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The objective of this study was to evaluate the cost-effectiveness of voriconazole versus amphotericin B as primary therapy for immunocompromised patients with aspergillosis. We used a pre-existent model in which two cohorts of patients received voriconazole or amphotericin B. The patients were followed for 12 weeks. The analysis was conducted from the perspective of the Italian National Health Service. We considered life years gained (LYG) and direct medical costs. LYG were based on the results of an international clinical trial and direct medical costs were based on Italian treatment patterns. Benefits were discounted at 3%. Sensitivity analysis on key clinical and economic parameters were performed. LYG with voriconazole compared with amphotericin B were respectively 13,87 and 11,36 years. The expected cost was € 25.366 with voriconazole and € 26.218 with amphotericin B. This cost-effectiveness analysis suggests that voriconazole is a dominant strategy compared with amphotericin B for the primary treatment of aspergillosis in immunocompromised patients.

Objective: Our study was designed to evaluate the effects of 2 dosage schedules of recombinant interferon (IFN)-α (IFNα-2a and IFNα-2b) in reducing serum ALT and eradicating serum hepatitis C virus (HCV) RNA in β-thalassaemic patients with chronic hepatitis C. Design: 38 Sicilian β-thalassaemic patients (22 males and 16 females) received intramuscular IFNα-2a (Roferon-A®; Roche) 5 MU/m2 3 times weekly for 6 months, followed by 3 MU/m2 3 times weekly for a further 6 months. 13 Sardinian β-thalassaemic patients (7 males and 6 females) received intramuscular IFNα-2b (Intron®; Schering-Plough) 3 MU/m2 3 times weekly for 12 months. Parallel control groups (n = 20 and n = 8, respectively) did not receive IFNα. All patients received continuous subcutaneous desferoxamine infusion. Results: 24 (63%) Sicilian patients had a positive clinical response to IFNα-2a therapy. Two different patterns of response were apparent: (i) early and progressive decrease in ALT values until stable normalisation; and (ii) slower reduction of ALT values, which fluctuated on the way to normalisation. Five (21%) patients relapsed during the 12-month follow-up period. ALT levels decreased early in 5 (38%) Sardinian patients and one patient (20%) relapsed during the 12-month follow-up period. In the control groups, ALT values spontaneously normalised in 3 (10%) untreated patients. None of the patients treated with IFNα developed anti-IFNα antibodies. Viral clearance was demonstrated in 19 (50%) of 38 patients in the Sicilian group and 4 of 13 patients (31%) in the Sardinian group. Conclusion: Treatment with intramuscular recombinant IFNα-2a 5 MU/m2 3 times weekly for 6 months, followed by 3 MU/m2 3 times weekly for 6 months, appeared to be more effective than intramuscular IFNα-2b 3 MU/m2 3 times weekly for 12 months.

Thirty-eight clinical strains of Helicobacter pylori were isolated from patients with chronic gastritis and gastroduodenal ulceration, and their susceptibility to macrolide antibiotics (roxithromycin, flurithromycin, azithromycin, erythromycin) in combination with proton-pump inhibitors (lansoprazole and omeprazole) and bismuth subcitrate was assayed. Chequerboard titration was used to analyse the results of antimicrobial interactions and showed that the activity of macrolides was enhanced by combining them with lansoprazole, omeprazole or, to a lesser extent, bismuth subcitrate. While the interactions between erythromycin and the proton-pump inhibitors or bismuth subcitrate were always additive, the combinations of roxithromycin-lansoprazole, flurithromycin-omeprazole and azithromycin-lansoprazole acted synergically on 82%, 60% and 60% of H. pylori strains, respectively. These results may, in part, account for the enhanced clinical efficacy of macrolides administered with proton-pump inhibitors in the treatment of H. pylori-associated diseases.

Thromboembolic (TE) events have been frequently reported in β-thalassemic patients in association with known risk factors such as diabetes, complex cardiopulmonary abnormalities, hypothyroidism, liver function anomalies, and postsplenectomy thrombocytosis. In a recent survey involving 9 Italian thalassemic centers, we identified 32 patients with TE episodes in a total of 735 subjects, of whom 683 had thalassemia major and 52 thalassemia intermedia, corresponding to 3.95 and 9.61%, respectively. There was a great variation in localization: the main one (16/32) was CNS, with a clinical picture of headache, seizures and hemiparesis. Other localizations were the pulmonary (3 patients), mesenteric (1 patient) and portal (2 patients) sites. There were 6 cases of deep venous thrombosis (2 in the upper limbs, 4 in the lower ones). Intracardiac thrombosis was found in 2 subjects and clinical and laboratory signs of DIC were observed in 2 others during pregnancy. Since our patients with TE events present a statistically significantly higher incidence of associated dysfunction (cardiomyopathy, diabetes, liver function anomalies, hypothyroidism) than those without TE events (50 vs. 13.8%), we suggest close monitoring of those patients who are at higher risk of developing TE events because of the presence of one or more of these predisposing factors.

