because it has the potential for large, long-duration fires and corresponding potential for high suppression expenditures. Modeling results generally confirmed that fire-treatment encounters are rare, such that median suppression cost savings are zero, but in extreme years, savings can more than offset upfront investments. Further, reductions in risk can expand areas where moderated suppression response would be appropriate, and these areas can be mapped in relation to fire control opportunities.

  15. Endovascular Treatment of Diabetic Foot in a Selected Population of Patients with Below-the-Knee Disease: Is the Angiosome Model Effective?

    Energy Technology Data Exchange (ETDEWEB)

    Fossaceca, Rita, E-mail: rfossaceca@hotmail.com; Guzzardi, Giuseppe, E-mail: guz@libero.it; Cerini, Paolo, E-mail: cerini84@hotmail.it [' Maggiore della Carita' Hospital, University of Eastern Piedmont ' Amedeo Avogadro' , Department of Diagnostic and Interventional Radiology (Italy); Cusaro, Claudio, E-mail: claudio.cusaro@libero.it [' Maggiore della Carita' Hospital, Department of Diabetic Complications (Italy); Stecco, Alessandro, E-mail: a.stecco@libero.it; Parziale, Giuseppe, E-mail: giuseppeparziale@gmail.com; Perchinunno, Marco, E-mail: marcoperchinunno@gmail.com; Bonis, Marco De, E-mail: marco_deb@hotmail.it; Carriero, Alessandro, E-mail: profcarriero@virgilio.it [' Maggiore della Carita' Hospital, University of Eastern Piedmont ' Amedeo Avogadro' , Department of Diagnostic and Interventional Radiology (Italy)

    2013-06-15

    Purpose. To evaluate the efficacy of percutaneous transluminal angioplasty (PTA) in a selected population of diabetic patients with below-the-knee (BTK) disease and to analyze the reliability of the angiosome model. Methods. We made a retrospective analysis of the results of PTA performed in 201 diabetic patients with BTK-only disease treated at our institute from January 2005 to December 2011. We evaluated the postoperative technical success, and at 1, 6, and 12 months' follow-up, we assessed the rates and values of partial and complete ulcer healing, restenosis, major and minor amputation, limb salvage, and percutaneous oximetry (TcPO{sub 2}) (Student's t test). We used the angiosome model to compare different clinicolaboratory outcomes in patients treated by direct revascularization (DR) from patients treated with indirect revascularization (IR) technique by Student's t test and the {chi}{sup 2} test. Results. At a mean {+-} standard deviation follow-up of 17.5 {+-} 12 months, we observed a mortality rate of 3.5 %, a major amputation rate of 9.4 %, and a limb salvage rate of 87 % with a statistically significant increase of TcPO{sub 2} values at follow-up compared to baseline (p < 0.05). In 34 patients, treatment was performed with the IR technique and in 167 by DR; in both groups, there was a statistically significant increase of TcPO{sub 2} values at follow-up compared to baseline (p < 0.05), without statistically significant differences in therapeutic efficacy. Conclusion. PTA of the BTK-only disease is a safe and effective option. The DR technique is the first treatment option; we believe, however, that IR is similarly effective, with good results over time.

  16. 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.

  17. Cost-effectiveness of Early Treatment of Hepatitis C Virus Genotype 1 by Stage of Liver Fibrosis in a US Treatment-Naive Population

    Science.gov (United States)

    Chahal, Harinder S.; Marseille, Elliot A.; Tice, Jeffrey A.; Pearson, Steve D.; Ollendorf, Daniel A.; Fox, Rena K.; Kahn, James G.

    2016-01-01

    IMPORTANCE Novel treatments for hepatitis C virus (HCV) infection are highly efficacious but costly. Thus, many insurers cover therapy only in advanced fibrosis stages. The added health benefits and costs of early treatment are unknown. OBJECTIVE To assess the cost-effectiveness of (1) treating all patients with HCV vs only those with advanced fibrosis and (2) treating each stage of fibrosis. DESIGN, SETTING, AND PARTICIPANTS This study used a decision-analytic model for the treatment of HCV genotype 1. The model used a lifetime horizon and societal perspective and was representative of all US patients with HCV genotype 1 who had not received previous treatment. Comparisons in the model included antiviral treatment of all fibrosis stages (METAVIR [Meta-analysis of Histological Data in Virial Hepatitis] stages F0 [no fibrosis] to F4 [cirrhosis]) vs treatment of stages F3 (numerous septa without cirrhosis) and F4 only and by specific fibrosis stage. Data were collected from March 1 to September 1, 2014, and analyzed from September 1, 2014, to June 30, 2015. INTERVENTIONS Six HCV therapy options (particularly combined sofosbuvir and ledipasvir therapy) or no treatment. MAIN OUTCOMES AND MEASURES Cost and health outcomes were measured using total medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), calculated as the difference in costs between strategies divided by the difference in QALYs. RESULTS We simulated 1000 individuals, but present the results normalized to a single HCV-infected person. In the base-case analysis, among patients receiving 8 or 12 weeks of sofosbuvir-ledipasvir treatment, treating all fibrosis stages compared with treating stages F3 and F4 adds 0.73 QALYs and $28 899, for an ICER of $39 475 per QALY gained. Treating at stage F2 (portal fibrosis with rare septa) costs $19 833 per QALY gained vs waiting until stage F3; treating at stage F1 (portal fibrosis without septa), $81 165 per QALY gained

  18. Comparative analysis of Lacistema pubescens and dexamethasone on topical treatment of skin inflammation in a chronic disease model and side effects.

    Science.gov (United States)

    da Silva, Josiane M; Conegundes, Jéssica L M; Pinto, Nícolas C C; Mendes, Renata F; Castañon, Maria Christina M N; Scio, Elita

    2018-04-01

    This study aimed to evaluate the chronic topical anti-inflammatory activity of the pharmaceutical formulation ProHLP containing the hexane fraction of Lacistema pubescens (HLP). It was also investigated the possible cutaneous and systemic adverse effects of HLP and ProHLP in mice when compared to dexamethasone. The chronic topical anti-inflammatory activity was determined by croton oil multiple application-induced mouse ear oedema model. Histopathological analyses of ear tissue samples sensitized with croton oil were performed. Cutaneous atrophy induced by HLP and topical glucocorticoid treatments and excision skin wounds model to evidenced possible adverse reactions were also determined. ProHLP significantly reduced the mice ear oedema and considerably accelerated the wound-healing process. Also, HLP did not lead cutaneous atrophy and preserved the clinical aspect of the thymus, adrenal and spleen, unlike dexamethasone. The results suggested that ProHLP is an efficient and safer pharmaceutical formulation to treat chronic inflammatory diseases. © 2018 Royal Pharmaceutical Society.

  19. Treatment of Radix Dipsaci extract prevents long bone loss induced by modeled microgravity in hindlimb unloading rats.

    Science.gov (United States)

    Niu, Yinbo; Li, Chenrui; Pan, Yalei; Li, Yuhua; Kong, Xianghe; Wang, Shuo; Zhai, YuanKun; Wu, Xianglong; Fan, Wutu; Mei, Qibing

    2015-01-01

    Radix Dipsaci is a kidney tonifying herbal medicine with a long history of safe use for treatment of bone fractures and joint diseases in China. Previous studies have shown that Radix Dipsaci extract (RDE) could prevent bone loss in ovariectomized rats. This study investigates the effect of RDE against bone loss induced by simulated microgravity. A hindlimb unloading rat model was established to determine the effect of RDE on bone mineral density and bone microarchitecture. Twenty-four male Sprague-Dawley rats were divided into four groups (n = 6 per group): control (CON), hindlimb unloading with vehicle (HLU), hindlimb unloading treated with alendronate (HLU-ALN, 2.0 mg/kg/d), and hindlimb unloading treated with RDE (HLU-RDE, 500 mg/kg/d). RDE or ALN was administrated orally for 4 weeks. Treatment with RDE had a positive effect on mechanical strength, BMD, BMC, bone turnover markers, and the changes in urinary calcium and phosphorus excretion. MicroCT analysis showed that RDE significantly prevented the reduction of the bone volume fraction, connectivity density, trabecular number, thickness, tissue mineral density, and tissue mineral content as well as improved the trabecular separation and structure model index. RDE was demonstrated to prevent the loss of bone mass induced by HLU treatment, which suggests the potential application of RDE in the treatment of microgravity-induced bone loss.

  20. Predictors for individual patient antibiotic treatment effect in hospitalized community-acquired pneumonia patients.

    Science.gov (United States)

    Simonetti, A F; van Werkhoven, C H; Schweitzer, V A; Viasus, D; Carratalà, J; Postma, D F; Oosterheert, J J; Bonten, M J M

    2017-10-01

    Our objective was to identify clinical predictors of antibiotic treatment effects in hospitalized patients with community-acquired pneumonia (CAP) who were not in the intensive care unit (ICU). Post-hoc analysis of three prospective cohorts (from the Netherlands and Spain) of adult patients with CAP admitted to a non-ICU ward having received either β-lactam monotherapy, β-lactam + macrolide, or a fluoroquinolone-based therapy as empirical antibiotic treatment. We evaluated candidate clinical predictors of treatment effects in multiple mixed-effects models by including interactions of the predictors with empirical antibiotic choice and using 30-day mortality, ICU admission and length of hospital stay as outcomes. Among 8562 patients, empirical treatment was β-lactam in 4399 (51.4%), fluoroquinolone in 3373 (39.4%), and β-lactam + macrolide in 790 (9.2%). Older age (interaction OR 1.67, 95% CI 1.23-2.29, p 0.034) and current smoking (interaction OR 2.36, 95% CI 1.34-4.17, p 0.046) were associated with lower effectiveness of fluoroquinolone on 30-day mortality. Older age was also associated with lower effectiveness of β-lactam + macrolide on length of hospital stay (interaction effect ratio 1.14, 95% CI 1.06-1.22, p 0.008). Older age and smoking could influence the response to specific antibiotic regimens. The effect modification of age and smoking should be considered hypothesis generating to be evaluated in future trials. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  1. Sclerostin Antibody Treatment Improves the Bone Phenotype of Crtap(-/-) Mice, a Model of Recessive Osteogenesis Imperfecta.

    Science.gov (United States)

    Grafe, Ingo; Alexander, Stefanie; Yang, Tao; Lietman, Caressa; Homan, Erica P; Munivez, Elda; Chen, Yuqing; Jiang, Ming Ming; Bertin, Terry; Dawson, Brian; Asuncion, Franklin; Ke, Hua Zhu; Ominsky, Michael S; Lee, Brendan

    2016-05-01

    Osteogenesis imperfecta (OI) is characterized by low bone mass, poor bone quality, and fractures. Standard treatment for OI patients is limited to bisphosphonates, which only incompletely correct the bone phenotype, and seem to be less effective in adults. Sclerostin-neutralizing antibodies (Scl-Ab) have been shown to be beneficial in animal models of osteoporosis, and dominant OI resulting from mutations in the genes encoding type I collagen. However, Scl-Ab treatment has not been studied in models of recessive OI. Cartilage-associated protein (CRTAP) is involved in posttranslational type I collagen modification, and its loss of function results in recessive OI. In this study, we treated 1-week-old and 6-week-old Crtap(-/-) mice with Scl-Ab for 6 weeks (25 mg/kg, s.c., twice per week), to determine the effects on the bone phenotype in models of "pediatric" and "young adult" recessive OI. Vehicle-treated Crtap(-/-) and wild-type (WT) mice served as controls. Compared with control Crtap(-/-) mice, micro-computed tomography (μCT) analyses showed significant increases in bone volume and improved trabecular microarchitecture in Scl-Ab-treated Crtap(-/-) mice in both age cohorts, in both vertebrae and femurs. Additionally, Scl-Ab improved femoral cortical parameters in both age cohorts. Biomechanical testing showed that Scl-Ab improved parameters of whole-bone strength in Crtap(-/-) mice, with more robust effects in the week 6 to 12 cohort, but did not affect the increased bone brittleness. Additionally, Scl-Ab normalized the increased osteoclast numbers, stimulated bone formation rate (week 6 to 12 cohort only), but did not affect osteocyte density. Overall, our findings suggest that Scl-Ab treatment may be beneficial in the treatment of recessive OI caused by defects in collagen posttranslational modification. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.

  2. A meta-analysis of the abscopal effect in preclinical models: Is the biologically effective dose a relevant physical trigger?

    Directory of Open Access Journals (Sweden)

    Raffaella Marconi

    Full Text Available Preclinical in vivo studies using small animals are considered crucial in translational cancer research and clinical implementation of novel treatments. This is of paramount relevance in radiobiology, especially for any technological developments permitted to deliver high doses in single or oligo-fractionated regimens, such as stereotactic ablative radiotherapy (SABR. In this context, clinical success in cancer treatment needs to be guaranteed, sparing normal tissue and preventing the potential spread of disease or local recurrence. In this work we introduce a new dose-response relationship based on relevant publications concerning preclinical models with regard to delivered dose, fractionation schedule and occurrence of biological effects on non-irradiated tissue, abscopal effects.We reviewed relevant publications on murine models and the abscopal effect in radiation cancer research following PRISMA methodology. In particular, through a log-likelihood method, we evaluated whether the occurrence of abscopal effects may be related to the biologically effective dose (BED. To this aim, studies accomplished with different tumor histotypes were considered in our analysis including breast, colon, lung, fibrosarcoma, pancreas, melanoma and head and neck cancer. For all the tumors, the α / β ratio was assumed to be 10 Gy, as generally adopted for neoplastic cells.Our results support the hypothesis that the occurrence rate of abscopal effects in preclinical models increases with BED. In particular, the probability of revealing abscopal effects is 50% when a BED of 60 Gy is generated.Our study provides evidence that SABR treatments associated with high BEDs could be considered an effective strategy in triggering the abscopal effect, thus shedding light on the promising outcomes revealed in clinical practice.

  3. Effect of Heat Treatment on the Hardness and Wear of Grinding Balls

    Science.gov (United States)

    Aissat, Sahraoui; Sadeddine, Abdelhamid; Bradai, Mohand Amokrane; Younes, Rassim; Bilek, Ali; Benabbas, Abderrahim

    2017-09-01

    The effect quenching and tempering by different regimes on Rockwell hardness and wear processes of grinding balls 50 and 70 mm in diameter made of two melts of chromium-molybdenum cast iron is studied. The heating temperature for quenching is 850, 950, and 1050°C; the tempering temperature is 250, 400, and 600°C. Iron is analyzed in an electron microscope. Diffraction patterns are obtained. A model of cast iron wear is suggested and compared to the Davis model and to experimental results. An optimum heat treatment regime is proposed.

