Survival gain in cost-effectiveness studies.
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Breast Neoplasms↗
Biomedical subjects
E Tendi
Publications and source records attributed to E Tendi.
Nitric oxide synthase induction in astroglial cell cultures: effect on heat shock protein 70 synthesis and oxidant/antioxidant balance.
Glial cells in the nervous system can produce nitric oxide in response to cytokines. This production is mediated by the inducible isoform of nitric oxide synthase. Radical oxygen species (ROS) and nitric oxide (NO) derivatives have been claimed to play a crucial role in many different processes, both physiological such as neuromodulation, synaptic plasticity, response to glutamate, and pathological such as ischemia and various neurodegenerative disorders. In the present study we investigated the effects of NO synthase (iNOS) induction in astrocyte cultures on the synthesis of heat shock proteins, the activity of respiratory chain complexes and the oxidant/antioxidant balance. Treatment of astrocyte cultures for 18 hr with LPS and INFgamma produced a dose dependent increase of iNOS associated with an increased synthesis of hsp70 stress proteins. This effect was abolished by the NO synthase inhibitor L-NMMA and significantly decreased by addition of SOD/CAT in the medium. Time course experiments showed that iNOS induced protein expression increased significantly by 2 hr after treatment with LPS and INFgamma and reached a plateau at 18 hr; hsp70 protein synthesis peaked around 18 and 36 hr after the same treatment. Addition to astrocytes of the NO donor sodium nitroprusside resulted in a dose dependent increase in hsp70 protein that was comparable to that found after a mild heat shock. Additionally, a decrease in cytochrome oxidase activity, a marked decrease in ATP and protein sulfhydryl contents, an increase in the activity of the antioxidant enzymes mt-SOD and catalase were found which were abolished by L-NMMA. These findings suggest the importance of mitochondrial energy impairment as a critical determinant of the susceptibility of astrocytes to neurotoxic processes and point to a possible pivotal role of hsp70 in the signalling pathways of stress tolerance.
Animals↗
Gains in life expectancy from medical interventions.
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Cost-Benefit Analysis↗
Treatments for newly diagnosed advanced ovarian cancer: analysis of survival data and cost-effectiveness evaluation.
The main therapeutic options currently available for patients with newly diagnosed advanced ovarian cancer include: (i) cisplatin-based chemotherapy at conventional doses without paclitaxel, (ii) paclitaxel+cisplatin at conventional doses and (iii) high-dose chemotherapy with autologous hematopoietic rescue. After conducting a literature search to identify large-scale clinical trials based on these three therapeutic modalities, we carried out an analysis of the survival data and evaluated the cost-effectiveness ratio where appropriate. Cost data were obtained from published information. Effectiveness was estimated by determining the values of mean lifetime survival (MLS). Our analysis included a total of 15 clinical trials. The values of MLS were 3.05 years per patient for cisplatin-based chemotherapy at conventional doses without paclitaxel (1931 patients), 2.95 years per patient for chemotherapy with paclitaxel+cisplatin at conventional doses (184 patients) and 5.76 years per patient for high-dose chemotherapy with autologous hematopoietic rescue (53 patients). As compared with cisplatin-based chemotherapy without paclitaxel, high-dose treatments with hematopoietic rescue yielded a significantly better survival. Using cisplatin-based chemotherapy as a reference term, the incremental cost-effectiveness ratio for high-dose treatments was $25641 per life year gained (discounted dollars per discounted life year gained). Sensitivity testing suggested that the ratio remained below $50000 under most circumstances. We conclude that in the treatment of patients with advanced ovarian cancer, high-dose chemotherapy with hematopoietic rescue seems to be more effective and more cost-effective than standard treatments with cisplatin-based regimens at conventional doses.
Antineoplastic Combined Chemotherapy Protocols↗
A retrospective cost-effectiveness analysis of interferon as adjuvant therapy in high-risk resected cutaneous melanoma.
