Context: An evidence base that addresses issues of complexity and context is urgently needed for large-system transformation (LST) and health care reform. Fundamental conceptual and methodological challenges also must be addressed. The Saskatchewan Ministry of Health in Canada requested a six-month synthesis project to guide four major policy development and strategy initiatives focused on patient-and family-centered care, primary health care renewal, quality improvement, and surgical wait lists. The aims of the review were to analyze examples of successful and less successful transformation initiatives, to synthesize knowledge of the underlying mechanisms, to clarify the role of government, and to outline options for evaluation. Methods:We used realist review, whose working assumption is that a particular intervention triggers particular mechanisms of change. Mechanisms may be more or less effective in producing their intended outcomes, depending on their interaction with various contextual factors. We explain the variations in outcome as the interplay between context and mechanisms. We nested this analytic approach in a macro framing of complex adaptive systems (CAS). Findings:Our rapid realist review identified five "simple rules" of LST that were likely to enhance the success of the target initiatives: (1) blend designated leadership with distributed leadership; (2) establish feedback loops; (3) attend to history; (4) engage physicians; and (5) include patients and families. These principles play out differently in different contexts affecting human Conclusions:Realist review methodology can be applied in combination with a complex system lens on published literature to produce a knowledge synthesis that informs a prospective change effort in large-system transformation. A collaborative process engaging both research producers and research users contributes to local applications of universal principles and mid-range theories, as well as to a more robust knowledge base for applied research. We conclude with suggestions for the future development of synthesis and evaluation methods.

Fibroblast growth factor stimulates proliferation and subsequent differentiation of precursor cells isolated from the neuroepithelium of embryonic day 10 mice in vitro. Here we show that fibroblast growth factor-induced proliferation is dependent on the presence of insulin-like growth factors (IGFs) and that IGF-I is endogenously produced by the neuroepithelial cells. Blocking of endogenous IGF-I activity with anti-IGF-I antibodies results in complete inhibition of fibroblast growth factor-mediated proliferation and in cell death. IGF-I alone acts as a survival agent. These observations correlate with the detection of transcripts for IGF-I and basic fibroblast growth factor in freshly isolated neuroepithelium and are consistent with an autocrine action of these factors in early brain development in vivo.We have employed a serum-and insulin-free assay to examine the relative effects of IGFs and FGFs on neural precursor proliferation and find that the proliferation of precursors observed with bFGF is markedly enhanced by insulin and the IGFs, with tIGF

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BackgroundThere is a growing emphasis in public health on the importance of evidence-based interventions to improve population health and reduce health inequities. Equally important is the need for knowledge about how to implement these interventions successfully. Yet, a gap remains between the development of evidence-based public health interventions and their successful implementation. Conventional systematic reviews have been conducted on effective implementation in health care, but few in public health, so their relevance to public health is unclear. In most reviews, stringent inclusion criteria have excluded entire bodies of evidence that may be relevant for policy makers, program planners, and practitioners to understand implementation in the unique public health context. Realist synthesis is a theory-driven methodology that draws on diverse data from different study designs to explain how and why observed outcomes occur in different contexts and thus may be more appropriate for public health.MethodsThis paper presents a realist review protocol to answer the research question: Why are some public health interventions successfully implemented and others not? Based on a review of implementation theories and frameworks, we developed an initial program theory, adapted for public health from the Consolidated Framework for Implementation Research, to explain the implementation outcomes of public health interventions within particular contexts. This will guide us through the review process, which comprises eight iterative steps based on established realist review guidelines and quality standards. We aim to refine this initial theory into a ‘final’ realist program theory that explains important context-mechanism-outcome configurations in the successful implementation of public health interventions.DiscussionDeveloping new public health interventions is costly and policy windows that support their implementation can be short lived. Ineffective implementation wastes scarce resources and is neither affordable nor sustainable. Public health interventions that are not implemented will not have their intended effects on improving population health and promoting health equity. This synthesis will provide evidence to support effective implementation of public health interventions taking into account the variable context of interventions. A series of knowledge translation products specific to the needs of knowledge users will be developed to provide implementation support.Systematic review registrationPROSPERO CRD42015030052Electronic supplementary materialThe online version of this article (doi:10.1186/s13643-016-0229-1) contains supplementary material, which is available to authorized users.

The successful implementation of an MDP approach to PHC requires moving away from physician-driven care. This can only be achieved once there is a change in the underlying structures, values, power relations, and roles defined by the health care system and the community at large, where physicians are traditionally ranked above other care providers. The CBPAR methodology allows community members and the health-related professionals who serve them to take ownership of the research and to critically reflect on iterative cycles of evaluation. This provides an opportunity for practitioners to implement relevant changes based on internally generated analyses.