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At least 685 records · Page 38Linked to original sources
PubMed2006

Reduction of carry-over in column-switching HPLC/MS system with automated system washing procedure for highly sensitive direct analysis of donepezil in dog plasma.

To solve the problem of carry-over--a persistent chromatographic challenge for bioanalytical assays with highly sensitive detector such as a mass spectrometry (MS)--a new on-line sample pretreatment HPLC/MS system using a column-switching technique was established. This system was designed to reduce carry-over based on a hydrophobic interaction mechanism using a washing function (multi-mobile phase flow system), as well as to remove impurities on-line in a mobile phase for the pretreatment. As a result, a washing function in this system was enabled to reduce carry-over and to remove impurities in a mobile phase by automatic operation. Therefore, concentration levels of donepezil (DH) in dog plasma as low as 10 pg/mL could be determined using this on-line sample pretreatment HPLC/MS system. In addition, method validation results of specificity, linearity, accuracy, precision, lower limit of quantitation (LLOQ), and carry-over demonstrated that this on-line sample pretreatment HPLC/MS system was robust and valid as a practical assay of drugs and metabolites in the biological samples.

Animals↗
PubMed2004

Sensitive PCR analysis of animal tissue samples for fragments of endogenous and transgenic plant DNA.

An optimized DNA extraction protocol for animal tissues coupled with sensitive PCR methods was used to determine whether trace levels of feed-derived DNA fragments, plant and/or transgenic, are detectable in animal tissue samples including dairy milk and samples of muscle (meat) from chickens, swine, and beef steers. Assays were developed to detect DNA fragments of both the high copy number chloroplast-encoded maize rubisco gene (rbcL) and single copy nuclear-encoded transgenic elements (p35S and a MON 810-specific gene fragment). The specificities of the two rbcL PCR assays and two transgenic DNA PCR assays were established by testing against a range of conventional plant species and genetically modified maize crops. The sensitivities of the two rbcL PCR assays (resulting in 173 and 500 bp amplicons) were similar, detecting as little as 0.08 and 0.02 genomic equivalents, respectively. The sensitivities of the p35S and MON 810 PCR assays were approximately 5 and 10 genomic equivalents for 123 bp and 149 bp amplicons, respectively, which were considerably less than the sensitivity of the rbcL assays in terms of plant cell equivalents, but approximately similar when the higher numbers of copies of the chloroplast genome per cell are taken into account. The 173 bp rbcL assay detected the target plant chloroplast DNA fragment in 5%, 15%, and 53% of the muscle samples from beef steers, broiler chickens, and swine, respectively, and in 86% of the milk samples from dairy cows. Reanalysis of new aliquots of 31 of the pork samples that were positive in the 173 bp rbcL PCR showed that 58% of these samples were reproducibly positive in this same PCR assay. The 500 bp rbcL assay detected DNA fragments in 43% of the swine muscle samples and 79% of the milk samples. By comparison, no statistically significant detections of transgenic DNA fragments by the p35S PCR assay occurred with any of these animal tissue samples.

Animal Feed↗
PubMed2003

The cost of microwave endometrial ablation under different anaesthetic and clinical settings.

OBJECTIVE: To compare the costs of microwave endometrial ablation under local anaesthetic and general anaesthetic in an operating theatre and to estimate the cost of performing treatment under local anaesthetic in a dedicated clinic setting. DESIGN: The costing study was undertaken alongside a randomised controlled trial comparing the acceptability of microwave endometrial ablation using local versus general anaesthetic in a theatre setting. SETTING: Department of Gynaecology, Aberdeen Royal Infirmary, Scotland. SAMPLES: One hundred and twenty-seven women undergoing microwave endometrial ablation who had been randomly allocated to general or local anaesthetic. METHODS: Health and non-health service resource use was recorded prospectively. Data on resource use were combined with unit costs estimated using standardised methods to determine the cost per patient for microwave endometrial ablation under local or general anaesthetic in theatre. A model was developed to estimate the health service cost of microwave endometrial ablation under local anaesthetic in a clinic setting. MAIN OUTCOME MEASURES: Health and non-health service costs. RESULTS: There was little difference in cost when treatments were performed under local or general anaesthetic in theatre. The median health and non-health cost of microwave endometrial ablation was 440 pounds and 120 pounds, respectively, under general anaesthetic and 428 pounds and 125 pounds per women under local anaesthetic. The health service cost of microwave endometrial ablation using local anaesthetic in a clinic setting was estimated to be 432 pounds per treatment; however, this varied from 389 pounds to 491 pounds in the sensitivity analysis. CONCLUSION: There are minimal cost savings to the patient or health service from using local rather than general anaesthetic for microwave endometrial ablation in a theatre setting. Cost modelling suggests that in a clinic setting microwave endometrial ablation has a similar cost to theatre based treatment once re-admissions for treatment under general anaesthetic are considered. Sensitivity analysis indicated that these findings were sensitive to assumptions in the model.

