Percutaneous drainage versus albendazole therapy in hepatic hydatidosis: a prospective, randomized study. Percutaneous drainage compared with surgery for hepatic hydatid cysts. An alternative non-macrolide, non-imidazole treatment regimen for curing Helicobacter pylori and duodenal ulcers: ranitidine bismuth citrate plus amoxicillin. The RBC H. pylori Study Group. A randomized study of adriamycin with and without dimethyl triazenoimidazole carboxamide in advanced uterine sarcomas. Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Successful implementation of the randomized discontinuation trial design: an application to the study of the putative antiangiogenic agent carboxyaminoimidazole in renal cell carcinoma--CALGB 69901. Albendazole versus metronidazole in the treatment of adult giardiasis: a randomized, double-blind, clinical trial. Treatment of Clostridium difficile associated diarrhea and colitis with an oral preparation of teicoplanin; a dose finding study. The Swedish CDAD Study Group. Randomized trial of fluconazole versus nystatin for the prophylaxis of Candida infection following liver transplantation.
Recently, drug treatment and percutaneous drainage have been used successfully when treating hepatic hydatid cysts. Until now, there is no published study comparing the relative safety and efficacy of these two forms of treatment.
                In a prospective study, 33 hepatic hydatid cysts were randomly distributed to receive percutaneous drainage (10), albendazole (10 mg.kg-1.day-1 for 8 weeks) plus percutaneous drainage (12), and albendazole alone (11). Patients were serially assessed by clinical and biochemical examinations, ultrasonography, and hydatid serology.
                On serial ultrasonography, cysts attained heterogeneous echopattern in 18, uniform echogenicity in 11, and disappearance in 3. All 22 cysts treated with percutaneous drainage and only 2 (18.2%) cysts treated with albendazole alone reduced in size and change in echopattern (P < 0.01). Maximum size reduction was observed in cysts treated with a combination of percutaneous drainage and albendazole (P < 0.05). Complications observed with drainage were cyst infection in 2 patients, fever in 3, cyst biliary rupture in 1, and urticaria in 2. These were managed successfully without any mortality. Three patients who received albendazole developed reversible elevation of liver cell enzymes.
                It was concluded that percutaneous drainage with albendazole therapy is an effective form of management for hepatic hydatid cysts. In recent years percutaneous drainage has been used successfully to treat the hepatic hydatid cysts of echinococcal disease. We performed a controlled trial to compare the safety and efficacy of percutaneous drainage with those of surgical cystectomy, the traditional treatment.
                In a prospective study, we randomly assigned 50 patients with hepatic hydatidosis to treatment with percutaneous drainage (25 patients) or cystectomy (25). Albendazole (10 mg per kilogram of body weight per day for eight weeks) was administered to the patients who underwent percutaneous drainage. Serial assessments included clinical and biochemical examinations, ultrasonography, and serologic tests of echinococcal-antibody titers.
                The mean (+/-SD) hospital stay was 4.2+/-1.5 days in the drainage group and 12.7+/-6.5 days in the surgery group (P<0.001). Over a mean follow-up period of 17 months, the mean cyst diameter decreased from 8.0+/-3.0 to 1.4+/-3.5 cm (P<0.001) after percutaneous drainage and from 9.1+/-3.0 to 0.9+/-1.8 cm (P<0.001) after surgery. The final cyst diameter did not differ significantly between the two groups (P=0.20). The cysts disappeared in 22 patients (88 percent) in the drainage group and in 18 (72 percent) in the surgery group (P=0.29). After an initial rise, the echinococcal-antibody titers fell progressively and at the last follow-up were negative (<1:160) in 19 patients (76 percent) in the drainage group and 17 (68 percent) in the surgery group (P=0.74). There were procedure-related complications in 8 patients (32 percent) in the drainage group and 21 (84 percent) in the surgery group, 17 of whom had fever postoperatively (P<0.001).
                Percutaneous drainage, combined with albendazole therapy, is an effective and safe alternative to surgery for the treatment of uncomplicated hydatid cysts of the liver and requires a shorter hospital stay. Because patients who fail to be cured of H. pylori infection following macrolide or imidazole therapy are difficult to treat, there is a clear need for a reasonably effective and simple second-line treatment regimen. The purpose of these two studies was to evaluate the efficacy of ranitidine bismuth citrate (RBC) plus amoxicillin for the cure of H. pylori infection and for healing duodenal ulcers and preventing ulcer relapse.
