Developing co-funded multi-sectoral partnerships for chronic disease prevention: a qualitative inquiry into federal governmental public health staff experience.

BACKGROUND: Multi-sectoral partnerships (MSPs) are frequently cited as a means by which governments can improve population health while leveraging the resources and expertise of the private and non-profit sectors. As part of their efforts in this area, the Public Health Agency of Canada (the Agency) introduced a novel funding programme requiring applicants to procure matched resources from private sources to support large-scale interventions for chronic disease prevention. The current literature on MSPs is limited in its applicability to this model of multi-sectoral engagement. The purpose of this study was to explore the experiences of Agency staff working with potential partners to develop programme applications, such that we might identify lessons from adopting this type of partnership approach. METHODS: Semi-structured interviews were conducted with the 12 staff working in the MSP programme. Interviews were recorded, transcribed and analysed using thematic analysis. Preliminary themes were used to inform follow up focus-groups sessions. A second round of analysis was conducted guided by a coding paradigm focused on understanding process. RESULTS: We identified "experiencing uncertainty" to be a central concept in participants' accounts of the MSP process, related specifically to the MSP programme's novel conditions, shifts that occurred in sectoral roles and demands for new capacities. In response, Agency staff employed strategies to clarify partner interests, build trust in inter-sectoral relationships, and support internal and partner capacity. Outcomes associated with this process include impacts on trust between the Agency and potential partners, a deeper understanding of other sectors, and programme adaptations and refinements to address challenges related to the programme model. CONCLUSIONS: The co-funding model employed by the Agency is a potentially popular one for government bodies wanting to leverage funding from private sector sources. Our study identifies the potential challenges that can occur under this model. Some challenges are related to addressing material conditions related to partner capacity, whereas other challenges speak to deeper and more difficult to address concerns regarding trust and alignment of motivations and interests between partners. Future research exploring the challenges associated with specific models of MSP engagement is necessary to inform approaches to addressing complex problems through collaborative efforts.

Cross-sector partnerships and public health: challenges and opportunities for addressing obesity and noncommunicable diseases through engagement with the private sector.

Over the past few decades, cross-sector partnerships with the private sector have become an increasingly accepted practice in public health, particularly in efforts to address infectious diseases in low- and middle-income countries. Now these partnerships are becoming a popular tool in efforts to reduce and prevent obesity and the epidemic of noncommunicable diseases. Partnering with businesses presents a means to acquire resources, as well as opportunities to influence the private sector toward more healthful practices. Yet even though collaboration is a core principle of public health practice, public-private or nonprofit-private partnerships present risks and challenges that warrant specific consideration. In this article, we review the role of public health partnerships with the private sector, with a focus on efforts to address obesity and noncommunicable diseases in high-income settings. We identify key challenges-including goal alignment and conflict of interest-and consider how changes to partnership practice might address these.

Systems science and obesity policy: a novel framework for analyzing and rethinking population-level planning.

OBJECTIVES: We demonstrate the use of a systems-based framework to assess solutions to complex health problems such as obesity. METHODS: We coded 12 documents published between 2004 and 2013 aimed at influencing obesity planning for complex systems design (9 reports from US and Canadian governmental or health authorities, 1 Cochrane review, and 2 Institute of Medicine reports). We sorted data using the intervention-level framework (ILF), a novel solutions-oriented approach to complex problems. An in-depth comparison of 3 documents provides further insight into complexity and systems design in obesity policy. RESULTS: The majority of strategies focused mainly on changing the determinants of energy imbalance (food intake and physical activity). ILF analysis brings to the surface actions aimed at higher levels of system function and points to a need for more innovative policy design. CONCLUSIONS: Although many policymakers acknowledge obesity as a complex problem, many strategies stem from the paradigm of individual choice and are limited in scope. The ILF provides a template to encourage natural systems thinking and more strategic policy design grounded in complexity science.

The global obesity pandemic: shaped by global drivers and local environments.

