The development, implementation and evaluation of clinical pathways for chronic obstructive pulmonary disease (COPD) in Saskatchewan: protocol for an interrupted times series evaluation

Background: Chronic obstructive pulmonary disease (COPD) has substantial economic and human costs; it isexpected to be the third leading cause of death worldwide by 2030. To minimize these costs high qualityguidelines have been developed. However, guidelines alone rarely result in meaningful change. One method ofintegrating guidelines into practice is the use of clinical pathways (CPWs). CPWs bring available evidence to a rangeof healthcare professionals by detailing the essential steps in care and adapting guidelines to the local context.Methods/design: We are working with local stakeholders to develop CPWs for COPD with the aims of improvingcare while reducing utilization. The CPWs will employ several steps including: standardizing diagnostic training,unifying components of chronic disease care, coordinating education and reconditioning programs, and ensuringcare uses best practices. Further, we have worked to identify evidence-informed implementation strategies whichwill be tailored to the local context.We will conduct a three-year research project using an interrupted time series (ITS) design in the form of a multiplebaseline approach with control groups. The CPW will be implemented in two health regions (experimental groups) andtwo health regions will act as controls (control groups). The experimental and control groups will each contain an urbanand rural health region. Primary outcomes for the study will be quality of care operationalized using hospital readmissionrates and emergency department (ED) presentation rates. Secondary outcomes will be healthcare utilization andguideline adherence, operationalized using hospital admission rates, hospital length of stay and general practitioner (GP)visits. Results will be analyzed using segmented regression analysis.Discussion: Funding has been procured from multiple stakeholders. The project has been deemed exempt from ethicsreview as it is a quality improvement project. Intervention implementation is expected to begin in summer of 2017.This project is expected to improve quality of care and reduce healthcare utilization. In addition it will provide evidenceon the effects of CPWs in both urban and rural settings. If the CPWs are found effective we will work with allstakeholders to implement similar CPWs in surrounding health regions

Interrogating Regulatory Mechanisms in Signaling Proteins by Allosteric Inhibitors and Activators: A Dynamic View Through the Lens of Residue Interaction Networks

Computational studies of allosteric interactions have witnessed a recent renaissance fueled by the growing interest in modeling of the complex molecular assemblies and biological networks. Allosteric interactions in protein structures allow for molecular communication in signal transduction networks. In this chapter, we discuss recent developments in understanding of allosteric mechanisms and interactions of protein systems, particularly in the context of structural, functional, and computational studies of allosteric inhibitors and activators. Computational and experimental approaches and advances in understanding allosteric regulatory mechanisms are reviewed to provide a systematic and critical view of the current progress in the development of allosteric modulators and highlight most challenging questions in the field. The abundance and diversity of genetic, structural, and biochemical data underlies the complexity of mechanisms by which targeted and personalized drugs can combat mutational profiles in protein kinases. Structural and computational studies of protein kinases have generated in recent decade significant insights that allowed leveraging knowledge about conformational diversity and allosteric regulation of protein kinases in the design and discovery of novel kinase drugs. We discuss recent developments in understanding multilayered allosteric regulatory machinery of protein kinases and provide a systematic view of the current state in understanding molecular basis of allostery mediated by kinase inhibitors and activators. In conclusion, we highlight the current status and future prospects of computational biology approaches in bridging the basic science of protein kinases with the discovery of anticancer therapies.https://digitalcommons.chapman.edu/scs_books/1049/thumbnail.jp