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)

Objectives To determine the effectiveness of ranitidine and sucralfate in the prevention of stress ulcer in critical patients and to assess if these treatments affect the risk of nosocomial pneumonia. Design Published studies retrieved through Medline and other databases. Five meta-analyses evaluated effectiveness in terms of bleeding rates (A: ranitidine v placebo; B: sucralfate v placebo) and infectious complications in terms of incidence of nosocomial pneumonia (C: ranitidine v placebo; D: sucralfate v placebo; E: ranitidine v sucralfate). Trial quality was determined with an empirical ad hoc procedure. Main outcome measures Rates of clinically important gastrointestinal bleeding and nosocomial pneumonia (compared between the two study arms and expressed with odds ratios specific for individual studies and meta-analytic summary odds ratios). Results Meta-analysis A (five studies) comprised 398 patients; meta-analysis C (three studies) comprised 311 patients; meta-analysis D (two studies) comprised 226 patients: and meta-analysis E (eight studies) comprised 1825 patients. Meta-analysis B was not carried out as the literature search selected only one clinical trial. In meta-analysis A ranitidine was found to have the same effectiveness as placebo (odds ratio of bleeding 0.72, 95% confidence interval 0.30 to 1.70, P = 0.46). In placebo controlled studies (meta-analyses C and D) ranitidine and sucralfate had no influence on the incidence of nosocomial pneumonia. In comparison with sucralfate, ranitidine significantly increased the incidence of nosocomial pneumonia (meta-analysis E: 1.35, 1.07 to 1.70, P = 0.012). The mean quality score in the four analyses (on a 0 to 10 scale) ranged from 5.6 in meta-analysis E to 6.6 in meta-analysis A. Conclusions Ranitidine is ineffective in the prevention of gastrointestinal bleeding in patients in intensive care and might increase the risk of pneumonia. Studies on sucralfate do not provide conclusive results. These findings are based on small numbers of patients, and firm conclusions cannot presently be proposed.

Sodium valproate (valproic acid) has been widely used in the last decade and is now considered a relatively safe and effective anticonvulsant agent. Recently, several investigators have proposed its use in the treatment of anxiety, alcoholism and mood disorders, although these indications require further clinical studies. Valproic acid is available in different oral formulations such as solutions, tablets, enteric-coated capsules and slow-release preparations. For most of these formulations bio-availability approaches 100%, while the absorption half-life varies from less than 30 minutes to 3 or 4 hours depending on the type of preparation used. Once absorbed, valproic acid is largely bound to plasma proteins and has a relatively small volume of distribution (0.1 to 0.4 L/kg). Its concentration in CSF is approximately one-tenth that in plasma and is directly correlated with the concentration found in tears. At therapeutic doses, valproic acid half-life varies from 10 to 20 hours in adults, while it is significantly shorter (6 to 9 hours) in children. Valproic acid undergoes extensive liver metabolism. Numerous metabolites have been positively identified and there is reasonable evidence that several of them contribute to its pharmacological and toxic actions. In fact, several valproic acid metabolites have anti-convulsant properties, while many of the side effects it may cause (e.g. those related to hyperammonaemia or liver damage) are most often observed in patients previously treated with phenobarbitone. This could indicate that induction of liver enzymes is responsible for the formation of toxic valproic acid metabolites.