The simultaneous increases in obesity in almost all countries seem to be driven mainly by changes in the global food system, which is producing more processed, affordable, and effectively marketed food than ever before. This passive overconsumption of energy leading to obesity is a predictable outcome of market economies predicated on consumption-based growth. The global food system drivers interact with local environmental factors to create a wide variation in obesity prevalence between populations. Within populations, the interactions between environmental and individual factors, including genetic makeup, explain variability in body size between individuals. However, even with this individual variation, the epidemic has predictable patterns in subpopulations. In low-income countries, obesity mostly affects middle-aged adults (especially women) from wealthy, urban environments; whereas in high-income countries it affects both sexes and all ages, but is disproportionately greater in disadvantaged groups. Unlike other major causes of preventable death and disability, such as tobacco use, injuries, and infectious diseases, there are no exemplar populations in which the obesity epidemic has been reversed by public health measures. This absence increases the urgency for evidence-creating policy action, with a priority on reduction of the supply-side drivers.

Changing the future of obesity: science, policy, and action.

The global obesity epidemic has been escalating for four decades, yet sustained prevention efforts have barely begun. An emerging science that uses quantitative models has provided key insights into the dynamics of this epidemic, and enabled researchers to combine evidence and to calculate the effect of behaviours, interventions, and policies at several levels--from individual to population. Forecasts suggest that high rates of obesity will affect future population health and economics. Energy gap models have quantified the association of changes in energy intake and expenditure with weight change, and have documented the effect of higher intake on obesity prevalence. Empirical evidence that shows interventions are effective is limited but expanding. We identify several cost-effective policies that governments should prioritise for implementation. Systems science provides a framework for organising the complexity of forces driving the obesity epidemic and has important implications for policy makers. Many parties (such as governments, international organisations, the private sector, and civil society) need to contribute complementary actions in a coordinated approach. Priority actions include policies to improve the food and built environments, cross-cutting actions (such as leadership, healthy public policies, and monitoring), and much greater funding for prevention programmes. Increased investment in population obesity monitoring would improve the accuracy of forecasts and evaluations. The integration of actions within existing systems into both health and non-health sectors (trade, agriculture, transport, urban planning, and development) can greatly increase the influence and sustainability of policies. We call for a sustained worldwide effort to monitor, prevent, and control obesity.

Leadership for systems change: Researcher practices for enhancing research impact in the prevention of chronic disease.

Introduction: Strengthening systems for chronic disease prevention is essential. Leadership for systems change is an important key to strengthening systems. Leadership in prevention research for supporting systems change remains a relatively abstract concept and there is limited empirical information about the leadership practices of prevention research teams when viewed through a complexity lens. In this paper we examine and describe some systems leadership practices for creating change through prevention research, as identified in a series of six case studies. Methods: A qualitative approach incorporating semi-structured interviews, participant observation, and document review was used to facilitate an in-depth investigation of the research topic. Results: Several researcher practices for enhancing research impact in the prevention of chronic disease were distilled from the data pertaining to how they sought to create change. These included persuasive communication, compassion and deep listening, reflective practice, and embedding themselves within the systems they sought to change. Discussion: The findings provide insights that may assist prevention researchers and other practitioners dedicated to creating change in chronic disease prevention.

Can We Build an Evidence Base on the Impact of Systems Thinking for Wicked Problems? Comment on "What Can Policy-Makers Get Out of Systems Thinking? Policy Partners' Experiences of a Systems-Focused Research Collaboration in Preventive Health".

The published literature on the application of systems thinking to influence policies and programs has grown in recent years. The original article by Haynes et al and the subsequent commentaries have focused on the upstream connection between capacity building for systems thinking and systems informed decision-making. This commentary explores the downstream connection between systems-informed decision-making and broader impacts on the health system, the health of the population and other economic and social benefits. Storytelling, systems-based syntheses and systems intervention principles are explored as approaches to strengthen the evidence base. For systems thinking to gain broader acceptance and application to complex health-related challenges, we need more of an evidence base demonstrating impact.

The Promise of Science, Knowledge Mobilization, and Rapid Learning Systems for COVID-19 Recovery.

The health, economic, and social crises created by the coronavirus disease 2019 (COVID-19) pandemic have been global in scope and inequitable in impact. The global road to recovery can be enhanced with robust, relevant, and timely scientific evidence. This commentary seeks to illustrate the power of science, scientific collaboration, and innovative research funding programs to inform pandemic recovery and inspire transformational changes for a more equitable, resilient, and sustainable future. Specifically, this commentary provides an introduction to the United Nations (UN) Research Roadmap for the COVID-19 Recovery that was published in November 2020. It introduces 5 scoping reviews that helped inform the UN Research Roadmap and that are now available open access within this series of special papers, and it provides an overview of an innovative research funding program that facilitated rapid mobilization and collaboration to produce the scoping reviews. The publication of the scoping reviews in this journal series will help complement and amplify the UN Research Roadmap by furthering knowledge mobilization efforts and informing COVID-19 recovery around the world, to ensure a more equitable, resilient, and sustainable postpandemic future.