Anesthesia, General↗
PubMed2006

Conversion of paper sludge to ethanol, II: process design and economic analysis.

Process design and economics are considered for conversion of paper sludge to ethanol. A particular site, a bleached kraft mill operated in Gorham, NH by Fraser Papers (15 tons dry sludge processed per day), is considered. In addition, profitability is examined for a larger plant (50 dry tons per day) and sensitivity analysis is carried out with respect to capacity, tipping fee, and ethanol price. Conversion based on simultaneous saccharification and fermentation with intermittent feeding is examined, with ethanol recovery provided by distillation and molecular sieve adsorption. It was found that the Fraser plant achieves positive cash flow with or without xylose conversion and mineral recovery. Sensitivity analysis indicates economics are very sensitive to ethanol selling price and scale; significant but less sensitive to the tipping fee, and rather insensitive to the prices of cellulase and power. Internal rates of return exceeding 15% are projected for larger plants at most combinations of scale, tipping fee, and ethanol price. Our analysis lends support to the proposition that paper sludge is a leading point-of-entry and proving ground for emergent industrial processes featuring enzymatic hydrolysis of cellulosic biomass.

Conservation of Natural Resources↗
PubMed1999

What is the cost utility of screening for hepatitis C virus (HCV) in intravenous drug users?

OBJECTIVES: To model the likely cost utility of the prevalence round of a screening programme for hepatitis C (HCV) in intravenous drug users (IVDUs) in contact with services in the South and West health region of the UK. METHODS: Information on the prevalence of HCV, performance of diagnostic tests, and effectiveness of interferon alpha (IFN alpha) for treatment of chronic hepatitis were brought together with estimates of the costs of service provision. A simple spreadsheet model was used to estimate cost utility (cost/quality adjusted life year (QALY)). Assumptions (including use of ribavirin plus IFN alpha combination therapy) were tested by a one way sensitivity analysis. RESULTS: About 5600 IVDUs live in the region. A combination of enzyme linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) testing has high sensitivity and specificity for detecting HCV. There is excellent evidence that IFN alpha is effective in producing sustained normalisation of liver function and, by inference, eradicating HCV. Evidence for long term benefits comes from modelling studies based on progression of HBV or non-A, non-B hepatitis and is considerably less robust. The cost of the prevalence round of screening in IVDUs would be about 700,000 Pounds and is likely to identify about 1400 people, of whom about 270 would be eligible for treatment and 20 would respond to IFN alpha. This gives a cost/QALY of 9300 Pounds for the screening programme. However, much uncertainty around the estimates used to inform the cost utility calculation limits confidence in the value of screening IVDUs for HCV. Sensitivity analysis shows a range of possible cost utility from 3333 Pounds to 81,438 Pounds. Estimates are particularly sensitive to adherence to liver biopsy and treatment and to discounting of benefits. CONCLUSIONS: Although potentially cost effective, many important uncertainties surround the assumptions used to estimate the long term effectiveness of screening and treatment. There is insufficient evidence to inform policy development and further research is required in this rapidly changing field.

Comorbidity↗
PubMed2004

A modified ICRP 66 iodine gas uptake model and its parametric uncertainty.

Intakes via inhalation may occur from radionuclides released in the form of a gas. The chemical characteristics pertaining to the release influence the intake and subsequent dose to an exposed individual. Gases are taken up or absorbed in the entire respiratory tract and the associated uptake mechanisms are quite different from deposition of particulates. Gaseous iodine can exist in various chemical forms, e.g., elemental iodine, inorganic, and organic iodine compounds. These different chemical species play an integral role in the gaseous uptake o f iodine in t he respiratory tract. Gas uptake in the various regions of the respiratory tract results in the intake of iodinated material into the body. The radioactive iodine taken up in the gas-exchange tissues is absorbed into the bloodstream of an individual and subsequently transferred to other organs. Iodine in the circulatory system can then be taken up by the thyroid gland, with resulting dose to the thyroid. The magnitude and uncertainty in regional gas uptake is important in the assessment of individuals exposed to airborne releases of radioiodine. The current ICRP 66 model is rudimentary and estimates regional gas uptake based on solubility and reactivity of the different radionuclides entering the respiratory tract. The modified model proposed here employs methodology and a mathematical structure to determine estimates of fractional gas uptake rather than defaulting to literature values, as in the current ICRP model. Model parameters have been assigned input distributions and estimates of uncertainty have been determined. A sensitivity analysis of these parameters has been performed to demonstrate the importance of each of these parameters. The sensitivity analysis ranks the model-input parameters by their importance to estimates of regional gas uptake. The model developed herein may be used for improved estimation of gas uptake in the respiratory tract and subsequent dose estimates from the different chemical forms of radioiodine.