  4. Modelling the epidemiological impact of intermittent preventive treatment against malaria in infants.

    Directory of Open Access Journals (Sweden)

    Amanda Ross

    Full Text Available BACKGROUND: Trials of intermittent preventive treatment against malaria in infants (IPTi using sulphadoxine-pyrimethamine (SP have shown a positive, albeit variable, protective efficacy against clinical malaria episodes. The impact of IPTi in different epidemiological settings and over time is unknown and predictions are hampered by the lack of knowledge about how IPTi works. We investigated mechanisms proposed for the action of IPTi and made predictions of the likely impact on morbidity and mortality. METHODS/PRINCIPAL FINDINGS: We used a comprehensive, individual-based, stochastic model of malaria epidemiology to simulate recently published trials of IPTi using SP with site-specific characteristics as inputs. This baseline model was then modified to represent hypotheses concerning the duration of action of SP, the temporal pattern of fevers caused by individual infections, potential benefits of avoiding fevers on immunity and the effect of sub-therapeutic levels of SP on parasite dynamics. The baseline model reproduced the pattern of results reasonably well. None of the models based on alternative hypotheses improved the fit between the model predictions and observed data. Predictions suggest that IPTi would have a beneficial effect across a range of transmission intensities. IPTi was predicted to avert a greater number of episodes where IPTi coverage was higher, the health system treatment coverage lower, and for drugs which were more efficacious and had longer prophylactic periods. The predicted cumulative benefits were proportionately slightly greater for severe malaria episodes and malaria-attributable mortality than for acute episodes in the settings modelled. Modest increased susceptibility was predicted between doses and following the last dose, but these were outweighed by the cumulative benefits. The impact on transmission intensity was negligible. CONCLUSIONS: The pattern of trial results can be accounted for by differences between

  5. Myeloma Cell Dynamics in Response to Treatment Supports a Model of Hierarchical Differentiation and Clonal Evolution.

    Science.gov (United States)

    Tang, Min; Zhao, Rui; van de Velde, Helgi; Tross, Jennifer G; Mitsiades, Constantine; Viselli, Suzanne; Neuwirth, Rachel; Esseltine, Dixie-Lee; Anderson, Kenneth; Ghobrial, Irene M; San Miguel, Jesús F; Richardson, Paul G; Tomasson, Michael H; Michor, Franziska

    2016-08-15

    Since the pioneering work of Salmon and Durie, quantitative measures of tumor burden in multiple myeloma have been used to make clinical predictions and model tumor growth. However, such quantitative analyses have not yet been performed on large datasets from trials using modern chemotherapy regimens. We analyzed a large set of tumor response data from three randomized controlled trials of bortezomib-based chemotherapy regimens (total sample size n = 1,469 patients) to establish and validate a novel mathematical model of multiple myeloma cell dynamics. Treatment dynamics in newly diagnosed patients were most consistent with a model postulating two tumor cell subpopulations, "progenitor cells" and "differentiated cells." Differential treatment responses were observed with significant tumoricidal effects on differentiated cells and less clear effects on progenitor cells. We validated this model using a second trial of newly diagnosed patients and a third trial of refractory patients. When applying our model to data of relapsed patients, we found that a hybrid model incorporating both a differentiation hierarchy and clonal evolution best explains the response patterns. The clinical data, together with mathematical modeling, suggest that bortezomib-based therapy exerts a selection pressure on myeloma cells that can shape the disease phenotype, thereby generating further inter-patient variability. This model may be a useful tool for improving our understanding of disease biology and the response to chemotherapy regimens. Clin Cancer Res; 22(16); 4206-14. ©2016 AACR. ©2016 American Association for Cancer Research.

  6. Molecular targets in urothelial cancer: detection, treatment, and animal models of bladder cancer

    Science.gov (United States)

    Smolensky, Dmitriy; Rathore, Kusum; Cekanova, Maria

    2016-01-01

    Bladder cancer remains one of the most expensive cancers to treat in the United States due to the length of required treatment and degree of recurrence. In order to treat bladder cancer more effectively, targeted therapies are being investigated. In order to use targeted therapy in a patient, it is important to provide a genetic background of the patient. Recent advances in genome sequencing, as well as transcriptome analysis, have identified major pathway components altered in bladder cancer. The purpose of this review is to provide a broad background on bladder cancer, including its causes, diagnosis, stages, treatments, animal models, as well as signaling pathways in bladder cancer. The major focus is given to the PI3K/AKT pathway, p53/pRb signaling pathways, and the histone modification machinery. Because several promising immunological therapies are also emerging in the treatment of bladder cancer, focus is also given on general activation of the immune system for the treatment of bladder cancer. PMID:27784990

  7. On the treatment of airline travelers in mathematical models.

    Directory of Open Access Journals (Sweden)

    Michael A Johansson

    Full Text Available The global spread of infectious diseases is facilitated by the ability of infected humans to travel thousands of miles in short time spans, rapidly transporting pathogens to distant locations. Mathematical models of the actual and potential spread of specific pathogens can assist public health planning in the case of such an event. Models should generally be parsimonious, but must consider all potentially important components of the system to the greatest extent possible. We demonstrate and discuss important assumptions relative to the parameterization and structural treatment of airline travel in mathematical models. Among other findings, we show that the most common structural treatment of travelers leads to underestimation of the speed of spread and that connecting travel is critical to a realistic spread pattern. Models involving travelers can be improved significantly by relatively simple structural changes but also may require further attention to details of parameterization.

  8. Development and validation of a Markov microsimulation model for the economic evaluation of treatments in osteoporosis.

    Science.gov (United States)

    Hiligsmann, Mickaël; Ethgen, Olivier; Bruyère, Olivier; Richy, Florent; Gathon, Henry-Jean; Reginster, Jean-Yves

    2009-01-01

    Markov models are increasingly used in economic evaluations of treatments for osteoporosis. Most of the existing evaluations are cohort-based Markov models missing comprehensive memory management and versatility. In this article, we describe and validate an original Markov microsimulation model to accurately assess the cost-effectiveness of prevention and treatment of osteoporosis. We developed a Markov microsimulation model with a lifetime horizon and a direct health-care cost perspective. The patient history was recorded and was used in calculations of transition probabilities, utilities, and costs. To test the internal consistency of the model, we carried out an example calculation for alendronate therapy. Then, external consistency was investigated by comparing absolute lifetime risk of fracture estimates with epidemiologic data. For women at age 70 years, with a twofold increase in the fracture risk of the average population, the costs per quality-adjusted life-year gained for alendronate therapy versus no treatment were estimated at €9105 and €15,325, respectively, under full and realistic adherence assumptions. All the sensitivity analyses in terms of model parameters and modeling assumptions were coherent with expected conclusions and absolute lifetime risk of fracture estimates were within the range of previous estimates, which confirmed both internal and external consistency of the model. Microsimulation models present some major advantages over cohort-based models, increasing the reliability of the results and being largely compatible with the existing state of the art, evidence-based literature. The developed model appears to be a valid model for use in economic evaluations in osteoporosis.

  9. Treatment Analysis in a Cancer Stem Cell Context Using a Tumor Growth Model Based on Cellular Automata.

    Science.gov (United States)

    Monteagudo, Ángel; Santos, José

    2015-01-01

    Cancer can be viewed as an emergent behavior in terms of complex system theory and artificial life, Cellular Automata (CA) being the tool most used for studying and characterizing the emergent behavior. Different approaches with CA models were used to model cancer growth. The use of the abstract model of acquired cancer hallmarks permits the direct modeling at cellular level, where a cellular automaton defines the mitotic and apoptotic behavior of cells, and allows for an analysis of different dynamics of the cellular system depending on the presence of the different hallmarks. A CA model based on the presence of hallmarks in the cells, which includes a simulation of the behavior of Cancer Stem Cells (CSC) and their implications for the resultant growth behavior of the multicellular system, was employed. This modeling of cancer growth, in the avascular phase, was employed to analyze the effect of cancer treatments in a cancer stem cell context. The model clearly explains why, after treatment against non-stem cancer cells, the regrowth capability of CSCs generates a faster regrowth of tumor behavior, and also shows that a continuous low-intensity treatment does not favor CSC proliferation and differentiation, thereby allowing an unproblematic control of future tumor regrowth. The analysis performed indicates that, contrary to the current attempts at CSC control, trying to make CSC proliferation more difficult is an important point to consider, especially in the immediate period after a standard treatment for controlling non-stem cancer cell proliferation.

  10. The effect of heat treatment on phosphorus segregation in a submerged-arc weld metal

    International Nuclear Information System (INIS)

    Beere, W.B.; Buswell, J.T.

    1999-01-01

    Intergranular fracture (IGF) has been observed in carbon-manganese steels after irradiation or high temperature exposure for prolonged periods. The effect is associated with an increase in the ductile-brittle transition temperature and has been related to phosphorus diffusion to grain boundaries. Phosphorus also diffuses thermally at the temperatures used for post-weld heat treatments such that in principle, the slightly different heat treatments given to different parts of a large vessel could lead to differing grain boundary phosphorus coverage and hence susceptibility to IGF. The effect of typical heat treatments on phosphorus coverage has been investigated using a finite difference model based on a theory that has been fitted to a wide range of constant temperature data. Regardless of previous history, the grain boundary coverage of phosphorus was predicted to depend on the final anneal and cooling rate. These differed insufficiently in the typical heat treatments to produce significant differences in segregation. It was concluded that the ductile-brittle transition temperature in submerged-arc welds would be unaffected in vessels that had seen typical post-weld heat treatments

  11. Modeling Correlation Effects in Nickelates with Slave Particles

    Science.gov (United States)

    Georgescu, Alexandru Bogdan; Ismail-Beigi, Sohrab

    Nickelate interfaces display interesting electronic properties including orbital ordering similar to that of cuprate superconductors and thickness dependent metal-insulator transitions. One-particle band theory calculations do not include dynamic localized correlation effects on the nickel sites and thus often incorrectly predict metallic systems or incorrect ARPES spectra. Building on two previous successful slave-particle treatments of local correlations, we present a generalized slave-particle method that includes prior models and allows us to produce new intermediate models. The computational efficiency of these slave-boson methods means that one can readily study correlation effects in complex heterostructures. We show some predictions of these methods for the electronic structure of bulk and thin film nickelates. Work supported by NSF Grant MRSEC DMR-1119826.

  12. Patients knowledge about side effects of orthodontic treatment

    Directory of Open Access Journals (Sweden)

    Mia Amalia

    2011-07-01

    Full Text Available Disharmonious of dental arrangement can possibly create problems for the patient, such as the masticatory function, esthetical, psychosocial, and also the increased risk of trauma and periodontal disease. These are reasons for a patient to seek orthodontic treatment. The aim of this study was to know the patient’s knowledge about the side effects possibility that they receive during orthodontic treatment. The side effects include pain experience during orthodontic treatment, the possibility of soft tissue damage, email demineralization, loss of tooth vitality, periodontal problem, root resorption, temporomandibular joint disorders, and relapse. A cross-sectional study was conducted in patients who registered at Orthodontic Department, Faculty of Dentistry, Universitas Indonesia on March-June 2009. The participants of this study were 100 patients, consist of 86 women and 14 men respectively. Twenty-seven questions about the side-effects of orthodontic treatment were used to obtain the patient’s knowledge and the result was categorized into 3 groups, good, average and poor. The result of the study showed that patient’s knowledge about the side effect of pain experience during orthodontic treatment was average and the patient’s knowledge about the possibility of soft tissue damage due to orthodontic treatment was good. However, the patient’s knowledge about the possibility of email demineralization, loss of tooth vitality, periodontal problem, root resorption, temporomandibular joint disorders and relapse due to orthodontic treatment was low.

  13. Comparison of three light doses in the photodynamic treatment of actinic keratosis using mathematical modeling

    Science.gov (United States)

    Vignion-Dewalle, Anne-Sophie; Betrouni, Nacim; Tylcz, Jean-Baptiste; Vermandel, Maximilien; Mortier, Laurent; Mordon, Serge

    2015-05-01

    Photodynamic therapy (PDT) is an emerging treatment modality for various diseases, especially for cancer therapy. Although high efficacy is demonstrated for PDT using standardized protocols in nonhyperkeratotic actinic keratoses, alternative light doses expected to increase efficiency, to reduce adverse effects or to expand the use of PDT, are still being evaluated and refined. We propose a comparison of the three most common light doses in the treatment of actinic keratosis with 5-aminolevulinic acid PDT through mathematical modeling. The proposed model is based on an iterative procedure that involves determination of the local fluence rate, updating of the local optical properties, and estimation of the local damage induced by the therapy. This model was applied on a simplified skin sample model including an actinic keratosis lesion, with three different light doses (red light dose, 37 J/cm2, 75 mW/cm2, 500 s blue light dose, 10 J/cm2, 10 mW/cm2, 1000 s and daylight dose, 9000 s). Results analysis shows that the three studied light doses, although all efficient, lead to variable local damage. Defining reference damage enables the nonoptimal parameters for the current light doses to be refined and the treatment to be more suitable.

  14. Randomized controlled trial of video self-modeling following speech restructuring treatment for stuttering.

    Science.gov (United States)

    Cream, Angela; O'Brian, Sue; Jones, Mark; Block, Susan; Harrison, Elisabeth; Lincoln, Michelle; Hewat, Sally; Packman, Ann; Menzies, Ross; Onslow, Mark

    2010-08-01

    In this study, the authors investigated the efficacy of video self-modeling (VSM) following speech restructuring treatment to improve the maintenance of treatment effects. The design was an open-plan, parallel-group, randomized controlled trial. Participants were 89 adults and adolescents who undertook intensive speech restructuring treatment. Post treatment, participants were randomly assigned to 2 trial arms: standard maintenance and standard maintenance plus VSM. Participants in the latter arm viewed stutter-free videos of themselves each day for 1 month. The addition of VSM did not improve speech outcomes, as measured by percent syllables stuttered, at either 1 or 6 months postrandomization. However, at the latter assessment, self-rating of worst stuttering severity by the VSM group was 10% better than that of the control group, and satisfaction with speech fluency was 20% better. Quality of life was also better for the VSM group, which was mildly to moderately impaired compared with moderate impairment in the control group. VSM intervention after treatment was associated with improvements in self-reported outcomes. The clinical implications of this finding are discussed.