International perspectives on the physical inactivity crisis--structural solutions over evidence generation?

Many programs to increase physical activity have been evaluated in developed countries, where 'leisure time physical activity' is the most frequent domain for interventions. In developing countries, and also with reference to global obesity prevention, different kinds of interventions targeting 'total physical activity' are needed. This requires efforts across agencies and sectors, and in the domains of work, active transport, reduced sitting time, as well as leisure time physical activity promotion. In considering possible solutions, this commentary examined the use of complex systems, where integrated efforts across sectors and agencies might, in combination, contribute to increasing total physical activity. The key sets of actions required globally to increase physical activity were, in our opinion, [i] efforts to disseminate individual-level behavior change programs to reach much larger populations rather than volunteers, [ii] social marketing and mass communication campaigns to change social norms in the community and among professionals and policymakers, [iii] efforts to influence the social and physical environment to make them more conducive to physical activity, and [iv] the development and implementation of national physical activity plans and strategies, with sufficient timelines and resources to achieve measurable change.

Quantification of the relationship between glycemia and beta-cell mass adaptation in vivo.

Beta-cell mass dynamics play an important role in the adaptation to obesity, as well as in the pathogenesis of type 2 diabetes. Here we used a 24-hour modified hyperglycemic clamp protocol to investigate the effect of increasing glucose concentrations (15, 20, 25, or 35 mmol/L) on beta-cell mass and rates of beta-cell replication, death, and neogenesis in 6-week-old Sprague Dawley rats (n = 40). During the first 4 h of glucose infusion, plasma insulin levels rose to an approximate steady state in each group, but by the end of 24 h, there was no difference in insulin levels between any of the groups. There was also no difference in beta-cell mass between groups. Mean beta-cell replication rates displayed a linear relationship to mean plasma glucose levels in all hyperglycemic animals (r(2) = 0.98, p < 0.05). Relative to the uninfused basal control animals, replication rates were significantly reduced in the 15 mmol/L glucose group. The percentage of TUNEL-positive beta-cells was not different between groups. There was also no significant difference in markers of neogenesis. Thus, these data demonstrate that hyperglycemia for 24 h had no effect on beta-cell mass, death, or neogenesis in 6-week-old Sprague Dawley rats. We demonstrate a linear relationship, however, between hyperglycemia and beta-cell replication rates in vivo.

A quantitative comparison of rates of phagocytosis and digestion of apoptotic cells by macrophages from normal (BALB/c) and diabetes-prone (NOD) mice.

Macrophages play an important role in clearing apoptotic debris from tissue. Defective or reduced clearance, seen, for instance, in non-obese diabetic (NOD) mice, has been correlated with initiation of autoimmune (Type 1) diabetes (T1D) (O'Brien BA, Huang Y, Geng X, Dutz JP, Finegood DT. Diabetes 51: 2481-2488, 2002). To validate such a link, it is essential to quantify the reduced clearance (for example, by comparison to BALB/c control mice) and to determine which elements of that clearance are impaired. Recently, we fit data for the time course of in vitro macrophage feeding experiments to basic models of macrophage clearance dynamics, thus quantifying kinetics of uptake and digestion of apoptotic cells in both mouse strains (Marée AFM, Komba M, Dyck C, Labeçki M, Finegood DT, Edelstein-Keshet L. J Theor Biol 233: 533-551, 2005). In the cycle of modeling and experimental investigation, we identified the importance of 1) measuring short-, intermediate-, and long-time data (to increase the accuracy of parameter fits), and 2) designing experiments with distinct observable regimes, including engulfment-only and digestion-only phases. Here, we report on new results from experiments so designed. In comparing macrophages from the two strains, we find that NOD macrophage engulfment of apoptotic cells is 5.5 times slower than BALB/c controls. Significantly, our new data demonstrate that digestion is at least two times slower in NOD, in contrast with previous conclusions. Moreover, new data enable us to detect an acceleration in engulfment (after the first engulfment) in both strains, but much smaller in NOD macrophages.