                Two identically designed randomized, double-blind, double-dummy studies were conducted in patients with an H. pylori-associated duodenal ulcer. Patients were treated with either RBC 400 mg bid for 4 weeks plus amoxicillin 500 mg qid for 2 weeks, RBC 400 mg bid for 4 weeks and placebo qid for 2 weeks, placebo bid for 4 weeks and amoxicillin 500 mg qid for 2 weeks, or placebo bid for 4 weeks and placebo qid for 2 weeks. Patients with healed ulcers after 4 weeks of treatment were eligible for entry into a 24-week observation phase for the assessment of H. pylori status (culture, histology, and CLOtest) and ulcer relapse.
                A total of 229 patients with confirmed H. pylori infection at baseline were evaluated. Of these, 132 whose ulcers had healed entered the 24-week posttreatment observation phase. The combination of RBC plus amoxicillin resulted in higher H. pylori cure rates (55%) and higher duodenal ulcer healing (74%) than did either treatment alone. All treatment were well tolerated.
                The combination of ranitidine bismuth citrate plus amoxicillin cures H. pylori infection in more than half of the patients treated. This treatment regimen shows promise as the basis for future non-macrolide, non-imidazole triple therapy regimens for curing H. pylori infection. Such regimens may be appropriate second-line treatment for patients who are resistant to or who are unable to tolerate macrolide- or imidazole-containing therapies. Various drug combinations including Adriamycin have been tested in soft tissue sarcomas, but optimal treatment remains unclear. We have evaluated Adriamycin with and without dimethyl-triazeno-imidazole-carboxamide (DTIC) in the treatment of Stage III or IV and recurrent sarcomas of the uterus. Two hundred and forty cases of these rare tumors were evaluable. Of 146 evaluable patients with measurable disease, 13/80 (16.3%) of Adriamycin-treated patients and 16/66 (24.2%) of patients receiving the combination showed an objective response (P greater than 0.05). Lung metastases responded more frequently (P equal to 0.04) to combination therapy, but there was no survival advantage. For patients with nonmeasurable disease the progression-free interval was similar (10.0 months for Adriamycin and 8.0 months for the combination). Leiomyosarcomas had a significantly longer survival than other cell types (12.1 versus 6.0 months, P less than 0.001) but there was no advantage for either regimen. There was a suggestion that heterologous mixed mesodermal sarcomas were more responsive to the combination (27.3 versus 8.7%). The addition of DTIC produced significantly more hematologic and gastrointestinal toxicity. Other Adriamycin combinations should be evaluated in uterine sarcomas. Benznidazole, a nitroimidazole derivative, has been recommended for the treatment of acute and congenital Trypanosoma cruzi infection (Chagas' disease). We have examined the safety and efficacy of this drug in the treatment of the early chronic phase of T cruzi infection.
                Between 1991 and 1995, we carried out a randomised, double-blind, placebo-controlled trial in a rural area of Brazil with endemic Chagas' disease. 82% of 2434 schoolchildren (aged 7-12 years) identified in a census were screened for antibodies to T cruzi by indirect immunofluorescence, indirect haemagglutination, and ELISA. 130 were positive in all tests and were randomly assigned benznidazole (7.5 mg/kg daily for 60 days by mouth) or placebo. The primary endpoint for efficacy was the disappearance of specific antibodies (negative seroconversion) by the end of 3-year follow-up. The secondary endpoint was the reduction of antibody titres on repeated serological tests. One child moved away from the area just after randomisation and was excluded from the analyses. Insecticidal measures were taken throughout the trial to reduce the risk of reinfection.
                Minor side-effects requiring no specific medication were recorded in a small proportion of individuals. On a chemiluminescent ELISA with purified trypomastigote glycoconjugate, serum from all participants was positive at the beginning of the trial. At the end of follow-up, 37 (58%) of the 64 benznidazole-treated participants and 3 (5%) of those who received placebo were negative for T cruzi antibodies. The efficacy of benznidazole treatment estimated by intention to treat was 55.8% (95% CI 40.8-67.0). At the end of follow-up, children who received benznidazole had five-fold lower geometric mean titres by indirect immunofluorescence than placebo-treated children (196[147-256] vs 1068[809-1408], p < 0.00001).
                The trial showed that a 60-day course of benznidazole treatment of early chronic T cruzi infection was safe and 55.8% effective in producing negative seroconversion of specific antibodies. The results are very encouraging and justify the recommendation of treatment for seropositive children as public health policy. To assess the disease-stabilizing activity of carboxyaminoimidazole (CAI) in patients with metastatic renal cell cancer (RCC) using a randomized discontinuation trial (RDT) design.
                Recruited patients had a performance status of 0 to 2, minimal neuropathy or cerebellar dysfunction, measurable disease, and normal organ function. Treatment with 250 mg/d CAI was initiated in all patients and continued until disease progression in those with an objective response. Protocol treatment was discontinued for unacceptable toxicity or progressive disease; patients with stable disease at the 16-week evaluation point were randomly assigned in a double-blind manner to continued CAI or placebo. The primary end point was the stable disease rate in the randomized groups.