  15. Erratum: Probabilistic application of a fugacity model to predict triclosan fate during wastewater treatment.

    Science.gov (United States)

    Bock, Michael; Lyndall, Jennifer; Barber, Timothy; Fuchsman, Phyllis; Perruchon, Elyse; Capdevielle, Marie

    2010-10-01

    The fate and partitioning of the antimicrobial compound, triclosan, in wastewater treatment plants (WWTPs) is evaluated using a probabilistic fugacity model to predict the range of triclosan concentrations in effluent and secondary biosolids. The WWTP model predicts 84% to 92% triclosan removal, which is within the range of measured removal efficiencies (typically 70% to 98%). Triclosan is predominantly removed by sorption and subsequent settling of organic particulates during primary treatment and by aerobic biodegradation during secondary treatment. Median modeled removal efficiency due to sorption is 40% for all treatment phases and 31% in the primary treatment phase. Median modeled removal efficiency due to biodegradation is 48% for all treatment phases and 44% in the secondary treatment phase. Important factors contributing to variation in predicted triclosan concentrations in effluent and biosolids include influent concentrations, solids concentrations in settling tanks, and factors related to solids retention time. Measured triclosan concentrations in biosolids and non-United States (US) effluent are consistent with model predictions. However, median concentrations in US effluent are over-predicted with this model, suggesting that differences in some aspect of treatment practices not incorporated in the model (e.g., disinfection methods) may affect triclosan removal from effluent. Model applications include predicting changes in environmental loadings associated with new triclosan applications and supporting risk analyses for biosolids-amended land and effluent receiving waters. © 2010 SETAC.

  16. Sulfanegen sodium treatment in a rabbit model of sub-lethal cyanide toxicity

    International Nuclear Information System (INIS)

    Brenner, Matthew; Kim, Jae G.; Lee, Jangwoen; Mahon, Sari B.; Lemor, Daniel; Ahdout, Rebecca; Boss, Gerry R.; Blackledge, William; Jann, Lauren; Nagasawa, Herbert T.; Patterson, Steven E.

    2010-01-01

    The aim of this study is to investigate the ability of intramuscular and intravenous sulfanegen sodium treatment to reverse cyanide effects in a rabbit model as a potential treatment for mass casualty resulting from cyanide exposure. Cyanide poisoning is a serious chemical threat from accidental or intentional exposures. Current cyanide exposure treatments, including direct binding agents, methemoglobin donors, and sulfur donors, have several limitations. Non-rhodanese mediated sulfur transferase pathways, including 3-mercaptopyruvate sulfurtransferase (3-MPST) catalyze the transfer of sulfur from 3-MP to cyanide, forming pyruvate and less toxic thiocyanate. We developed a water-soluble 3-MP prodrug, 3-mercaptopyruvatedithiane (sulfanegen sodium), with the potential to provide a continuous supply of substrate for CN detoxification. In addition to developing a mass casualty cyanide reversal agent, methods are needed to rapidly and reliably diagnose and monitor cyanide poisoning and reversal. We use non-invasive technology, diffuse optical spectroscopy (DOS) and continuous wave near infrared spectroscopy (CWNIRS) to monitor physiologic changes associated with cyanide exposure and reversal. A total of 35 animals were studied. Sulfanegen sodium was shown to reverse the effects of cyanide exposure on oxyhemoglobin and deoxyhemoglobin rapidly, significantly faster than control animals when administered by intravenous or intramuscular routes. RBC cyanide levels also returned to normal faster following both intramuscular and intravenous sulfanegen sodium treatment than controls. These studies demonstrate the clinical potential for the novel approach of supplying substrate for non-rhodanese mediated sulfur transferase pathways for cyanide detoxification. DOS and CWNIRS demonstrated their usefulness in optimizing the dose of sulfanegen sodium treatment.

  17. Hyperoxic treatment induces mesenchymal-to-epithelial transition in a rat adenocarcinoma model.

    Directory of Open Access Journals (Sweden)

    Ingrid Moen

    Full Text Available Tumor hypoxia is relevant for tumor growth, metabolism and epithelial-to-mesenchymal transition (EMT. We report that hyperbaric oxygen (HBO treatment induced mesenchymal-to-epithelial transition (MET in a dimethyl-alpha-benzantracene induced mammary rat adenocarcinoma model, and the MET was associated with extensive coordinated gene expression changes and less aggressive tumors. One group of tumor bearing rats was exposed to HBO (2 bar, pO(2 = 2 bar, 4 exposures à 90 minutes, whereas the control group was housed under normal atmosphere (1 bar, pO(2 = 0.2 bar. Treatment effects were determined by assessment of tumor growth, tumor vascularisation, tumor cell proliferation, cell death, collagen fibrils and gene expression profile. Tumor growth was significantly reduced (approximately 16% after HBO treatment compared to day 1 levels, whereas control tumors increased almost 100% in volume. Significant decreases in tumor cell proliferation, tumor blood vessels and collagen fibrils, together with an increase in cell death, are consistent with tumor growth reduction and tumor stroma influence after hyperoxic treatment. Gene expression profiling showed that HBO induced MET. In conclusion, hyperoxia induced MET with coordinated expression of gene modules involved in cell junctions and attachments together with a shift towards non-tumorigenic metabolism. This leads to more differentiated and less aggressive tumors, and indicates that oxygen per se might be an important factor in the "switches" of EMT and MET in vivo. HBO treatment also attenuated tumor growth and changed tumor stroma, by targeting the vascular system, having anti-proliferative and pro-apoptotic effects.

  18. On the Inclusion of Short-distance Bystander Effects into a Logistic Tumor Control Probability Model.

    Science.gov (United States)

    Tempel, David G; Brodin, N Patrik; Tomé, Wolfgang A

    2018-01-01

    Currently, interactions between voxels are neglected in the tumor control probability (TCP) models used in biologically-driven intensity-modulated radiotherapy treatment planning. However, experimental data suggests that this may not always be justified when bystander effects are important. We propose a model inspired by the Ising model, a short-range interaction model, to investigate if and when it is important to include voxel to voxel interactions in biologically-driven treatment planning. This Ising-like model for TCP is derived by first showing that the logistic model of tumor control is mathematically equivalent to a non-interacting Ising model. Using this correspondence, the parameters of the logistic model are mapped to the parameters of an Ising-like model and bystander interactions are introduced as a short-range interaction as is the case for the Ising model. As an example, we apply the model to study the effect of bystander interactions in the case of radiation therapy for prostate cancer. The model shows that it is adequate to neglect bystander interactions for dose distributions that completely cover the treatment target and yield TCP estimates that lie in the shoulder of the dose response curve. However, for dose distributions that yield TCP estimates that lie on the steep part of the dose response curve or for inhomogeneous dose distributions having significant hot and/or cold regions, bystander effects may be important. Furthermore, the proposed model highlights a previously unexplored and potentially fruitful connection between the fields of statistical mechanics and tumor control probability/normal tissue complication probability modeling.

  19. Effects of Astragalus polysaccharides on memory impairment in a diabetic rat model

    Directory of Open Access Journals (Sweden)

    Dun C

    2016-07-01

    Full Text Available Changping Dun,1 Junqian Liu,1 Fucheng Qiu,1 Xueda Wu,2 Yakun Wang,3 Yongyan Zhao,4 Ping Gu1 1Department of Neurology, the First Hospital of Hebei Medical University, 2Department of Cardiac Surgery, the Second Hospital of Hebei Medical University, 3Department of Endocrinology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 4Department of Nursing, Maternal and Child Health Hospital of Tangshan City, Tangshan, People’s Republic of China Objective: Astragalus polysaccharides (APS are active constituents of Astragalus membranaceus. In this study, we aimed to investigate the effects of APS on memory impairment in a diabetic rat model and their mechanisms. Methods: A diabetic model was established in 50 male Wistar rats with streptozotocin intraperitoneal injection. A blood glucose level higher than 16.7 mmol/L obtained 72 hours after the injection was regarded as a successful diabetic model. The modeled rats were divided into model group, high, medium, and low doses of APS, and piracetam groups (positive control. A group of ten rats without streptozotocin-induced diabetes were used as a normal control. After respective consecutive 8-week treatments, the levels of blood fasting plasma glucose, insulin, hemoglobin A1c, memory performance, hippocampal malondialdehyde, and superoxide dismutase were determined. Results: After the 8-week APS treatment, serum fasting plasma glucose, hemoglobin A1c, and insulin levels were decreased compared with those of the model group (P<0.05. Importantly, memory impairment in the diabetic model was reversed by APS treatments. In addition, hippocampal malondialdehyde concentration was lowered, whereas that of superoxide dismutase was higher after APS treatments. Conclusion: APS are important active components responsible for memory improvement in rats with streptozotocin-induced diabetes. The potential mechanism of action is associated with the effects of APS on glucose and lipid metabolism, and

  20. Experimental model of the burn wound topical treatment

    Directory of Open Access Journals (Sweden)

    Amra Čabaravdić

    2003-11-01

    Full Text Available AbstractBACKGROUND AND PURPOSE:Clinical research of drugs is a researching step subsequent to the preclinical studies in experimental animals. The aim of our research was to evaluate animal model of wound healing process after the burninducement and effects of the ointment containing natural plants on the process of burn healing.MATERIAL AND METHODS:Burn wounds were experimentally induced in two species of experimental animals which were treated with topically applied herbal preparation with concomitant monitoring of the healing process. Experimental groups (1 of 15 animals each (mice and rats, while control group (2 of 10 animals each (mice and rats that were not being treated with herbal ointment. After the hair removal, burn was induced on the back of animals by heated brass seal. Different clinical symptoms including oedema of surrounding tissue, redness, exudation, size of the burn surface, histological and microbiological findings were monitored on the days 1, 3, 7, 14 and 21. A statistically significant difference was observed throughout descriptive statistics and paired Student's t-test.CONCLUSION:Physiological healing processes of the acute burn wound following the topical application of herbal preparation can be monitored on the utilized animal model. A three-week treatment resulted in the 90% of completed epithelization in both animal species, indicating the effectiveness of topically applied herbal preparation.

  1. Cost-Effectiveness of Treatments for Relapsing Remitting Multiple Sclerosis: A French Societal Perspective.

    Directory of Open Access Journals (Sweden)

    Julie Chevalier

    Full Text Available The paper aimed to estimate the incremental cost-effectiveness ratio (ICER at the public published price for delayed-release dimethyl fumarate versus relevant Multiple Sclerosis disease-modifying therapies available in France in June 2015.The economic model was adapted to the French setting in accordance with the Haute Autorité de Santé guidelines using a model previously developed for NICE. A cohort of Relapsing Remitting Multiple Sclerosis patients was simulated over a 30-year time horizon. Twenty one health states were taken into account: Kurtzke Expanded Disability Status Scale (EDSS 0-9 for Relapsing Remitting Multiple Sclerosis patients, EDSS 0-9 for Secondary Progressive Multiple Sclerosis patients, and death. Estimates of relative treatment efficacy were determined using a mixed-treatment comparison. Probabilities of events were derived from the dimethyl fumarate pivotal clinical trials and the London Ontario Dataset. Costs and utilities were extracted from the published literature from both the payer and societal perspectives. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model results.From both perspectives, dimethyl fumarate and interferon beta-1a (IFN beta-1a 44 mcg were the two optimal treatments, as the other treatments (IFN beta-1a 30 mcg, IFN beta-1b 250 mcg, teriflunomide, glatiramer acetate, fingolimod were dominated on the efficiency frontier. From the societal perspective, dimethyl fumarate versus IFN beta-1a 44 mcg incurred an incremental cost of €3,684 and an incremental quality-adjusted life year (QALY of 0.281, corresponding to an ICER of €13,110/QALY.Despite no reference threshold for France, dimethyl fumarate can be considered as a cost-effective option as it is on the efficiency frontier.

  2. Cost-Effectiveness of Treatments for Relapsing Remitting Multiple Sclerosis: A French Societal Perspective.

    Science.gov (United States)

    Chevalier, Julie; Chamoux, Catherine; Hammès, Florence; Chicoye, Annie

    2016-01-01

    The paper aimed to estimate the incremental cost-effectiveness ratio (ICER) at the public published price for delayed-release dimethyl fumarate versus relevant Multiple Sclerosis disease-modifying therapies available in France in June 2015. The economic model was adapted to the French setting in accordance with the Haute Autorité de Santé guidelines using a model previously developed for NICE. A cohort of Relapsing Remitting Multiple Sclerosis patients was simulated over a 30-year time horizon. Twenty one health states were taken into account: Kurtzke Expanded Disability Status Scale (EDSS) 0-9 for Relapsing Remitting Multiple Sclerosis patients, EDSS 0-9 for Secondary Progressive Multiple Sclerosis patients, and death. Estimates of relative treatment efficacy were determined using a mixed-treatment comparison. Probabilities of events were derived from the dimethyl fumarate pivotal clinical trials and the London Ontario Dataset. Costs and utilities were extracted from the published literature from both the payer and societal perspectives. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model results. From both perspectives, dimethyl fumarate and interferon beta-1a (IFN beta-1a) 44 mcg were the two optimal treatments, as the other treatments (IFN beta-1a 30 mcg, IFN beta-1b 250 mcg, teriflunomide, glatiramer acetate, fingolimod) were dominated on the efficiency frontier. From the societal perspective, dimethyl fumarate versus IFN beta-1a 44 mcg incurred an incremental cost of €3,684 and an incremental quality-adjusted life year (QALY) of 0.281, corresponding to an ICER of €13,110/QALY. Despite no reference threshold for France, dimethyl fumarate can be considered as a cost-effective option as it is on the efficiency frontier.

  3. Comparing Effectiveness of Treatments for Borderline Personality Disorder in Communal Mental Health Care: The Oulu BPD Study.

    Science.gov (United States)

    Leppänen, V; Hakko, H; Sintonen, H; Lindeman, S

    2016-02-01

    The implementation of effective psychotherapies in community mental health care is challenging. This study aimed to create a well-structured and easily applicable treatment model for patients with severe borderline personality disorder (BPD). We integrated a schema therapy based psycho-educational group into an available individual therapy. Two groups were formed: (1) community treatment by experts (CTBE) patients (n = 24) receiving new treatment and (2) treatment as usual (TAU) patients (n = 47). Changes in symptoms were measured by Borderline Personality Disorder Severity Index-IV interview and quality of life by the 15D health-related quality of life questionnaire. After 1 year the CTBE patients showed a significant reduction in a wider range of BPD symptoms and better quality of life than TAU patients. The results of this study are encouraging. A well-structured treatment model was successfully implemented into community mental health care with improved patient adherence to treatment and superior treatment outcomes compared to TAU patients.

  4. Effectiveness of complementary and self-help treatments for anxiety disorders.

    Science.gov (United States)

    Jorm, Anthony F; Christensen, Helen; Griffiths, Kathleen M; Parslow, Ruth A; Rodgers, Bryan; Blewitt, Kelly A

    2004-10-04

    To review the evidence for the effectiveness of complementary and self-help treatments for anxiety disorders. Systematic literature search using PubMed, PsycLit, and the Cochrane Library. 108 treatments were identified and grouped under the categories of medicines and homoeopathic remedies, physical treatments, lifestyle, and dietary changes. We give a description of the 34 treatments (for which evidence was found in the literature searched), the rationale behind the treatments, a review of studies on effectiveness, and the level of evidence for the effectiveness studies. The treatments with the best evidence of effectiveness are kava (for generalised anxiety), exercise (for generalised anxiety), relaxation training (for generalised anxiety, panic disorder, dental phobia and test anxiety) and bibliotherapy (for specific phobias). There is more limited evidence to support the effectiveness of acupuncture, music, autogenic training and meditation for generalised anxiety; for inositol in the treatment of panic disorder and obsessive-compulsive disorder; and for alcohol avoidance by people with alcohol-use disorders to reduce a range of anxiety disorders.

