Predictive factors of short-term survival from acute myocardial infarction in early and late patients in Isfahan and Najafabad, Iran

Background: Cardiovascular disease (CVD) is the primary cause of mortality in the world and Iran. The aim of this study was to determine the prognostic factors of short-term survival from acute myocardial infarction (AMI) in early and late patients in the Najafabad and Isfahan County, Iran. Methods: This hospital-based cohort study was conducted using the hospital registry of 1999-2009 in Iran. All patients (n = 14426) with an AMI referred to hospitals of Isfahan and Najafabad were investigated. To determine prognostic factors of short-term (28-days) survival in early and late patients, unadjusted and adjusted hazard ratio (HR) was calculated using univariate and multivariate Cox regression. Results: The short-term (28-day) survival rate of early and late patients was 96.6 and 89.4 (P < 0.001), respectively. In 80.0 of early and 79.3 of late patients, mortality occurred during the first 7 days of disease occurrence. HR of death was higher in women in the two groups; it was 1.97 in early patients was confidence interval (CI) 95%: 1.32-2.92 and 1.35 in late patients (CI 95%: 1.19-1.53) compared to men. HR of death had a rising trend with the increasing of age in the two groups. Conclusion: Short-term survival rate was higher in early patients than in late patients. In addition, case fatality rate (CFR) of AMI in women was higher than in men. In both groups, sex, age, an atomic location of myocardial infarction based on the International Classification of Disease, Revision 10 (ICD10), cardiac enzymes, and clinical symptoms were significant predictors of survival in early and late patients following AMI. © 2016, Isfahan University of Medical Sciences(IUMS). All rights reserved

Formulation, stabilisation and encapsulation of bacteriophage for phage therapy

Against a backdrop of global antibiotic resistance and increasing awareness of the importance of the human microbiota, there has been resurgent interest in the potential use of bacteriophages for therapeutic purposes, known as phage therapy. A number of phage therapy phase I and II clinical trials have concluded, and shown phages don’t present significant adverse safety concerns. These clinical trials used simple phage suspensions without any formulation and phage stability was of secondary concern. Phages have a limited stability in solution, and undergo a significant drop in phage titre during processing and storage which is unacceptable if phages are to become regulated pharmaceuticals, where stable dosage and well defined pharmacokinetics and pharmacodynamics are de rigueur. Animal studies have shown that the efficacy of phage therapy outcomes depend on the phage concentration (i.e. the dose) delivered at the site of infection, and their ability to target and kill bacteria, arresting bacterial growth and clearing the infection. In addition, in vitro and animal studies have shown the importance of using phage cocktails rather than single phage preparations to achieve better therapy outcomes. The in vivo reduction of phage concentration due to interactions with host antibodies or other clearance mechanisms may necessitate repeated dosing of phages, or sustained release approaches. Modelling of phage-bacterium population dynamics reinforces these points. Surprisingly little attention has been devoted to the effect of formulation on phage therapy outcomes, given the need for phage cocktails, where each phage within a cocktail may require significantly different formulation to retain a high enough infective dose. This review firstly looks at the clinical needs and challenges (informed through a review of key animal studies evaluating phage therapy) associated with treatment of acute and chronic infections and the drivers for phage encapsulation. An important driver for formulation and encapsulation is shelf life and storage of phage to ensure reproducible dosages. Other drivers include formulation of phage for encapsulation in micro- and nanoparticles for effective delivery, encapsulation in stimuli responsive systems for triggered controlled or sustained release at the targeted site of infection. Encapsulation of phage (e.g. in liposomes) may also be used to increase the circulation time of phage for treating systemic infections, for prophylactic treatment or to treat intracellular infections. We then proceed to document approaches used in the published literature on the formulation and stabilisation of phage for storage and encapsulation of bacteriophage in micro- and nanostructured materials using freeze drying (lyophilization), spray drying, in emulsions e.g. ointments, polymeric microparticles, nanoparticles and liposomes. As phage therapy moves forward towards Phase III clinical trials, the review concludes by looking at promising new approaches for micro- and nanoencapsulation of phages and how these may address gaps in the field