Applying systematic review search methods to the grey literature: a case study examining guidelines for school-based breakfast programs in Canada

Grey literature is an important source of information for large-scale review syntheses. However, there are many characteristics of grey literature that make it difficult to search systematically. Further, there is no ‘gold standard’ for rigorous systematic grey literature search methods and few resources on how to conduct this type of search. This paper describes systematic review search methods that were developed and applied to complete a case study systematic review of grey literature that examined guidelines for school-based breakfast programs in Canada. Methods: A grey literature search plan was developed to incorporate four different searching strategies: (1) grey literature databases, (2) customized Google search engines, (3) targeted websites, and (4) consultation with contact experts. These complementary strategies were used to minimize the risk of omitting relevant sources. Since abstracts are often unavailable in grey literature documents, items’ abstracts, executive summaries, or table of contents (whichever was available) were screened. Screening of publications’ full-text followed. Data were extracted on the organization, year published, who they were developed by, intended audience, goal/objectives of document, sources of evidence/resources cited, meals mentioned in the guidelines, and recommendations for program delivery. Results: The search strategies for identifying and screening publications for inclusion in the case study review was found to be manageable, comprehensive, and intuitive when applied in practice. The four search strategies of the grey literature search plan yielded 302 potentially relevant items for screening. Following the screening process, 15 publications that met all eligibility criteria remained and were included in the case study systematic review. The high-level findings of the case study systematic review are briefly described. Conclusions: This article demonstrated a feasible and seemingly robust method for applying systematic search strategies to identify web-based resources in the grey literature. The search strategy we developed and tested is amenable to adaptation to identify other types of grey literature from other disciplines and answering a wide range of research questions. This method should be further adapted and tested in future research syntheses

A mini-review of non-parenteral clonidine preparations for paediatric sedation

OBJECTIVE: To provide an overview of non-parenteral clonidine formulations and assess the feasibility of their use for paediatric sedation. / METHODS: A literature search was conducted using electronic databases and a combination of search terms. Forty articles met the inclusion criteria. Publications were grouped into different dosage forms and assessed for their potential application for sedation of children in intensive care. / KEY FINDINGS: Several routes of clonidine administration have been investigated for numerous indications in children, including perioperative sedation and analgesia. These include oral liquids, tablets, oral transmucosal systems, nasal sprays and rectal suspensions. Conflicting studies on oral transmucosal clonidine formulations suggest that further research is required to fully establish efficacy. Nasal sprays and rectal suspensions have the advantages of rapid onset of action and potential for dose flexibility, but predictable absorption is difficult to obtain. CONCLUSIONS: Provided age-appropriate strengths are available, IV formulations remain the most predictable in terms of bioavailability and flexible in terms of dose adjustment. However, as with all routes, down-titration is difficult given the long half-life of clonidine. Oral transmucosal systems, nasal sprays and rectal suspensions have potential in a less acute setting, but significant clinical work is required to elucidate a full pharmacokinetic and pharmacodynamic profile

Systematic Search and Reporting Techniques Applied to the Gray Literature: A Review of Canadian School Breakfast Program Guidelines

This poster was presented at the Mosaic ’16 (Medical Library Association) Conference on May 17, 2016, Toronto, Ontario. Abstract: Methods: A grey literature search plan was developed to incorporate four different searching strategies: i) grey literature databases, ii) customized Google search engines, iii) targeted websites; and, iv) consultation with contact experts. These complementary strategies were used to minimize the risk of omitting relevant sources. Since abstracts are often unavailable in grey literature documents, items’ abstracts, executive summaries, or table of contents (whichever was available) were screened. Screening of publications’ full-text followed. Data were extracted on the organization, year published, who they were developed by, intended audience, goal/objectives of document, sources of evidence/resources cited, meals mentioned in the guidelines, and recommendations for program delivery. Results: The search strategies for identifying and screening publications for inclusion in the case study review was found to be manageable, comprehensive, and intuitive when applied in practice. The four search strategies of the grey literature search plan yielded 302 potentially relevant items for screening. Following the screening process, 15 publications that met all eligibility criteria remained and were included in the case study systematic review. Conclusions: This presentation demonstrates a feasible and seemingly robust method for applying systematic search strategies to identify web-based resources in the grey literature. The search strategy we developed and tested is amenable to adaptation to identify other types of grey literature from other disciplines and answering a wide range of research questions. This method should be further adapted and tested in future research syntheses

Does anaesthesia cause postoperative cognitive dysfunction? A randomised study of regional versus general anaesthesia in 438 elderly patients

