Compliance with biologic therapies for rheumatoid arthritis: do patient out-of-pocket payments matter?

OBJECTIVE: To assess the impact of patient out-of-pocket (OOP) expenditures on adherence and persistence with biologics in patients with rheumatoid arthritis (RA). METHODS: An inception cohort of RA patients with pharmacy claims for etanercept or adalimumab during 2002-2004 was selected from an insurance claims database of self-insured employer health plans (n=2,285) in the US. Adherence was defined as medication possession ratio (MPR): the proportion of the 365 followup days covered by days supply. Persistence was determined using a survival analysis of therapy discontinuation during followup. Patient OOP cost was measured as the patient's coinsurance and copayments per week of therapy, and as the proportion of the total medication charges paid by the patient. Multivariate linear regression models of MPR and proportional hazards models of persistence were used to estimate the impact of cost, adjusting for insurance type and demographic and clinical variables. RESULTS: Mean +/- SD OOP expenditures averaged $7.84+/-$14.15 per week. Most patients (92%) paid less than $20 OOP for therapy/week. The mean +/- SD MPR was 0.52+/-0.31. Adherence significantly decreased with increased weekly OOP (coeff= -0.0035, P<0.0001) and with a higher proportion of therapy costs paid by patients (coeff= -0.8794, P<0.0001), translating into approximately 1 week of therapy lost per $5.50 increase in weekly OOP. Patients whose weekly cost exceeded $50 were more likely to discontinue than patients with lower costs (hazard ratio 1.58, P<0.001). CONCLUSION: Most patients pay less than $20/week for biologics, but a small number have high OOP expenses, associated with lower medication compliance. The adverse impact of high OOP costs on adherence, persistence, and outcomes must be considered when making decisions about increasing copayments.

Cytokine gene polymorphisms in gastric cancer patients from two Italian areas at high and low cancer prevalence.

Polymorphisms of interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL1-RN), and tumor necrosis factor-alpha (TNF-alpha) genes are supposed to be key determinants of gastric cancer risk. Our aim was to study the association between these polymorphisms and gastric cancer in two areas characterized by high (Pavia/Bologna, North Italy) and low (San Giovanni Rotondo, South Italy) gastric cancer prevalence. Genomic DNA was obtained from 216 healthy donors and 98 gastric cancer patients from Pavia and Bologna, and 146 healthy donors and 86 gastric cancer patients from San Giovanni Rotondo. Two SNP in IL-1beta (-511 C/T) and TNF-alpha (-308 G/A) as well as the VNTR polymorphism of IL-1RN locus were studied. A significant linkage disequilibrium was found between IL-1beta -511 and IL-1RN. Genotype and allele frequencies at the IL-1beta, IL-1RN, and TNF-alpha loci in gastric cancer cases were not significantly different from controls. An epistatic effect between IL-1beta -511 and IL-1RN was found with the IL-1beta -511C/IL-1RN*2 haplotype conferring a significant protection against the intestinal-type of gastric cancer in the Southern population. In conclusion, IL-1beta, IL1-RN, and TNF-alpha genotypes are not associated with gastric cancer in Italian patients. An epistatic interrelationship between IL-1beta -511 and IL-1RN confers protection against gastric cancer in low-risk Italian population.

Evaluation of quality of life in a clinical trial with nonrandom dropout: the effect of epoetin alfa in anemic cancer patients.

Quality of life (QOL) endpoints from a randomized, placebo-controlled trial of anemic cancer patients treated with nonplatinum-containing chemotherapy who received epoetin alfa or placebo were subjected to a sensitivity analysis. Three QOL instruments were used: the Functional Assessment of Cancer Therapy-Anemia (FACT-An), the Cancer Linear Analog Scale (CLAS), and the Medical Outcomes Study Short Form-36 (SF-36). The seven primary endpoints chosen a priori for analysis were: the Functional Assessment of Cancer Therapy-General (FACT-G) Total, FACT-An fatigue subscale, CLAS energy, CLAS daily activities, CLAS overall QOL, and the SF-36 physical and mental component summary scales. Lower QOL scores were reported for patients who discontinued early, suggesting a nonrandom dropout process. Significant correlations (ranging from 0.37 to 0.77) between individual rates of change and the time to early termination of therapy or death supported this conclusion. Estimates of within-treatment-arm QOL change over time are more conservative with the missing not at random (MNAR) assumption as compared with the more optimistic estimates with the assumption that missing QOL data are missing at random (MAR). However, the between-treatment-arm comparisons were consistent across analyses, demonstrating statistically significant differences in favor of the epoetin alfa arm for four of the seven outcome measures.

Assessing the clinical significance of health-related quality of life (HrQOL) improvements in anaemic cancer patients receiving epoetin alfa.

