Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: a meta-analysis.

We conducted a two-part meta-analysis to assess the effectiveness of fluoroquinolones for preventing bacterial infections in granulocytopenic patients who are receiving chemotherapy for malignancies. Overall, 19 randomized studies met selection criteria and were included in this meta-analysis of 2,112 patients. Thirteen studies that compared the fluoroquinolones alone with control regimens (co-trimoxazole, oral nonabsorbable antibiotics, or placebo) and six studies that compared the fluoroquinolones plus prophylaxis for bacteremia due to gram-positive bacteria with control regimens (fluoroquinolones or oral nonabsorbable antibiotics) were included in the two meta-analyses. The results of the first meta-analysis indicate that fluoroquinolones alone are effective in preventing gram-negative bacteremia (overall odds ratio [OR], 0.09; 95% confidence interval [CI], 0.05-0.16; P < .001), but not gram-positive bacteremia (OR, 1.05; 95% CI, 0.76-1.45; P = .7), fever-related morbidity (OR, 0.76; 95% CI, 0.56-1.04; P = .09), and infection-related mortality (OR, 0.79; 95% CI, 0.47-1.34; P = .4). The results of the second meta-analysis indicate that a combination of fluoroquinolones plus prophylaxis for gram-positive bacteremia (penicillin, vancomycin, or macrolides) significantly reduces the occurrence of gram-positive bacteremia (OR, 0.46; CI, 0.33-0.63; P < .001) without affecting the incidence of fever-related morbidity (OR, 0.83; 95% CI, 0.62-1.13; P = .2) and infection-related mortality (OR, 0.74; 95% CI, 0.40-1.38; P = .3)

Effectiveness of gabexate mesilate in acute pancreatitis. A metaanalysis.

Since the effectiveness of gabexate mesilate in patients with acute pancreatitis is controversial, a metaanalysis of the published literature was conducted to address this problem. Five randomized trials were identified by our literature search. Three end points (mortality, complications, and complications requiring surgery) were evaluated. The results of our metaanalysis indicate that the treatment with gabexate mesilate does not affect mortality at 90 days (P = 0.27), but significantly reduces the incidence of complications requiring surgery (odds ratio = 0.61, 95% CI: 0.41-0.89; P < 0.05) and of complications in general (odds ratio = 0.69, 95% CI: 0.54-0.89; P < 0.05). Because the drug proves to be beneficial only to a low proportion of the treated patients, its clinical impact seems to be small. A pharmacoeconomic evaluation shows that its use in all patients with acute pancreatitis would imply a very high cost for preventing each complication. The administration of the drug to select patients who are at higher risk of complications could have a better cost-effectiveness ratio. However, specific studies on this point are still lacking.

Effectiveness of Immunoglobulins for the Prevention of Systemic Infections : A Meta-Analysis of 8 Clinical Studies in Premature Infants.

The prophylactic administration of immunoglobulins to preterm neonates has a controversial effectiveness in reducing the incidence of nosocomial infections. Since the clinical trials conducted so far have given conflicting results, a metaanalysis was carried out to summarise the overall information presently available on this issue. Eight randomised clinical trials were identified by our literature search that met the inclusion criteria of our meta-analysis. In each study, the effectiveness of intravenous immunoglobulins was compared with that of no treatment or placebo. The overall number of patients included in our metaanalysis was 3739. The end-point was the incidence of proven infections. The results of our meta-analysis demonstrate that prophylactic immunoglobulins significantly reduced the incidence of proven infections (pooled odds ratio = 0.79, 95% CI: 0.69 to 0.91; p = 0.0014; reduction in the incidence of infection from 23.2 to 19.3%). There was, however, a significant intertriai heterogeneity. A cost-effectiveness analysis indicated that the prophylactic administration of immunoglobulins implies a cost of approximately $US8000 to prevent each case of infection in premature infants. This cost seems to be at least equal to the cost of treating an episode of sepsis in an infant.

Effectiveness of 5-aminosalicylic acid for maintaining remission in patients with Crohn's disease: a meta-analysis.

OBJECTIVES: We conducted a meta-analysis of the published randomized clinical trials to evaluate the effectiveness of 5-aminosalicylic acid (5-ASA) for maintaining remission in inactive Crohn's disease. METHODS: The trials were identified by standard computerized techniques for literature search. All studies included in the meta-analysis were aimed at evaluating the effectiveness of 5-ASA in comparison with a control group receiving either no treatment or placebo. RESULTS: Our meta-analysis of five clinical trials published as full-length articles indicates that 5-ASA significantly reduces the relapse frequency in patients with inactive Crohn's disease [odds-ratios (95% CI): 0.56 (0.37-0.84) at 6 months, 0.47 (0.33-0.67) at 12 months, 0.53 (0.38-0.73) at 24 months]. The pooled relapse-free rates in the treatment group were 91% at 6 months, 84% at 12 months, and 72% at 24 months; the corresponding rates in the control group were 77%, 60%, and 52%. A second meta-analysis, conducted using the additional information deriving from four randomized trials published as abstracts, gave essentially the same results. CONCLUSIONS: Whereas our meta-analysis shows that the effectiveness of 5-ASA is statistically significant, a simple pharmacoeconomic assessment indicates that the cost for preventing each relapse can lie between $4,000 and $10,000. This cost compares favorably with the average cost for treating a relapse.

Efficacy of hyperimmune anti-cytomegalovirus immunoglobulins for the prevention of cytomegalovirus infection in recipients of allogeneic bone marrow transplantation: a meta-analysis.

We carried out an analysis of the randomized clinical trials published on the effectiveness of hyperimmune immunoglobulins for prevention of cytomegalovirus (CMV) infection or disease in CMV-seronegative recipients of allogeneic bone marrow transplantation (BMT). The clinical trials were identified by searching a number of computerized literature databases, by reviewing bibliographies of the paper examined and by consulting experts. All studies we selected were randomized and were aimed at evaluating the efficacy of hyperimmune immunoglobulins in comparison with a control group receiving no immunoglobulins. The results of this analysis indicate that hyperimmune immunoglobulins reduce the frequency of CMV infection (overall odds ratio = 0.444; 95% confidence interval 0.237-0.832, p = 0.011) and CMV related disease (overall odds ratio = 0.445; 95% confidence interval 0.223-0.887, p = 0.021) in CMV-seronegative recipients of allogeneic BMT.

Meta-analysis of clinical trials based on censored end-points: simplified theory and implementation of the statistical algorithms on a microcomputer.

Meta-analysis is increasingly being used in clinical research. While the meta-analytical algorithms for pooling the results of studies using non-censored end-points are now sufficiently standardized, the management of trials based on censored end-points is still controversial, and specific algorithms of meta-analysis are still needed (for example, censored end-points are commonly used in survival studies of cancer patients). In the present article we review the various algorithms that have thus far been utilized to perform a meta-analysis based on censored end-points, and we propose a new and original approach that combines two of the existing algorithms. Our approach is designed to formulate any meta-analysis of survival studies in terms of the calculation of an odds ratio. The meta-analytical odds ratio proposed here is called the 'log-rank' odds ratio of meta-analysis. A microcomputer program is described that implements the various methods of meta-analysis that can handle clinical trials based on censored end-points. Some examples are presented to illustrate the use of the program.