Adult↗
PubMed2003

Effectiveness and cost-effectiveness of prognostic markers in prostate cancer.

This paper demonstrates how economic modelling can be used to derive estimates of the cost-effectiveness of prognostic markers in the management of clinically localised and moderately graded prostate cancer. The model uses a Markov process and is populated using published evidence and local data. The robustness of the results has been tested using sensitivity analysis. Three treatment policies of 'monitoring' (observation), radical prostatectomy, or a selection-based management policy using DNA-ploidy as an experimental marker, have been evaluated. Modelling indicates that a policy of managing these tumours utilising experimental markers has an estimated cost per quality-adjusted life year (QALY) of pound 12 068. Sensitivity analysis shows the results to be relatively sensitive to quality-of-life variables. If novel and experimental markers can achieve specificity in excess of 80%, then a policy of radical surgery for those identified as being at high risk and conservative treatment for the remainder would be both better for patients and cost-effective. The analysis suggests that a radical prostatectomy treatment policy for the moderately graded tumours (Gleason grades -7) modelled in this paper may be inferior to a conservative approach in the absence of reliable prognostic markers, being both more costly and yielding fewer QALYs.

Cost-Benefit Analysis↗
PubMed2006

Ovine progressive pneumonia virus capsid is B-cell immunodominant using Western blot analysis: a comparison of sensitivity between Western blot analysis and immunoprecipitation.

A Western blot assay was developed and analyzed against the comparable standard, immunoprecipitation of (35)[S]-methionine/cysteine-labeled ovine progressive pneumonia virus (OPPV) proteins, for its ability to detect anti-OPPV antibodies using endpoint titers. Western blot analysis is 12-fold more sensitive in detecting endpoint anti-capsid antibody titers than IP, and the capsid is the B-cell immunodominant OPPV protein when utilizing Western blot analysis. Since the surface envelope glycoprotein is the B-cell immunodominant OPPV protein when utilizing immunoprecipitation, this suggests immunoprecipitation and Western blot analysis measure different types of antibody that are more specific for conformational and linear OPPV protein epitopes, respectively.

Animals↗
PubMed1993

Use of morphometry as an aid in the differential diagnosis of large cell carcinoma of the lung.

In a previous cytopathologic study a regression equation was generated that aided in the differential diagnosis of large cell carcinoma (LCC) of the lung from poorly differentiated adenocarcinoma (AC). This study was undertaken to validate and extend those findings. Cytopathologic and histopathologic specimens from 20 new patients were examined using computerized morphometry. There were 28 specimens from 10 cases of LCC and 25 specimens from 10 cases of AC (10-25 cells measured from each specimen). Histopathologic review by an expert (S.D.G.) provided the "gold standard" diagnosis. Morphometric parameters studied were (1) nucleolar/nuclear area ratio, (2) cell area, (3) cell form factor, and (4) nuclear form factor. Sensitivity analysis validated the diagnostic utility of our prior equation. A logistic regression with these parameters determined the probability that each sample was LCC. Relative operating characteristic curve analysis determined an optimum logistic cutoff point of 0.83. At this decision level the equation had a sensitivity of 72% for distinguishing LCC. Specificity was 46%, positive predictive value was 65%, negative predictive value was 55%, and classification efficiency was 61%. Morphometry of histopathologic material contributed no important additional information. Therefore, our logistic regression and sensitivity analysis supported the clinical utility of certain morphometric measurements in the cytopathologic, but not histopathologic, diagnosis of LCC.

Adenocarcinoma↗
PubMed1999

Cost-effectiveness of the diagnostic evaluation of vertigo.

