Aminoglycosides for Intra-Abdominal Infection: Equal to the Challenge?

Background: Aminoglycosides, combined with antianaerobic agents, have been used widely for the treatment of intra-abdominal infection. However, some prospective randomized controlled trials and other data suggested that aminoglycosides were less efficacious than newer comparators for the treatment of these infections. We therefore performed a meta-analysis of all prospective randomized controlled trials utilizing aminoglycosides to reevaluate the efficacy of these agents for the treatment of intra-abdominal infection. Methods: Published English-language prospective randomized controlled trials comparing aminoglycosides with other agents for treatment of intra-abdominal infection were identified by MEDLINE search. For each study, data were collected regarding the number of patients enrolled and evaluated, their basic demographic characteristics, the sources of the intra-abdominal infections, the number of failures as determined by the study investigators, quality score, and the use of serum drug concentrations to monitor aminoglycoside therapy. These data were combined to calculate odds ratios for risk of therapeutic failure, which were assessed for significance using Chi-square analysis. Results: Forty-seven prospective randomized controlled trials comparing aminoglycosides to other agents were identified. These were published between 1981 and 2000, and included a total of 5,182 evaluable patients. Analysis of all studies combined revealed an odds ratio that slightly, but significantly, favored the comparators. After excluding six trials using comparators that lacked accepted antianaerobic efficacy, the odds ratio more strongly favored comparators. Trials published since 1990 also notably favored comparators. Analyzing results by quality score or the use of aminoglycoside monitoring did not alter these findings. Conclusions: In this meta-analysis, aminoglycosides were less efficacious than newer comparators for the treatment of intra-abdominal infection. Given the well-known toxicities of these agents, we conclude that they should not be used as first-line therapy for these infections

Improved Survival Associated with Neoadjuvant Chemoradiation in Patients with Clinical Stage IIIA(N2) Non–Small-Cell Lung Cancer

IntroductionOptimal management of clinical stage IIIA-N2 non–small-cell lung cancer (NSCLC) is controversial. This study examines whether neoadjuvant chemoradiation plus surgery improves survival rates when compared with other recommended treatment strategies.MethodsAdult patients from the National Cancer Database, with clinical stage IIIA-N2 disease definitively treated between 1998 and 2004 at American College of Surgeons Commission on Cancer accredited facilities, were included in the study. Treatment was defined as neoadjuvant chemoradiation plus either lobectomy (NeoCRT+L) or pneumonectomy (NeoCRT+P), lobectomy plus adjuvant therapy (L+AT), pneumonectomy plus adjuvant therapy (P+AT), and concurrent chemoradiation (CRT). Median follow-up and overall survival (OS) were defined from date of diagnosis to last contact. Five-year OS was estimated using Kaplan–Meier methods. Cox proportional hazard regression was used to estimate hazard ratios and 95% confidence intervals (CIs), adjusting for sociodemographic, clinical, and facility characteristics.ResultsMedian follow-up was 11.8 months for 11,242 eligible patients. Five-year OS was 33.5%, 20.7%, 20.3%, 13.35%, and 10.9% for NeoCRT+L, NeoCRT+P, L+AT, P+AT, and CRT, respectively (p < 0.0001). On multivariable analysis, the estimated hazard ratio was 0.51 (CI: 0.45–0.58) for NeoCRT+L; 0.77 (0.63–0.95) for NeoCRT+P; 0.66 (0.59–0.75) for L+AT; 0.69 (0.54–0.88) for P+AT; and 1.0 (reference) for the CRT group. Comorbidity did not attenuate the relationship between treatment and survival.ConclusionThis large study demonstrates that patients with clinical stage IIIA-N2 NSCLC, who underwent neoadjuvant chemoradiation followed by lobectomy, were associated with an improved survival

DC readout experiment in Enhanced LIGO

The two 4 km long gravitational wave detectors operated by the Laser Interferometer Gravitational-wave Observatory (LIGO) were modified in 2008 to read out the gravitational wave channel using the DC readout form of homodyne detection and to include an optical filter cavity at the output of the detector. As part of the upgrade to Enhanced LIGO, these modifications replaced the radio-frequency (RF) heterodyne system used previously. We describe the motivations for and the implementation of DC readout and the output mode cleaner in Enhanced LIGO. We present characterizations of the system, including measurements and models of the couplings of the noises from the laser source to the gravitational wave readout channel. We show that noise couplings using DC readout are improved over those for RF readout, and we find that the achieved shot-noise-limited sensitivity is consistent with modeled results