The process of developing evidence-based guidance in medicine and public health: a qualitative study of views from the inside.

BACKGROUND: There has been significant investment in developing guidelines to improve clinical and public health practice. Though much is known about the processes of evidence synthesis and evidence-based guidelines implementation, we know little about how evidence presented to advisory groups is interpreted and used to form practice recommendations or what happens where evidence is lacking. This study investigates how members of advisory groups of NICE (National Institute of Health and Clinical Excellence) conceptualize evidence and experience the process. METHODS: Members of three advisory groups for acute physical, mental and public health were interviewed at the beginning and end of the life of the group. Seventeen were interviewed at both time points; five were interviewed just once at time one; and 17 were interviewed only once after guidance completion. Using thematic and content analysis, interview transcripts were analysed to identify the main themes. RESULTS: Three themes were identified:1. What is the task? Different members conceptualized the task differently; some emphasized the importance of evidence at the top of the quality hierarchy while others emphasized the importance of personal experience.2. Who gets heard? Managing the diversity of opinion and vested interests was a challenge for the groups; service users were valued and as was the importance of fostering good working relationships between group members.3. What is the process? Group members valued debate and recognized the need to marshal discussion; most members were satisfied with the process and output. CONCLUSIONS: Evidence doesn't form recommendations on its own, but requires human judgement. Diversity of opinion within advisory groups was seen as key to making well-informed judgments relevant to forming recommendations. However, that diversity can bring tensions in the evaluation of evidence and its translation into practice recommendations

Gastrointestinal Cell Injury and Percieved Symptoms after Running the Boston Marathon

Gastrointestinal (GI) disturbances are a prevalent cause of marathon related complaints, and in extreme cases can promote life-threatening conditions such as exertional heat stroke. PURPOSE: Our aim was to study intestinal cell injury (via intestinal fatty acid binding protein [I-FABP]) and perceived GI distress symptoms among marathon runners. Potential risk factors (e.g., inadequate sleep) that could exacerbate GI disturbances in healthy, trained endurance runners were also examined. METHODS: A parallel mixed-methods study design was utilized. 2019 Boston Marathon participants were recruited via email. Before the race subjects completed surveys describing demographics and training history. Immediately pre-race, post-race, and 24-hours post-race participants completed a GI questionnaire to assess presence and severity of symptoms, a survey regarding risk factors (e.g., recent illness, medications) that could promote GI disturbances, and provided a urine sample. Due to weather, blood samples were only collected immediately and 24-hours post-race. RESULTS: A total of 40 runners (males: n = 19, age = 44.9 ± 10.8 years; females: n = 21, age = 44.8 ± 10.6 years) completed this study. I-FABP significantly decreased from post-race (3367.5 ± 2633.5 pg/ml) to 24-hours post-race (1657.3 ± 950.7 pg/ml, t(39) = -4.228, p \u3c .001, d = -.669). A significant difference in overall GI symptom scores across the three time points occurred (F(2, 39) = 41.37, p \u3c .001). Compared to pre-race (.09 ± .12) and 24-hour post-race (.44 ± .28), the highest average score occurred post-race (.84 ± .68). Post-race I-FABP (r = .31, p = .048) and post-race urine specific gravity (r = .33, p = .041) were significantly correlated with post-race GI symptom scores. CONCLUSION: Our study further supports the individualized presentation of GI disturbances, with participants experiencing a wide range of risk factors that can influence the extent of GI damage and perceived symptoms during and after exercise

Identifying the gene(s) that allow tigriopus californicus to survive under thermal stress