OBJECTIVE: To evaluate the cost-effectiveness of several diagnostic tests used in the evaluation of vertigo. STUDY DESIGN: Cost-effectiveness analysis, using data from retrospective case review. METHODS: Charts and test results were reviewed from 192 outpatients seen in an academic tertiary referral center for evaluation of vertigo. Cost-effectiveness analysis was performed using decision analysis software, data from office and hospital charges, and expert-based estimations of the utility of different test outcomes. Sensitivity analysis was performed using standard algorithms and wide variable ranges. RESULTS: We found that audiologic testing, posturography, and electronystagmography were the most cost-effective tests, and that magnetic resonance imaging and blood tests had the lowest cost-effectiveness. The analysis was sensitive to the effects of financial costs of tests but, with a few exceptions, was typically not sensitive to the utility of test outcomes or the distribution of test results. CONCLUSIONS: The use of cost-effectiveness analysis, the estimation of utility of test outcomes, and techniques of sensitivity analysis should help guide the clinician's decision making on appropriate testing for patients with vertigo.

Audiometry, Pure-Tone↗
PubMed2001

Restricted surface matching--numerical optimization and technical evaluation.

Accurate and reliable registration is one of the most important issues in computer-aided surgery, as small errors may have a large influence on the overall accuracy of the system. The restricted surface-matching algorithm (RSM), initially developed for periacetabular osteotomy surgery (PAO), has been improved to become numerically more stable and reliable. To assess the accuracy and sensitivity of registration, a framework is presented that evaluates two aspects of registration: the sensitivity and raw performance of the registration algorithm are tested in a stand-alone environment, and the integration into a CAS system is analyzed by evaluating the accuracy of the complete system. For the latter tests, spherical-headed titanium screws used as fiducial landmarks provide a reference transformation for the registration. This framework was used to analyze the performance of RSM for PAO surgery. The sensitivity analysis showed the algorithm to be insensitive to noise up to a magnitude of 3 mm. Both the sensitivity analysis and simulated surgical environment tests showed that an accuracy can be attained of better than 2 mm in the region of interest, and better than 4 mm far away from the region of interest. This is sufficient for safely assisting PAO surgeries.

Algorithms↗
PubMed2005

The blue cross blue shield assessment technology review: summary of findings.

Epoetin (EPO; erythropoietin) treatment offers an attractive but costly alternative to red blood cell transfusion for managing anemia associated with cancer therapy. The goal of this paper is to review the findings of the 2001 Blue Cross/Blue Shield Association Technology Evaluation Center overview on EPO use in oncology, which served the foundation for the 2002 ASH/ASCO clinical guideline on this subject. The BC/BS review had two major aims: (1) to quantify the effects of EPO on the likelihood of transfusion and on quality of life in patients with cancer treatment-related anemia, and (2) to evaluate whether outcomes are superior when EPO treatment is initiated at higher hemoglobin thresholds. Two independent reviewers followed a prospective protocol for identifying relevant studies published between 1985 and 1998. Outcomes data were combined with the use of a random-effects meta-analysis model. Double-blind, randomized controlled trials that minimized patient exclusions were defined as higher quality for sensitivity analysis; randomized, but unblinded trials and trials with excessive exclusions were included in the meta-analysis, but were defined as lower quality. Twenty-two trials (n=1927) met inclusion criteria, and 12 (n=1390) could be combined for estimation of odds of transfusion. EPO decreased the percentage of patients transfused by 9-45% in adults with mean baseline hemoglobin concentrations of 10g/dL or less (7 trials; n=1080), by 7-47% in those with hemoglobin concentrations greater than 10g/dL, but less than 12g/dL (7 trials; n=431), and by 7-39% in those with hemoglobin concentrations of 12g/dL or higher (5 trials; n=308). In a sensitivity analysis, the combined odds ratio for transfusion in EPO-treated patients as compared with controls was 0.45 (95% confidence interval [CI]=0.33-0.62) in higher quality studies and 0.14 (95% CI=0.06-0.31) in lower quality studies. The number of treated patients needed to prevent one transfusion is 4.4 for all studies, 5.2 for higher quality studies, and 2.6 for lower quality studies. Only studies with mean baseline hemoglobin concentrations of 10g/dL or less reported statistically significant effects of EPO treatment on quality of life; quality-of-life data were insufficient for meta-analysis. No studies addressed the effects of EPO on anemia-related symptoms. The review concluded that EPO reduced the odds of transfusion for cancer patients undergoing therapy. Evidence was insufficient to determine whether initiating EPO earlier spares more patients from transfusion or results in better quality of life than waiting until hemoglobin concentrations decline to nearly 10g/dL. An update of this review, which includes information on quality of life, transfusion requirment, survival and tumor response, for first and second-generation epoetin products is ongoing.

