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M Zagari

Publications and source records attributed to M Zagari.

At least 19 recordsLinked to original sources
PubMed2003

Changes in cost-effectiveness over time. The case of Epoetin Alfa for renal replacement therapy patients in the UK.

We analysed the factors influencing cost-effectiveness of a health care intervention over time using economic evaluations of erythropoietin as a case study. The analytical framework of a study conducted in 1990 was used to revisit the cost-effectiveness of erythropoietin. Study variables were updated to 2000 using meta-analysis, published sources, and expert opinion. After 10 years of further experience with the use of erythropoietin the cost-effectiveness ratio now falls within the range considered acceptable in the UK. The analysis shows that the vast proportion of the reduction in the cost-effectiveness ratio achieved since 1990 results from reductions in the dose and price of erythropoietin. True cost-effectiveness of a treatment can change over time, and early analysis can reach incorrect conclusions because of data deficiencies. The existence of a body such as NICE might have delayed the widespread adoption of erythropoietin in the UK, but the higher standards of clinical and economic evidence demanded by such a body might have expedited the appropriate pricing,dosage, and hence utilisation of the treatment.

Journal Article↗
PubMed2002

Multivariate regression analyses of data from a randomised, double-blind, placebo-controlled study confirm quality of life benefit of epoetin alfa in patients receiving non-platinum chemotherapy.

Cancer-related anaemia is associated with a wide spectrum of symptoms that can negatively affect quality of life. Because epoetin alfa has demonstrated efficacy in correcting cancer-related anaemia, the impact of this treatment on quality of life was evaluated in a multinational, randomised, double-blind, placebo-controlled trial in 375 anaemic cancer patients receiving non-platinum-based chemotherapy. The cancer-specific measures of quality of life included the general scale (FACT-G Total) and fatigue subscale (FACT-An Fatigue subscale) of the Functional Assessment of Cancer Therapy-Anaemia and the Cancer Linear Analogue Scales measuring energy, ability to do daily activities, and overall quality of life. These measures were also used to examine the relationship between haemoglobin levels and quality of life. Both univariate and multiple linear regression analyses of quality of life data were performed. Results of the univariate analysis have been reported previously. The a priori-planned multiple linear regression analysis, which accounted for the effects of disease progression and several other possibly confounding variables on quality of life, showed a significant advantage for epoetin alfa over placebo for the five scales (all, P<0.05), and confirmed the results of the univariate analysis. For cancer-specific measures, significant correlations were demonstrated between baseline haemoglobin and quality of life (r, range: 0.14-0.26, all P<0.05) and between change in haemoglobin and change in quality of life (r, range: 0.26-0.34, all P<0.01). These findings provide evidence that increasing haemoglobin levels by epoetin alfa administration can significantly improve cancer patients' quality of life.

Activities of Daily Living↗
PubMed1999

What can be learnt from the new data about antibiotic resistance? Are there any practical clinical consequences of Helicobacter pylori antibiotic resistance?

Effective treatment regimens are now available for the eradication of Helicobacter pylori, but one of the factors limiting their efficacy is antibiotic resistance. Omeprazole-based triple therapy (omeprazole plus two antibiotics) can, at present, be considered the treatment of choice for H. pylori infection; some of the best results have been achieved by combining omeprazole with either amoxycillin and clarithromycin or metronidazole and clarithromycin. However, the potential effectiveness of nitroimidazole derivatives and clarithromycin must be weighed against the possibility that resistance can develop to these agents. Eradication in metronidazole-resistant strains is lower than in sensitive strains, but is still about 75% (versus 97%). However, clarithromycin resistance is thought to have more clinical significance, reducing the eradication rate of 95% in sensitive strains to 40% in resistant strains, although the overall importance of clarithromycin resistance for H. pylori eradication is still likely to be relatively low. Recent data on secondary resistance indicate that the rate is at least 50% for both metronidazole and clarithromycin in patients in whom eradication has failed. If, in the future, a large number of H. pylori-positive individuals undergo such treatment, treatment failures may become a major issue, and the problem of antibiotic resistance will have to be overcome.

Anti-Bacterial Agents↗
PubMed1998

The cost-effectiveness of octreotide acetate in the treatment of carcinoid syndrome and VIPoma.

Markov modeling was used to evaluate the cost-effectiveness of octreotide in treating carcinoid syndrome and VIPoma. For each condition, using octreotide was associated with doubled survival time. Octreotide was cost-effective for treating carcinoid tumor ($752 per additional year of life, two additional years on average), and cost saving for VIPoma.