The copepod species, Tigriopus californicus, is one of the most thermally adaptable species in the biosphere. They have been found in tide pools from the coast of Alaska down to the coast of Southern California. However, as all other organisms have limits, the T. californicus are only able to tolerate temperatures up to 34ºC. By comparing gene expression between specimens exposed to high temperatures and those expressed to optimal temperatures, we identified the genes responsible for conferring tolerance to increasing temperatures. After testing gene expression between copepods at 20ºC and at 34ºC, we have determined that both the hsp70 gene and the toll-like receptors of the T. californicus play a role in tolerance to temperature variance.L’espèce copépode, Tigriopus californicus, est une des espèces les plus thermiquement adaptables de la biosphère. On les trouve dans les bâches depuis la côte de l’Alaska jusqu’à la côte sud de la Californie. Toutefois, comme tous les autres organ¬ismes, les Tigriopus californicus ont des limites et ne peuvent pas tolérer des températures supérieures à 34oC. En comparant l’expression génétique entre les spécimens exposés à des températures élevées et ceux exposés à des températures optimales, nous avons identifié les gènes responsables de la tolérance à des températures en hausse. Après avoir testé l’expression génétique entre les copépodes à 20oC et à 34oC, nous avons déterminé que le gène hsp70 et les récepteurs de type Toll du T. californicus jouent tous deux un rôle dans la tolérance aux variations de température

New project to support scientific collaboration electronically

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95417/1/eost10181.pd

Towards a methodology for cluster searching to provide conceptual and contextual "richness" for systematic reviews of complex interventions: case study (CLUSTER)

Background Systematic review methodologies can be harnessed to help researchers to understand and explain how complex interventions may work. Typically, when reviewing complex interventions, a review team will seek to understand the theories that underpin an intervention and the specific context for that intervention. A single published report from a research project does not typically contain this required level of detail. A review team may find it more useful to examine a “study cluster”; a group of related papers that explore and explain various features of a single project and thus supply necessary detail relating to theory and/or context. We sought to conduct a preliminary investigation, from a single case study review, of techniques required to identify a cluster of related research reports, to document the yield from such methods, and to outline a systematic methodology for cluster searching. Methods In a systematic review of community engagement we identified a relevant project – the Gay Men’s Task Force. From a single “key pearl citation” we conducted a series of related searches to find contextually or theoretically proximate documents. We followed up Citations, traced Lead authors, identified Unpublished materials, searched Google Scholar, tracked Theories, undertook ancestry searching for Early examples and followed up Related projects (embodied in the CLUSTER mnemonic). Results Our structured, formalised procedure for cluster searching identified useful reports that are not typically identified from topic-based searches on bibliographic databases. Items previously rejected by an initial sift were subsequently found to inform our understanding of underpinning theory (for example Diffusion of Innovations Theory), context or both. Relevant material included book chapters, a Web-based process evaluation, and peer reviewed reports of projects sharing a common ancestry. We used these reports to understand the context for the intervention and to explore explanations for its relative lack of success. Additional data helped us to challenge simplistic assumptions on the homogeneity of the target population. Conclusions A single case study suggests the potential utility of cluster searching, particularly for reviews that depend on an understanding of context, e.g. realist synthesis. The methodology is transparent, explicit and reproducible. There is no reason to believe that cluster searching is not generalizable to other review topics. Further research should examine the contribution of the methodology beyond improved yield, to the final synthesis and interpretation, possibly by utilizing qualitative sensitivity analysis

Pediatric Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (CoSTR) for pediatric life support is based on the most extensive evidence evaluation ever performed by the Pediatric Life Support Task Force. Three types of evidence evaluation were used in this review: systematic reviews, scoping reviews, and evidence updates. Per agreement with the evidence evaluation recommendations of the International Liaison Committee on Resuscitation, only systematic reviews could result in a new or revised treatment recommendation. Systematic reviews performed for this 2020 CoSTR for pediatric life support included the topics of sequencing of airway-breaths-compressions versus compressions-airway-breaths in the delivery of pediatric basic life support, the initial timing and dose intervals for epinephrine administration during resuscitation, and the targets for oxygen and carbon dioxide levels in pediatric patients after return of spontaneous circulation. The most controversial topics included the initial timing and dose intervals of epinephrine administration (new treatment recommendations were made) and the administration of fluid for infants and children with septic shock (this latter topic was evaluated by evidence update). All evidence reviews identified the paucity of pediatric data and the need for more research involving resuscitation of infants and children

Quantitative analyses and modelling to support achievement of the 2020 goals for nine neglected tropical diseases