To assess the cost per life year gained of alpha interferon (IFN) as adjuvant therapy for patients with high-risk resected melanoma, we conducted a retrospective, incremental cost-effectiveness analysis on clinical data from a previously published ECOG trial [9]. The Gompertz model was used to estimate the total lifetime values of patient-years of subjects receiving IFN in comparison with subjects given no adjuvant treatment. The ECOG trial involved 143 patients treated with high-dose IFN and 137 given no adjuvant treatment. Estimated drug expenditures were based on the assumption of a cost of $109.25 per 10 MU of IFN. Our analysis of the ECOG results showed that the adjuvant treatment of 100 subjects with high-dose IFN improved survival expectancy by 133.6 discounted life years or 308 undiscounted life years. The use of IFN (compared with no adjuvant treatment) implied an incremental cost of $16,467 per discounted life year saved (95% CI of $4752-50,000) or $7143 per undiscounted life year saved (95% CI of $3226-33,846). Sensitivity testing, in which variations were introduced in the main factors influencing cost and effectiveness, showed that this value always remained below $50,000. Our pharmacoeconomic analysis indicates that adjuvant treatment with high-dose IFN in patients with high-risk resected melanoma implies a favourable cost-effectiveness ratio. Because two other studies showed no significant survival benefit in patients receiving adjuvant IFN at lower values of total dose per patient, the controversy remains and confirmation data are needed for the ECOG trial's results. If these clinical results are confirmed, our analysis shows that the dosage of IFN given in this trial has a favourable pharmacoeconomic profile.
Antineoplastic Agents↗
Pharmacoeconomic profile of paclitaxel as a first-line treatment for patients with advanced ovarian carcinoma. A lifetime cost-effectiveness analysis.
BACKGROUND: Analysis of published survival curves has recently been proposed as a method for conducting incremental cost-effectiveness analysis in which two treatments are compared with each other in terms of cost per year of life gained. In patients with advanced ovarian carcinoma, the combination of paclitaxel and cisplatin has been reported to improve survival more significantly than standard therapy with cyclophosphamide and cisplatin. However, the high cost of paclitaxel indicates a need for an evaluation of the pharmacoeconomic profile of these treatments. METHODS: The authors conducted an incremental cost-effectiveness analysis to assess the paclitaxel-based regimen in terms of cost per year of life gained. The analysis utilized data from a published controlled long term trial involving 184 patients treated with paclitaxel and cisplatin and 202 patients treated with cyclophosphamide and cisplatin. Gompertz' law was employed to obtain the lifetime estimate of the years gained by patients given the first treatment in comparison with patients given the second. RESULTS: The paclitaxel-based treatment was found to improve life expectancy by 46 years for every 100 patients. Costs of chemotherapy were higher in the paclitaxel group than in the standard-therapy group (the cost difference was $901,723 for every 100 patients; costs for treating febrile neutropenia induced by chemotherapy were taken into account). On the basis of these data of cost and effectiveness, the administration of paclitaxel and cisplatin was found to imply a cost per year of life gained of $19,603 more than standard chemotherapy. CONCLUSIONS: The pharmacoeconomic profile of paclitaxel compares favorably with economic data previously calculated for other types of pharmacologic treatment.
Antineoplastic Agents↗
Cost-effectiveness of adjuvant chemotherapy with cyclophosphamide+methotrexate+fluorouracil in patients with node-positive breast cancer.
BACKGROUND: The analysis of published survival curves can be used as the basis for incremental cost-effectiveness analyses in which two treatments are compared with each other in terms of cost per life year saved. In patients with node-positive breast cancer adjuvant chemotherapy with cyclophosphamide+ methotrexate+fluorouracil has been reported to improve survival in comparison with patients who are not given this treatment. METHODS: To assess the pharmacoeconomic profile of this adjuvant chemotherapeutic regimen in terms of cost per life-year gained, we conducted an incremental cost-effectiveness analysis in which the Gompertz model was used to calculate the lifetime estimate of the patient-years gained by treated subjects compared to controls. RESULTS: Using data from a published, controlled long-term trial involving 207 patients treated with cyclophosphamide+methotrexate+fluorouracil and 179 controls, we estimated that this adjuvant chemotherapy improved life expectancy by 357 patient-years per 100 subjects. Direct costs, which were almost exclusively related to the administration of chemotherapy, were estimated to be US $159,516 per 100 patients. On the basis of these data, adjuvant chemotherapy was found to imply an incremental cost of US $447 per life-year saved. CONCLUSIONS: The cost-effectiveness ratio of adjuvant chemotherapy with cyclophosphamide+methotrexate+fluorouracil in patients with node-positive breast cancer seems to be particularly favourable in comparison with estimates of cost per life-year saved previously calculated for other types of pharmacological intervention.