  5. Cost-effectiveness of pressure-relieving devices for the prevention and treatment of pressure ulcers.

    Science.gov (United States)

    Fleurence, Rachael L

    2005-01-01

    The cost-effectiveness of alternating pressure-relieving devices, mattress replacements, and mattress overlays compared with a standard hospital (high-specification foam mattress) for the prevention and treatment of pressure ulcers in hospital patients in the United Kingdom was investigated. A decision-analytic model was constructed to evaluate different strategies to prevent or treat pressure ulcers. Three scenarios were evaluated: the prevention of pressure ulcers, the treatment of superficial ulcers, and the treatment of severe ulcers. Epidemiological and effectiveness data were obtained from the clinical literature. Expert opinion using a rating scale technique was used to obtain quality of life data. Costs of the devices were obtained from manufacturers, whereas costs of treatment were obtained from the literature. Uncertainty was explored through probabilistic sensitivity analysis. Using 30,000 pounds sterling/QALY (quality-adjusted life year) as the decision-maker's cut off point (the current UK standard), in scenario 1 (prevention), the cost-effective strategy was the mattress overlay at 1, 4, and 12 weeks. In scenarios 2 and 3, the cost-effective strategy was the mattress replacement at 1, 4, and 12 weeks. Standard care was a dominated intervention in all scenarios for values of the decision-maker's ceiling ratio ranging from 5,000 pounds sterling to 100,000 pounds sterling/QALY. However, the probabilistic sensitivity analysis results reflected the high uncertainty surrounding the choice of devices. Current information suggests that alternating pressure mattress overlays may be cost-effective for the prevention of pressure ulcers, whereas alternating pressure mattress replacements appears to be cost-effective for the treatment of superficial and severe pressure ulcers.

  6. Effects of Vitamin D Treatment on Skeletal Muscle Histology and Ultrastructural Changes in a Rodent Model

    Directory of Open Access Journals (Sweden)

    Sobhy M. Yakout

    2012-07-01

    Full Text Available Vitamin D is well known for its role in maintaining calcium and phosphorus homeostasis and in promoting bone mineralization; however, more of its pleiotropic effects have been described recently. The aim of the present investigation was to study the effect of vitamin D treatment on skeletal muscles changes under different dietary conditions using an animal model. Four groups of C57BL/6J mice (n = 11 each were maintained on either low fat diet (LFD or high fat diet ‎‎(HFD with and without 1α,25–dihydroxyvitamin D3 (calcitriol for 16 weeks. Animal weigh was recorded at baseline and then regular intervals, and at the end of the study, skeletal muscle tissues were harvested for the evaluation of the histopathological and ultrastructural changes. When control C57BL/6J mice were fed high-fat diet for 12 weeks, body weight gain was significantly increased compared with mice fed a LFD. (30.2% vs. 8.4%, p < 0.01. There was a significant gradual decrease in the weight of HFD fed mice that were treated with vitamin D as compared with a steady increase in the weights of controls (6.8% vs. 28.7%, p < 0.01. While the LFD group showed some ultrastructural changes, HDF fed on mice showed great muscle structural abnormalities. The whole sarcosome along with its membrane and cristae were severely damaged with scattered myocytes in HFD group. Furthermore, the mitochondria appeared weak and were on the verge of degenerations. The bands were diminished with loss of connections among myofibrils. These changes were attenuated in the HFD group treated with vitamin D with tissues have regained their normal structural appearance. The current findings indicate an important effect of vitamin D on skeletal muscle histology under HFD conditions.

  7. Model of Inclusion Evolution During Calcium Treatment in the Ladle Furnace

    Science.gov (United States)

    Tabatabaei, Yousef; Coley, Kenneth S.; Irons, Gordon A.; Sun, Stanley

    2018-04-01

    Calcium treatment of steel is typically employed to modify alumina inclusions to liquid calcium aluminates. However, injected calcium also reacts with the dissolved sulfur to form calcium sulfide. The current work aims to develop a kinetic model for the evolution of oxide and sulfide inclusions in Al-killed alloyed steel during Ca treatment in the ladle refining process. The model considers dissolution of the calcium from the calcium bubbles into the steel and reduction of calcium oxide in the slag to dissolved calcium. A steel-inclusion kinetic model is used for mass transfer to the inclusion interface and diffusion within the calcium aluminate phases formed on the inclusion. The inclusion-steel kinetic model is then coupled with a previously developed steel-slag kinetic model. The coupled inclusion-steel-slag kinetic model is applied to the chemical composition changes in molten steel, slag, and evolution of inclusions in the ladle. The result of calculations is found to agree well with an industrial heat for species in the steel as well as inclusions during Ca treatment.

  8. 4D radiobiological modelling of the interplay effect in conventionally and hypofractionated lung tumour IMRT.

    Science.gov (United States)

    Selvaraj, J; Uzan, J; Baker, C; Nahum, A

    2015-01-01

    To study the impact of the interplay between respiration-induced tumour motion and multileaf collimator leaf movements in intensity-modulated radiotherapy (IMRT) as a function of number of fractions, dose rate on population mean tumour control probability ([Formula: see text]) using an in-house developed dose model. Delivered dose was accumulated in a voxel-by-voxel basis inclusive of tumour motion over the course of treatment. The effect of interplay on dose and [Formula: see text] was studied for conventionally and hypofractionated treatments using digital imaging and communications in medicine data sets. Moreover, the effect of dose rate on interplay was also studied for single-fraction treatments. Simulations were repeated several times to obtain [Formula: see text] for each plan. The average variation observed in mean dose to the target volumes were -0.76% ± 0.36% for the 20-fraction treatment and -0.26% ± 0.68% and -1.05% ± 0.98% for the three- and single-fraction treatments, respectively. For the 20-fraction treatment, the drop in [Formula: see text] was -1.05% ± 0.39%, whereas for the three- and single-fraction treatments, it was -2.80% ± 1.68% and -4.00% ± 2.84%, respectively. By reducing the dose rate from 600 to 300 MU min(-1) for the single-fraction treatments, the drop in [Formula: see text] was reduced by approximately 1.5%. The effect of interplay on [Formula: see text] is negligible for conventionally fractionated treatments, whereas considerable drop in [Formula: see text] is observed for the three- and single-fraction treatments. Reduced dose rate could be used in hypofractionated treatments to reduce the interplay effect. A novel in silico dose model is presented to determine the impact of interplay effect in IMRT treatments on [Formula: see text].

  9. Cost-Effectiveness of Dolutegravir in HIV-1 Treatment-Experienced (TE Patients in France.

    Directory of Open Access Journals (Sweden)

    Gilles Pialoux

    Full Text Available To evaluate the cost-effectiveness of a new generation integrase inhibitor (INI, dolutegravir (DTG, in France, in treatment-experienced (TE and INI-naïve HIV-infected adults with at least two classes resistance compared to raltegravir (RAL, by adapting previously published Anti-Retroviral Analysis by Monte Carlo Individual Simulation (ARAMIS model.ARAMIS is a microsimulation Markov model with a lifetime time horizon and a monthly cycle length. Health states are defined as with or without opportunistic infection and death. In the initial cohort, efficacy and safety data were derived from a phase III study comparing DTG to RAL. Antiretroviral treatment algorithms, accounting for patient history, were based on French guidelines and experts opinion. Costs are mainly including treatment costs, routine HIV and opportunistic infection care, and death. Utilities depend on CD4+ cell count and the occurrence of opportunistic infections.The ARAMIS model indicates in the TE population that DTG compared to RAL over a life time is associated with 0.35 additional quality-adjusted life years (QALY; 10.75 versus 10.41 and additional costs of €7,266 (€390,001 versus €382,735. DTG increased costs are mainly related to a 9.1-month increase in life expectancy for DTG compared with RAL, and consequently a longer time spent on ART. The incremental cost-effectiveness ratio (ICER for DTG compared with RAL is €21,048 per QALY gained. About 83% and 14% of total lifetime costs are associated with antiretroviral therapy and routine HIV care respectively. Univariate deterministic sensitivity analyses demonstrate the robustness of the model.DTG is cost-effective in the management of TE INI naive patients in France, from a collective perspective. These results could be explained by the superior efficacy of DTG in this population and its higher genetic barrier to resistance compared to RAL. These data need to be confirmed with longer-term real life data.

  10. Generation of synthetic influent data for performing (micro) pollutant wastewater treatment modelling studies

    DEFF Research Database (Denmark)

    Snip, L. J. P.; Aymerich, I.; Flores-Alsina, X.

    2015-01-01

    The use of Activated Sludge Models (ASM) (Henze et al., 2000) is constantly growing and both industry and academia are increasingly applying these tools when performing wastewater treatment plant (WWTP) engineering studies. Besides describing the behaviour of traditional pollutants such as organic...... carbon (C), nitrogen(N) and phosphorus(P), ASM models have been successfully upgraded to predict the fate of different types of micro-pollutants (Benedetti et al., 2013). Indeed, the potential adverse effects of micro-pollutants in aquatic environments have been an object of intensive research during...... (Gernaey et al., 2011). This is an important point since realistic data representing the influent wastewater dynamics are crucial to accomplish any WWTP modelling project (Rieger et al., 2012). For this reason, model-based influent generators/synthetic data are an alternative that has recently gained...

  11. A Multiple Indicators Multiple Causes (MIMIC) model of internal barriers to drug treatment in China.

    Science.gov (United States)

    Qi, Chang; Kelly, Brian C; Liao, Yanhui; He, Haoyu; Luo, Tao; Deng, Huiqiong; Liu, Tieqiao; Hao, Wei; Wang, Jichuan

    2015-03-01

    Although evidence exists for distinct barriers to drug abuse treatment (BDATs), investigations of their inter-relationships and the effect of individual characteristics on the barrier factors have been sparse, especially in China. A Multiple Indicators Multiple Causes (MIMIC) model is applied for this target. A sample of 262 drug users were recruited from three drug rehabilitation centers in Hunan Province, China. We applied a MIMIC approach to investigate the effect of gender, age, marital status, education, primary substance use, duration of primary drug use, and drug treatment experience on the internal barrier factors: absence of problem (AP), negative social support (NSS), fear of treatment (FT), and privacy concerns (PC). Drug users of various characteristics were found to report different internal barrier factors. Younger participants were more likely to report NSS (-0.19, p=0.038) and PC (-0.31, p<0.001). Compared to other drug users, ice users were more likely to report AP (0.44, p<0.001) and NSS (0.25, p=0.010). Drug treatment experiences related to AP (0.20, p=0.012). In addition, differential item functioning (DIF) occurred in three items when participant from groups with different duration of drug use, ice use, or marital status. Individual characteristics had significant effects on internal barriers to drug treatment. On this basis, BDAT perceived by different individuals could be assessed before tactics were utilized to successfully remove perceived barriers to drug treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. The effect of albendazole treatment on seizure outcomes in patients with symptomatic neurocysticercosis.

    Science.gov (United States)

    Romo, Matthew L; Wyka, Katarzyna; Carpio, Arturo; Leslie, Denise; Andrews, Howard; Bagiella, Emilia; Hauser, W Allen; Kelvin, Elizabeth A

    2015-11-01

    Randomized controlled trials have found an inconsistent effect of anthelmintic treatment on long-term seizure outcomes in neurocysticercosis. The objective of this study was to further explore the effect of albendazole treatment on long-term seizure outcomes and to determine if there is evidence for a differential effect by seizure type. In this trial, 178 patients with active or transitional neurocysticercosis cysts and new-onset symptoms were randomized to 8 days of treatment with albendazole (n=88) or placebo (n=90), both with prednisone, and followed for 24 months. We used negative binomial regression and logistic regression models to determine the effect of albendazole on the number of seizures and probability of recurrent or new-onset seizures, respectively, over follow-up. Treatment with albendazole was associated with a reduction in the number of seizures during 24 months of follow-up, but this was only significant for generalized seizures during months 1-12 (unadjusted rate ratio [RR] 0.19; 95% CI: 0.04-0.91) and months 1-24 (unadjusted RR 0.06; 95% CI: 0.01-0.57). We did not detect a significant effect of albendazole on reducing the number of focal seizures or on the probability of having a seizure, regardless of seizure type or time period. Albendazole treatment may be associated with some symptomatic improvement; however, this association seems to be specific to generalized seizures. Future research is needed to identify strategies to better reduce long-term seizure burden in patients with neurocysticercosis. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Neuroimaging in aphasia treatment research: Standards for establishing the effects of treatment

    Science.gov (United States)

    Kiran, Swathi; Ansaldo, Ana; Bastiaanse, Roelien; Cherney, Leora R.; Howard, David; Faroqi-Shah, Yasmeen; Meinzer, Marcus; Thompson, Cynthia K

    2012-01-01

    The goal of this paper is to discuss experimental design options available for establishing the effects of treatment in studies that aim to examine the neural mechanisms associated with treatment-induced language recovery in aphasia, using functional magnetic resonance imaging (fMRI). We present both group and single-subject experimental or case-series design options for doing this and address advantages and disadvantages of each. We also discuss general components of and requirements for treatment research studies, including operational definitions of variables, criteria for defining behavioral change and treatment efficacy, and reliability of measurement. Important considerations that are unique to neuroimaging-based treatment research are addressed, pertaining to the relation between the selected treatment approach and anticipated changes in language processes/functions and how such changes are hypothesized to map onto the brain. PMID:23063559

  14. Neuroinflammatory targets and treatments for epilepsy validated in experimental models.

    Science.gov (United States)

    Aronica, Eleonora; Bauer, Sebastian; Bozzi, Yuri; Caleo, Matteo; Dingledine, Raymond; Gorter, Jan A; Henshall, David C; Kaufer, Daniela; Koh, Sookyong; Löscher, Wolfgang; Louboutin, Jean-Pierre; Mishto, Michele; Norwood, Braxton A; Palma, Eleonora; Poulter, Michael O; Terrone, Gaetano; Vezzani, Annamaria; Kaminski, Rafal M

    2017-07-01

    A large body of evidence that has accumulated over the past decade strongly supports the role of inflammation in the pathophysiology of human epilepsy. Specific inflammatory molecules and pathways have been identified that influence various pathologic outcomes in different experimental models of epilepsy. Most importantly, the same inflammatory pathways have also been found in surgically resected brain tissue from patients with treatment-resistant epilepsy. New antiseizure therapies may be derived from these novel potential targets. An essential and crucial question is whether targeting these molecules and pathways may result in anti-ictogenesis, antiepileptogenesis, and/or disease-modification effects. Therefore, preclinical testing in models mimicking relevant aspects of epileptogenesis is needed to guide integrated experimental and clinical trial designs. We discuss the most recent preclinical proof-of-concept studies validating a number of therapeutic approaches against inflammatory mechanisms in animal models that could represent novel avenues for drug development in epilepsy. Finally, we suggest future directions to accelerate preclinical to clinical translation of these recent discoveries. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  15. Abatacept Treatment Does Not Preserve Renal Function in the Streptozocin-Induced Model of Diabetic Nephropathy.

