Can We Systematically Review Studies That Evaluate Complex Interventions?

In three Viewpoints, Sasha Shepperd and colleagues, Geoff Wong, and Aziz Sheikh explore various approaches to help systematic reviewers who wish to review complex health interventions

Level models of continuing professional development evaluation: a grounded review and critique

Continuing professional development (CPD) evaluation in education has been heavily influenced by ‘level models’, deriving from the work of Kirkpatrick and Guskey in particular, which attempt to trace the processes through which CPD interventions achieve outcomes. This paper considers the strengths and limitations of such models, and in particular the degree to which they are able to do justice to the complexity of CPD and its effects. After placing level models within the broader context of debates about CPD evaluation, the paper reports our experience of developing such models heuristically for our own evaluation practice. It then draws on positivist, realist and constructivist traditions to consider some more fundamental ontological and epistemological questions to which they give rise. The paper concludes that level models can be used in a number of ways and with differing emphases, and that choices made about their use will need to reflect both theoretical choices and practical considerations

Explaining the effects of a multifaceted intervention to improve inpatient care in rural Kenyan hospitals -- interpretation based on retrospective examination of data from participant observation, quantitative and qualitative studies

<p>Abstract</p> <p>Background</p> <p>We have reported the results of a cluster randomized trial of rural Kenyan hospitals evaluating the effects of an intervention to introduce care based on best-practice guidelines. In parallel work we described the context of the study, explored the process and perceptions of the intervention, and undertook a discrete study on health worker motivation because this was felt likely to be an important contributor to poor performance in Kenyan public sector hospitals. Here, we use data from these multiple studies and insights gained from being participants in and observers of the intervention process to provide our explanation of how intervention effects were achieved as part of an effort to better understand implementation in low-income hospital settings.</p> <p>Methods</p> <p>Initial hypotheses were generated to explain the variation in intervention effects across place, time, and effect measure (indicator) based on our understanding of theory and informed by our implementation experience and participant observations. All data sources available for hospitals considered as cases for study were then examined to determine if hypotheses were supported, rejected, or required modification. Data included transcriptions of interviews and group discussions, field notes and that from the detailed longitudinal quantitative investigation. Potentially useful explanatory themes were identified, discussed by the implementing and research team, revised, and merged as part of an iterative process aimed at building more generic explanatory theory. At the end of this process, findings were mapped against a recently reported comprehensive framework for implementation research.</p> <p>Results</p> <p>A normative re-educative intervention approach evolved that sought to reset norms and values concerning good practice and promote 'grass-roots' participation to improve delivery of correct care. Maximal effects were achieved when this strategy and external support supervision helped create a soft-contract with senior managers clarifying roles and expectations around desired performance. This, combined with the support of facilitators acting as an expert resource and 'shop-floor' change agent, led to improvements in leadership, accountability, and resource allocation that enhanced workers' commitment and capacity and improved clinical microsystems. Provision of correct care was then particularly likely if tasks were simple and a good fit to existing professional routines. Our findings were in broad agreement with those defined as part of recent work articulating a comprehensive framework for implementation research.</p> <p>Conclusions</p> <p>Using data from multiple studies can provide valuable insight into how an intervention is working and what factors may explain variability in effects. Findings clearly suggest that major intervention strategies aimed at improving child and newborn survival in low-income settings should go well beyond the fixed inputs (training, guidelines, and job aides) that are typical of many major programmes. Strategies required to deliver good care in low-income settings should recognize that this will need to be co-produced through engagement often over prolonged periods and as part of a directive but adaptive, participatory, information-rich, and reflective process.</p

Contributions of a global network of tree diversity experiments to sustainable forest plantations

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Computational Analysis of Phosphopeptide Binding to the Polo-Box Domain of the Mitotic Kinase PLK1 Using Molecular Dynamics Simulation