Antineoplastic Combined Chemotherapy Protocols↗
Cost effectiveness of adjuvant intraportal chemotherapy in patients with colorectal cancer.
Recent studies have shown that the analysis of published survival curves allows cost-effectiveness evaluations in which two treatments are compared with each other in terms of cost per life-year saved. In patients with colorectal cancer, the administration of adjuvant intraportal chemotherapy (with mitomycin and fluorouracil) has been reported to improve long-term survival in comparison with patients who are not given this treatment. To assess the pharmacoceconomic profile of this adjuvant chemotherapy, we carried out an incremental cost-effectiveness analysis in which we used the Gompertz model to estimate lifetime patient years gained by patients given this chemotherapy in comparison with controls. Using the data of a published controlled long-term trial involving 252 patients treated with intraportal chemotherapy and 253 controls who were given no such therapy, we estimated that the adjuvant treatment improved life expectancy by 89 discounted patient years (or 218 undiscounted patient years) every 100 patients. Cost of chemotherapy was calculated as $107,720 for every 100 patients. On the basis of these data, the administration of adjuvant intraportal chemotherapy was found to imply an incremental cost of $1,210 per discounted life-year saved or $494 per undiscounted life-year saved. The cost-effectiveness ratio of adjuvant intraportal chemotherapy in patients with colorectal cancer seems to be particularly favorable in comparison with estimates of cost per life-year saved previously obtained in many other areas of pharmacological intervention. Even though systemic fluorouracil + levamisole is the form of adjuvant chemotherapy most widely used in these patients, intraportal chemotherapy has the best cost-effectiveness profile.
Antineoplastic Combined Chemotherapy Protocols↗
G-CSF for the prophylaxis of neutropenic fever in patients with small cell lung cancer receiving myelosuppressive antineoplastic chemotherapy: meta-analysis and pharmacoeconomic evaluation.
Standard meta-analytical and pharmacoeconomic techniques were used to study the clinical effectiveness and the cost-effectiveness ratio of the prophylactic (or pre-emptive) administration of G-CSF to patients with small cell lung cancer treated with conventional myelosuppressive cytotoxic chemotherapy. In the first part of our study, we conducted a meta-analysis of the randomized clinical trials evaluating G-CSF for this clinical indication. Three trials were identified by our literature search and were included in the meta-analysis (overall number of patients = 606). The end-points for evaluating G-CSF included mortality from infection and the cumulative incidence of neutropenic fever over six cycles of chemotherapy. The results of our meta-analysis demonstrate that prophylactic G-CSF did not affect mortality but significantly reduced the incidence of neutropenic fever from 68.3% to 38.7% (pooled odds ratio = 0.29, 95% CI: 0.21-0.40; P < 0.001). In the second part of our study, we carried out a pharmacoeconomic analysis to estimate the cost-effectiveness ratio of pre-emptive G-CSF (i.e. the 'average' cost associated with the prevention of an episode of neutropenic fever). This cost-effectiveness ratio was US$ 14,372 using the Italian price of the drug converted into dollars, or US$ 41 088 using the US price. Finally, we estimated the revenue-neutral price of G-CSF based on American data of the cost-of-illness. The price ranged from US$ 395 to US$ 569 per cycle, a figure higher than the value (US$ 150) previously reported in the literature.
Antineoplastic Agents↗
Pharmacy education and hospital pharmacy practice in Italy.
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Curriculum↗
A calculator program for clinical application of the Bayesian method of predicting plasma drug levels.
A pharmacokinetic program that allows individualization of drug dosage regimens through the Bayesian method is described. The program, which is designed for the Hewlett-Packard HP-41 CV calculator, is based upon the one-compartment open model with either instantaneous or zero-order absorption. Individualized estimation of the patient's kinetic parameters (clearance and volume of distribution) is performed by analyzing the plasma levels measured in the patient as well as considering the population data of the drug. After estimating the individual kinetic parameters by the Bayesian method, the program predicts the dosage regimen that will elicit the desired peak and trough plasma levels at steady state. For comparison purposes, the least-squares estimates for clearance and volume of distribution are calculated, and dosage prediction can also be made on the basis of the least-squares estimates. The least-squares estimates can be used to calculate population pharmacokinetic parameters according to the Standard Two-Stage method. Several examples of clinical use of the program are presented. The examples refer to patients with classic hemophilia who were treated with Factor VIII concentrates. In these patients, the Bayesian kinetic parameters of Factor VIII have been estimated through the calculator program. The Bayesian parameter estimates generated by the HP-41 have been compared with those determined by a Bayesian program (ADVISE) designed for microcomputers.