    Directory of Open Access Journals (Sweden)

    Jenny Norlin

    Full Text Available Diabetic nephropathy (DN is one of the most severe complications of diabetes and remains the largest cause of end-stage renal disease in the Western world. Treatment options are limited and novel therapies that effectively slow disease progression are warranted. Previous work suggested that treatment with CTLA4-Ig (abatacept, a molecule that binds and blocks B7-1 and is licensed for the treatment of rheumatoid arthritis, could ameliorate DN. This study was designed to assess whether B7-1 signalling constitutes a promising therapeutic pathway for DN. Mice injected with streptozotocin (STZ were treated with abatacept and glycemia and renal function were assessed. No differences were found in diabetes progression, albumin excretion rates or albumin/creatine ratios, while mesangial expansion was unaltered at endpoint. Except for increased renal CCL5, treatment did not affect a panel of gene expression endpoints reflecting early fibrotic changes, inflammation and kidney injury. Finally, abatacept treatment effectively reduced the accumulation of activated CD4+ T cells in the kidney, suggesting that renal T cell inflammation is not a driving factor in the pathology of the STZ model. In conjunction with the recent data discounting the expression of B7-1 on podocytes, our present data do not support a role for abatacept in DN treatment.

  16. Finite element modeling of acoustic wave propagation and energy deposition in bone during extracorporeal shock wave treatment

    Science.gov (United States)

    Wang, Xiaofeng; Matula, Thomas J.; Ma, Yong; Liu, Zheng; Tu, Juan; Guo, Xiasheng; Zhang, Dong

    2013-06-01

    It is well known that extracorporeal shock wave treatment is capable of providing a non-surgical and relatively pain free alternative treatment modality for patients suffering from musculoskeletal disorders but do not respond well to conservative treatments. The major objective of current work is to investigate how the shock wave (SW) field would change if a bony structure exists in the path of the acoustic wave. Here, a model of finite element method (FEM) was developed based on linear elasticity and acoustic propagation equations to examine SW propagation and deflection near a mimic musculoskeletal bone. High-speed photography experiments were performed to record cavitation bubbles generated in SW field with the presence of mimic bone. By comparing experimental and simulated results, the effectiveness of FEM model could be verified and strain energy distributions in the bone were also predicted according to numerical simulations. The results show that (1) the SW field will be deflected with the presence of bony structure and varying deflection angles can be observed as the bone shifted up in the z-direction relative to SW geometric focus (F2 focus); (2) SW deflection angels predicted by the FEM model agree well with experimental results obtained from high-speed photographs; and (3) temporal evolutions of strain energy distribution in the bone can also be evaluated based on FEM model, with varied vertical distance between F2 focus and intended target point on the bone surface. The present studies indicate that, by combining MRI/CT scans and FEM modeling work, it is possible to better understand SW propagation characteristics and energy deposition in musculoskeletal structure during extracorporeal shock wave treatment, which is important for standardizing the treatment dosage, optimizing treatment protocols, and even providing patient-specific treatment guidance in clinic.

  17. SARS: systematic review of treatment effects.

    Directory of Open Access Journals (Sweden)

    Lauren J Stockman

    2006-09-01

    Full Text Available BACKGROUND: The SARS outbreak of 2002-2003 presented clinicians with a new, life-threatening disease for which they had no experience in treating and no research on the effectiveness of treatment options. The World Health Organization (WHO expert panel on SARS treatment requested a systematic review and comprehensive summary of treatments used for SARS-infected patients in order to guide future treatment and identify priorities for research. METHODS AND FINDINGS: In response to the WHO request we conducted a systematic review of the published literature on ribavirin, corticosteroids, lopinavir and ritonavir (LPV/r, type I interferon (IFN, intravenous immunoglobulin (IVIG, and SARS convalescent plasma from both in vitro studies and in SARS patients. We also searched for clinical trial evidence of treatment for acute respiratory distress syndrome. Sources of data were the literature databases MEDLINE, EMBASE, BIOSIS, and the Cochrane Central Register of Controlled Trials (CENTRAL up to February 2005. Data from publications were extracted and evidence within studies was classified using predefined criteria. In total, 54 SARS treatment studies, 15 in vitro studies, and three acute respiratory distress syndrome studies met our inclusion criteria. Within in vitro studies, ribavirin, lopinavir, and type I IFN showed inhibition of SARS-CoV in tissue culture. In SARS-infected patient reports on ribavirin, 26 studies were classified as inconclusive, and four showed possible harm. Seven studies of convalescent plasma or IVIG, three of IFN type I, and two of LPV/r were inconclusive. In 29 studies of steroid use, 25 were inconclusive and four were classified as causing possible harm. CONCLUSIONS: Despite an extensive literature reporting on SARS treatments, it was not possible to determine whether treatments benefited patients during the SARS outbreak. Some may have been harmful. Clinical trials should be designed to validate a standard protocol for dosage

  18. The emergence and treatment of anorexia and bulimia nervosa. A comprehensive and practical model.

    Science.gov (United States)

    Blank, Shulamit; Zadik, Zvi; Katz, Inbal; Mahazri, Yemima; Toker, Iris; Barak, Igal

    2002-01-01

    The objective was to propose and describe a new bio-psycho-social model of emergence and maintenance of anorexia nervosa and bulimia nervosa, and demonstrate its application to treatment. An original model, based on literature review and our own clinical experience, was created. Therapeutic guidelines were derived from the theoretical model and applied in the treatment of 97 anorexia and bulimia nervosa patients presented at the eating disorders unit at Kaplan Hospital in Israel over 18 months. A team comprising a pediatrician, a child psychiatrist, a dietician, and trained nurses collaborated in a comprehensive systemic therapeutic approach involving parents, schools, and community agents. Ninety-one girls and six boys were treated in the eating disorder unit (55 had AN, 29 had BN and 13 had EDNOS). Thirty-seven patients were hospitalized and sixty were treated in the outpatient clinic. Mean hospitalization time of the first five patients was 108 days. Mean hospitalization time of the remaining 32 patients was reduced to 32 days. The mean number of outpatient clinic interventions was 12. At the one-year follow up, 74 patients were doing well in all respects. Fourteen patients still needed a lot of supervision in eating. Five are still hospitalized and four were lost to follow up. The proposed model proves to be more than just another theory in that it is successfully applied in treatment. Short systemic therapy is very effective. The longer the delay in drastic, aggressive treatment, the worse the prognosis. Extended hospitalization periods worsen the prognosis. Weakness of the parental unit is a strong indication for inpatient care. The longer the experience in treating eating disorders, the shorter the hospitalization and number of interventions.

  19. Hydraulic modelling of drinking water treatment plant operations

    NARCIS (Netherlands)

    Worm, G.I.M.; Mesman, G.A.M.; Van Schagen, K.M.; Borger, K.J.; Rietveld, L.C.

    2009-01-01

    The flow through a unit of a drinking water treatment plant is one of the most important parameters in terms of a unit's effectiveness. In the present paper, a new EPAnet library is presented with the typical hydraulic elements for drinking water treatment processes well abstraction, rapid sand

  20. Cost effectiveness of Tuberculosis Treatment from the Patients ...

    African Journals Online (AJOL)

    ... Directly Observed Treatment Short course is more cost effective from the patients' point of view. DOTS needs to be re-focused out of the hospitals and clinics and made community based in view of the increasing TB caseload occasioned by HI V/AIDS. Key Words: Cost effectiveness, Tuberculosis treatment, personal cost, ...

  1. Impact of Treatment Integrity on Intervention Effectiveness

    Science.gov (United States)

    Fryling, Mitch J.; Wallace, Michele D.; Yassine, Jordan N.

    2012-01-01

    Treatment integrity has cogent implications for intervention effectiveness. Understanding these implications is an important, but often neglected, undertaking in behavior analysis. This paper reviews current research on treatment integrity in applied behavior analysis. Specifically, we review research evaluating the relation between integrity…

  2. The Cost-Effectiveness of an Intensive Treatment Protocol for Severe Dyslexia in Children

    Science.gov (United States)

    Hakkaart-van Roijen, Leona; Goettsch, Wim G.; Ekkebus, Michel; Gerretsen, Patty; Stolk, Elly A.

    2011-01-01

    Studies of interventions for dyslexia have focused entirely on outcomes related to literacy. In this study, we considered a broader picture assessing improved quality of life compared with costs. A model served as a tool to compare costs and effects of treatment according to a new protocol and care as usual. Quality of life was measured and valued…

  3. Single treatments that have lasting effects: some thoughts on the antidepressant effects of ketamine and botulinum toxin and the anxiolytic effect of psilocybin.

    Science.gov (United States)

    Young, Simon N

    2013-03-01

    Recent clinical trials suggest that 3 single biological treatments have effects that persist. Based on research showing that the muscles involved in facial expressions can feed back to influence mood, a single trial diminishing glabella frown lines with botulinum toxin demonstrated a significant antidepressant effect for 16 weeks. Based primarily on research with animal models of depression suggesting that glutamate may be involved in depression, the N-methyl-D-aspartate antagonist ketamine has been tested in several trials. A single dose decreased depression for up to a week. The reported effects of the use of mushrooms containing psilocybin by a number of cultures around the world has stimulated several trials showing beneficial effects of a single dose of psilocybin for over a year in healthy people, and for up to 3 months in patients with anxiety disorders who have advanced cancer. This article discusses these studies, their rationale, their possible mechanisms of action, the future clinical research required to establish these therapies and the basic research required to optimize single treatments that have lasting effects.

  4. Modelling Potential Consequences of Different Geo-Engineering Treatments for the Baltic Sea Ecosystem

    Science.gov (United States)

    Schrum, C.; Daewel, U.

    2017-12-01

    From 1950 onwards, the Baltic Sea ecosystem suffered increasingly from eutrophication. The most obvious reason for the eutrophication is the huge amount of nutrients (nitrogen and phosphorus) reaching the Baltic Sea from human activities. However, although nutrient loads have been decreasing since 1980, the hypoxic areas have not decreased accordingly. Thus, geo-engineering projects were discussed and evaluated to artificially ventilate the Baltic Sea deep water and suppress nutrient release from the sediments. Here, we aim at understanding the consequences of proposed geo-engineering projects in the Baltic Sea using long-term scenario modelling. For that purpose, we utilize a 3d coupled ecosystem model ECOSMO E2E, a novel NPZD-Fish model approach that resolves hydrodynamics, biogeochemical cycling and lower and higher trophic level dynamics. We performed scenario modelling that consider proposed geo-engineering projects such as artificial ventilation of Baltic Sea deep waters and phosphorus binding in sediments with polyaluminium chlorides. The model indicates that deep-water ventilation indeed suppresses phosphorus release in the first 1-4 years of treatment. Thereafter macrobenthos repopulates the formerly anoxic bottom regions and nutrients are increasingly recycled in the food web. Consequently, overall system productivity and fish biomass increases and toxic algae blooms decrease. However, deep-water ventilation has no long-lasting effect on the ecosystem: soon after completion of the ventilation process, the system turns back into its original state. Artificial phosphorus binding in sediments in contrast decreases overall ecosystem productivity through permanent removal of phosphorus. As expected it decreases bacterial production and toxic algae blooms, but it also decreases fish production substantially. Contrastingly to deep water ventilation, artificial phosphorus binding show a long-lasting effect over decades after termination of the treatment.

  5. Scheduling cisplatin and radiotherapy in the treatment of squamous cell carcinomas of the head and neck: a modelling approach

    International Nuclear Information System (INIS)

    Marcu, L; Bezak, E; Olver, I

    2006-01-01

    The aim of the present work was to implement the kinetics of cisplatin into a previously developed tumour growth model and to simulate the combined cisplatin-radiotherapy treatment with the emphasis on time sequencing and scheduling of drug and radiation. An investigation into whether the effect of cisplatin-radiation is determined by independent cell kill or by cisplatin-produced radiosensitization was also undertaken. It was shown that cisplatin administered before radiation conferred similar tumour control to the post-radiation sequencing of the drug. The killing effect of the combined modality treatment on tumour increased with the increase in cell recruitment. Furthermore, the individual cell kill produced by the two cytotoxins led to an additive only tumour response when the treatments were given concurrently, suggesting that for a synergistic effect, cisplatin must potentiate the effect of radiation, through the radiosensitizing mechanisms addressed in the literature. It was concluded that the optimal timing of cisplatin should be close to radiation. The model showed that daily administration of cisplatin led to a 35% improvement of tumour control as compared to radiation alone, while weekly cisplatin has improved radiotherapy by only 6%

  6. Improvement in latent variable indirect response modeling of multiple categorical clinical endpoints: application to modeling of guselkumab treatment effects in psoriatic patients.

    Science.gov (United States)

    Hu, Chuanpu; Randazzo, Bruce; Sharma, Amarnath; Zhou, Honghui

    2017-10-01

    Exposure-response modeling plays an important role in optimizing dose and dosing regimens during clinical drug development. The modeling of multiple endpoints is made possible in part by recent progress in latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate the level of improvement achievable by jointly modeling two such endpoints in the latent variable IDR modeling framework through the sharing of model parameters. This is illustrated with an application to the exposure-response of guselkumab, a human IgG1 monoclonal antibody in clinical development that blocks IL-23. A Phase 2b study was conducted in 238 patients with psoriasis for which disease severity was assessed using Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA) scores. A latent variable Type I IDR model was developed to evaluate the therapeutic effect of guselkumab dosing on 75, 90 and 100% improvement of PASI scores from baseline and PGA scores, with placebo effect empirically modeled. The results showed that the joint model is able to describe the observed data better with fewer parameters compared with the common approach of separately modeling the endpoints.

