Chemical-free inactivated whole influenza virus vaccine prepared by ultrashort pulsed laser treatment.

There is an urgent need for rapid methods to develop vaccines in response to emerging viral pathogens. Whole inactivated virus (WIV) vaccines represent an ideal strategy for this purpose; however, a universal method for producing safe and immunogenic inactivated vaccines is lacking. Conventional pathogen inactivation methods such as formalin, heat, ultraviolet light, and gamma rays cause structural alterations in vaccines that lead to reduced neutralizing antibody specificity, and in some cases, disastrous T helper type 2-mediated immune pathology. We have evaluated the potential of a visible ultrashort pulsed (USP) laser method to generate safe and immunogenic WIV vaccines without adjuvants. Specifically, we demonstrate that vaccination of mice with laser-inactivated H1N1 influenza virus at about a 10-fold lower dose than that required using conventional formalin-inactivated influenza vaccines results in protection against lethal H1N1 challenge in mice. The virus, inactivated by the USP laser irradiation, has been shown to retain its surface protein structure through hemagglutination assay. Unlike conventional inactivation methods, laser treatment did not generate carbonyl groups in protein, thereby reducing the risk of adverse vaccine-elicited T helper type 2 responses. Therefore, USP laser treatment is an attractive potential strategy to generate WIV vaccines with greater potency and safety than vaccines produced by current inactivation techniques.

Liberal versus restricted fluid resuscitation strategies in trauma patients: a systematic review and meta-analysis of randomized controlled trials and observational studies*.

OBJECTIVE: Hemorrhage is responsible for most deaths that occur during the first few hours after trauma. Animal models of trauma have shown that restricting fluid administration can reduce the risk of death; however, studies in patients are difficult to conduct due to logistical and ethical problems. To maximize the value of the existing evidence, we performed a meta-analysis to compare liberal versus restricted fluid resuscitation strategies in trauma patients. DATA SOURCES: Medline and Embase were systemically searched from inception to February 2013. STUDY SELECTION: We selected randomized controlled trials and observational studies that compared different fluid administration strategies in trauma patients. There were no restrictions for language, population, or publication year. DATA EXTRACTION: Four randomized controlled trials and seven observational studies were identified from 1,106 references. One of the randomized controlled trials suffered from a high protocol violation rate and was excluded from the final analysis. DATA SYNTHESIS: The quantitative synthesis indicated that liberal fluid resuscitation strategies might be associated with higher mortality than restricted fluid strategies, both in randomized controlled trials (risk ratio, 1.25; 95% CI, 1.01-1.55; three trials; I(2), 0) and observational studies (odds ratio, 1.14; 95% CI, 1.01-1.28; seven studies; I(2), 21.4%). When only adjusted odds ratios were pooled for observational studies, odds for mortality with liberal fluid resuscitation strategies increased (odds ratio, 1.19; 95% CI, 1.02-1.38; six studies; I(2), 26.3%). CONCLUSIONS: Current evidence indicates that initial liberal fluid resuscitation strategies may be associated with higher mortality in injured patients. However, available studies are subject to a high risk of selection bias and clinical heterogeneity. This result should be interpreted with great caution.

Multiplex PCR system for rapid detection of pathogens in patients with presumed sepsis - a systemic review and meta-analysis.

BACKGROUND: Blood culture is viewed as the golden standard for the diagnosis of sepsis but suffers from low sensitivity and long turnaround time. LightCycler SeptiFast (LC-SF) is a real-time multiplex polymerase chain reaction test able to detect 25 common pathogens responsible for bloodstream infections within hours. We aim to assess the accuracy of LC-SF by systematically reviewing the published studies. METHOD: Related literature on Medline, Embase, and Cochrane databases was searched up to October 2012 for studies utilizing LC-SF to diagnose suspected sepsis and that provided sufficient data to construct two-by-two tables. RESULTS: A total of 34 studies enrolling 6012 patients of suspected sepsis were included. The overall sensitivity and specificity for LC-SF to detect bacteremia or fungemia was 0·75 (95% CI: 0·65-0·83) and 0·92 (95%CI:0·90-0·95), respectively. LC-SF had a high positive likelihood ratio (10·10) and a moderate negative likelihood ratio (0·27). Specifically, LC-SF had a sensitivity of 0·80 (95%CI: 0·70-0·88) and a specificity of 0·95(95%CI: 0·93-0·97) for the bacteremia outcome, and a sensitivity of 0·61 (95%CI: 0·48-0·72) and a specificity of 0·99 (95%CI: 0·99-0·99) for the fungemia outcome. High heterogeneity was found in the bacteremia outcome subgroup but not in the fungemia outcome subgroup. CONCLUSION: LC-SF is of high rule-in value for early detection of septic patients. In a population with low pretest probability, LC-SF test can still provide valuable information for ruling out bacteremia or fungemia.

Outcome of inadequate empirical antibiotic therapy in emergency department patients with community-onset bloodstream infections.

BACKGROUND: Studies on the effect of inadequate empirical antibiotic therapy on the outcome of patients with systemic infection have led to inconsistent results. METHODS: We analysed data from a comprehensive clinical database collected prospectively in a university hospital between 2008 and 2009. All adult patients who registered in the emergency department (ED) with a bloodstream infection (BSI) were enrolled. Empirical therapy was considered adequate if it included antimicrobials to which the specific isolate displayed in vitro susceptibility and that were administered within 24 h of ED admission. The propensity score (PS) was created by a logistic regression model predicting inadequate empirical therapy. PS-adjusted multivariate analysis was performed by the Cox regression model. The Mortality in Emergency Department Sepsis (MEDS) score was used for the adjustment of residual confounding due to differences in the baseline clinical severity of disease. RESULTS: Out of 937 episodes of bacteraemia, 255 (27.2%) patients received inadequate empirical antimicrobial therapy. A crude analysis showed that inadequate antibiotic therapy was associated with higher mortality rates (hazard ratio 1.78, 95% CI 1.30-2.45). PS-adjusted multivariate analyses also showed a significant adverse impact (hazard ratio 1.59, 95% CI 1.14-2.28). The clinical disease severity significantly modified the effect of inadequate antibiotic therapy on survival. The magnitude of the adverse impact of inadequate antibiotic therapy decreased with the increasing severity of sepsis (P=0.009). CONCLUSIONS: Inadequate empirical antimicrobial therapy for community-onset BSI was associated with higher 30 day mortality rates. Study populations with different clinical severities may have different results, which may help to partly explain the heterogeneous findings in many similar studies.