Anemia↗
PubMedDate not supplied

Designing specific protein kinase inhibitors: insights from computer simulations and comparative sequence/structure analysis.

Protein kinases are important targets for designing therapeutic drugs. We describe here a computational approach to extend the usefulness of a single protein-inhibitor structure in aiding the design of protein kinase inhibitors. This approach is based on using sensitivity analysis to identify the most significant functional groups of a lead compound in accounting for binding affinity and on using comparative sequence/structure analysis to examine whether these functional groups would present specificity. A sensitivity analysis study is similar to genetic or chemical modification experiments in which specific features of a lead compound are modified to examine whether they affect properties such as binding affinity. In this study, the binding affinity was estimated by using an implicit-solvent model in which the electrostatic contributions were obtained by solving the Poisson equation, and the hydrophobic effects were accounted for by using surface-area-dependent terms. The comparative sequence/structure analysis involves the study of the amino acid distributions of a large number of protein kinases (384 in this study) near the ligand-binding sites. This analysis provides useful guiding principles for designing specific inhibitors targeted towards a particular kinase. Here, we illustrate the utility of these computational approaches by applying them to identify the determinants of the recognition between the protein kinase A and two of its inhibitors. One inhibitor, balanol, binds to the ATP-binding pocket. The other, protein kinase inhibitor, binds to the substrate-binding site. These analyses have helped to construct pharmacophore models for mining new drug leads from small-molecule libraries and for suggesting how a lead compound or a peptide inhibitor may be modified to generate selective inhibitors.

Azepines↗
PubMed1998

Cloning of a cDNA coding for an amino acid carrier from Ricinus communis (RcAAP1) by functional complementation in yeast: kinetic analysis, inhibitor sensitivity and substrate specificity.

A cDNA for the amino acid permease gene RcAAP1 has been isolated from Ricinus communis by yeast complementation and subjected to a detailed kinetic analysis. RcAAP1 cDNA is 1.5 kb with an open reading frame that codes for a protein with 486 amino acids and a calculated molecular mass of 53.1 kDa. RcAAP1-mediated histidine uptake was pH dependent with highest transport rates at acidic pH; it was sensitive to protonophores and uncouplers and the Km for histidine uptake was 96 microM. The substrate specificity was investigated by measuring the levels of inhibition of histidine uptake by a range of amino acids. The basic amino acids (histidine, lysine and arginine) showed strongest inhibition of uptake whereas acidic amino acids competed less effectively. Alanine was the most efficient competitor of the neutral amino acids. Glutamine, serine, asparagine, methionine and cysteine showed moderate inhibition whereas threonine, isoleucine, leucine, phenylalanine, tyrosine and tryptophan showed only low levels of inhibition. Glycine, proline and citrulline caused slight stimulation. More detailed competition kinetics indicated that both lysine and arginine showed simple competitive inhibition of histidine uptake. When direct uptake measurements were carried out, both lysine and arginine were found to be effective substrates for RcAAP1.

Amino Acid Sequence↗
PubMed2000

Modeling of pH and acidity for industrial cheese production.

A three-layer feedforward neural network was successfully used to model and predict the pH of cheese curd at various stages during the cheese-making process. An extended database, containing more than 1800 vats over 3 yr of production of Cheddar cheese with eight different starters, from a large cheese plant was used for model development and parameter estimation. Neural network models were developed with inputs selected among 33 quantitative and qualitative process variables for final pH of cheese, pH at cutting, and acidity at whey drawing-off and at pressing. In all cases, very high correlation coefficients, ranging from 0.853 to 0.926, were obtained with the validation data. A sensitivity analysis of neural network models allowed the relative importance of each input process variable to be identified. The sensitivity analysis in conjunction with a priori knowledge permitted a significant reduction in the size of the model input vector. A neural network model using only nine input process variables was able to predict the final pH of cheese with the same accuracy as for the complete model with 33 original input variables. This significant decrease in the size of neural networks is important for applications of process control in cheese manufacturing.

Biotechnology↗
PubMed1996

Evaluation of a stochastic dynamic replacement and insemination model for dairy cattle.

