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Background: Pentoxifylline possess antiinflammatory and rheological properties and has been tested in heart failure (HF). Methods: A comprehensive search was performed from 1980 until July 2013 in PubMed, to identify randomized controlled trials evaluating pentoxifylline versus placebo in HF, to determine impact on mortality. Search strategy is as follows: "Pentoxifylline" AND "heart" AND "trial". Study selection of six randomized controlled trials evaluating mortality as outcome. Then, we conducted a meta-analysis of randomized controlled trials versus placebo in HF. Determination of Mantel-Haenszel fixed effect and random-effect pooled odds ratios for all-cause mortality and corresponding 95% confidence intervals. Results: Data from a total of 221 patients with LVEF ≤40% from six randomized controlled trials were included in this analysis. Pentoxifylline 1200 mg per day was administered during 6 months, except in one study (administered during 1 month for severe acute HF). The use of pentoxifylline was not significantly associated with a reduction in mortality in HF in individual studies. The pooled data including 221 patients showed a nearly fourfold reduction in mortality (5.4% vs. 18.3%; OR 0.29; CI 0.12-0.74; P < 0.01) with homogenous results (I² 0%). Conclusion: A meta-analysis evaluating pentoxifylline versus placebo in HF suggested a significant nearly fourfold decrease in all-cause mortality in the pentoxifylline group.

The pharmacokinetic parameters of ibuprofen enantiomers after a single 600 mg dose and repeated 3 x 400 mg doses of Nurofen were determined in 12 healthy volunteers. Terminal half-lives were similar for both enantiomers, but plasma levels of S-ibuprofen were higher than those of R-ibuprofen, due to the chiral inversion and differences in distribution and metabolism. Comparison of maximal concentrations and areas under the concentration vs time curves between the first and last doses for each enantiomer indicated linear pharmacokinetics with no time-dependency. A large inter-individual variability in the ratio of S- to R-ibuprofen average concentrations at steady-state was observed (mean +/- SD 1.89 +/- 0.89) and probably accounts for the known lack of correlation between racemic ibuprofen concentrations and therapeutic efficacy.

Blood culture (BC) efficiency is critical for the diagnosis of bloodstream infection (BSI). We evaluated the impact on standard care of implementing the new BacT/ALERT® FAPlus and FNPlus BC bottles containing antibiotic-binding polymeric beads. We measured positivity rates and time to detection (TTD) during the first 10 months of implementation (PF) and during the previous 10-month period (PS) during which we were using standard aerobic (SA) or standard anaerobic (SN) BC bottles. For each period, the same number of consecutive patients (n = 3,918) was included. Per patient, a median of 1 BC set (1 aerobic and 1 anaerobic bottles) has been sampled. A higher positivity rate was measured during PF than PS when counting per BC bottle (7.0 % vs 5.8 % with 1,456 and 1,237 positive bottles respectively, P < 0.0001) and per BC set (9.6 % vs 7.8 % with 995 and 832 positive BC sets respectively, P < 0.0001). In PF, an increased number of cases due to staphylococci (P < 0.0001) and to Gram-negative bacilli (P < 0.005) was observed, whereas the contamination rate was similar during the two periods (2.4 % of BC sets in PF and 2.3 % in PS). Although antibiotic consumption and medical activity were similar during the two periods, BSI case detection increased from 2.2 to 2.6 per 1,000 hospital-days, especially in intensive care units (ICU; 35.1 to 55.7). Mean TTD for pathogenic microorganisms was significantly shorter in PF than in PS (15.5 h vs 18.0 h, P < 0.01). In conclusion, the use of the new FAPlus/FNPlus BC bottles improved the diagnosis of bacteremia in our hospital, especially in ICU patients.

The pharmacokinetics of fluconazole (50 mg, single oral dose) in saliva and plasma were determined for five healthy subjects and five patients who underwent radiotherapy (dose, >45 Gy over a 6-week period) in the salivary gland area and suffered from oropharyngeal candidiasis. Saliva was collected after electrical stimulation. Fluconazole was measured by liquid chromatography. From healthy volunteers and patients, saliva and plasma were sampled from 0 to 24 h. Although fluconazole penetration kinetics were significantly slowed down in irradiated patients, saliva concentrations of fluconazole were higher than those in the plasma, except at 1 h. In the postdistribution phase, the saliva/plasma concentration ratio was in the range of 1.2 to 1.4, and there was no significant difference between healthy subjects and patients. The saliva concentration of fluconazole was over 1 mg/liter throughout the entire interval 2 to 24 h after drug intake. From these results, the clinical efficacy of fluconazole for oropharyngeal candidiasis is not expected to be less than that in subjects with normal salivary glands, provided that salivary secretion remains.Fluconazole is a broad-spectrum antifungal agent approved in several countries for the treatment of some superficial and deep mycoses. Comparative trials have shown fluconazole to be equal or superior to ketoconazole in the treatment of oropharyngeal candidiasis in patients with AIDS (7) or cancer (17). Fluconazole exhibits a high penetration into body tissues as demonstrated recently by positron emission tomography (9). The volume of distribution of fluconazole approximates that of total body water, the drug exhibits a low level of protein binding (12%) to plasma proteins, and concentrations in saliva, sputum, and vaginal and blister fluid equal those measured in plasma (4). Fluconazole also penetrates into the central nervous system, with levels in the cerebrospinal fluid between 50 and 90% of corresponding levels in plasma, even in the absence of meningitis (11). However, physiological or pathological events can affect tissue penetration and thus possibly clinical outcome. Among these events, irradiation of the salivary glands at a dose greater than 45 Gy results in stomatitis, opportunistic infections (especially candidiasis), increased viscosity of saliva, and qualitative and quantitative modifications of its composition (14,20,22). These modifications are able to decrease penetration of drugs into the salivary gland (13, 18). Although there is no clear relation between fluconazole levels in saliva and clinical outcome, very low levels in saliva or absence of saliva caused by irradiation would be a priori detrimental to efficacy. Indeed, the only clinical failure in the study by Dupont and Drouhet (8) was in an irradiated patient who had no salivary secretion. Thus, the pharmacokinetic parameters describing fluconazole assimilation into saliva were determined for a population of patients who underwent radiotherapy in the salivary gland area.* Corresponding author. MATERIA...