  7. Comparison of the Effects of Video Modeling with Narration vs. Video Modeling on the Functional Skill Acquisition of Adolescents with Autism

    Science.gov (United States)

    Smith, Molly; Ayres, Kevin; Mechling, Linda; Smith, Katie

    2013-01-01

    The purpose of this study was to compare the effects of two forms of video modeling: video modeling that includes narration (VMN) and video models without narration (VM) on skill acquisition of four adolescent boys with a primary diagnosis of autism enrolled in an Extended School Year (ESY) summer program. An adapted alternating treatment design…

  8. Cost-effectiveness of available treatment options for patients suffering from severe COPD in the UK: a fully incremental analysis

    Directory of Open Access Journals (Sweden)

    Hertel N

    2012-03-01

    Full Text Available Nadine Hertel1, Robert W Kotchie1, Yevgeniy Samyshkin1, Matthew Radford1, Samantha Humphreys2, Kevin Jameson21IMS Consulting Group, London, UK; 2MSD Ltd, Hoddesdon, UKPurpose: Frequent exacerbations which are both costly and potentially life-threatening are a major concern to patients with chronic obstructive pulmonary disease (COPD, despite the availability of several treatment options. This study aimed to assess the lifetime costs and outcomes associated with alternative treatment regimens for patients with severe COPD in the UK setting.Patients and methods: A Markov cohort model was developed to predict lifetime costs, outcomes, and cost-effectiveness of various combinations of a long-acting muscarinic antagonist (LAMA, a long-acting beta agonist (LABA, an inhaled corticosteroid (ICS, and roflumilast in a fully incremental analysis. Patients willing and able to take ICS, and those refusing or intolerant to ICS were analyzed separately. Efficacy was expressed as relative rate ratios of COPD exacerbation associated with alternative treatment regimens, taken from a mixed treatment comparison. The analysis was conducted from the UK National Health Service (NHS perspective. Parameter uncertainty was explored using one-way and probabilistic sensitivity analysis.Results: Based on the results of the fully incremental analysis a cost-effectiveness frontier was determined, indicating those treatment regimens which represent the most cost-effective use of NHS resources. For ICS-tolerant patients the cost-effectiveness frontier suggested LAMA as initial treatment. Where patients continue to exacerbate and additional therapy is required, LAMA + LABA/ICS can be a cost-effective option, followed by LAMA + LABA/ICS + roflumilast (incremental cost-effectiveness ratio [ICER] versus LAMA + LABA/ICS: £16,566 per quality-adjusted life-year [QALY] gained. The ICER in ICS-intolerant patients, comparing LAMA + LABA + roflumilast versus LAMA + LABA, was £13

  9. Cost-effectiveness analysis of secukinumab for the treatment of active psoriatic arthritis: a Canadian perspective.

    Science.gov (United States)

    Goeree, Ron; Chiva-Razavi, Sima; Gunda, Praveen; Graham, Christopher N; Miles, LaStella; Nikoglou, Efthalia; Jugl, Steffen M; Gladman, Dafna D

    2018-02-01

    The study evaluates the cost-effectiveness of secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, vs currently licensed biologic treatments in patients with active psoriatic arthritis (PsA) from a Canadian healthcare system perspective. A decision analytic semi-Markov model evaluated the cost-effectiveness of secukinumab 150 mg and 300 mg compared to subcutaneous biologics adalimumab, certolizumab pegol, etanercept, golimumab, and ustekinumab, and intravenous biologics infliximab and infliximab biosimilar in biologic-naive and biologic-experienced patients over a lifetime horizon. The response to treatments was evaluated after 12 weeks by PsA Response Criteria (PsARC) response rates. Non-responders or patients discontinuing initial-line of biologic treatment were allowed to switch to subsequent-line biologics. Model input parameters (Psoriasis Area Severity Index [PASI], Health Assessment Questionnaire [HAQ], withdrawal rates, costs, and resource use) were collected from clinical trials, published literature, and other Canadian sources. Benefits were expressed as quality-adjusted life years (QALYs). An annual discount rate of 5% was applied to costs and benefits. The robustness of the study findings were evaluated via sensitivity analyses. Biologic-naive patients treated with secukinumab achieved the highest number of QALYs (8.54) at the lowest cost (CAD 925,387) over a lifetime horizon vs all comparators. Secukinumab dominated all treatments, except for infliximab and its biosimilar, which achieved minimally more QALYs (8.58). However, infliximab and its biosimilar incurred more costs than secukinumab (infliximab: CAD 1,015,437; infliximab biosimilar: CAD 941,004), resulting in higher cost-effectiveness estimates relative to secukinumab. In the biologic-experienced population, secukinumab dominated all treatments as it generated more QALYs (8.89) at lower costs (CAD 954,692). Deterministic sensitivity analyses

  10. Modeling Tolerance Development for the Effect on Heart Rate of the Selective S1P1 Receptor Modulator Ponesimod.

    Science.gov (United States)

    Lott, Dominik; Lehr, Thorsten; Dingemanse, Jasper; Krause, Andreas

    2017-09-15

    Ponesimod is a selective sphingosine-1-phosphate-1 (S1P 1 ) receptor modulator currently under investigation for the treatment of multiple sclerosis. S1P receptor modulators reduce heart rate following treatment initiation. This effect disappears with repeated dosing, enabling development of innovative uptitration regimens to optimize patient safety. There are currently no published pharmacokinetic/pharmacodynamic models describing the heart rate reduction of S1P receptor modulators in humans. The model developed here provides quantification of this effect for ponesimod. A direct-effect I max model with estimated maximum reduction of 45%, tolerance development, and circadian variation best described this effect. The pooled data from nine clinical studies enabled characterization of interindividual variability. The model was used to simulate different treatment regimens to compare the effect of high initial doses vs. gradual uptitration with respect to the occurrence of bradycardia. The results indicate a better safety profile when using gradual uptitration. The model allows studying dosing regimens not clinically tested in silico. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  11. Bayesian informative dropout model for longitudinal binary data with random effects using conditional and joint modeling approaches.

    Science.gov (United States)

    Chan, Jennifer S K

    2016-05-01

    Dropouts are common in longitudinal study. If the dropout probability depends on the missing observations at or after dropout, this type of dropout is called informative (or nonignorable) dropout (ID). Failure to accommodate such dropout mechanism into the model will bias the parameter estimates. We propose a conditional autoregressive model for longitudinal binary data with an ID model such that the probabilities of positive outcomes as well as the drop-out indicator in each occasion are logit linear in some covariates and outcomes. This model adopting a marginal model for outcomes and a conditional model for dropouts is called a selection model. To allow for the heterogeneity and clustering effects, the outcome model is extended to incorporate mixture and random effects. Lastly, the model is further extended to a novel model that models the outcome and dropout jointly such that their dependency is formulated through an odds ratio function. Parameters are estimated by a Bayesian approach implemented using the user-friendly Bayesian software WinBUGS. A methadone clinic dataset is analyzed to illustrate the proposed models. Result shows that the treatment time effect is still significant but weaker after allowing for an ID process in the data. Finally the effect of drop-out on parameter estimates is evaluated through simulation studies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Model for Quantitative Evaluation of Enzyme Replacement Treatment

    Directory of Open Access Journals (Sweden)

    Radeva B.

    2009-12-01

    Full Text Available Gaucher disease is the most frequent lysosomal disorder. Its enzyme replacement treatment was the new progress of modern biotechnology, successfully used in the last years. The evaluation of optimal dose of each patient is important due to health and economical reasons. The enzyme replacement is the most expensive treatment. It must be held continuously and without interruption. Since 2001, the enzyme replacement therapy with Cerezyme*Genzyme was formally introduced in Bulgaria, but after some time it was interrupted for 1-2 months. The dose of the patients was not optimal. The aim of our work is to find a mathematical model for quantitative evaluation of ERT of Gaucher disease. The model applies a kind of software called "Statistika 6" via the input of the individual data of 5-year-old children having the Gaucher disease treated with Cerezyme. The output results of the model gave possibilities for quantitative evaluation of the individual trends in the development of the disease of each child and its correlation. On the basis of this results, we might recommend suitable changes in ERT.

  13. Adult-Onset Fluoxetine Treatment Does Not Improve Behavioral Impairments and May Have Adverse Effects on the Ts65Dn Mouse Model of Down Syndrome

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    Markus Heinen

    2012-01-01

    Full Text Available Down syndrome is caused by triplication of chromosome 21 and is associated with neurocognitive phenotypes ranging from severe intellectual disability to various patterns of more selective neuropsychological deficits, including memory impairments. In the Ts65Dn mouse model of Down syndrome, excessive GABAergic neurotransmission results in local over-inhibition of hippocampal circuits, which dampens hippocampal synaptic plasticity and contributes to cognitive impairments. Treatments with several GABAA receptor antagonists result in increased plasticity and improved memory deficits in Ts65Dn mice. These GABAA receptor antagonists are, however, not suitable for clinical applications. The selective serotonin reuptake inhibitor fluoxetine, in contrast, is a widely prescribed antidepressant that can also enhance plasticity in the adult rodent brain by lowering GABAergic inhibition. For these reasons, we wondered if an adult-onset 4-week oral fluoxetine treatment restores spatial learning and memory impairments in Ts65Dn mice. Fluoxetine did not measurably improve behavioral impairments of Ts65Dn mice. On the contrary, we observed seizures and mortality in fluoxetine-treated Ts65Dn mice, raising the possibility of a drug × genotype interaction with respect to these adverse treatment outcomes. Future studies should re-address this in larger animal cohorts and determine if fluoxetine treatment is associated with adverse treatment effects in individuals with Down syndrome.

  14. Effect of short-term intensive atorvastatin treatment on interventional treatment effect and cardiac function of patients with acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Yu Lei

    2016-06-01

    Full Text Available Objective: To study the effect of short-term intensive atorvastatin treatment on interventional treatment effect and cardiac function of patients with acute coronary syndrome. Methods: A total of 104 cases of patients with acute coronary syndrome who received PCI treatment in Emergency Department of our hospital from May 2014 to November 2015 were retrospectively analyzed and divided into intensive group and routine group according to different atorvastatin treatment methods, and then biochemical indexes, cardiac ultrasound indicators and inflammatory indexes of two groups were compared. Results: Serum TG, TC, LDL-C, hs- CRP, LDH, α-HBDH, CK and CK-MB content of intensive group were significantly lower than those of routine group while HDL-C content was higher than that of routine group; E/ A ratio and LVEF of intensive group were higher than those of routine group while Tei index, systolic index and diastolic index were lower than those of routine group; TLR4 and NF-kB expression levels in peripheral blood as well as TNF-α and IL-6 content in serum of intensive group were significantly lower than those of routine group. Conclusion: Short-term intensive atorvastatin treatment improves the interventional treatment effect of patients with acute coronary syndrome, and can reduce myocardial injury, improve cardiac diastolic and systolic function and inhibit the inflammation mediated by TLR4/NF-kB.

  15. Correlation effects in the Ising model in an external field

    International Nuclear Information System (INIS)

    Borges, H.E.; Silva, P.R.

    1983-01-01

    The thermodynamic properties of the spin-1/2 Ising Model in an external field are evaluated through the use of the exponential differential operator method and Callen's exact relations. The correlations effects are treated in a phenomenological approach and the results are compared with other treatments. (Author) [pt

  16. Protective effect of treatment with thiamine or benfotiamine on liver oxidative damage in rat model of acute ethanol intoxication.

    Science.gov (United States)

    Portari, Guilherme Vannucchi; Ovidio, Paula Payão; Deminice, Rafael; Jordão, Alceu Afonso

    2016-10-01

    The aim of this study was to evaluate possible beneficial effects of treatment with thiamine or benfotiamine in an animal model of acute ethanol intoxication. Thirty male Wistar rats were separated at random into three groups of 10 animals each: Ethanol (E), Ethanol treated with thiamine (T) and Ethanol treated with benfotiamine (BE). Rats were gavaged with single dose of ethanol (5g/kg, 40% v:v). After 30min of ethanol gavage the animals were treated with thiamine or benfotiamine. Six hours after first gavage, the animals were euthanized and blood and liver samples were collected for ethanol and oxidative stress biomarkers quantification. Serum ethanol levels were higher in animals treated with thiamine or benfotiamine while hepatic alcohol levels were higher in animals of the group treated with benfotiamine comparing to controls or thiamine treated groups. The lipid peroxidation biomarkers were diminished for the groups treated with thiamine or benfotiamine comparing to E animals. Concerning protein oxidative damage parameters, they were enhanced for animals treated with benfotiamine in relation to other groups. In conclusion, the treatment with thiamine or benfotiamine even 30min after the massive dose of ethanol has proven to be beneficial against liver damage. Improved results were obtained with benfotiamine in relation to oxidative damage from aqueous compartments. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Treatment Analysis in a Cancer Stem Cell Context Using a Tumor Growth Model Based on Cellular Automata.

    Directory of Open Access Journals (Sweden)

    Ángel Monteagudo

    Full Text Available Cancer can be viewed as an emergent behavior in terms of complex system theory and artificial life, Cellular Automata (CA being the tool most used for studying and characterizing the emergent behavior. Different approaches with CA models were used to model cancer growth. The use of the abstract model of acquired cancer hallmarks permits the direct modeling at cellular level, where a cellular automaton defines the mitotic and apoptotic behavior of cells, and allows for an analysis of different dynamics of the cellular system depending on the presence of the different hallmarks. A CA model based on the presence of hallmarks in the cells, which includes a simulation of the behavior of Cancer Stem Cells (CSC and their implications for the resultant growth behavior of the multicellular system, was employed. This modeling of cancer growth, in the avascular phase, was employed to analyze the effect of cancer treatments in a cancer stem cell context. The model clearly explains why, after treatment against non-stem cancer cells, the regrowth capability of CSCs generates a faster regrowth of tumor behavior, and also shows that a continuous low-intensity treatment does not favor CSC proliferation and differentiation, thereby allowing an unproblematic control of future tumor regrowth. The analysis performed indicates that, contrary to the current attempts at CSC control, trying to make CSC proliferation more difficult is an important point to consider, especially in the immediate period after a standard treatment for controlling non-stem cancer cell proliferation.

  18. Adverse effects of orthodontic treatment: A clinical perspective

    Science.gov (United States)

    Talic, Nabeel F.

    2011-01-01

    Orthodontic treatment is associated with a number of adverse effects, such as root resorption, pain, pulpal changes, periodontal disease, and temporomandibular dysfunction (TMD). Orthodontists should be aware of these effects and associated risk factors. Risk factors linked to root resorption include the duration of treatment, length, and shape of the root, trauma history, habits, and genetic predisposition. PMID:24151415

  19. Chronic melatonin treatment rescues electrophysiological and neuromorphological deficits in a mouse model of Down syndrome.