An approach to evaluating results from a stochastic, dynamic model for insemination and replacement of dairy cattle was devised using sensitivity and behavioral analyses. Sensitivity analysis was defined as the quantification of the various outputs resulting from uncertain price and production inputs. Behavioral analysis determined how outputs changed when model specifications were changed. The variation in outputs that were identified by sensitivity analysis was used as an objective measure to assess variation caused by behavioral analysis scenarios. A contemporary model was modified, and a base run was defined using Florida values for input variables. The model specifications that were varied were decision horizon, number of milk production levels, and number of days open classes. Effects of including seasonality of milk production, milk price, and conception rate were examined. The necessary decision horizon was shorter than other works would suggest. Optimal policies were influenced greatly by the number of days open classes, but not by the number of milk production levels. Removal of seasonality of milk production and conception rate resulted in meaningful changes in seasonal patterns of all outputs measured. Our results suggest that model specifications could affect results and should be evaluated objectively when models are being developed.

Animals↗
PubMed2006

[Meta-analysis of diagnostic capability of frequency-doubling technology (FDT) for primary glaucoma].

OBJECTIVE: To evaluate the overall diagnostic capabilities of frequency-doubling technology (FDT) in patients of primary glaucoma, with standard automated perimetry (SAP) and/or optic disc appearance as the gold standard. METHODS: A comprehensive electric search in MEDLINE, EMBASE, Cochrane Library, BIOSIS, Previews, HMIC, IPA, OVID, CNKI, CBMdisc, VIP information, CMCC, CCPD, SSreader and 21dmedia and a manual search in related textbooks, journals, congress articles and their references were performed to identify relevant English and Chinese language articles. Criteria for adaptability were established according to validity criteria for diagnostic research published by the Cochrane Methods Group on Screening and Diagnostic Tests. Quality of the included articles was assessed and relevant materials were extracted for studying. Statistical analysis was performed with Meta Test version 0.6 software. Heterogeneity of the included articles was tested, which was used to select appropriate effect model to calculate pooled weighted sensitivity and specificity. Summary Receiver Operating Characteristic (SROC) curve was established and the area under the curve (AUC) was calculated. Finally, sensitivity analysis was performed. RESULTS: Fifteen English articles (21 studies) of 206 retrieved articles were included in the present study, with a total of 3172 patients. The reported sensitivity of FDT ranged from 0.51 to 1.00, and specificity from 0.58 to 1.00. The pooled weighted sensitivity and specificity for FDT with 95% confidence intervals (95% CI) after correction for standard error were 0.86 (0.80 - 0.90), 0.87 (0.81 - 0.91), respectively. The AUC of SROC was 93.01%. Sensitivity analysis demonstrated no disproportionate influences of individual study. CONCLUSIONS: The included articles are of good quality and FDT can be a highly efficient diagnostic test for primary glaucoma based on Meta-analysis. However, a high quality perspective study is still required for further analysis.

Aged↗
PubMed2004

Economic consequences of the adverse reactions related with antipsychotics: an economic model comparing tolerability of ziprasidone, olanzapine, risperidone, and haloperidol in Spain.

Frequency of adverse reactions (ARs) related with antipsychotics usage is high. Along with clinical implications, economic impact might be important. The purpose of this study was to model the economic consequences of ARs related with ziprasidone, olanzapine, risperidone, and haloperidol in Spain, by means of a cost-effectiveness model developed using a Markov modeling approach. The model simulated treatment of a cohort of 1000 schizophrenics for 12 months, initiating treatment with one of four antipsychotic drugs; haloperidol, risperidone, olanzapine and ziprasidone. Conditional probabilities of developing any of four adverse events were calculated. Treatment was modified (decrease dose, switch medication) according to incidence of ARs and physician judgments, obtained from a local cross-sectional study and clinical trials previously published. The analysis was conducted in year 2002 from a third party payer perspective. Results are shown as annual cost per month with psychotic symptoms controlled and included univariate sensitivity analysis. The therapeutic strategy starting with ziprasidone showed the lower costs and the greater number of months with symptoms controlled in most scenarios evaluated versus the other options considered, although the differences were weak: 9.6, 9.3, 9.5 and 9.5 controlled months per patient in base scenario, with annual cost per patient per month with symptoms controlled of 1035 Euros, 1084 Euros, 1087 Euros and 1090 Euros for ziprasidone, haloperidol, risperidone and olanzapine, respectively. Results were robust to one-way sensitivity analysis. Despite the unlike drug prices of antipsychotics, a considerable economic impact due to adverse reactions was seen in our setting. These results should be taken into account by health decision makers and clinicians in the management of patients with schizophrenia.

Antipsychotic Agents↗