Making sense of complexity in context and implementation: the Context and Implementation of Complex Interventions (CICI) framework.

BACKGROUND: The effectiveness of complex interventions, as well as their success in reaching relevant populations, is critically influenced by their implementation in a given context. Current conceptual frameworks often fail to address context and implementation in an integrated way and, where addressed, they tend to focus on organisational context and are mostly concerned with specific health fields. Our objective was to develop a framework to facilitate the structured and comprehensive conceptualisation and assessment of context and implementation of complex interventions. METHODS: The Context and Implementation of Complex Interventions (CICI) framework was developed in an iterative manner and underwent extensive application. An initial framework based on a scoping review was tested in rapid assessments, revealing inconsistencies with respect to the underlying concepts. Thus, pragmatic utility concept analysis was undertaken to advance the concepts of context and implementation. Based on these findings, the framework was revised and applied in several systematic reviews, one health technology assessment (HTA) and one applicability assessment of very different complex interventions. Lessons learnt from these applications and from peer review were incorporated, resulting in the CICI framework. RESULTS: The CICI framework comprises three dimensions-context, implementation and setting-which interact with one another and with the intervention dimension. Context comprises seven domains (i.e., geographical, epidemiological, socio-cultural, socio-economic, ethical, legal, political); implementation consists of five domains (i.e., implementation theory, process, strategies, agents and outcomes); setting refers to the specific physical location, in which the intervention is put into practise. The intervention and the way it is implemented in a given setting and context can occur on a micro, meso and macro level. Tools to operationalise the framework comprise a checklist, data extraction tools for qualitative and quantitative reviews and a consultation guide for applicability assessments. CONCLUSIONS: The CICI framework addresses and graphically presents context, implementation and setting in an integrated way. It aims at simplifying and structuring complexity in order to advance our understanding of whether and how interventions work. The framework can be applied in systematic reviews and HTA as well as primary research and facilitate communication among teams of researchers and with various stakeholders

Environmental Interventions to Reduce the Consumption of Sugar-Sweetened Beverages: Abridged Cochrane Systematic Review

BACKGROUND Regular consumption of sugar-sweetened beverages (SSB) can increase the risk for obesity, type 2 diabetes, cardiovascular disease, and dental caries. Interventions that alter the physical or social environment in which individuals make beverage choices have been proposed to reduce the consumption of SSB. METHODS We included randomised controlled, non-randomised controlled, and interrupted time series studies on environmental interventions, with or without behavioural co-interventions, implemented in real-world settings, lasting at least 12 weeks, and including at least 40 individuals. Studies on the taxation of SSB were not included, as these are subject of a separate Cochrane review. We used standard Cochrane methods for data extraction, risk of bias assessment, and evidence grading and synthesis. Searches were updated to January 24, 2018. RESULTS We identified 14,488 unique records and assessed 1,030 full texts for eligibility. We included 58 studies comprising a total of 1,180,096 participants and a median length of follow-up of 10 months. We found moderate-certainty evidence for consistent associations with decreases in SSB consumption or sales for the following interventions: traffic light labelling, price increases on SSB, in-store promotion of healthier beverages in supermarkets, government food benefit programs with incentives for purchasing fruits and vegetables and restrictions on SSB purchases, multi-component community campaigns focused on SSB, and interventions improving the availability of low-calorie beverages in the home environment. For the remaining interventions we found low- to very-low-certainty evidence for associations showing varying degrees of consistency. CONCLUSIONS With observed benefits outweighing observed harms, we suggest that environmental interventions to reduce the consumption of SSB be considered as part of a wider set of measures to improve population-level nutrition. Implementation should be accompanied by evaluations using appropriate methods. Future studies should examine population-level effects of interventions suitable for large-scale implementation, and interventions and settings not yet studied thoroughly

The diagnostic value of ultrasonography-derived edema of the temporal artery wall in giant cell arteritis: a second meta-analysis

<p>Abstract</p> <p>Background</p> <p>Ultrasonography of temporal arteries is not commonly used in the approach of patients with suspected giant cell arteritis (GCA) in clinical practice. A meta-analysis of primary studies available through April 2004 concluded that ultrasonography could indeed be helpful in diagnosing GCA. We specifically re-examined the diagnostic value of the ultrasonography-derived halo sign, a dark hypoechoic circumferential thickening around the artery lumen, indicating vasculitic wall edema, in GCA.</p> <p>Methods</p> <p>Original, prospective studies in patients with suspected GCA that examined ultrasonography findings of temporal arteries using the ACR 1990 classification criteria for GCA as reference standard, published through 2009, were identified. Only eight studies involving 575 patients, 204 of whom received the final diagnosis of GCA, fulfilled technical quality criteria for ultrasound. Weighted sensitivity and specificity estimates of the halo sign were assessed, their possible heterogeneity was investigated and pooled diagnostic odds ratio was determined.</p> <p>Results</p> <p>Unilateral halo sign achieved an overall sensitivity of 68% (95% CI, 0.61-0.74) and specificity of 91% (95% CI, 0.88-0.94) for GCA. The values of inconsistency coefficient (I²) of both sensitivity and specificity of the halo sign, showed significant heterogeneity concerning the results between studies. Pooled diagnostic odds ratio, expressing how much greater the odds of having GCA are for patients with halo sign than for those without, was 34 (95% CI, 8.21-138.23). Diagnostic odds ratio was further increased to 65 (95% CI, 17.86-236.82) when bilateral halo signs were present (sensitivity/specificity of 43% and 100%, respectively). In both cases, it was found that DOR was constant across studies.</p> <p>Conclusion</p> <p>Temporal artery edema demonstrated as halo sign should be always looked for in ultrasonography when GCA is suspected. Providing that currently accepted technical quality criteria are fulfilled, halo sign's sensitivity and specificity are comparable to those of autoantibodies used as diagnostic tests in rheumatology. Validation of revised GCA classification criteria which will include the halo sign may be warranted.</p