Antineoplastic Agents, Hormonal↗
PubMed1998

Evaluation of short-term low-dose triple therapy for the eradication of Helicobacter pylori by factorial design in a randomized, double-blind, controlled study.

BACKGROUND: Studies demonstrating the efficacy of short-term low-dose triple therapies including omeprazole (O), clarithromycin (C) and a nitroimidazole (tinidazole, T) for Helicobacter pylori eradication have largely been open and uncontrolled, and have not assessed antibiotic sensitivity. Simpler regimens using the component drugs have not been evaluated. AIM: To evaluate the OCT regimen in a randomized, controlled trial, testing for pre- and post-treatment antibiotic resistance and comparing, in a factorial design, the OCT regimen with simpler combinations of its components. METHODS: One hundred and twenty-eight patients (68 males, 60 females, age 22-80 years, mean 53 years) with H. pylori gastritis were randomly assigned to one of the following four treatment groups: (C) clarithromycin 250 mg b.d.; (OC) omeprazole 20 mg o.d. + clarithromycin 250 mg b.d.; (CT) clarithromycin 250 mg b.d. + tinidazole 500 mg b.d.; (OCT) omeprazole 20 mg q.d.s. + clarithromycin 250 mg b.d. + tinidazole 500 mg b.d. The drugs were administered for 1 week. Medical interview, upper gastrointestinal endoscopy (with four antral and four corpus biopsies) and the 13C-urea breath test were carried out for all patients prior to and 4 weeks after treatment. Biopsy specimens were used for the urease test, histology, and culture and sensitivities. RESULTS: All but one patient completed treatment. Side-effects were rare and mild in all groups. The eradication rate was 93.8% in group OCT, 59.4% in group CT, 31.3% in group OC and 6.3% in group C. Pre-treatment metronidazole resistance was 12.8%, clarithromycin 1.1% and, to both antibiotics, 2.1%. In patients with pre-treatment metronidazole resistance, the eradication rate was 75% in group OCT and 33% in group CT. Post-treatment resistance to clarithromycin was induced in 28.5% of the failures in group C, but in none of group OC. Resistance to both antibiotics occurred in 22.2% of the failures in group CT and in none of group OCT. CONCLUSIONS: (i) The high efficacy of the OCT regimen is proved and each of the individual components of the regimen is essential to the result, possibly via a synergistic effect. (ii) Pre-treatment metronidazole resistance is scarcely relevant to the outcome. (iii) Acquired resistance is essentially nil if omeprazole is part of the regimen.

Adult↗
PubMed1998

Ranitidine bismuth citrate plus clarithromycin 7-day regimen is effective in eradicating Helicobacter pylori in patients with duodenal ulcer.

BACKGROUND: No clinical study has been performed to-date to evaluate the efficacy of the dual therapy of ranitidine bismuth citrate (RBC) plus clarithromycin (C) 500 mg b.d. given for 7 days for the eradication of H. pylori. AIM: To assess the eradication rates achieved by treatment with RBC 400 mg b.d. for 28 days combined with clarithromycin 500 mg b.d. for 7 days in H. pylori-positive duodenal ulcer patients. METHODS: One hundred and twelve H. pylori-positive patients with endoscopically proven active duodenal ulcer were included in a multicentre, open, randomized trial. H. pylori infection was initially detected by CLO-test and histology on antral and corpus biopsies, and by 13C-urea breath test (UBT). Patients were included if at least two of the tests were positive for H. pylori infection. Patients were randomized to receive RBC 400 mg b.d. for 4 weeks combined with clarithromycin 500 mg b.d. for the first 7 days (Group A) or 14 days (Group B). A second endoscopy was performed at least 28 days after the end of therapy for the assessment of ulcer healing and H. pylori infection. Eradication was assumed if all the tests (CLO-test, histology and UBT) were negative for H. pylori. RESULTS: Fifty patients in Group A and 55 in Group B were assessed for H. pylori eradication and ulcer healing. The eradication rates according to intention-to-treat analysis were 75% in Group A and 80% in Group B. Considering only those patients with evaluable data at least 28 days after the end of therapy, H. pylori eradication was achieved in 84% and 82% in Group A and B, respectively. No statistically significant difference in eradication was found between the two groups by Mantel-Haenszel test. Only one patient, in Group A, was withdrawn because of adverse events (epigastric pain and pruritus).

Anti-Bacterial Agents↗
PubMed1998

Efficacy and safety of three 7-day Helicobacter pylori eradication regimens containing ranitidine bismuth citrate.