    Science.gov (United States)

    Corrales, Andrea; Vidal, Rebeca; García, Susana; Vidal, Verónica; Martínez, Paula; García, Eva; Flórez, Jesús; Sanchez-Barceló, Emilio J; Martínez-Cué, Carmen; Rueda, Noemí

    2014-01-01

    The Ts65Dn mouse (TS), the most commonly used model of Down syndrome (DS), exhibits several key phenotypic characteristics of this condition. In particular, these animals present hypocellularity in different areas of their CNS due to impaired neurogenesis and have alterations in synaptic plasticity that compromise their cognitive performance. In addition, increases in oxidative stress during adulthood contribute to the age-related progression of cognitive and neuronal deterioration. We have previously demonstrated that chronic melatonin treatment improves learning and memory and reduces cholinergic neurodegeneration in TS mice. However, the molecular and physiological mechanisms that mediate these beneficial cognitive effects are not yet fully understood. In this study, we analyzed the effects of chronic melatonin treatment on different mechanisms that have been proposed to underlie the cognitive impairments observed in TS mice: reduced neurogenesis, altered synaptic plasticity, enhanced synaptic inhibition and oxidative damage. Chronic melatonin treatment rescued both impaired adult neurogenesis and the decreased density of hippocampal granule cells in trisomic mice. In addition, melatonin administration reduced synaptic inhibition in TS mice by increasing the density and/or activity of glutamatergic synapses in the hippocampus. These effects were accompanied by a full recovery of hippocampal LTP in trisomic animals. Finally, melatonin treatment decreased the levels of lipid peroxidation in the hippocampus of TS mice. These results indicate that the cognitive-enhancing effects of melatonin in adult TS mice could be mediated by the normalization of their electrophysiological and neuromorphological abnormalities and suggest that melatonin represents an effective treatment in retarding the progression of DS neuropathology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Individualized cost-effective conventional ovulation induction treatment in normogonadotrophic anovulatory infertility (WHO group 2).

    Science.gov (United States)

    Eijkemans, Marinus J C; Polinder, Suzanne; Mulders, Annemarie G M G J; Laven, Joop S E; Habbema, J Dik F; Fauser, Bart C J M

    2005-10-01

    Conventional treatment in normogonadotrophic anovulatory infertility (WHO 2) consists of clomiphene citrate (CC), followed by exogenous gonadotrophins (FSH) and IVF. Response to these treatments may be predicted on the basis of individual patient characteristics. We aimed to devise a patient-tailored, cost-effective treatment algorithm involving the above-mentioned treatment modalities, based on individual patient characteristics. Sixteen prognostic groups are defined, according to the presence or absence of: age >30 years, amenorrhea, elevated androgen levels and obesity. The chances of response with each of the three treatments were calculated using prediction models. Treatment costs were based on the data of 240 patients visiting a specialist academic fertility unit. Outcome was an ongoing pregnancy within 12 months after initiation of treatment. The costs per pregnancy of three different strategies were compared, with a threshold for cost-effectiveness of 10 000. The strategy CC + FSH + IVF compared with FSH + IVF generated more pregnancies against lower costs. Compared with CC + IVF, it also produced more pregnancies, but at higher costs. For costs per pregnancy were less than 10 000. For women >30 years old, costs per pregnancy were 25 000 and over 200 000, when presenting with normal or elevated androgen levels, respectively. The conventional treatment protocol is efficient for women aged 30 years old with elevated androgen levels, FSH may be skipped.

  1. Can modeling of HIV treatment processes improve outcomes? Capitalizing on an operations research approach to the global pandemic

    Directory of Open Access Journals (Sweden)

    Hollingsworth Eric B

    2008-08-01

    Full Text Available Abstract Background Mathematical modeling has been applied to a range of policy-level decisions on resource allocation for HIV care and treatment. We describe the application of classic operations research (OR techniques to address logistical and resource management challenges in HIV treatment scale-up activities in resource-limited countries. Methods We review and categorize several of the major logistical and operational problems encountered over the last decade in the global scale-up of HIV care and antiretroviral treatment for people with AIDS. While there are unique features of HIV care and treatment that pose significant challenges to effective modeling and service improvement, we identify several analogous OR-based solutions that have been developed in the service, industrial, and health sectors. Results HIV treatment scale-up includes many processes that are amenable to mathematical and simulation modeling, including forecasting future demand for services; locating and sizing facilities for maximal efficiency; and determining optimal staffing levels at clinical centers. Optimization of clinical and logistical processes through modeling may improve outcomes, but successful OR-based interventions will require contextualization of response strategies, including appreciation of both existing health care systems and limitations in local health workforces. Conclusion The modeling techniques developed in the engineering field of operations research have wide potential application to the variety of logistical problems encountered in HIV treatment scale-up in resource-limited settings. Increasing the number of cross-disciplinary collaborations between engineering and public health will help speed the appropriate development and application of these tools.

  2. Reconstruction versus conservative treatment after rupture of the anterior cruciate ligament: cost effectiveness analysis

    Directory of Open Access Journals (Sweden)

    Farshad Mazda

    2011-11-01

    Full Text Available Abstract Background The decision whether to treat conservatively or reconstruct surgically a torn anterior cruciate ligament (ACL is an ongoing subject of debate. The high prevalence and associated public health burden of torn ACL has led to continuous efforts to determine the best therapeutic approach. A critical evaluation of benefits and expenditures of both treatment options as in a cost effectiveness analysis seems well-suited to provide valuable information for treating physicians and healthcare policymakers. Methods A literature review identified four of 7410 searched articles providing sufficient outcome probabilities for the two treatment options for modeling. A transformation key based on the expert opinions of 25 orthopedic surgeons was used to derive utilities from available evidence. The cost data for both treatment strategies were based on average figures compiled by Orthopaedic University Hospital Balgrist and reinforced by Swiss national statistics. A decision tree was constructed to derive the cost-effectiveness of each strategy, which was then tested for robustness using Monte Carlo simulation. Results Decision tree analysis revealed a cost effectiveness of 16,038 USD/0.78 QALY for ACL reconstruction and 15,466 USD/0.66 QALY for conservative treatment, implying an incremental cost effectiveness of 4,890 USD/QALY for ACL reconstruction. Sensitivity analysis of utilities did not change the trend. Conclusion ACL reconstruction for reestablishment of knee stability seems cost effective in the Swiss setting based on currently available evidence. This, however, should be reinforced with randomized controlled trials comparing the two treatment strategies.

  3. Effect of chronic treatment with a cyclooxygenase inhibitor on reproductive parameters in male rat

    International Nuclear Information System (INIS)

    Saeed, S.A.; Anwar, N.; Khan, K.M.; Sarfraz, N.

    2009-01-01

    Indomethacin is a member of non-steroidal anti-inflammatory drugs (NSAIDs) commonly used for treatment of gout, arthritis, and other inflammatory conditions. It has been shown to inhibit ovarian prostaglandins synthesis in mammals, birds, fish and reptiles. However, the effects of its chronic administration on male reproductive functions remain largely unknown. Using rat as a model, we studied the effect of chronic treatment with indomethacin on the male reproductive system. Methods: Testosterone was measured in the serum, testicular tissue, and testicular interstitial fluid by radioimmunoassay. Moreover, we also studied the direct effect of indomethacin in vitro on luteinizing hormone stimulated testosterone secretion from the Leydig cells isolated from various treatment groups. Results: Indomethacin treatment for 50 days caused a significant but reversible decrease in prostate weight, epididymal sperm reserves and sperm motility score compared with control rats (p<0.05). In vitro stimulation of Leydig cells isolated from treated rat's testes with luteinizing hormone (250 mu IU) produced significantly reduced testosterone compared with cells from control groups (p<0.05). Furthermore, stimulatory effect of luteinizing hormone on the control Leydig cells was significantly reduced when these cells were challenged with luteinizing hormone in the presence of indomethacin, (p<0.05). Testosterone concentration in the testicular tissue and testicular interstitial fluid reduced after indomethacin treatment (p<0.05). Conclusion: Due to its significant inhibition of key reproductive hormones, indomethacin effectively inhibits reproductive functions if used on a long-term basis. In his study, we have identified potential risks in the long-term use of cyclooxygenase inhibitors. (author)

  4. Model of mechanical properties change of steel during rolling with use of hightemperature thermomechanical treatment

    International Nuclear Information System (INIS)

    Zhadan, V.T.; Gubenko, V.T.; Bernshtejn, M.L.; Binarskij, M.S.

    1975-01-01

    A mathematical model is proposed of changes in the mechanical properties of the steel-50KHGA in the process of rolling with application of a high-temperature thermomechanical treatment (HTTMT). The model accounts for all the main particularities of the structure formation processes during a high temperature deformation of metals and alloys. The nonmonotonic dependence of the steel mechanical properties on the deformation velocity can be presented as a result of a summary effect of three parallel processes on the formation of these properties: hot working, softening and substructural hardening. The mathematical model has been constructed by the iteration method

  5. Development and assessment of an integrated ecological modelling framework to assess the effect of investments in wastewater treatment on water quality.

    Science.gov (United States)

    Holguin-Gonzalez, Javier E; Boets, Pieter; Everaert, Gert; Pauwels, Ine S; Lock, Koen; Gobeyn, Sacha; Benedetti, Lorenzo; Amerlinck, Youri; Nopens, Ingmar; Goethals, Peter L M

    2014-01-01

    Worldwide, large investments in wastewater treatment are made to improve water quality. However, the impacts of these investments on river water quality are often not quantified. To assess water quality, the European Water Framework Directive (WFD) requires an integrated approach. The aim of this study was to develop an integrated ecological modelling framework for the River Drava (Croatia) that includes physical-chemical and hydromorphological characteristics as well as the ecological river water quality status. The developed submodels and the integrated model showed accurate predictions when comparing the modelled results to the observations. Dissolved oxygen and nitrogen concentrations (ammonium and organic nitrogen) were the most important variables in determining the ecological water quality (EWQ). The result of three potential investment scenarios of the wastewater treatment infrastructure in the city of Varaždin on the EWQ of the River Drava was assessed. From this scenario-based analysis, it was concluded that upgrading the existing wastewater treatment plant with nitrogen and phosphorus removal will be insufficient to reach a good EWQ. Therefore, other point and diffuse pollution sources in the area should also be monitored and remediated to meet the European WFD standards.

  6. Evaluating the cost effectiveness of donepezil in the treatment of Alzheimer's disease in Germany using discrete event simulation

    Directory of Open Access Journals (Sweden)

    Hartz Susanne

    2012-02-01

    Full Text Available Abstract Background Previous cost-effectiveness studies of cholinesterase inhibitors have modeled Alzheimer's disease (AD progression and treatment effects through single or global severity measures, or progression to "Full Time Care". This analysis evaluates the cost-effectiveness of donepezil versus memantine or no treatment in Germany by considering correlated changes in cognition, behavior and function. Methods Rates of change were modeled using trial and registry-based patient level data. A discrete event simulation projected outcomes for three identical patient groups: donepezil 10 mg, memantine 20 mg and no therapy. Patient mix, mortality and costs were developed using Germany-specific sources. Results Treatment of patients with mild to moderately severe AD with donepezil compared to no treatment was associated with 0.13 QALYs gained per patient, and 0.01 QALYs gained per caregiver and resulted in average savings of €7,007 and €9,893 per patient from the healthcare system and societal perspectives, respectively. In patients with moderate to moderately-severe AD, donepezil compared to memantine resulted in QALY gains averaging 0.01 per patient, and savings averaging €1,960 and €2,825 from the healthcare system and societal perspective, respectively. In probabilistic sensitivity analyses, donepezil dominated no treatment in most replications and memantine in over 70% of the replications. Donepezil leads to savings in 95% of replications versus memantine. Conclusions Donepezil is highly cost-effective in patients with AD in Germany, leading to improvements in health outcomes and substantial savings compared to no treatment. This holds across a variety of sensitivity analyses.

  7. Sclerostin antibody treatment improves the bone phenotype of Crtap−/− mice, a model of recessive Osteogenesis Imperfecta

    Science.gov (United States)

    Grafe, Ingo; Alexander, Stefanie; Yang, Tao; Lietman, Caressa; Homan, Erica P; Munivez, Elda; Chen, Yuqing; Jiang, Ming Ming; Bertin, Terry; Dawson, Brian; Asuncion, Franklin; Ke, Hua Zhu; Ominsky, Michael S; Lee, Brendan

    2016-01-01

    Osteogenesis Imperfecta (OI) is characterized by low bone mass, poor bone quality and fractures. Standard treatment for OI patients is limited to bisphosphonates, which only incompletely correct the bone phenotype, and seem to be less effective in adults. Sclerostin neutralizing antibodies (Scl-Ab) have been shown to be beneficial in animal models of osteoporosis, and dominant OI resulting from mutations in the genes encoding type I collagen. However, Scl-Ab treatment has not been studied in models of recessive OI. Cartilage associated protein (CRTAP) is involved in posttranslational type I collagen modification, and its loss of function results in recessive OI. In this study, we treated 1 and 6 week old Crtap−/− mice with Scl-Ab for 6 weeks (25 mg/kg, s.c., twice per week), to determine the effects on the bone phenotype in models of “pediatric” and “young adult” recessive OI. Vehicle treated Crtap−/− and wildtype (WT) mice served as controls. Compared with control Crtap−/− mice, microCT analyses showed significant increases in bone volume and improved trabecular microarchitecture in Scl-Ab treated Crtap−/− mice in both age cohorts, in both vertebrae and femurs. Additionally, Scl-Ab improved femoral cortical parameters in both age cohorts. Biomechanical testing showed that Scl-Ab improved parameters of whole bone strength in Crtap−/− mice, with more robust effects in the week 6–12 cohort, but did not affect the increased bone brittleness. Additionally, Scl-Ab normalized the increased osteoclast numbers, stimulated bone formation rate (week 6–12 cohort only), but did not affect osteocyte density. Overall, our findings suggest that Scl-Ab treatment may be beneficial in the treatment of recessive OI caused by defects in collagen post-translational modification. PMID:26716893

  8. A discrete event modelling framework for simulation of long-term outcomes of sequential treatment strategies for ankylosing spondylitis.

    Science.gov (United States)

    Tran-Duy, An; Boonen, Annelies; van de Laar, Mart A F J; Franke, Angelinus C; Severens, Johan L

    2011-12-01

    To develop a modelling framework which can simulate long-term quality of life, societal costs and cost-effectiveness as affected by sequential drug treatment strategies for ankylosing spondylitis (AS). Discrete event simulation paradigm was selected for model development. Drug efficacy was modelled as changes in disease activity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) and functional status (Bath Ankylosing Spondylitis Functional Index (BASFI)), which were linked to costs and health utility using statistical models fitted based on an observational AS cohort. Published clinical data were used to estimate drug efficacy and time to events. Two strategies were compared: (1) five available non-steroidal anti-inflammatory drugs (strategy 1) and (2) same as strategy 1 plus two tumour necrosis factor α inhibitors (strategy 2). 13,000 patients were followed up individually until death. For probability sensitivity analysis, Monte Carlo simulations were performed with 1000 sets of parameters sampled from the appropriate probability distributions. The models successfully generated valid data on treatments, BASDAI, BASFI, utility, quality-adjusted life years (QALYs) and costs at time points with intervals of 1-3 months during the simulation length of 70 years. Incremental cost per QALY gained in strategy 2 compared with strategy 1 was €35,186. At a willingness-to-pay threshold of €80,000, it was 99.9% certain that strategy 2 was cost-effective. The modelling framework provides great flexibility to implement complex algorithms representing treatment selection, disease progression and changes in costs and utilities over time of patients with AS. Results obtained from the simulation are plausible.