Getting from analysis to action: framing obesity research, policy and practice with a solution-oriented complex systems lens.

Public policy aimed at reducing obesity is just one of many avenues that must be pursued to address the still-growing obesity pandemic. The complexity of the problem is illustrated in ecological frameworks and system maps of the determinants. These conceptual maps illustrate the complexity by acknowledging the influence of many different factors such as social norms and values; sectors of influence such as the food and beverage industries, media and transportation; behavioural settings including home and family, school and community; and individual factors such as genetics, psychosocial and other personal elements. But to solve such a complex problem, we need to move from an analysis of the determinants or causes of the problem to a solution orientation; the frameworks used to describe the problem may not be the right ones for building the "best" solutions. Solution-oriented frameworks, like those presented by Hobbs and Seeman, have been based on parameters such as the sector of influence (e.g., public policy) but would benefit from the consideration of complexity and the leverage points for intervention in complex systems, which are a function of parameters such as the structure of relationships and the presence or absence of feedback loops.

Prediction of spontaneous autoimmune diabetes in NOD mice by quantification of autoreactive T cells in peripheral blood.

Autoimmune (type 1) diabetes mellitus results from the destruction of insulin-producing pancreatic beta cells by T lymphocytes. Prediction of cell-mediated autoimmune diseases by direct detection of autoreactive T cells in peripheral blood has proved elusive, in part because of their low frequency and reduced avidity for peptide MHC ligands. This article was published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org.

beta-cell neogenesis during prolonged hyperglycemia in rats.

beta-cell neogenesis from ductal precursors, and possibly from other pancreatic cell types, contributes to the expansion of beta-cell mass during development and after diabetogenic insults in rodents. Using a mathematical model-based analysis of beta-cell mass, replication, and size, we recently demonstrated that neogenesis is also quantitatively important to the expansion of beta-cell mass during prolonged hyperglycemia. In the present study, we examined the morphological appearance of neogenic focal areas, duct cell replication, and beta-cell cluster size distribution in male Sprague Dawley rats infused with either saline or 50% glucose (2 ml/h) for 0, 1, 2, 3, 4, 5, or 6 days. Pancreatic tissue characterized by a high density of small duct-like structures, previously described as neogenic focal areas, were present in glucose-infused rats after 2, 3, or 4 days of infusion. The cross-sectional area of the pancreas characterized as focal tissue peaked after 3 days of infusion at 2.9 +/- 0.8%. In contrast to the partial pancreatectomy model of beta-cell regeneration, duct cell replication was not increased before or during focal area formation. However, the replication rate of cells in the duct-like structures of the focal areas was twofold greater than in cells of the common pancreatic duct and 15- to 40-fold greater than in cells of small, medium, and large ducts. Duct-cell replication was significantly reduced in small, medium, and large ducts of glucose as compared to saline-infused rats (0.21 +/- 0.02 vs. 0.48 +/- 0.04%; P < 0.03). Duct-associated beta-cell mass was not different in glucose- and saline-infused rats (P = 0.78), whereas the number of acinar-associated single beta -cells increased by 70% after 3 and 4 days of glucose infusion. In addition to small duct-like structures, focal areas had considerable T-cell infiltration (151 +/- 30 T-cells/ mm(2)). There was also an increase in T-cell infiltration in acinar tissue of glucose as compared to saline-infused rats (0.43 +/- 0.11 vs. 0.03 +/- 0. 01 T-cells/mm(2); P < 0.0001). In conclusion, these data suggest that neogenic focal areas in these glucose-infused rats do not arise from replication and differentiation of ductal progenitor cells. Rather, acinar cell transdifferentiation into beta-cells and acinar cell dedifferentiation into neogenic focal areas lead to new beta-cell formation during prolonged hyperglycemia.

Phagocytosis of apoptotic cells by macrophages from NOD mice is reduced.