Quantitative analysis and mathematical models are useful tools in informing strategies to control or eliminate disease. Currently, there is an urgent need to develop these tools to inform policy to achieve the 2020 goals for neglected tropical diseases (NTDs). In this paper we give an overview of a collection of novel model-based analyses which aim to address key questions on the dynamics of transmission and control of nine NTDs: Chagas disease, visceral leishmaniasis, human African trypanosomiasis, leprosy, soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. Several common themes resonate throughout these analyses, including: the importance of epidemiological setting on the success of interventions; targeting groups who are at highest risk of infection or re-infection; and reaching populations who are not accessing interventions and may act as a reservoir for infection,. The results also highlight the challenge of maintaining elimination ‘as a public health problem’ when true elimination is not reached. The models elucidate the factors that may be contributing most to persistence of disease and discuss the requirements for eventually achieving true elimination, if that is possible. Overall this collection presents new analyses to inform current control initiatives. These papers form a base from which further development of the models and more rigorous validation against a variety of datasets can help to give more detailed advice. At the moment, the models’ predictions are being considered as the world prepares for a final push towards control or elimination of neglected tropical diseases by 2020

Building blocks for meta-synthesis: data integration tables for summarising, mapping, and synthesising evidence on interventions for communicating with health consumers

<p>Abstract</p> <p>Background</p> <p>Systematic reviews have developed into a powerful method for summarising and synthesising evidence. The rise in systematic reviews creates a methodological opportunity and associated challenges and this is seen in the development of overviews, or reviews of systematic reviews. One of these challenges is how to summarise evidence from systematic reviews of complex interventions for inclusion in an overview. Interventions for communicating with and involving consumers in their care are frequently complex. In this article we outline a method for preparing data integration tables to enable review-level synthesis of the evidence on interventions for communication and participation in health.</p> <p>Methods and Results</p> <p>Systematic reviews published by the Cochrane Consumers and Communication Review Group were utilised as the basis from which to develop linked steps for data extraction, evidence assessment and synthesis. The resulting output is called a data integration table. Four steps were undertaken in designing the data integration tables: first, relevant information for a comprehensive picture of the characteristics of the review was identified from each review, extracted and summarised. Second, results for the outcomes of the review were assessed and translated to standardised evidence statements. Third, outcomes and evidence statements were mapped into an outcome taxonomy that we developed, using language specific to the field of interventions for communication and participation. Fourth, the implications of the review were assessed after the mapping step clarified the level of evidence available for each intervention.</p> <p>Conclusion</p> <p>The data integration tables represent building blocks for constructing overviews of review-level evidence and for the conduct of meta-synthesis. Individually, each table aims to improve the consistency of reporting on the features and effects of interventions for communication and participation; provides a broad assessment of the strength of evidence derived from different methods of analysis; indicates a degree of certainty with results; and reports outcomes and gaps in the evidence in a consistent and coherent way. In addition, individual tables can serve as a valuable tool for accurate dissemination of large amounts of complex information on communication and participation to professionals as well as to members of the public.</p

Polarisation of a T-helper cell immune response by activation of dendritic cells with CpG-containing oligonucleotides: a potential therapeutic regime for bladder cancer immunotherapy

Intravesical bacillus Calmette-Guerin (BCG) is a treatment for transitional cell carcinoma (TCC) and carcinoma in situ (cis) of the urinary bladder, but some patients remain refractory. The mechanism of cancer clearance is not known, but T cells are thought to play a contributory role. Tissue dendritic cells (DCs) are known to initiate antigen-specific immune responses following activation of receptors, which recognise molecular patterns on the surface of microorganisms. A family of these receptors, the toll-like receptors (TLRs), are also crucial for activating DC to produce cytokines that polarise the T-cell response towards a T helper (Th)1 or Th2 phenotype. This study compared the potential of intact BCG to activate DC with that of the defined TLR4 ligand lipopolysaccharide (LPS) and the TLR9 ligand CpG-oligonucleotide. It was found that all three stimuli efficiently activated normal DC, but cells expressing a mutant TLR4 responded poorly to stimulation with LPS. Importantly, stimulation with BCG induced both IL-12 and IL-10, suggesting subsequent development of a poorly focused T-cell immune response containing both Th1 and Th2 immune function. By contrast, LPS- and CpG-oligonucleotides induced only IL-12, indicating the potential to produce a Th1 response, which is likely to clear cancer most efficiently. Given the toxicity of LPS, our data suggest that CpG-oligonucleotides may be beneficial for intravesical therapy of bladder cancer