Inadequate statistical power of published comparative cohort studies on ventilator-associated pneumonia to detect mortality differences.

BACKGROUND: Comparative cohort studies are often conducted to identify novel therapeutic strategies or prognostic factors for ventilator-associated pneumonia (VAP). We aimed to evaluate the power of such studies to provide clinically and statistically significant conclusions with regard to mortality differences. METHODS: We searched in PubMed and Scopus for comparative cohort studies that evaluated mortality in patients with VAP. We calculated the central estimates and corresponding 95% confidence intervals (CIs) for mortality differences between compared patient groups. We also calculated the statistical power of the included studies to detect a difference in mortality that corresponds to a risk ratio of 0.80. RESULTS: We identified 39 (20 prospective) comparative cohort studies on VAP as eligible for inclusion in this analysis. The median absolute risk difference in mortality between compared groups was 10% (interquartile range [IQR], 5%-18%), and the median width of the 95% CI of the absolute risk difference in mortality was 34% (IQR, 28%-42.5%). The median power of the included studies to detect a risk ratio for mortality of 0.80 was 14.7% (IQR, 10.6%-21.8%). CONCLUSIONS: There is considerable uncertainty around the central estimate of comparative cohort studies on VAP with regard to mortality differences. For a wiser use of resources allocated to research, we emphasize the need to conduct cohort studies with larger sample size so that potential differences between the compared groups are more likely to be shown.

Comparison of adverse events between oral and intravenous formulations of antimicrobial agents: a systematic review of the evidence from randomized trials.

BACKGROUND: Some clinicians may favor a strategy of early switch to oral antimicrobial therapy for patients responding to initial intravenous therapy. An important relevant consideration refers to the comparative safety and tolerability between oral and intravenous antimicrobial therapy. LITERATURE SEARCH/STUDY SELECTION: We sought to evaluate the above-mentioned issue by performing a systematic review of randomized studies comparing the occurrence of adverse events between oral and intravenous antimicrobial therapy with the same agents. FINDINGS: Ten relevant studies (five randomized controlled trials, three randomized cross-over studies, and two randomized, placebo-controlled, parallel-design studies) were included. Seven of the studies evaluated antibacterials (fluoroquinolones in four, and telithromycin, amoxicillin-clavulanic acid, and linezolid in one study each, respectively), whereas two studies evaluated ganciclovir, and one evaluated isavuconazole. No difference was observed in the rate of total adverse events between oral and intravenous administration of the same antimicrobial agents in any of the included studies that reported specific relevant data. Injection site reactions were noted more frequently with intravenous treatment in one study. No serious drug-related adverse events were reported, while study withdrawals due to adverse events did not considerably differ between the compared groups in any of the included studies. CONCLUSION: There are only limited comparative data regarding the adverse events associated with the administration of the same antimicrobial agents by the oral and intravenous route. Our review indicates that the adverse event profile of oral and intravenous antimicrobial therapy does not differ considerably; however, this issue requires validation by further studies.

Outcome of antimicrobial therapy in documented biofilm-associated infections: a review of the available clinical evidence.

Numerous laboratory findings indicate that microbial biofilms may be encountered in several types of human infections, affecting the activity of antimicrobial agents. We evaluated the clinical evidence regarding the effectiveness of antimicrobial therapy for infections documented to be biofilm-associated, by performing a review of 15 relevant studies, excluding dental and eye infections. In a clinical trial, a significant difference was noted in the effectiveness of antibacterial agents used for catheter-related urinary tract infections in which substantial bacterial adherence on uroepithelial cells was observed. In case series and case reports, 28 patients with biofilm-associated infections documented by electron microscopy scanning were identified. Infection sites included ear, urinary tract, CNS, bloodstream and foreign body implantation site. Pseudomonas and Staphylococcus spp. were the predominant microorganisms among the bacterial or fungal causative pathogens. In 24 cases, infections related to the presence of foreign bodies. Treatment failure or recurrence was noted in all eight patients in whom targeted antimicrobial therapy was instituted before foreign body removal. Foreign body removal coupled with antimicrobial therapy was effective in all ten relevant cases. In four cases of native tissue urinary tract infections, the outcome of the initial antimicrobial therapy was poor. The limited available relevant clinical evidence indicates that conventional antimicrobial therapy alone is not adequately effective against documented biofilm-associated infections. Although some regimens might be more appropriate in this setting, further research on novel therapeutic strategies is needed to improve the outcome of patients with biofilm-associated infections.