                A total of 368 patients were accrued and received therapy. Ninety percent had a performance status of 0 or 1, 80% underwent a prior nephrectomy, and 41% had received no prior systemic therapy. Serious or life-threatening toxicity was experienced by 34%, with asthenia (15%) and neuropsychiatric difficulties (7%) being most common. At the randomization point, 51% of patients had progressed, 30% withdrew, 1% experienced a partial response, and 17% had stable disease and were randomly assigned. A Bayesian futility analysis utilizing the first 49 randomly assigned patients suggested that the probability of demonstrating a higher stable disease rate in the experimental group was less than 9% even under the most optimistic a priori assumptions, and further trial accrual was halted.
                CAI is inactive in RCC. The RDT design should be further explored for evaluating activity of putative disease stabilizing agents. Albendazole (ABZ) is a benzimidazole carbamate compound currently in use for human medical practice against enterobiasis and soil-transmitted helminthiasis (STH); However, its spectrum of activity is broad and goes beyond these infections.
                This study compares the efficacy and safety of ABZ versus metronidazole (MTZ) in human giardiasis.
                A randomized, double-blind, clinical trial was carried out at the Centre of Hygiene, Epidemiology and Microbiology in Matanzas City, Cuba. Adult patients with confirmed symptomatic G. duodenalis mono-infection were randomly assigned to receive either ABZ [400 mg daily (n = 75)] or MTZ [250 mg t.i.d. (n = 75)], both for 5 days. Follow-up fecal samples were obtained at 3, 5, 7 days after treatment end.
                The efficacy was similar for both treatment groups: ABZ (82.6%) and MTZ (85.3%); p > 0.05. Side-effects including bitter taste, headache, vomiting and dizziness were significantly higher in the MTZ group. Abdominal pain was significantly higher in ABZ group.
                ABZ was found as effective as MTZ in the treatment of G. duodenalis infections in adult patients from Cuba and could be a useful drug in areas where co-infection with STH infections is common. 92 patients with antibiotic-associated diarrhea were randomized to receive oral teicoplanin 100 mg twice daily for 7 days (BID group); or 50 mg 4 times daily for 3 days, followed by 100 mg twice daily for 4 days (QID group) in a randomized, double-blind, multicentre study. Clostridium difficile was demonstrated by culture and/or cytotoxin test in 49 (53%) patients, of whom 47 (23 male, 24 females, mean age 65 years; 23 in the BID group, 24 in the QID group) were evaluable for clinical efficacy. Prior treatment with cephalosporins was registered in 49%, isoxazolyl-penicillins in 33% and clindamycin in 20% of the C. difficile positive patients. On the last day of treatment, 96% (23 of 24 patients) in the QID group were found cured, compared with 70% (16 of 23 patients) in the BID group (p = 0.02). On days 2 and 3 of treatment, QID group patients had significantly fewer loose stools per day (p < 0.05) than those of the BID group. Clinical recurrence, within 4 weeks post-treatment, occurred in 35% and 33% of the patients in the BID and QID groups, respectively. The bacteriological elimination rate 4 weeks post-treatment was 55% in the BID group and 59% in the QID group. The study was terminated prematurely due to the unexpectedly high clinical failure and recurrence rate in C. difficile positive patients treated with the BID dosage regimen. A prospective, randomized, multicenter study addressed the safety and efficacy of fluconazole therapy in 143 liver transplant patients. Seventy-six patients received daily oral fluconazole (100 mg), and 67 received nystatin (4 X 10(6) U) during the first 28 days after transplantation. Candida colonization occurred in 25% and 53% of patients in the fluconazole and nystatin groups, respectively (P = .04), and 13% and 34% of patients in the respective groups had Candida infections (P = .022). Of these patients, 10.5% in the fluconazole group and 25.3% in the nystatin group had superficial candidal infections (P = .024). Invasive candidiasis developed in 2 patients in the fluconazole group (2.6%) and 6 in the nystatin group (9.0%) (P = .12). There was no increased hepatotoxicity, cyclosporine interaction, or emergence of clinically relevant resistant Candida strains attributable to fluconazole. Thus, oral fluconazole (100 mg) is safe and reduces Candida colonization and infection after liver transplantation.
PAIR seems promising, but there is insufficient evidence to support or refute PAIR with or without benzimidazole coverage for treating patients with uncomplicated hepatic hydatid cyst. Further well-designed randomised clinical trials are necessary to address the topic.