Bacteriophage Therapy Rescues Mice Bacteremic from a Clinical Isolate of Vancomycin-Resistant Enterococcus faecium

Colonization of the gastrointestinal tract with vancomycin-resistant Enterococcus faecium (VRE) has become endemic in many hospitals and nursing homes in the United States. Such colonization predisposes the individual to VRE bacteremia and/or endocarditis, and immunocompromised patients are at particular risk for these conditions. The emergence of antibiotic-resistant bacterial strains requires the exploration of alternative antibacterial therapies, which led our group to study the ability of bacterial viruses (bacteriophages, or phages) to rescue mice with VRE bacteremia. The phage strain used in this study has lytic activity against a wide range of clinical isolates of VRE. One of these VRE strains was used to induce bacteremia in mice by intraperitoneal (i.p.) injection of 10(9) CFU. The resulting bacteremia was fatal within 48 h. A single i.p. injection of 3 x 10(8) PFU of the phage strain, administered 45 min after the bacterial challenge, was sufficient to rescue 100% of the animals. Even when treatment was delayed to the point where all animals were moribund, approximately 50% of them were rescued by a single injection of this phage preparation. The ability of this phage to rescue bacteremic mice was demonstrated to be due to the functional capabilities of the phage and not to a nonspecific immune effect. The rescue of bacteremic mice could be effected only by phage strains able to grow in vitro on the bacterial host used to infect the animals, and when such strains are heat inactivated they lose their ability to rescue the infected mice.     

Phase II, randomized, double-blind, placebo-controlled studies of ruprintrivir nasal spray 2-percent suspension for prevention and treatment of experimentally induced rhinovirus colds in healthy volunteers

Human rhinovirus (HRV) infections are usually self-limited but may be associated with serious consequences, particularly in those with asthma and chronic respiratory disease. Effective antiviral agents are needed for preventing and treating HRV illnesses. Ruprintrivir (Agouron Pharmaceuticals, Inc., San Diego, Calif.) selectively inhibits HRV 3C protease and shows potent, broad-spectrum anti-HRV activity in vitro. We conducted three double-blind, placebo-controlled clinical trials in 202 healthy volunteers to assess the activity of ruprintrivir in experimental HRV infection. Subjects were randomized to receive intranasal ruprintrivir (8 mg) or placebo sprays as prophylaxis (two or five times daily [2x/day or 5x/day] for 5 days) starting 6 h before infection or as treatment (5x/day for 4 days) starting 24 h after infection. Ruprintrivir prophylaxis reduced the proportion of subjects with positive viral cultures (for 5x/day dosing groups, 44% for ruprintrivir treatment group versus 70% for placebo treatment group [P=0.03]; for 2x/day dosing groups, 60% for ruprintrivir group versus 92% for placebo group [P=0.004]) and viral titers but did not decrease the frequency of colds. Ruprintrivir treatment reduced the mean total daily symptom score (2.2 for ruprintrivir treatment group and 3.3 for the placebo treatment group [P=0.014]) by 33%. Secondary endpoints, including viral titers, individual symptom scores, and nasal discharge weights, were also reduced by ruprintrivir treatment. Overall, ruprintrivir was well tolerated; blood-tinged mucus and nasal passage irritation were the most common adverse effects reported. Pharmacokinetic analysis of plasma and nasal ruprintrivir concentrations revealed intranasal drug residence with minimal systemic absorption. Results from these studies in experimental rhinoviral infection support continued investigation of intranasal ruprintrivir in the setting of natural HRV infection.     

Detection of pancreatic pathology by ultrasonography and endoscopic retrograde cholangiopancreatography

Retrospective evaluation of the results of endoscopic retrograde cholangiopancreatography (ERCP) and pancreatic ultrasonography in identifying those patients with a normal pancreas and those with a pancreatic abnormality revealed ultrasonography to have an overall accuracy of approximately 73%, whereas ERCP had an 85% accuracy, and both modalities had a combined accuracy of 92%. Both procedures were most accurate in the identification of patients with no disease, and both were least accurate in the identification of patients with chronic pancreatitis.     

Trajectories of perceived social support in acute coronary syndrome

Quality of Life Research - Perceived social support is known to be an important predictor of health outcomes in patients with acute coronary syndrome (ACS). This study investigates patterns of...     

Referral rate and outcomes of cardiac rehabilitation after cardiac catheterization in a large Canadian city

PURPOSE: The benefits of cardiac rehabilitation (CR) for patients with coronary artery disease are extensive and compelling, demonstrating reductions in mortality. However, some reports suggest that only 10% to 20% of eligible patients currently participate in formal CR programs. The purpose of this study was to identify the proportion of patients referred to CR in a large Canadian city, and to determine their statistically adjusted survival rates relative to patients not referred to CR. METHODS: Subjects eligible for this study included all adult residents with coronary artery disease from 1995 to 1999 in the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry. All 5,081 patients who survived 6 months or more after catheterization were included in the analysis. Survival data were adjusted using a Cox proportional hazards model. RESULTS: Referral to a CR program (28.9% of patients) was significantly more likely for young male patients who had undergone a prior revascularization procedure, presented with an ejection fraction exceeding 50%, and did not report cerebrovascular, peripheral vascular, or renal disease. Crude hazard ratios indicated that referral to a CR program remained significantly associated with lower mortality after control was used for clinical, anatomic, treatment and comorbid conditions recorded at catheterization (hazard ratio, 0.68; 95% confidence interval, 0.51-0.90; P = .005). CONCLUSIONS: Despite the proven efficacy of CR in clinical trials, fewer than one third of the patients undergoing cardiac catheterization are referred to a CR program. The better survival outcomes noted for patients referred to CR suggests that there is an opportunity to improve care and outcomes through increased referral of patients to such programs.     

Health-seeking behaviors of elderly Chinese Americans: shifts in expectations

PURPOSE: This study reported a qualitative analysis of health-seeking behaviors of community-dwelling elderly Chinese Americans on the influences of family network, cultural values, and immigrant experience in their use of health resources. Barriers to health care, pathway of health care, and adaptation of health care by use of self-treatment and Eastern and Western medicines were also examined. DESIGN AND METHODS: The investigators used content analysis to obtain themes and key points of focus group interview data (N = 25) to explore the elderly participants' attitudes, values, and practices in their use of health resources. Survey questionnaires in Chinese were used to compile demographic data. RESULTS: Findings suggested a shift from traditional expectations of filial piety to more dependence on neighbors and friends, and a genuine adaptability to combining Eastern and Western health care modalities. Immigration was not proposed by these Chinese elders as an explanation of shifts in expectations for family support or values. IMPLICATIONS: This study has implications for research, service delivery, and policy making for health care of ethnic elderly persons, particularly in addressing structural and cultural issues in access and compliance.