BACKGROUND: This multicentre, randomized study was designed to assess the clinical efficacy, safety and tolerability of three novel 7-day triple therapies containing ranitidine bismuth citrate (RBC) and two antibiotics. METHODS: We studied patients with non-ulcer dyspepsia and gastritis who were randomly assigned to one of three treatment regimens given for 7 days in a b.d. dosing schedule: RBC 400 mg plus clarithromycin 250 mg and tinidazole 500 mg (RBCCT): RBC 400 mg plus clarithromycin 500 mg and amoxycillin 1 g (RBCCA); RBC 400 mg plus tinidazole 500 mg and amoxycillin 1 g (RBCTA). H. pylori status was determined by CLO-test, histology and 13C-urea breath test. A repeat breath test was performed at least 28 days after completion of therapy to assess eradication. RESULTS: One hundred and fifty-seven patients were eligible for intention-to-treat analysis (ITT) and 140 patients completed the study and returned for assessment of eradication. Intention-to-treat cure rates were 78% with RBCCT, 71% with RBCCA and 61% with RBCTA. An all-patients-treated analysis (APT), performed on evaluable patients, demonstrated eradication rates of 85% with RBCCT, 81% with RBCCA and 70% with RBCTA. No statistically significant difference was found between treatment groups. Twenty-four patients experienced side-effects, but in only seven cases was treatment discontinued due to adverse events. CONCLUSIONS: A 7-day course of RBC, clarithromycin and either tinidazole or amoxycillin provides a good rate of H. pylori eradication. Three novel RBC-based triple therapies proved to be safe and well tolerated, with discontinuations due to side-effects occurring in less than 5% of cases.

Adolescent↗
PubMed1998

Efficacy of lansoprazole in eradicating Helicobacter pylori: a meta-analysis.

BACKGROUND: The combination of lansoprazole with antibiotics either as double or triple therapy has demonstrated an H. pylori eradication rate of between 80 and 90%. With the aim of providing a complete revision of the results of these clinical studies and a quantification of the efficacy of lansoprazole in eradicating H. pylori and healing peptic ulcers, we have undertaken a meta-analysis of all the controlled studies published in the literature. METHODS: This meta-analysis reviewed all randomized, controlled clinical trials published as full text articles in English between 1993 and 1996 that reported the efficacy of lansoprazole treatment as monotherapy or in combination with antibiotics in the treatment of peptic ulcer and in eradicating H. pylori. Articles were identified from the literature, which included both manual and computerized research (MEDLINE) and references provided by articles in this area. In order to compare the efficacy of triple therapy comprising lansoprazole vs. another PPI, data from abstracts (n = 5) were used, as no full text articles were located. RESULTS: This systematic review of the literature documents that lansoprazole has a high degree of efficacy in eradicating H. pylori, above all when used within treatment schemes including amoxicillin or clarithromycin, and metronidazole or tinidazole. This efficacy is comparable to that of other PPIs. CONCLUSIONS: Triple therapy allows the eradication of H. pylori in more than 85% of cases in patients with peptic ulcer. In addition, there is a substantial comparability of the efficacy of lansoprazole and omeprazole when they are used together with other anti-infective agents. Thus, lansoprazole appears to offer an option in the eradication of H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Diagnosis of Helicobacter pylori infection: non-invasive diagnostic tests.

The non-invasive urea breath test can demonstrate the presence of Helicobacter pylori infection with the same accuracy as invasive methods (histology, rapid urease test, culture), but with less distress and inconvenience to the patient. It is evident that this test can and should substitute invasive methods in patients with uncomplicated duodenal ulcer, in those with non-ulcer dyspepsia and in all who have gastrointestinal disorders that do not require endoscopic examination. The urea breath test has a primary role for determining the success of eradication therapy. It is ideal for short- and long-term follow-up, particularly in the case of duodenal ulcer, which is strictly related to the presence of Helicobacter pylori. In serious disease, when endoscopic examination is mandatory, such as complicated ulcer or mucose associated lymphoid tissue lymphoma, the urea breath test can still improve the diagnostic accuracy of Helicobacter pylori infection as it does not imply sampling error, to which biopsy is subject.

Biopsy↗
PubMed1997

Pharmacoeconomic comparison of treatments for the eradication of Helicobacter pylori.

