Overview of the VA Quality Enhancement Research Initiative (QUERI) and QUERI theme articles: QUERI Series

Background

The recent development and publication of evidence-based clinical practice guidelines (CPGs) for acute low back pain (LBP) has resulted in evidence-based recommendations that, if implemented, have the potential to improve the quality and safety of care for acute LBP. While a strategy has been specified for dissemination of the CPG for acute LBP in Australia, there is no accompanying plan for active implementation. Evidence regarding the cost-effectiveness of active implementation of CPGs for acute LBP is sparse. The IMPLEMENT study will consider the incremental benefits and costs of progressing beyond development and dissemination to implementation.

Methods/design

Cost-effectiveness and cost-utility analyses alongside the IMPLEMENT cluster randomised controlled trial (CRCT) from a societal perspective to quantify the additional costs (savings) and health gains associated with a targeted implementation strategy as compared with access to the CPG via dissemination only.

Discussion

The protocol provided here registers our intent to conduct an economic evaluation alongside the IMPLEMENT study, facilitates peer-review of proposed methods and provides a transparent statement of planned analyses.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN012606000098538     

EQUIP: Implementing chronic care principles and applying formative evaluation methods to improve care for schizophrenia: QUERI Series

Background

The PARiHS framework (Promoting Action on Research Implementation in Health Services) has proved to be a useful practical and conceptual heuristic for many researchers and practitioners in framing their research or knowledge translation endeavours. However, as a conceptual framework it still remains untested and therefore its contribution to the overall development and testing of theory in the field of implementation science is largely unquantified.

Discussion

This being the case, the paper provides an integrated summary of our conceptual and theoretical thinking so far and introduces a typology (derived from social policy analysis) used to distinguish between the terms conceptual framework, theory and model – important definitional and conceptual issues in trying to refine theoretical and methodological approaches to knowledge translation. Secondly, the paper describes the next phase of our work, in particular concentrating on the conceptual thinking and mapping that has led to the generation of the hypothesis that the PARiHS framework is best utilised as a two-stage process: as a preliminary (diagnostic and evaluative) measure of the elements and sub-elements of evidence (E) and context (C), and then using the aggregated data from these measures to determine the most appropriate facilitation method. The exact nature of the intervention is thus determined by the specific actors in the specific context at a specific time and place. In the process of refining this next phase of our work, we have had to consider the wider issues around the use of theories to inform and shape our research activity; the ongoing challenges of developing robust and sensitive measures; facilitation as an intervention for getting research into practice; and finally to note how the current debates around evidence into practice are adopting wider notions that fit innovations more generally.

Summary

The paper concludes by suggesting that the future direction of the work on the PARiHS framework is to develop a two-stage diagnostic and evaluative approach, where the intervention is shaped and moulded by the information gathered about the specific situation and from participating stakeholders. In order to expedite the generation of new evidence and testing of emerging theories, we suggest the formation of an international research implementation science collaborative that can systematically collect and analyse experiences of using and testing the PARiHS framework and similar conceptual and theoretical approaches. We also recommend further refinement of the definitions around conceptual framework, theory, and model, suggesting a wider discussion that embraces multiple epistemological and ontological perspectives.     

Lessons for non-VA care delivery systems from the U.S. Department of Veterans Affairs Quality Enhancement Research Initiative: QUERI Series

The U.S. Veterans Health Administration (VHA) may have a very different structure and function from the organizations and practices that provide medical care to most Americans, but those organizations and practices could learn a lot from the VHA's Quality Enhancement Research Initiative (QUERI). There are at least six topics of increasing importance for implementation research where QUERI experience should be of value to other non-VHA organizations, both within and external to the United States: 1) Researcher-clinical leader partnerships for care improvement; 2) Attention to culture, capacity, leadership, and a supportive infrastructure; 3) Practical economic evaluation of quality implementation efforts; 4) Human subject protection problems; 5) Sustainability of improvements; and 6) Scale-up and spread of improvements. The articles in Implementation Science's QUERI Series provide the details of those lessons for others who are willing to invest the time to translate them into their different settings.     

Measuring the persistence length of MCF7 cell microtubules in vitro

The dynamic and mechanical properties of mammalian neural microtubules have been widely studied; however, similar knowledge about these properties is limited for non-neural microtubules, which, unlike neural microtubules, consist of different β-tubulin isotypes. In this study, we report, for the first time, an estimated value for the persistence length of a single non-neural microtubule polymerized from purified tubulin from human breast cancer cell lines (MCF7 tubulin). The method of measurement is based on an analysis of the local curvature of a microtubule as a result of thermal fluctuations. In parallel, we measured the persistence length of a single bovine brain microtubule under similar conditions. The results of our measurements indicate a higher value for the persistence length of MCF7 microtubules in vitro as compared to the persistence length of a neural microtubule. The difference can be associated with different β-tubulin isotypes in the structure of MCF7 microtubules.     

Tuberculosis: a problem with persistence

Mycobacterium tuberculosis is one of most successful pathogens of mankind, infecting one-third of the global population and claiming two million lives every year. The ability of the bacteria to persist in the form of a long-term asymptomatic infection, referred to as latent tuberculosis, is central to the biology of the disease. The persistence of bacteria in superficially normal tissue was recognized soon after the discovery of the tubercle bacillus, and much of our knowledge about persistent populations of M. tuberculosis dates back to the first half of the last century. Recent advances in microbial genetics and host immunity provide an opportunity for renewed investigation of this persistent threat to human health.     