  9. Identifying cost-effective treatment with raloxifene in postmenopausal women using risk algorithms for fractures and invasive breast cancer.

    Science.gov (United States)

    Ivergård, M; Ström, O; Borgström, F; Burge, R T; Tosteson, A N A; Kanis, J

    2010-11-01

    The National Osteoporosis Foundation (NOF) recommends considering treatment in women with a 20% or higher 10-year probability of a major fracture. However, raloxifene reduces both the risk of vertebral fractures and invasive breast cancer so that raloxifene treatment may be clinically appropriate and cost-effective in women who do not meet a 20% threshold risk. The aim of this study was to identify cost-effective scenarios of raloxifene treatment compared to no treatment in younger postmenopausal women at increased risk of invasive breast cancer and fracture risks below 20%. A micro-simulation model populated with data specific to American Caucasian women was used to quantify the costs and benefits of 5-year raloxifene treatment. The population evaluated was selected based on 10-year major fracture probability as estimated with FRAX® being below 20% and 5-year invasive breast cancer risk as estimated with the Gail risk model ranging from 1% to 5%. The cost per QALY gained ranged from US $22,000 in women age 55 with 5% invasive breast cancer risk and 15-19.9% fracture probability, to $110,000 in women age 55 with 1% invasive breast cancer risk and 5-9.9% fracture probability. Raloxifene was progressively cost-effective with increasing fracture risk and invasive breast cancer risk for a given age cohort. At lower fracture risk in combination with lower invasive breast cancer risk or when no preventive raloxifene effect on invasive breast cancer was assumed, the cost-effectiveness of raloxifene worsened markedly and was not cost-effective given a willingness-to-pay of US $50,000. At fracture risk of 15-19.9% raloxifene was cost-effective also in women at lower invasive breast cancer risk. Raloxifene is potentially cost-effective in cohorts of young postmenopausal women, who do not meet the suggested NOF 10-year fracture risk threshold. The cost-effectiveness is contingent on their 5-year invasive breast cancer risk. The result highlights the importance of considering

  10. A support system in virtual reality for effective hyperthermia treatments. Heating properties of needle applicator for brain tumors

    International Nuclear Information System (INIS)

    Shindo, Yasuhiro; Iseki, Yuya; Nakane, Kazuya; Mimoto, Naoki; Kubo, Mitsunori; Kato, Kazuo; Takahashi, Hideaki; Uzuka, Takeo; Fujii, Yukihiko

    2011-01-01

    This paper describes the effectiveness of the developed simulator system for performing an effective hyperthermia treatment with a needle applicator in virtual reality (VR). The human brain is protected by the skull, which makes it difficult to non-invasively heat deep brain tumors with electromagnetic energy. Generally, needle applicators were used in clinical practice to heat brain tumors. However, some problems exist. One is that this heating method has a small heating area around the needle. In order to expand the heating area of a needle applicator, we developed a new type of needle applicator made from a shape memory alloy (SMA). The thermal properties of the SMA were checked experimentally using the developed heating system. As a result, the proposed needle applicator made of SMA is useful to create a wider heating area inside a tumor. Another problem is that medical doctors find it difficult to put a needle applicator into a target point inside of tumors. Therefore, a support system for performing an effective hyperthermia treatment is required in the clinic. In this paper, first, we constructed an anatomical 3-D model from magnetic resonance imaging (MRI) and X-ray computed tomography (CT) images by using 3-D computer aided design (CAD) software. Second, we presented the finite element method (FEM) model which is divided into non-linear elements on 3-D computer graphics (CG). Finally, we calculated temperature distributions using the 3-D FEM model with blood perfusion during hyperthermia treatments. From these results, it was found that the proposed VR system is effective for performing hyperthermia treatments. (author)

  11. Observations on the Prevalence, Characteristics, and Effects of Self-Treatment

    Directory of Open Access Journals (Sweden)

    Shuangge eMa

    2016-04-01

    Full Text Available Aims: When facing illness, a person may choose self-treatment as an alternative to hospital (and primary care-based treatment. Despite its important role in healthcare, the study on self-treatment remains limited. The goal is to collectively report the observations in the literature on the prevalence, characteristics, and effects of self-treatment.Methods: Extensive literature search was conducted, and relevant information was extracted.Results: Published studies have reported that in some regions, the prevalence of self-treatment is high and varies across illness conditions and treatment approaches. Self-medication is the most popular self-treatment approach. Multiple regional, demographic, personal, cultural and religious factors have been implicated in the pursuit of self-treatment. In addition, accessibility of healthcare also plays a role. Self-treatment in general has a positive clinical and financial effect. However there have been concerns on abuse and possible negative effects. Conclusions: This article reviews observations made in recent studies on several important aspects of self-treatment. Comprehensive and systematic study is still lacking. Interventions are needed to solve several problems associated with self-treatment.

  12. Modeling the effects of different fuel treatment mosaics on wildfire spread and behavior in a Mediterranean agro-pastoral area.

    Science.gov (United States)

    Salis, Michele; Del Giudice, Liliana; Arca, Bachisio; Ager, Alan A; Alcasena-Urdiroz, Fermin; Lozano, Olga; Bacciu, Valentina; Spano, Donatella; Duce, Pierpaolo

    2018-04-15

    Wildfire spread and behavior can be limited by fuel treatments, even if their effects can vary according to a number of factors including type, intensity, extension, and spatial arrangement. In this work, we simulated the response of key wildfire exposure metrics to variations in the percentage of treated area, treatment unit size, and spatial arrangement of fuel treatments under different wind intensities. The study was carried out in a fire-prone 625 km 2 agro-pastoral area mostly covered by herbaceous fuels, and located in Northern Sardinia, Italy. We constrained the selection of fuel treatment units to areas covered by specific herbaceous land use classes and low terrain slope (post-treatment wildfire behavior by the Minimum Travel Time (MTT) fire spread algorithm. The simulations replicated a set of southwestern wind speed scenarios (16, 24 and 32 km h -1 ) and the driest fuel moisture conditions observed in the study area. Our results showed that fuel treatments implemented near the existing road network were significantly more efficient than the other alternatives, and this difference was amplified at the highest wind speed. Moreover, the largest treatment unit sizes were the most effective in containing wildfire growth. As expected, increasing the percentage of the landscape treated and reducing wind speed lowered fire exposure profiles for all fuel treatment alternatives, and this was observed at both the landscape scale and for highly valued resources. The methodology presented in this study can support the design and optimization of fuel management programs and policies in agro-pastoral areas of the Mediterranean Basin and herbaceous type landscapes elsewhere, where recurrent grassland fires pose a threat to rural communities, farms and infrastructures. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. The effectiveness of crisis resolution/home treatment teams for older people with mental health problems: a systematic review and scoping exercise.

    Science.gov (United States)

    Toot, Sandeep; Devine, Mike; Orrell, Martin

    2011-12-01

    To assess the effectiveness of crisis resolution/home treatment services for older people with mental health problems. A systematic review was conducted to report on the effectiveness of crisis resolution/home treatment teams (CRHTTs) for older people with mental health problems. As part of the review, we also carried out a scoping exercise to assess the typologies of older people's CRHTTs in practice, and to review these in the context of policy and research findings. The literature contains Grade C evidence, according to the Oxford Centre of Evidence Based Medicine (CEBM) guidelines, that CRHTTs are effective in reducing numbers of admissions to hospitals. Outcomes such as length of hospital stay and maintenance of community residence were reviewed but evidence was inadequate for drawing conclusions. The scoping exercise defined three types of home treatment service model: generic home treatment teams; specialist older adults home treatment teams; and intermediate care services. These home treatment teams seemed to be effectively managing crises and reducing admissions. This review has shown a lack of evidence for the efficacy of crisis resolution/home treatment teams in supporting older people with mental health problems to remain at home. There is clearly a need for a randomised controlled trial to establish the efficacy of crisis resolution/home treatment services for older people with mental health problems, as well as a more focussed assessment of the different home treatment service models which have developed in the UK. Copyright © 2011 John Wiley & Sons, Ltd.

  14. Gingival enlargement in orthodontic patients: Effect of treatment duration.

    Science.gov (United States)

    Pinto, Alice Souza; Alves, Luana Severo; Zenkner, Júlio Eduardo do Amaral; Zanatta, Fabrício Batistin; Maltz, Marisa

    2017-10-01

    In this study, we aimed to assess the effect of the duration of fixed orthodontic treatment on gingival enlargement (GE) in adolescents and young adults. The sample consisted of 260 subjects (ages, 10-30 years) divided into 4 groups: patients with no fixed orthodontic appliances (G0) and patients undergoing orthodontic treatment for 1 year (G1), 2 years (G2), or 3 years (G3). Participants completed a structured questionnaire on sociodemographic characteristics and oral hygiene habits. Clinical examinations were conducted by a calibrated examiner and included the plaque index, the gingival index, and the Seymour index. Poisson regression models were used to assess the association between group and GE. We observed increasing means of plaque, gingivitis, and GE in G0, G1, and G2. No significant differences were observed between G2 and G3. Adjusted Poisson regression analysis showed that patients undergoing orthodontic treatment had a 20 to 28-fold increased risk for GE than did those without orthodontic appliances (G1, rate ratio [RR] = 20.2, 95% CI = 9.0-45.3; G2, RR = 27.0, 95% CI = 12.1-60.3; G3 = 28.1; 95% CI = 12.6-62.5). The duration of orthodontic treatment significantly influenced the occurrence of GE. Oral hygiene instructions and motivational activities should target adolescents and young adults undergoing orthodontic treatment. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

  15. Greater expectations: using hierarchical linear modeling to examine expectancy for treatment outcome as a predictor of treatment response.

    Science.gov (United States)

    Price, Matthew; Anderson, Page; Henrich, Christopher C; Rothbaum, Barbara Olasov

    2008-12-01

    A client's expectation that therapy will be beneficial has long been considered an important factor contributing to therapeutic outcomes, but recent empirical work examining this hypothesis has primarily yielded null findings. The present study examined the contribution of expectancies for treatment outcome to actual treatment outcome from the start of therapy through 12-month follow-up in a clinical sample of individuals (n=72) treated for fear of flying with either in vivo exposure or virtual reality exposure therapy. Using a piecewise hierarchical linear model, outcome expectancy predicted treatment gains made during therapy but not during follow-up. Compared to lower levels, higher expectations for treatment outcome yielded stronger rates of symptom reduction from the beginning to the end of treatment on 2 standardized self-report questionnaires on fear of flying. The analytic approach of the current study is one potential reason that findings contrast with prior literature. The advantages of using hierarchical linear modeling to assess interindividual differences in longitudinal data are discussed.

  16. Effects of ionic strength and ion pairing on (plant-wide) modelling of anaerobic digestion

    DEFF Research Database (Denmark)

    Solon, Kimberly; Flores Alsina, Xavier; Mbamba, Christian Kazadi

    2015-01-01

    Plant-wide models of wastewater treatment (such as the Benchmark Simulation Model No. 2 or BSM2) are gaining popularity for use in holistic virtual studies of treatment plant control and operations. The objective of this study is to show the influence of ionic strength (as activity corrections....... The paper describes: 1) how the anaerobic digester performance is affected by physico-chemical corrections; 2) the effect on pH and the anaerobic digestion products (CO2, CH4 and H2); and, 3) how these variations are propagated from the sludge treatment to the water line. Results at high ionic strength...

  17. Vocational Training for Prison Inmates: A Treatment Model.

    Science.gov (United States)

    Uche, Greg N.

    1995-01-01

    Components of a treatment model are diagnosis of offenders' work history and training needs, in relation to labor market requirements; provision of appropriate job and entrepreneurial skills; and after care services. Focus is on vocational adjustment to ensure successful rehabilitation. (SK)

  18. Extending the linear model with R generalized linear, mixed effects and nonparametric regression models

    CERN Document Server

    Faraway, Julian J

    2005-01-01

    Linear models are central to the practice of statistics and form the foundation of a vast range of statistical methodologies. Julian J. Faraway''s critically acclaimed Linear Models with R examined regression and analysis of variance, demonstrated the different methods available, and showed in which situations each one applies. Following in those footsteps, Extending the Linear Model with R surveys the techniques that grow from the regression model, presenting three extensions to that framework: generalized linear models (GLMs), mixed effect models, and nonparametric regression models. The author''s treatment is thoroughly modern and covers topics that include GLM diagnostics, generalized linear mixed models, trees, and even the use of neural networks in statistics. To demonstrate the interplay of theory and practice, throughout the book the author weaves the use of the R software environment to analyze the data of real examples, providing all of the R commands necessary to reproduce the analyses. All of the ...

  19. Parent perspectives on information about late effects of childhood cancer treatment and their role in initial treatment decision making.

    Science.gov (United States)

    Greenzang, Katie A; Dauti, Angela; Mack, Jennifer W

    2018-06-01

    Though most childhood cancer survivors experience late effects of treatment, we know little about parent preferences for late effects information during therapy, or how parents weigh late effects when making treatment decisions. Our objective was to explore how parents of children with cancer consider late effects in initial treatment decision making and during active cancer treatment. Semistructured interviews were conducted with 12 parents of children with cancer who were actively receiving treatment at Dana-Farber/Boston Children's Cancer and Blood Disorders Center. Interviews were audio-recorded, transcribed verbatim, and qualitatively analyzed using thematic analysis. Ten of 12 parents reported that they had to decide between two or more treatment options for their child's cancer. Of those, 50% (5/10) considered late effects to be an important factor in their decision making. Most parents wanted early and detailed information about their child's risk of late effects to make treatment decisions and to feel prepared for the future. However, a few parents felt too overwhelmed to focus on late effects at diagnosis. While many recalled extensive late effects information in informed consent discussions, some parents felt these issues were minimally addressed. Parents desire detailed information about late effects to make informed treatment decisions and prepare for the future. Despite the role of late effects in treatment decision making, some parents feel that late effects are either inadequately addressed or too overwhelming to process at diagnosis. Parents may benefit from early assessment of their information needs and a return to these issues over time. © 2018 Wiley Periodicals, Inc.

  20. The modelling of health effects in COSYMA

    International Nuclear Information System (INIS)

    Ehrhardt, J.; Steinhauer, C.

    1991-01-01

    The presentation gives a brief overview of the types of health effects considered in each of the three subsystems of COSYMA, the way that the corresponding models are implemented and their present default parameter values. The risk of early effects is calculated using hazard functions, as recently recommended by US Nuclear Regulatory Commission and NRPB. The early fatal effects specified in COSYMA comprise those following the irradiation of the bone marrow (hematopoietic syndrome), the lung (pulmonary syndrome), the GI-tract (gastrointestinal syndrome) and skin (skin burns). In addition the mortality of pre-and neonates after exposure in utero is quantified. Of the possible non-fatal effects the only ones included are those which lead to a severe disability of the affected person for the rest of their life or which require medical treatment and/or social care