BACKGROUND: Patients with Helicobacter pylori-induced duodenal ulcer should have their infection eradicated. The optimal choice of antibiotic therapy, however, is less clear. OBJECTIVE: To evaluate costs and outcomes of treatment with 8 antibiotic regimens with documented activity against H pylori vs maintenance therapy with histamine2-receptor antagonists (H2RA). METHODS: A meta-analysis for 119 studies enrolling 6416 patients to determine aggregate eradication rates. The complexity of each regimen was used to determine the anticipated compliance rate and actual effectiveness. A decision analytic model with Monte Carlo simulation determined annual costs and health outcomes. RESULTS: Average annual total costs of testing for H pylori infection and antibiotic treatment ranged from $223 to $410 and prevented ulcer recurrence in 70% to 86% of patients. The H2RA maintenance therapy cost $425 and prevented recurrence in 72% of patients. The lowest costs and recurrence rates were achieved by 3 regimens: standard triple therapy (a combination of bismuth subsalicylate, metronidazole, and tetracycline hydrochloride) for 14 days ($223, with 18% recurrence); a combination of clarithromycin, metronidazole, and a proton pump inhibitor for 7 days ($235, with 15% recurrence); and standard triple therapy with a proton pump inhibitor for 7 days ($236, with 14% recurrence). CONCLUSION: Treatment with any regimen resulted in lower costs compared with H2RA maintenance therapy. Three antibiotic regimens had consistently lower costs and better outcomes: standard triple therapy for 14 days, metronidazole, clarithromycin, and a proton pump inhibitor for 7 days, and standard triple therapy plus a proton pump inhibitor for 7 days.

Anti-Bacterial Agents↗
PubMed1997

Urea breath tests for the detection of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori is recognized as an important human pathogen. The urea breath test, using either 13C or 14C, provides a noninvasive diagnostic method for the detection of active H. pylori infection. METHODS: We review the data regarding the utility of the urea breath test in the diagnosis and follow-up of patients with suspected H. pylori infection. RESULTS: Following its ingestion, labeled urea is hydrolyzed by H. pylori urease, producing ammonia and labeled CO2, which is absorbed and can be detected in expired breath. The urea breath test provides a semiquantitative assessment of the load of H. pylori and overcomes the problem of the sampling error due to the patchy distribution of the infection. 13C-urea breath test has an advantage over the 14C version, because the 13C isotope is a nonradioactive natural isotope; therefore, a user's license is unnecessary, making simple the handling and mailing of samples. The 13C-urea breath test is preferred in children and expectant mothers. CONCLUSION: The high sensitivity, and specificity of the 13C-urea breath test are such that it can be considered a clinical gold standard against which other diagnostic methods can be validated. This test can be used as the sole method for evaluating the effectiveness of treatment of H. pylori infection.

Helicobacter Infections↗
PubMed1997

Nitroarenes of photochemical origin: a possible source of risk to human health.

Nitrated polynuclear aromatics (NPAH) have been recognized as mutagenic even without enzymatic activation. NPAH have been found in the urban air of the U.S.A. and Western Europe. Their detection in the atmosphere has been related mainly to in situ photochemical production. In this study, the ubiquity of NPAH in the air is presented despite their rare and scarce occurrence in emissions released by mobile and stationary sources. NPAH seem to effectively contribute to both the direct and indirect mutagenicity of air soot (in European countries more than in the U.S.A.). Moreover, they can be taken as a suitable index of the occurrence of reactive nitrogen compounds in the air.

Gas Chromatography-Mass Spectrometry↗
PubMed1996

Dexrazoxane cardioprotection for patients receiving FAC chemotherapy: a pharmacoeconomic evaluation.

Anthracyclines are among the most effective and commonly-prescribed antitumor agents but have dose-limiting cumulative cardiotoxicity. We performed a pharmacoeconomic evaluation of the ability of dexrazoxane to prevent cardiac-related adverse events in patients with Stage IIIB or IV metastatic breast cancer who were treated with a median of 10 cycles of intravenous FAC (5-fluorouracil, doxorubicin and cyclophosphamide) at doses of 500/50/500 mg/m2 respectively. Dexrazoxane was given at 500 mg/m2 commencing at the seventh cycle of treatment. We determined the cost of each cardiac event prevented and the cost of each additional life-year saved by dexrazoxane use. The cost per cardiac event prevented was CDN $5745 and the cost per additional life-year saved was CDN $2856. With the increasing use of anthracyclines in Stages I and II breast cancer, these favorable clinical and economic results may broaden the range of therapeutic possibilities for anthracyclines in adjuvant and metastatic therapy of breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[Effects of therapy with bis-hemisuccinate of ursodeoxycholic acid bisodium salt in patients with chronic hepatitis].