The Polo-Like Kinase 1 (PLK1) acts as a central regulator of mitosis and is over-expressed in a wide range of human tumours where high levels of expression correlate with a poor prognosis. PLK1 comprises two structural elements, a kinase domain and a polo-box domain (PBD). The PBD binds phosphorylated substrates to control substrate phosphorylation by the kinase domain. Although the PBD preferentially binds to phosphopeptides, it has a relatively broad sequence specificity in comparison with other phosphopeptide binding domains. We analysed the molecular determinants of recognition by performing molecular dynamics simulations of the PBD with one of its natural substrates, CDC25c. Predicted binding free energies were calculated using a molecular mechanics, Poisson-Boltzmann surface area approach. We calculated the per-residue contributions to the binding free energy change, showing that the phosphothreonine residue and the mainchain account for the vast majority of the interaction energy. This explains the very broad sequence specificity with respect to other sidechain residues. Finally, we considered the key role of bridging water molecules at the binding interface. We employed inhomogeneous fluid solvation theory to consider the free energy of water molecules on the protein surface with respect to bulk water molecules. Such an analysis highlights binding hotspots created by elimination of water molecules from hydrophobic surfaces. It also predicts that a number of water molecules are stabilized by the presence of the charged phosphate group, and that this will have a significant effect on the binding affinity. Our findings suggest a molecular rationale for the promiscuous binding of the PBD and highlight a role for bridging water molecules at the interface. We expect that this method of analysis will be very useful for probing other protein surfaces to identify binding hotspots for natural binding partners and small molecule inhibitors

THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Ion channels

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15539. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate

Marine Mammal Ecosystem Component

ICES Divisions VII e,f,g &amp; h This document contains the supporting information prepared for the assessment. This consists of short reports describing fisheries interactions with the various ecological components; these were available to the members of the working group. Information on marine teleost fish ecosystem component for Seafish Ecological risk assessment of South West fisheries; Oct 201

Monitoring of discarding and retention by trawl fisheries in Western Waters and the Irish Sea in relation to stock assessment and technical measures

Westem Waters fisheries face major challenges in relation to the depleted state of the fishery resources and in implementing the adjustments required to bring exploitation of these resources on to a more sustainable basis. Fisheries assessments, as carried out by ICES working groups, use data from market sampling of the landed catch, reported landings and effort figures and also research vessel data to assess the state of fish stocks and to produce short term forecasts for setting Total Allowable Catches. Since the discards may constitute a significant source of extra mortality in some fisheries there is clearly a requirement to adequately describe the levels of discarded fish in order to improve stock assessment and the likelihood of sustainability. In deciding a strategy for improved sustainability there is also a requirement to understand the factors motivating the fishers to target and retain, or discard, fish of a given species and to relate this to the current management and market situation. This, and stock assessment information, could be used to guide research into the most appropriate technology and measures to reduce discarding and hence place the harvesting of these stocks on a more sustainable basis. The project studied the pattem of discarding and retention, using an onboard observer programme, in the main demersal trawl fisheries of the participating nations' in Westem Waters (ICES Divisions VIa,b VIIa,b,c,e(western part), f,g,h and k and from VIIIa,b,c,d and IXa) and describes the use of these data in ICES stock assessments. It assessed the feasibility of using these data to understand the economic aspects of discarding and retention, to assess the impact of technical measures and investigated the effects of trawling on ecosystems. Data on discarded megrim from Spanish Baka trawlers were used in the assessment of the Northem Stock of this species at the ICES Southem Shelf Demersal Working Group. These results show that including discard data in the assessment improved the description of the strength of incoming year classes, growth and spawning stock biomass. The impact of technical measures designed to reduce discarding was assessed by examining the effect of the implementation of EC regulation 850/98 on Jan 1st 2000. In the midwater demersal trawl fishery in the Irish Sea there was a reduction in the catch per effort of discarded and retained whiting. For the baka trawlers exploiting megrim in Sub areas VI and VII there was a change in the discarding practices. Discarding and retention is discussed in relation to economic factors and the exploitation pattem. Possible changes in some métiers were suggested but the very mixed nature some of the fisheries means that what is selective for one species could result in the loss of economically important catch of other species. It was found that discarding practices were most closely related to economic values, which were a stronger influence than fishery management measures. Measures which are designed to reduce discarding without taking into account market forces, are unlikely to succeed. Limited studies of the impact of technical measures were carried out by developing a model designed to predict the returns which could be obtained by improving selectivity, but these were intended only to develop the model not to use it on Westem Waters fisheries during this project