Chlamydia trachomatis persistence: an update

Chlamydial persistence is a reversible state generated during conditions deleterious to growth. In persistence, Chlamydia trachomatis remains viable but atypical, with an enlarged, aberrant form and quiescent metabolism. It favours chronic chlamydiosis, leading to serious sequelae. Although the mechanism of persistence formation is still unknown, more reliable molecular approaches tend to confirm that its occurs in vivo, even lasting 3 years. One approach consists of identifying unprocessed rRNA found only in viable Chlamydia, when infection is not apparent. Another approach, referring to the fact that immunity is type-specific, consists of showing by genotyping that multiple recurrences are due to the same genovar. At the molecular level, persistence is characterized by increased expression of ct755, one of the three heat shock protein (hsp60)-coding genes. In addition, chromosomal replication occurs continuously, and cell division is blocked possibly due to the repression of genes such as ftsW and amiA. At the immunological level, persistence reveals the failure of host-defence mechanisms because of reduced or suppressed pro-inflammatory or cytotoxic responses.     

Measuring the metabolism of marine organisms in continuous flow-through systems: A mathematical justification and practical implementation of a method

This paper presents a method for measuring the metabolism of macrophytes, macrophytobenthos, periphyton, corals, and other benthic organisms in flow-through systems in non-equilibrium and equilibrium states and provides its mathematical justification. An experimental system has been designed for measuring the rate of metabolic exchange of O₂, CO₂, NH₄, NO₂, NO₃, PO₄, dissolved organic matter (DOM), etc. between aquatic organisms and the environment in situ and in vitro repeatedly during a 24-hour experimental period. Using of this system, production characteristics (photosynthesis and respiration) were calculated for benthic marine organisms and the dependence of the rates of their metabolism on environmental factors was determined.     

Scales of persistence: transmission and the microbiome

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Babesiosis: persistence in the face of adversity

Many babesial parasites establish infections of long duration in immune hosts. Among different species, at least four mechanisms are known that could facilitate evasion of the host immune response, although no one species is (yet) known to use them all. This update strives to illustrate the ramifications of these mechanisms and the interplay between them.     

Asymmetric division: motor persistence pays off

A new study shows that an antagonistic force model can explain a number of complex mitotic spindle movements in the first mitosis of the Caenorhabditis elegans embryo by simply assuming that cortical force generators become increasingly persistent in their interaction with microtubules during mitosis.     

Closed loops: persistence of the protein chain returns

It has recently been discovered that globular proteins are universally built from standard loop-n-lock units of about 30 amino acid residues. The hypothesis has been put forward on the loop stage in the protein evolution when the units were autonomous. Later they joined together making longer chains. One would expect that the early individual loop-n-lock elements might still be detected in modern protein sequences as remnants of the hypothetical 30-residue sequence prototypes. Among several strong sequence motifs, extracted from protein sequences of 23 complete bacterial proteomes, one 32-residue prototype was studied here in detail. Numerous sequence segments related to the prototype are identified in the crystal structures of proteins of a PDB_SELECT database. Analysis of the respective chain trajectories for the cases with different degrees of sequence conservation confirms that the majority of the segments correspond to the closed loops. In the evolutionary diversification of the prototypes the secondary structure yields first, while the sequence is still moderately conserved. The last feature to go is the chain return property. Apparently, the opening of the loops would severely destabilize the protein fold, which explains their conservation.     

Mycobacterial persistence: adaptation to a changing environment

Mycobacterium tuberculosis is a bacterial pathogen that can persist within an infected individual for extended periods of time without causing overt, clinical disease, in a state normally referred to as latent or chronic tuberculosis. Although the replicative state of the bacterium during this period is a matter of some conjecture, recent developments have indicated that the bacterium requires the regulated expression of a set of genes and metabolic pathways to maintain a persistent infection in an immunocompetent host. The characterization of these gene products and their role in bacterial metabolism and physiology is starting to provide insights into the mechanisms that M. tuberculosis has evolved to adopt its highly successful mode of pathogenicity.     

HIV persistence: Chemokines and their signalling pathways

Latently infected resting CD4+ T cells are the major barrier to curing HIV. We have recently demonstrated that chemokines, which bind to the chemokine receptors CCR7, CXCR3 and CCR6, facilitate efficient HIV nuclear localisation and integration in resting CD4+ T cells, leading to latency. As latently infected cells are enriched in lymphoid tissues, where chemokines are highly concentrated, this may provide a mechanism for the generation of latently infected cells in vivo. Here we review the role of chemokines in HIV persistence; the main signalling pathways that are involved; and how these pathways may be exploited to develop novel strategies to reduce or eliminate latently infected cells.     

Spatial frequency and visual persistence: cortical reset

Psychophysical studies show that the duration of visual persistence increases with spatial frequency of gratings. Previous theories ascribe this finding to differences between the spatial and temporal properties of sustained and transient pathways. This paper proposes an alternative account that explains persistence as a side-effect of excitatory feedback in neural circuits for contour extraction. Mechanisms to break excitatory feedback include inhibitory reset signals at stimulus offset. Simulations demonstrate how gratings with lower spatial frequency generate stronger inhibitory reset signals, thereby resulting in shorter persistence for lower spatial frequencies. Additional simulations account for interactions of spatial frequency with stimulus duration, effects of adaptation, and properties of residual traces, as opposed to visual persistence.