Context and implementation: A concept analysis towards conceptual maturity.

Context and implementation of health interventions have received increasing attention over the past decade, in particular with respect to their influence on the effectiveness and reach of complex interventions. The underlying concepts are both considered partially mature, limiting their operationalization in research and practice. We conducted systematic literature searches and pragmatic utility (PU) concept analyses to provide a state-of-the-art assessment of the concepts of "context" and "implementation" in the health sciences to create a common understanding for their use within systematic reviews and HTA. We performed two separate searches, one for context (EMBASE, MEDLINE) and the other for implementation (Google Scholar) to identify relevant models, theories and frameworks. 17 publications on context and 35 articles on implementation met our inclusion criteria. PU concept analysis comprises three guiding principles: selection of the literature, organization and structuring of the literature, and asking analytic questions of the literature. Both concepts were analyzed according to four features of conceptual maturity, i.e., consensual definitions, clear characteristics, fully described preconditions and outcomes, and delineated boundaries. Context and implementation are highly intertwined, with both concepts influencing and interacting with each other. Context is defined as a set of characteristics and circumstances that surround the implementation effort. Implementation is conceptualized as a planned and deliberately initiated effort with the intention to put an intervention into practice. The concept of implementation presents largely consensual definitions and relatively well-defined boundaries, while distinguishing features, preconditions and outcomes are not yet fully articulated. In contrast, definitions of context vary widely, and boundaries with neighbouring concepts, such as setting and environment, are blurred; characteristics, preconditions and outcomes are ill-defined. Therefore, the maturity of both concepts should be further improved to facilitate operationalization in systematic reviews and HTAs

Adapting evidence-informed complex population health interventions for new contexts : a systematic review of guidance

Background Adapting interventions that have worked elsewhere can save resources associated with developing new interventions for each specific context. While a developing body of evidence shows benefits of adapted interventions compared with interventions transported without adaptation, there are also examples of interventions which have been extensively adapted, yet have not worked in the new context. Decisions on when, to what extent, and how to adapt interventions therefore are not straightforward, particularly when conceptualising intervention effects as contingent upon contextual interactions in complex systems. No guidance currently addresses these questions comprehensively. To inform development of an overarching guidance on adaptation of complex population health interventions, this systematic review synthesises the content of the existing guidance papers. Methods We searched for papers published between January 2000 and October 2018 in 7 bibliographic databases. We used citation tracking and contacted authors and experts to locate further papers. We double screened all the identified records. We extracted data into the following categories: descriptive information, key concepts and definitions, rationale for adaptation, aspects of adaptation, process of adaptation, evaluating and reporting adapted interventions. Data extraction was conducted independently by two reviewers, and retrieved data were synthesised thematically within pre-specified and emergent categories. Results We retrieved 6694 unique records. Thirty-eight papers were included in the review representing 35 sources of guidance. Most papers were developed in the USA in the context of implementing evidence-informed interventions among different population groups within the country, such as minority populations. We found much agreement on how the papers defined key concepts, aims, and procedures of adaptation, including involvement of key stakeholders, but also identified gaps in scope, conceptualisation, and operationalisation in several categories. Conclusions Our review found limitations that should be addressed in future guidance on adaptation. Specifically, future guidance needs to be reflective of adaptations in the context of transferring interventions across countries, including macro- (e.g. national-) level interventions, better theorise the role of intervention mechanisms and contextual interactions in the replicability of effects and accordingly conceptualise key concepts, such as fidelity to intervention functions, and finally, suggest evidence-informed strategies for adaptation re-evaluation and reporting

Designing high-quality implementation research: development, application, feasibility and preliminary evaluation of the implementation science research development (ImpRes) tool and guide