Osteoporosis in beta-thalassemia major has emerged as a topic of interest since optimized transfusion regimens have increased life expectancy and quality in these patients. Although the pathogenesis of thalassemic osteopathy is multifactorial, the evidence of an increased resorption phase suggests that the use of antiresorptive drugs such as bisphosphonates can be considered a valuable therapeutic strategy to reduce bone turnover and the risk of fragility fractures. We compared the effects of long-term cyclical clodronate therapy (300 mg intravenous infusion every 3 weeks for 2 years) and of an active placebo (calcium 1 vitamin D) on bone mass and bone turnover in 30 male patients with beta-thalassemia major. We also tested the possibility of using quantitative ultrasound (QUS) for assessing bone involvement in thalassemic osteopenia and in monitoring the response to antiresorptive therapy. Broadband ultrasound attenuation (BUA) was significantly reduced in patients with beta-thalassemia major as compared to healthy controls. In calcium and vitamin D-treated patients, a significant decline in spine, femoral, and total body areal bone density was observed. In the patients given intravenous clodronate we measured a substantial stability of bone mass, which was not significantly changed at the end of the study. The urinary excretion of deoxypyridinoline (a marker of bone resorption) showed a progressive significant decline throughout the study period in clodronate-treated patients. No significant change was observed in BUA values in both groups of patients. These results indicate that intermittent intravenous clodronate administration was not able to increase areal bone density in our thalassemic patients. Moreover, this is the first study to have assessed the usefulness of broadband ultrasound measurements in beta-thalassemia major.

The case of a young man effected by homozygous beta-thalassemia is reported who had serologic findings of a prior HBV infection and who presented with clinical and biochemical acute HBV infection probably caused by HBV reactivation after allogeneic bone marrow transplantation. The patient's clinical history suggests that HBV can persist without serological findings of HBsAg and HBV-DNA in persons previously infected by HBV and that HBV reactivation can occur 2 years after allogeneic bone marrow transplantation, as a result of immunosuppressive therapy or an HCV activation.

We evaluated the immune status with respect to HBV and the immune response to readministration of HBV vaccine in a series of 20 patients with homozygous beta-thalassemia, aged 6-23 years (mean age: 13.0 +/- 4.2) who had undergone allogeneic bone marrow transplantation (BMT). Thirteen of them (group A), had received three doses of plasma-derived HBV vaccine from 7 to 5 years before BMT and 4-5 weeks after the last dose of vaccine, they had had high serum levels of HBV antibodies (anti-HBs). The remaining seven patients (group B) had had clinical symptoms and laboratory evidence of HBV infection in childhood with markedly elevated serum of anti-HBs. Before revaccination, a significantly lower percentage of patients (P < 0.005) with seropositive levels of anti-HBs was observed in group A than in group B. After administration of the second dose of HBV vaccine the percentage of subjects with protective levels of anti-HBs rose to 100% in both groups of patients even if the geometric mean of titers of anti-HBs increased more significantly in group B patients than in group A. We conclude that the serum levels of anti-HBs afforded by HBV vaccine administered from 7 to 5 years previously are very low and probably non-protective in most beta-thalassemic patients after allogeneic BMT, and that at least two doses of HBV vaccine should be readministered from 18 to 24 months after BMT to achieve adequate and long-term protection from HBV.

Sixteen patients with thalassaemia major were treated with subcutaneous desferrioxamine (DF) 50 mg/kg/d, 5 consecutive days a week, for 8 weeks. Every other week the total dose was administered by 12 h infusion pump or by rapid injection of the same dose (25 x 2 mg/kg) twice a day. The two methods of DF administration produced no significant differences in urinary iron excretion. No significant changes in serum ferritin levels were observed at the end of the study. Compared with continuous infusion, rapid injection is equally efficacious, does not induce serious side-effects, is better accepted by the patients, and can improve their compliance to the iron-chelating therapy.