It has recently been shown that ursodeoxycholic acid administration improves liver function tests in patients with chronic liver diseases. Aim of the present study was to evaluate an ursodeoxycholic acid derivative (bis-hemisuccinate bisodic salt Ursodamor, Farmaceutici Damor, Napoli) in patients with chronic hepatitis. Forty patients (15 M, 25 F) with biopsy proven chronic liver disease participated to the study. Patients were randomly allocated to two treatment groups. Twenty patients (4 PBC, 11 CAH/CPH, 5 cirrhosis) received the ursodeoxycholic acid derivate at the dose of 600 mg/day, while 20 patients (1 PBC, 11 CAH/CPH, 8 cirrhosis) received a placebo. For both groups the treatment period was six months. ALT serum levels were significantly reduced in the treated group (from 84 +/- 14 to 62 +/- 14 p less than 0.0005) while no significant change was observed in the placebo group. In the treated group but not in the placebo group alkaline phosphatases and gamma-GT were also significantly reduced (from 268 +/- 56 to 160 +/- 23 p less than 0.0005 and from 79 +/- 21 to 45 +/- 10 p less than 0.0005). In conclusion, our results suggest that the administration of the ursodeoxycholic acid derivate, bis-hemisuccinate, bisodic salt, improves liver function tests in patients with chronic liver hepatitis. Similarly to ursodeoxycholic acid this new derivate probably interferes with bile acid pool composition by replacing the more detergent and probably more toxic endogenous bile acid.

Alkaline Phosphatase↗
PubMed1989

Relationship of cytosolic ion fluxes and protein kinase C activation to platelet-derived growth factor induced competence and growth in BALB/c-3T3 cells.

Platelet-derived growth factor (PDGF) and other agents that activate protein kinase C (PKC) rapidly alter cytosolic pH (pHi) and intracellular free calcium ([Ca++]i) in BALB/c-3T3 fibroblasts. To define whether changes in pHi or [Ca++]i are linked to PDGF-stimulated mitogenesis, these parameters were assessed in control and PKC depleted fibroblasts. PDGF addition to BALB/c-3T3 fibroblasts resulted in transient acidification of the cytoplasm followed by prolonged cytosolic alkalinization. Exposure of cells to 12-tetradecanoylphorbol-13-acetate (TPA), a phorbol ester that activates PKC, resulted in cytosolic alkalinization without prior acidification. Overnight incubation with 600 nM TPA decreased the total cell PKC histone phosphorylating activity in BALB/c-3T3 fibroblasts by greater than 90%. In PKC-deficient fibroblasts, TPA, and PDGF-induced alkalinization was abolished. In addition, the transient drop in pHi seen initially in control cells treated with PDGF is sustained to the point where pHi is fully 0.6-0.7 pH units below control cell values for up to 30 minutes. PDGF increased [Ca++]i threefold; this transient rise in [Ca++]i was only minimally affected (less than 15%) by lowering of the extracellular calcium level with ethylene glycol bis(b-aminoethyl ether)0 N,N,N' tetraacetic acid (EGTA) or blocking calcium influx with CoCl2. In contrast, 8-(diethylamine)-octyl-3,4,5-trimethoxybenzoate (TMB-8), an agent thought to inhibit calcium release from intracellular stores, substantially inhibited the rise in [Ca++]i caused by PDGF. TPA and 1-oleoyl-2-acetylglycerol (OAG) increased [Ca++]i but in contrast to PDGF this effect was blocked by pretreatment of cells with EGTA or CoCl2. In PKC-deficient fibroblasts, PDGF still increased [Ca++]i and stimulated DNA synthesis as effectively as in controls. TPA and OAG however, no longer increased [Ca++]i. The continued ability of PDGF to stimulate DNA synthesis in the face of sustained acidification and the absence of PKC activity suggests that cytosolic alkalinization and PKC activation are not essential for PDGF-induced competence in BALB/c-3T3 fibroblasts.

Animals↗
PubMed1988

Inhibition of early platelet-derived growth factor responses in BALB/c-3T3 cells by interferon.

Stimulation of total inositol phosphate production, alteration of cytosolic free calcium [( Ca++]i), vinculin disruption from adhesion plaques, and DNA synthesis caused by PDGF were examined in normal and INF pretreated density arrested BALB/c-3T3 fibroblasts. In normal cells, PDGF caused an increase in total inositol phosphates, a rapid, transient increase in [Ca++]i, disappearance of vinculin from adhesion plaques, and stimulation of DNA synthesis. Pretreatment of cells with INF inhibited PDGF-stimulated increases in [Ca++]i, vinculin disruption from adhesion plaques, and DNA synthesis, but had no effect on PDGF-induced increase in total inositol phosphate levels. These findings suggest that INF prevents entry of quiescent BALB/c-3T3 cells into G1 by inhibiting PDGF-induced release of Ca++ from intracellular stores.

Animals↗