Computers↗
Kinetic evaluation of four Factor VIII concentrates by model-independent methods.
Single-dose kinetics of 4 Factor VIII concentrates (Kryobulin, Hemofil T, Koate, cryoprecipitate) were studied in 41 patients with haemophilia-A. Model-independent methods were adopted for calculating the kinetic parameters (area under the curve, clearance, area under the moment curve, mean residence time, volume of distribution at steady-state). No substantial difference was observed in the kinetic characteristics of the 4 Factor VIII concentrates. A considerable interindividual variability of the calculated kinetic parameters was demonstrated for all concentrates. Our findings support the need to individualize Factor VIII dosage.
Adolescent↗
Calculator programs for weighted least-squares iterative fits in pharmacokinetics.
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Computers↗
Clinical application of the Mullen and Foster method for individualizing phenytoin dosage.
The Mullen and Foster method was prospectively applied for individualizing phenytoin dosage in 24 epileptic patients. Accuracy and reliability of the method were assessed by comparing predicted and measured values of plasma phenytoin steady-state concentration. The absolute difference between predicted and measured phenytoin levels was less than 15 percent in 22 of 35 cases (63 percent), between 15 and 25 percent in 8 of 35 cases (23 percent) and more than 25 percent in 6 of 35 cases (17 percent).
Aged↗
Individualization of Factor VIII dosage.
The usefulness of a calculator programme that enables individualization of the dosage of Factor VIII, based on the concentration-time data measured after a test-dose, was assessed. The programme was tested in 12 haemophiliacs who required multiple-dose treatment with Factor VIII. Individual kinetic parameters were estimated in each patient from the plasma level data following the test-dose. Then, each patient received the multiple dose treatment with Factor VIII according to the dosage regimen suggested by the calculator programme. The time-curve of Factor VIII plasma levels at steady state was predicted by using the kinetic variables previously estimated. The plasma levels of Factor VIII were measured in all patients at steady state. As a result, good agreement between predicted and measured steady state concentrations was observed (r2 = 0.9797; P less than 0.001). The calculator programme tested in the present study appears to be a useful tool for individualizing the dosage regimen of Factor VIII in haemophiliacs.
Adolescent↗
A weighted least-squares approach for fitting to kinetic models the plasma concentration data of phenytoin and Factor VIII.
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Factor VIII↗
Comparative analysis of the pharmacokinetic techniques available for individualizing phenytoin dosage.
Over the past few years, numerous pharmacokinetic techniques based on Michaelis-Menten principles have been proposed to individualize PHT dosage and predict plasma levels. The choice of one of these techniques for clinical use depends on the number of steady state concentration-versus-dose (Css-D) data pairs that are known in the patient for whom the predictive technique is to be applied. The most frequent clinical situations in which these predictions are made can be divided into three groups for each patient considered--Case A: only one previous Css-D data pair is known; Case B: two previous Css-D data pairs are known; Case C: three previous Css-D data pairs are known. Of the available techniques that can be applied in case A, we compared the population clearance (PC) method and the Bayesian feedback (BF) method. The procedure for comparing the predictive capabilities of these methods was very similar to that adopted in a recent report by Vozeh et al. Our findings showed that the PC method should be preferred for clinical use under this circumstance. Two predictive techniques suitable for use in Case B (BF and Mullen & Foster methods) were compared. In this case, the BF method was shown to be more accurate. As regards Case C, three pharmacokinetic techniques were compared: the Mullen and Foster method, the iterative least-squares (ILS) technique, and the BF method. The ILS technique was found to be the most accurate in this case. Finally, we describe a programmable calculator procedure which uses the PC, BF or ILS methods in Cases A, B and C respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Bayes Theorem↗
Pharmacokinetic predictions based on a variable dosage frequency in chronic treatment.
After repeated intramuscular or oral administration, plasma drug levels are predicted by using a programmable calculator. Predictions are based on a one-compartment, open model with first-order absorption. The actual times of dosing are considered, so that the assumption of a constant dosing interval is not required. A brief analysis of the pharmacokinetic consequences that may result from a variable dosage frequency is presented.
Computers↗