Linezolid for patients with neutropenia: are bacteriostatic agents appropriate?

A long-held doctrine is that bactericidal antibiotics are required for infections in neutropenic patients. We evaluated the available published evidence regarding the role of linezolid, a bacteriostatic antibiotic, in neutropenic patients with Gram-positive infection. We retrieved two prospective comparative studies (one of them a double-blind, randomized, controlled trial), a prospective cohort study, two retrospective studies and eight case reports that focused on the use of linezolid for Gram-positive bacterial infections in neutropenic patients. Linezolid was administered to 438 neutropenic patients, mainly on a compassionate-use basis, as other antibiotics failed to cure the infection or were associated with significant adverse events. The clinical cure rate ranged between 57 and 87.3% in the intention-to-treat population of the prospective studies. In total, 56 out of 438 (12.7%) neutropenic patients that received linezolid died during therapy. In the only randomized controlled trial that compared linezolid with vancomycin in the treatment of Gram-positive infections in neutropenic patients, mortality was 5.6 versus 7.6%, respectively (p = 0.4). In conclusion, the available evidence suggests that linezolid may be successful in a significant proportion of neutropenic patients with infection, despite the fact that it is a bacteriostatic agent. Such data seem to justify further studies regarding the role of linezolid in this patient population.

Comparison of SCImago journal rank indicator with journal impact factor.

The application of currently available sophisticated algorithms of citation analysis allows for the incorporation of the "quality" of citations in the evaluation of scientific journals. We sought to compare the newly introduced SCImago journal rank (SJR) indicator with the journal impact factor (IF). We retrieved relevant information from the official Web sites hosting the above indices and their source databases. The SJR indicator is an open-access resource, while the journal IF requires paid subscription. The SJR indicator (based on Scopus data) lists considerably more journal titles published in a wider variety of countries and languages, than the journal IF (based on Web of Science data). Both indices divide citations to a journal by articles of the journal, during a specific time period. However, contrary to the journal IF, the SJR indicator attributes different weight to citations depending on the "prestige" of the citing journal without the influence of journal self-citations; prestige is estimated with the application of the PageRank algorithm in the network of journals. In addition, the SJR indicator includes the total number of documents of a journal in the denominator of the relevant calculation, whereas the journal IF includes only "citable" articles (mainly original articles and reviews). A 3-yr period is analyzed in both indices but with the use of different approaches. Regarding the top 100 journals in the 2006 journal IF ranking order, the median absolute change in their ranking position with the use of the SJR indicator is 32 (1st quartile: 12; 3rd quartile: 75). Although further validation is warranted, the novel SJR indicator poses as a serious alternative to the well-established journal IF, mainly due to its open-access nature, larger source database, and assessment of the quality of citations.

Probiotics for the treatment of allergic rhinitis and asthma: systematic review of randomized controlled trials.

OBJECTIVE: To evaluate the clinical evidence for the use of probiotics as a therapeutic modality for allergic rhinitis (AR) and asthma. DATA SOURCES: PubMed was searched to identify randomized controlled trials (RCTs) that studied the effects of probiotics on AR (n = 12) and asthma (n = 4). STUDY SELECTION: RCTs that studied the effects of probiotics administration on the treatment but not the prevention of AR and asthma were selected for inclusion in this review. RESULTS: Nine of the 12 RCTs that evaluated clinical outcomes in AR showed an improvement due to the use of probiotics. All the RCTs that studied perennial AR showed lower symptom scoring and medication use with the use of probiotics compared with placebo. Also, 5 of the 8 RCTs that referred to seasonal AR suggested an improvement in clinical outcomes. Nine RCTs that reported various immunologic measurements of allergy found no significant probiotic effects. The RCTs that studied the effect of probiotic administration on the treatment of asthma showed no positive effects. CONCLUSIONS: Probiotics may have a beneficial effect in AR by reducing symptom severity and medication use. Many more good-quality studies are needed to resolve this issue.