A 10-mo-old baby girl with homozygous beta0 thalassemia and alphaJOxford, presenting the clinical picture of homozygous beta thalassemia is described. Hemoglobin electrophoresis showed three bands: the first two with the mobilities of hemoglobin Hb A2 (1%) and Hb F (69%), respectively, the third migrating a little faster than Hb A (30%). About 30% of her alpha chains were J Oxford which, bound to her gamma chains, produced a new alkali-resistant hemoglobin, alpha2 J Oxford gamma F2, which has not been described previously. Hemoglobin synthesis in vitro showed the absence of beta chain synthesis and an alpha/non-alpha ratio of 2. The patient's father was heterozygous for both the Hb J Oxford and beta0 thalassemia genes, the mother a carrier of beta0 thalassemia; four other relatives were carriers of Hb J Oxford, and one was a carrier of beta thalassemia.

Haemoglobin synthesis was studied in bone marrow erythroblasts and in reticulocytes of 4 children with β°- thalassaemia major and of 7 children with β+ -thalassaemi

Eight Sicilian patients with Hb H disease and their families have been studied. The standard haematological tests and the alpha/beta chain synthesis ratios showed significantly different results in the patients with Hb H disease as compared with alpha thalassaemia carriers, except for Hb A2 values. There was no significant difference in the mean RBC, MCV, Hb A2, Hb A1 and Hb F of alpha thalassaemia carriers compared with normal controls. On the contrary significant difference was found between the mean alpha/beta chain synthesis ratio of alpha thalassaemia carriers and that of the normal controls; however, the extensive overlapping of alpha/beta values between these two conditions make this parameter insufficiently discriminant. No correlation was found between MCV, MCH, RBC and alpha/beta chain synthesis ratio in patients with alpha thalassaemia trait, suggesting that the ratio cannot be used to distinguish between carriers of a mild gene ('silent' carrier) and carriers of the more severe alpha thalassaemia gene. A possible genetic model for alpha thalassaemia in Sicily is presented.

Lymphocyte subpopulations were studied in 20 hypertransfused patients with beta-thalassaemia major, some of whom had been splenectomised. B-lymphocytes were normal but T-lymphocytes were decreased in all patients. The T-cell count was lower in the splenectomised patients than in the nonsplenectomised ones. In the former, the active rosette-forming lymphocytes were also diminished, but the difference was not significant. In all patients the percentage of null cells was greater and the activity of K-cells increased compared with controls.

In a prospective study, 144 patients undergoing thoracotomy were randomized to two groups: In 71 cases cryoanalgesia was applied intraoperatively to the intercostal nerves above and below the incision to relieve postoperative pain, and 73 (control group) received bupivacaine-adrenaline intercostal blockade at the end of the operation. The amount of administered narcotic and mild analgesics, the visual analogue pain scores, the need for further intercostal blockade and the number of postoperative bronchoscopies to clear retained secretion were significantly less in the cryoanalgesia group than in the controls. There were no late nerve complications after cryoanalgesia, which is recommended for routine use in thoracotomy.

A 10-mo-old baby girl with homozygous beta0 thalassemia and alphaJOxford, presenting the clinical picture of homozygous beta thalassemia is described. Hemoglobin electrophoresis showed three bands: the first two with the mobilities of hemoglobin Hb A2 (1%) and Hb F (69%), respectively, the third migrating a little faster than Hb A (30%). About 30% of her alpha chains were J Oxford which, bound to her gamma chains, produced a new alkali-resistant hemoglobin, alpha2 J Oxford gamma F2, which has not been described previously. Hemoglobin synthesis in vitro showed the absence of beta chain synthesis and an alpha/non-alpha ratio of 2. The patient's father was heterozygous for both the Hb J Oxford and beta0 thalassemia genes, the mother a carrier of beta0 thalassemia; four other relatives were carriers of Hb J Oxford, and one was a carrier of beta thalassemia.

The results of hematological and biosynthetic studies in 15 subjects carriers of Hb Lepore and in 5 double heterozygotes for Hb Lepore and thalassemia are presented. In the carriers the hematological and biosynthetic data are compared with carriers of thal., while the five double heterozygous patients were compared with ° and + thal. major subjects. In the carriers of Hb Lepore no synthesis of chains was observed in the peripheral blood cells, on the contrary we found a peak in the bone marrow. Double heterozygous subject with circulating nucleated red cells showed in the peripheral blood chains synthesis.