Introducing New Priority Setting and Resource Allocation Processes in a Canadian Healthcare Organization: A Case Study Analysis Informed by Multiple Streams Theory

Background: In this article, we analyze one case instance of how proposals for change to the priority setting and resource allocation (PSRA) processes at a Canadian healthcare institution reached the decision agenda of the organization’s senior leadership. We adopt key concepts from an established policy studies framework – Kingdon’s multiple streams theory – to inform our analysis. Methods: Twenty-six individual interviews were conducted at the IWK Health Centre in Halifax, NS, Canada. Participants were asked to reflect upon the reasons leading up to the implementation of a formal priority setting process – Program Budgeting and Marginal Analysis (PBMA) – in the 2012/2013 fiscal year. Responses were analyzed qualitatively using Kingdon’s model as a template. Results: The introduction of PBMA can be understood as the opening of a policy window. A problem stream – defined as lack of broad engagement and information sharing across service lines in past practice – converged with a known policy solution, PBMA, which addressed the identified problems and was perceived as easy to use and with an evidence-base from past applications across Canada and elsewhere. Conditions in the political realm allowed for this intervention to proceed, but also constrained its potential outcomes. Conclusion: Understanding in a theoretically-informed way how change occurs in healthcare management practices can provide useful lessons to researchers and decision-makers whose aim is to help health systems achieve the most effective use of available financial resource

ONCOLYTIC VIRUS-MEDIATED REVERSAL OF IMPAIRED TUMOR ANTIGEN PRESENTATION

Anti-tumor immunity can eliminate existing cancer cells and also maintain a constant surveillance against possible relapse. Such an antigen-specific adaptive response begins when tumor-specific T cells become activated. T cell activation requires two signals on antigen presenting cells (APCs): antigen presentation through MHC molecules and co-stimulation. In the absence of one or both of these signals, T cells remain inactivated or can even become tolerized. Cancer cells and their associated microenvironment strategically hinder the processing and presentation of tumor antigens and consequently prevent the development of anti-tumor immunity. Many studies, however, demonstrate that interventions that overturn tumor-associated immune evasion mechanisms can establish anti-tumor immune responses of therapeutic potential. One such intervention is oncolytic virus (OV)-based anti-cancer therapy. Here we discuss how OV-induced immunological events override tumor-associated antigen presentation impairment and promote appropriate T cell:APC interaction. Detailed understanding of this phenomenon is pivotal for devising the strategies that will enhance the efficacy of OV-based anti-cancer therapy by complementing its inherent oncolyti

Role of lymphatic system in the persistence and pathogenesis of woodchuck hepatitis virus infection

Hepatitis B virus (HBV) causes acute liver inflammation that apparently resolves completely or advances to chronic hepatitis, cirrhosis and hepatocellular carcinoma. These differential outcomes of HBV infection are orchestrated to a large extent by the virus-specific T cell responses, which characteristically appear late after exposure to hepadnavirus. In this context, the objective of this study was to delineate the kinetics and understand inter-relationships between virus-specific and non-specific T cell proliferative, humoral as well as innate cytokine responses, along with serological and molecular markers of hepadnaviral infection induced after exposure and re-exposure to liver pathogenic or nonpathogenic doses of woodchuck hepatitis virus (WHV). Our results revealed that infection of woodchucks with either a liver pathogenic (>10³ virions) or nonpathogenic (<10³ virions) dose of WHV induced strong, but delayed, virus-specific T cell responses with comparable kinetics. Interestingly, immediately after exposure to virus, the non-specific proliferative capacity of lymphocytes in response to mitogenic stimulation was heightened and then subsided preceding the appearance of WHV-specific T cell response. This augmented non-specific proliferative reactivity was accompanied by the increased expression of interferon-alpha (IFN-α), interleukin-12 (IL-12) and IL-2 in circulating lymphoid cells; while its decline was associated with activation-induced cell death of lymphocytes. Importantly, the postponement of virus-specific T cell response coincided with the absence of TNF-α expression, while its rise was marked by synchronously elevated expression of TNF-α, IFN-α, IFN-γ, IL-2, IL-12, and IL-10 in lymphoid cells. Nonetheless, the virus-specific T cell responses induced during low-dose (occult) infection, in contrast to infection caused by liver pathogenic dose, did not provide protection against viral hepatitis. -- We conclude that hepadnavirus infections induce delayed virus-specific T cell proliferative responses irrespective of the dose of invading virus and symptomatic or asymptomatic outcome of the infection. This postponement of anti-viral T cell responses is preceded by the aberrant activation of lymphocyte and innate cytokine responses. Such an impaired activation of immune responses following hepadnavirus infection represents a possible mechanism that allows evasion of initial clearance and subsequent elimination of virus, permits its dissemination, and contributes to the establishment of persistence

Introducing New Priority Setting and Resource Allocation Processes in a Canadian Healthcare Organization: A Case Study Analysis Informed by Multiple Streams Theory

Background: In this article, we analyze one case instance of how proposals for change to the priority setting and resource allocation (PSRA) processes at a Canadian healthcare institution reached the decision agenda of the organization’s senior leadership. We adopt key concepts from an established policy studies framework – Kingdon’s multiple streams theory – to inform our analysis. Methods:Twenty-six individual interviews were conducted at the IWK Health Centre in Halifax, NS, Canada. Participants were asked to reflect upon the reasons leading up to the implementation of a formal priority setting process – Program Budgeting and Marginal Analysis (PBMA) – in the 2012/2013 fiscal year. Responses were analyzed qualitatively using Kingdon’s model as a template. Results:The introduction of PBMA can be understood as the opening of a policy window. A problem stream – defined as lack of broad engagement and information sharing across service lines in past practice – converged with a known policy solution, PBMA, which addressed the identified problems and was perceived as easy to use and with an evidence-base from past applications across Canada and elsewhere. Conditions in the political realm allowed for this intervention to proceed, but also constrained its potential outcomes. Conclusion:Understanding in a theoretically-informed way how change occurs in healthcare management practices can provide useful lessons to researchers and decision-makers whose aim is to help health systems achieve the most effective use of available financial resources

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field