Background:  Designing implementation research can be a complex and daunting task, especially for applied health researchers who have not received specialist training in implementation science. We developed the Implementation Science Research Development (ImpRes) tool and supplementary guide to address this challenge and provide researchers with a systematic approach to designing implementation research. Methods:  A multi-method and multi-stage approach was employed. An international, multidisciplinary expert panel engaged in an iterative brainstorming and consensus-building process to generate core domains of the ImpRes tool, representing core implementation science principles and concepts that researchers should consider when designing implementation research. Simultaneously, an iterative process of reviewing the literature and expert input informed the development and content of the tool. Once consensus had been reached, specialist expert input was sought on involving and engaging patients/service users; and economic evaluation. ImpRes was then applied to 15 implementation and improvement science projects across the National Institute of Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South London, a research organisation in London, UK. Researchers who applied the ImpRes tool completed an 11-item questionnaire evaluating its structure, content and usefulness. Results:  Consensus was reached on ten implementation science domains to be considered when designing implementation research. These include implementation theories, frameworks and models, determinants of implementation, implementation strategies, implementation outcomes and unintended consequences. Researchers who used the ImpRes tool found it useful for identifying project areas where implementation science is lacking (median 5/5, IQR 4–5) and for improving the quality of implementation research (median 4/5, IQR 4–5) and agreed that it contained the key components that should be considered when designing implementation research (median 4/5, IQR 4–4). Qualitative feedback from researchers who applied the ImpRes tool indicated that a supplementary guide was needed to facilitate use of the tool. Conclusions:  We have developed a feasible and acceptable tool, and supplementary guide, to facilitate consideration and incorporation of core principles and concepts of implementation science in applied health implementation research. Future research is needed to establish whether application of the tool and guide has an effect on the quality of implementation research

Embracing complexity and uncertainty to create impact: Exploring the processes and transformative potential of co-produced research through development of a social impact model

© 2018 The Author(s). The potential use, influence and impact of health research is seldom fully realised. This stubborn problem has caused burgeoning global interest in research aiming to address the implementation 'gap' and factors inhibiting the uptake of scientific evidence. Scholars and practitioners have questioned the nature of evidence used and required for healthcare, highlighting the complex ways in which knowledge is formed, shared and modified in practice and policy. This has led to rapid expansion, expertise and innovation in the field of knowledge mobilisation and funding for experimentation into the effectiveness of different knowledge mobilisation models. One approach gaining prominence involves stakeholders (e.g. researchers, practitioners, service users, policy-makers, managers and carers) in the co-production, and application, of knowledge for practice, policy and research (frequently termed integrated knowledge translation in Canada). Its popularity stems largely from its potential to address dilemmas inherent in the implementation of knowledge generated using more reductionist methods. However, despite increasing recognition, demands for co-produced research to illustrate its worth are becoming pressing while the means to do so remain challenging. This is due not only to the diversity of approaches to co-production and their application, but also to the ways through which different stakeholders conceptualise, measure, reward and use research. While research co-production can lead to demonstrable benefits such as policy or practice change, it may also have more diffuse and subtle impact on relationships, knowledge sharing, and in engendering culture shifts and research capacity-building. These relatively intangible outcomes are harder to measure and require new emphases and tools. This opinion paper uses six Canadian and United Kingdom case studies to explore the principles and practice of co-production and illustrate how it can influence interactions between research, policy and practice, and benefit diverse stakeholders. In doing so, we identify a continuum of co-production processes. We propose and illustrate the use of a new 'social model of impact' and framework to capture multi-layered and potentially transformative impacts of co-produced research. We make recommendations for future directions in research co-production and impact measurement

Functional Interactions between KCNE1 C-Terminus and the KCNQ1 Channel

The KCNE1 gene product (minK protein) associates with the cardiac KvLQT1 potassium channel (encoded by KCNQ1) to create the cardiac slowly activating delayed rectifier, IKs. Mutations throughout both genes are linked to the hereditary cardiac arrhythmias in the Long QT Syndrome (LQTS). KCNE1 exerts its specific regulation of KCNQ1 activation via interactions between membrane-spanning segments of the two proteins. Less detailed attention has been focused on the role of the KCNE1 C-terminus in regulating channel behavior. We analyzed the effects of an LQT5 point mutation (D76N) and the truncation of the entire C-terminus (Δ70) on channel regulation, assembly and interaction. Both mutations significantly shifted voltage dependence of activation in the depolarizing direction and decreased IKs current density. They also accelerated rates of channel deactivation but notably, did not affect activation kinetics. Truncation of the C-terminus reduced the apparent affinity of KCNE1 for KCNQ1, resulting in impaired channel formation and presentation of KCNQ1/KCNE1 complexes to the surface. Complete saturation of KCNQ1 channels with KCNE1-Δ70 could be achieved by relative over-expression of the KCNE subunit. Rate-dependent facilitation of K+ conductance, a key property of IKs that enables action potential shortening at higher heart rates, was defective for both KCNE1 C-terminal mutations, and may contribute to the clinical phenotype of arrhythmias triggered by heart rate elevations during exercise in LQTS mutations. These results support several roles for KCNE1 C-terminus interaction with KCNQ1: regulation of channel assembly, open-state destabilization, and kinetics of channel deactivation