Health-related quality of life (HrQOL) assessments are gaining importance as outcome measures in cancer clinical trials. A recently published clinical trial reported statistically significant (P<0.001) increases in haemoglobin (Hb) levels and significantly (P<0.01) increased HrQOL scores following the administration of recombinant human erythropoietin (r-HuEPO, epoetin alfa) versus placebo to anaemic cancer patients who received non-platinum chemotherapy. This study employed five cancer-specific HrQOL instruments. Hb and HrQOL data from this trial were analysed to estimate the minimally important difference (MID) in HrQOL measures that could be interpreted as clinically meaningful, with Hb level selected as the best external standard. Patients were assigned to two groups: improved (Hb increases of >/=1 g/dL) or stable (change in Hb of-1 g/dL to <1 g/dL). The MID was first determined as the difference between the mean changes in HrQOL in the improved group versus the stable group. By this analysis, the differences in HrQOL scores between the epoetin alfa group and the placebo group were clinically important for all Hb-sensitive, cancer-specific HrQOL evaluations. Linear regression analyses performed to provide estimates of the MID for specific values of Hb change confirmed that the differences in HrQOL scores between patient groups were clinically significant. These analyses were repeated using a data set from a separate clinical trial, which further supported the conclusion that observed HrQOL changes demonstrated in the multicentre, double-blind study were clinically important. These methods provide one means for interpreting the clinical relevance of changes in HrQOL evaluated in clinical trials.

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.

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.

A cost analysis of diabetic lower-extremity ulcers.

OBJECTIVE: Our objectives were to 1) estimate the prevalence of diabetes and diabetic lower-extremity ulcers in the Medicare population, 2) characterize Medicare population-specific costs for lower-extremity ulcer episodes, and 3) evaluate potential cost savings associated with better healing of lower-extremity ulcers. RESEARCH DESIGN AND METHODS: Prevalence and costs of diabetic lower-extremity ulcers were obtained by an analysis of Medicare claims data from 1995 and 1996 Standard Analytic Files (5% sample). RESULTS: Medicare expenditures for lower-extremity ulcer patients were on average 3 times higher than those for Medicare patients in general ($15,309 vs. $5,226). Lower-extremity ulcer-related spending accounted for 24% of total spending for lower-extremity ulcer patients. Most of the ulcer-related costs accrued on the inpatient side (73.7%); proportionately smaller amounts went to physicians and nursing home facilities. To determine the potential effect of better diabetic ulcer management, a model was created that estimated the impact on costs with improved healing rates. Improving the 20-week healing rate from 31 to 40% would save Medicare $189 per episode. CONCLUSIONS: Lower-extremity ulcers cost the Medicare system $1.5 billion in 1995. Any wound care intervention that could prevent even a small percentage of wounds from progressing to the stage at which inpatient care is required may have a favorable cost effect on the Medicare system.

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.

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.

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.

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.

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.

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).

Costs and duration of care for lower extremity ulcers in patients with diabetes.

Medical and pharmaceutical insurance claims associated with lower extremity diabetic ulcers were examined retrospectively to better understand the costs and duration of treatment in clinical practice. The study population consisted of working-age individuals (18 to 64 years old) with health care benefits provided through private employer-sponsored insurance plans. Diagnostic information contained in the claims database was used to identify the severity of the ulcers, and the charges associated with treatment were based on claims data. Claims for lower extremity ulcers were found in 5.1% of individuals with diabetes. Although many lower extremity ulcers heal with standard treatment, some are more resistant to treatment and require costly ongoing medical care. Almost half of these cases were associated with deep infection, osteomyelitis, or amputation. Total payments for treatment of lower extremity ulcers in this population averaged $2687 per patient per year, or $4595 per ulcer episode, with inpatient expenditures accounting for more than 80% of these costs. Costs were significantly higher for patients with more severe ulcers or with inadequate vascular status in the affected limb. We concluded that lower extremity ulcers occur in a large number of working-age people with diabetes and contribute significantly to the morbidity associated with this disease. The high cost of treating diabetic foot ulcers suggested by this analysis argues for the development of better treatment strategies and outcomes assessments for these patients.

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.

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.

A pharmacoeconomic evaluation of the use of dexrazoxane in preventing anthracycline-induced cardiotoxicity in patients with stage IIIB or IV metastatic breast cancer.

A Markov model was developed to determine the cost of treating patients with stage IIIB or IV metastatic breast cancer with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) and dexrazoxane (administered after six courses of FAC) versus FAC alone. The primary end point in our economic study was cost per cardiac event avoided. Cost per life-year saved was also calculated, even though the survival advantage needs to be confirmed in follow-up studies. The model incorporated the direct medical costs of treating patients with chemotherapy, as well as the costs associated with treatment of any cardiac events that occurred. Data were collected for this analysis from several sources, including completed clinical trials on FAC plus dexrazoxane versus FAC plus placebo (obtained from two patient groups randomized at different time points), a panel of three oncologists, and a panel of three cardiologists. Analyses showed that therapy with dexrazoxane costs $5661.77 per cardiac event prevented. Sensitivity analyses on model variables were performed and showed that the basic results of the model did not change when parameters were varied. The clinical efficacy and cost-effectiveness of dexrazoxane as shown by the results of the current study encourage further investigation of the uses of dexrazoxane in other populations and against other comparators.

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.

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.

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.