Evaluation of RNAi therapeutics VIR-2218 and ALN-HBV for chronic hepatitis B: Results from randomized clinical trials.

Background & Aims: Current therapy for chronic hepatitis B virus (cHBV) infection involves lifelong treatment. New treatments that enable HBV functional cure would represent a clinically meaningful advance. ALN-HBV and VIR-2218 are investigational RNA interference therapeutics that target all major HBV transcripts.

Clinical and Preclinical Single-Dose Pharmacokinetics of VIR-2218, an RNAi Therapeutic Targeting HBV Infection.

Background And Objective: VIR-2218 is an investigational N-acetylgalactosamine-conjugated RNA interference therapeutic in development for chronic hepatitis B virus (HBV) infection. VIR-2218 was designed to silence HBV transcripts across all genotypes and uses Enhanced Stabilization Chemistry Plus (ESC+) technology. This study was designed to evaluate the single-dose pharmacokinetics of VIR-2218 in preclinical species and healthy volunteers.

Evaluation of Plazomicin, Tigecycline, and Meropenem Pharmacodynamic Exposure against Carbapenem-Resistant Enterobacteriaceae in Patients with Bloodstream Infection or Hospital-Acquired/Ventilator-Associated Pneumonia from the CARE Study (ACHN-490-007).

Introduction: CARE was a Phase 3, randomized study evaluating the efficacy and safety of plazomicin-based combination therapy compared with colistin-based combination therapy for the treatment of patients with bloodstream infections or hospital-acquired/ventilator-associated pneumonia due to carbapenem-resistant Enterobacteriaceae (CRE). Adjunctive therapies included either tigecycline or meropenem. We sought to understand the contribution of tigecycline and meropenem to plazomicin-treated-patient outcomes by determining their observed pharmacodynamic exposures against baseline pathogens.

Outcomes of high-dose levofloxacin therapy remain bound to the levofloxacin minimum inhibitory concentration in complicated urinary tract infections.

Background: Fluoroquinolones are a guideline-recommended therapy for complicated urinary tract infections, including pyelonephritis. Elevated drug concentrations of fluoroquinolones in the urine and therapy with high-dose levofloxacin are believed to overcome resistance and effectively treat infections caused by resistant bacteria. The ASPECT-cUTI phase 3 clinical trial (ClinicalTrials.

Efficacy of ceftolozane/tazobactam against urinary tract and intra-abdominal infections caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae: a pooled analysis of Phase 3 clinical trials.

Objectives: The increase in infections caused by drug-resistant ESBL-producing Enterobacteriaceae (ESBL-ENT) is a global concern. The characteristics and outcomes of patients infected with ESBL-ENT were examined in a pooled analysis of Phase 3 clinical trials of ceftolozane/tazobactam in patients with complicated urinary tract infections (ASPECT-cUTI) and complicated intra-abdominal infections (ASPECT-cIAI).

Methods: Trials were randomized and double blind.

Efficacy of ceftolozane/tazobactam versus levofloxacin in the treatment of complicated urinary tract infections (cUTIs) caused by levofloxacin-resistant pathogens: results from the ASPECT-cUTI trial.

Objectives: Empirical fluoroquinolone therapy is widely used in treating complicated urinary tract infections (cUTIs), even in areas of high fluoroquinolone resistance. While it is believed that high antibiotic concentrations in urine might be sufficient to overcome and effectively treat infections caused by resistant bacteria, clinical trial data validating this assumption are limited. This post hoc analysis evaluated the efficacy of ceftolozane/tazobactam versus levofloxacin in the subgroup of patients with cUTIs caused by levofloxacin-resistant pathogens in a randomized, controlled trial (NCT01345929/NCT01345955).

Surgical site infections following transcatheter apical aortic valve implantation: incidence and management.

Objective: The present study was undertaken to examine the incidence and management of surgical site infection (SSI) in patients submitted to transapical transcatheter aortic valve implantation (TA-TAVI).

Methods: From April 2007 to December 2011, 154 patients underwent TA-TAVI with an Edwards Sapien bioprosthesis (ES) at the Institut Universitaire de Cardiologie et Pneumologie de Québec (IUCPQ) as part of a multidisciplinary program to prospectively evaluate percutaneous aortic valve implantation. Patient demographics, perioperative variables, and postoperative complications were recorded in a prospective registry.

Impact of deep sternal wound infection management with vacuum-assisted closure therapy followed by sternal osteosynthesis: a 15-year review of 23,499 sternotomies.

Objective: This study was undertaken to examine the outcome of patients with deep sternal wound infection (DSWI) now treated with vacuum-assisted closure (VAC) therapy as a bridge to sternal osteosynthesis with horizontal titanium plate fixation.

Methods: From 1992 to 2007, a consecutive cohort of 23,499 patients underwent open-heart surgery (OHS) in our institution. The period under study was divided in two according to the use of therapeutic modalities: conventional (1992-2001, N=118 DSWI): debridement/drainage with primary closure and irrigation (N=37), debridement/drainage, open packing followed by pectoralis myocutaneous flaps (PMFs) (N=81); contemporary (2002-2007, N=149 DSWI): conventional treatment (N=24) and VAC therapy (N=125/83.

Recurrent sternal infection following treatment with negative pressure wound therapy and titanium transverse plate fixation.

Objective: To provide a definition for recurrent sternal infection (RSI), analyse the risk factors and describe the management of this complication following treatment of deep sternal wound infection (DSWI) with horizontal titanium sternal osteosynthesis and coverage with pectoralis major myocutaneous flaps.

Methods: Between 2002 and 2007, 10665 patients were submitted to open-heart surgery (OHS) in our institution, of whom 149 (1.4%) developed a DSWI.

Decoupling of light intensity effects on the growth and development of C3 and C4 weed species through sucrose supplementation.

Light availability has a profound effect on plant growth and development. One of the ways to study the effects of light intensity on plant growth and development without the confounding problem of photosynthate availability is sucrose injection/supplementation. A greenhouse experiment was conducted to evaluate the effects of light levels (0% and 75% shade) and sucrose injection (distilled water or 150 g sucrose l(-1)) on three weed species: redroot pigweed (Amaranthus retroflexus L.