Macrophages limit inflammatory responses by clearing apoptotic cells. Deficiencies in apoptotic cell phagocytosis have been linked to autoimmunity. In this study, we determined the efficiency with which macrophages from diabetes-prone NOD and diabetes-resistant NOR, Idd5, Balb/c, and C57BL/6 mice phagocytose apoptotic thymocytes and NIT-1 insulinoma cells. Peritoneal and bone marrow-derived macrophages from NOD mice engulfed fewer apoptotic thymocytes than macrophages from Balb/c mice (P < 0.05). Peritoneal macrophages from NOR and Idd5 NOD congenic mice were more proficient at engulfment than their NOD counterparts. Annexin V blockade diminished apoptotic thymocyte clearance and heat-labile serum factors augmented clearance. Binding of apoptotic thymocytes to NOD macrophages was also reduced, suggesting that the deficiency in phagocytosis may be partly attributable to a recognition defect. Peritoneal macrophages from female Balb/c and NOD mice were equally efficient in the engulfment of microspheres, suggesting that the phagocytic deficiency observed in NOD mice was specific for apoptotic cells. In summary, we have demonstrated a deficiency in phagocytic function of macrophages from NOD mice. Normal and diabetes-prone neonatal rodents have a wave of beta-cell apoptosis coincident with the onset of target organ inflammation. A constitutive defect in the clearance of apoptotic beta-cells may be contributory to the initiation of autoimmunity.

Defining optimal immunosuppression for islet transplantation based on reduced diabetogenicity in canine islet autografts.

BACKGROUND: The recent results of clinical islet transplantation have improved substantially with the introduction of a more potent but less diabetogenic immunosuppressant protocol. The successful development of this protocol was based in part on the outcomes of studies reported herein, addressing the diabetogenic potential of a series of immunosuppressant agents used alone or in combination in a canine islet autograft model. Although it is recognized that failure to achieve long-term insulin independence in human islet allotransplantation has been multifactorial, with low engraftment mass, acute or chronic rejection, autoimmune recurrence, loss of islet-acinar integrity, heterotopic site, denervation, and insulin resistance all being implicated to varying degrees, avoidance of diabetogenic immunosuppression has been pivotal to the enhanced outcomes of clinical islet transplantation. We here explore the effects of clinically relevant doses of cyclosporine or tacrolimus when given alone or in combination with glucocorticoids on long-term canine islet autograft function. METHOD: Dogs (n=8) underwent total pancreatectomy, islet isolation, and intrasplenic autotransplantation and were normoglycemic with stable long-term graft function 3 months to 8 years posttransplant. The frequently sampled intravenous glucose tolerance test (FSIGT) was performed predrug (baseline), at 1 month of therapy (on drug), and again 1 month after withdrawal of therapy (postdrug). RESULTS: Monotherapy treatments with low- or high-dose prednisone, Neoral, or tacrolimus had minimal impact on islet autograft function. The combination of Neoral and prednisone led to a marked impairment in glucose decay (25% decline from 1.77+/-0.2 to 1.24+/-0.2, P<0.05), without significant change in insulin responsiveness or glucose effectiveness. However, insulin sensitivity was markedly impaired while on therapy (7.10+/-1.2 to 3.10+/-0.5, P<0.01). Importantly, glucose decay and insulin sensitivity failed to return to baseline after withdrawal of therapy. The combination of tacrolimus and glucocorticoids led to permanent and irreversible diabetes in all recipients (n=6, P<0.001). Similar treatment of healthy control dogs led to a 44% decrease in glucose decay (P<0.01). CONCLUSIONS: Immunosuppression must be specifically tailored for islet transplantation and be glucocorticoid free if insulin independence is to be sustained clinically.

Health communication cards as a tool for behaviour change.

Individuals seeking healthcare treatment in the context of obesity often experience difficulty engaging in discussions around their health and face challenges finding consensus with practitioners on care plans that best suit their lives. The complex set of biological, social, and environmental variables that have contributed to the higher prevalence of obesity are well illustrated in the foresight obesity system map. Effectively understanding and addressing key variables for each individual has proven to be difficult, with clinicians facing barriers and limited resources to help address patients' unique needs. However, productive discussions inspired by patient centered care may be particularly effective in promoting behaviour change. Tools based on systems science that facilitate patient centered care and help identify behaviour change priorities have not been developed to help treat adult obesity. This project created and pilot tested a card based clinical communication tool designed to help facilitate conversations with individuals engaged in health behaviour change. The health communication cards were designed to help direct conversation between patients and healthcare providers toward issues relevant to the individual. Use of the cards to facilitate patient driven conversations in clinical care may help to streamline conversations, set realistic care plan goals, and improve long term rates of compliance.