Keywords:anesthesia;cognitive function;complications;postoperative period;regional anesthesia;surgery Background: Postoperative cognitive dysfunction (POCD) is a common complication after cardiac and major non-cardiac surgery with general anaesthesia in the elderly. We hypothesized that the incidence of POCD would be less with regional anaesthesia rather than general. Methods: We included patients aged over 60 years undergoing major non-cardiac surgery. After giving written informed consent, patients were randomly allocated to general or regional anaesthesia. Cognitive function was assessed using four neuropsychological tests undertaken preoperatively and at 7 days and 3 months postoperatively. POCD was defined as a combined Z score >1.96 or a Z score >1.96 in two or more test parameters. Results: At 7 days, POCD was found in 37/188 patients (19.7%, [14.3–26.1%]) after general anaesthesia and in 22/176 (12.5%, [8.0–18.3%]) after regional anaesthesia, P = 0.06. After 3 months, POCD was present in 25/175 patients (14.3%, [9.5–20.4%]) after general anaesthesia vs. 23/165 (13.9%, [9.0–20.2%]) after regional anaesthesia, P = 0.93. The incidence of POCD after 1 week was significantly greater after general anaesthesia when we excluded patients who did not receive the allocated anaesthetic: 33/156 (21.2%[15.0–28.4%]) vs. 20/158 (12.7%[7.9–18.9%]) (P = 0.04). Mortality was significantly greater after general anaesthesia (4/217 vs. 0/211 (P <0.05)). Conclusion: No significant difference was found in the incidence of cognitive dysfunction 3 months after either general or regional anaesthesia in elderly patients. Thus, there seems to be no causative relationship between general anaesthesia and long-term POCD. Regional anaesthesia may decrease mortality and the incidence of POCD early after surgery

The Costs of Photorespiration to Food Production Now and in the Future

Photorespiration is essential for C3 plants but operates at the massive expense of fixed carbon dioxide and energy. Photorespiration is initiated when the initial enzyme of photosynthesis, ribulose-1,5-bisphosphate carboxylase/ oxygenase (Rubisco), reacts with oxygen instead of carbon dioxide and produces a toxic compound that is then recycled by photorespiration. Photorespiration can be modeled at the canopy and regional scales to determine its cost under current and future atmospheres. A regional-scale model reveals that photorespiration currently decreases US soybean and wheat yields by 36% and 20%, respectively, and a 5% decrease in the losses due to photorespiration would be worth approximately $500 million annually in the United States. Furthermore, photorespiration will continue to impact yield under future climates despite increases in carbon dioxide, with models suggesting a 12–55% improvement in gross photosynthesis in the absence of photorespiration, even under climate change scenarios predicting the largest increases in atmospheric carbon dioxide concentration. Although photorespiration is tied to other important metabolic functions, the benefit of improving its efficiency appears to outweigh any potential secondary disadvantages.This article is from Annual Review of Plant Biology 67 (2016): 107, doi: 10.1146/annurev-arplant-043015-111709. Posted with permission.</p

HPV16 oncogene expression levels during early cervical carcinogenesis are determined by the balance of epigenetic chromatin modifications at the integrated virus genome.

In cervical squamous cell carcinomas, high-risk human papillomavirus (HRHPV) DNA is usually integrated into host chromosomes. Multiple integration events are thought to be present within the cells of a polyclonal premalignant lesion and the features that underpin clonal selection of one particular integrant remain poorly understood. We previously used the W12 model system to generate a panel of cervical keratinocyte clones, derived from cells of a low-grade premalignant lesion naturally infected with the major HRHPV type, HPV16. The cells were isolated regardless of their selective advantage and differed only by the site of HPV16 integration into the host genome. We used this resource to test the hypothesis that levels of HPV16 E6/E7 oncogene expression in premalignant cells are regulated epigenetically. We performed a comprehensive analysis of the epigenetic landscape of the integrated HPV16 DNA in selected clones, in which levels of virus oncogene expression per DNA template varied ~6.6-fold. Across the cells examined, higher levels of virus expression per template were associated with more open chromatin at the HPV16 long control region, together with greater loading of chromatin remodelling enzymes and lower nucleosome occupancy. There were higher levels of histone post-translational modification hallmarks of transcriptionally active chromatin and lower levels of repressive hallmarks. There was greater abundance of the active/elongating form of the RNA polymerase-II enzyme (RNAPII-Ser2P), together with CDK9, the component of positive transcription elongation factor b complex responsible for Ser2 phosphorylation. The changes observed were functionally significant, as cells with higher HPV16 expression per template showed greater sensitivity to depletion and/or inhibition of histone acetyltransferases and CDK9 and less sensitivity to histone deacetylase inhibition. We conclude that virus gene expression per template following HPV16 integration is determined through multiple layers of epigenetic regulation, which are likely to contribute to selection of individual cells during cervical carcinogenesis.This work was supported by Cancer Research UK (Programme Grant A13080); the Medical Research Council; The Pathological Society of Great Britain and Ireland (E.L.A.K.); and the Agency for Science, Technology and Research, Singapore (Q.Y.A).This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/onc.2016.

Financial considerations in the conduct of multi-centre randomised controlled trials: evidence from a qualitative study.

National Coordinating Centre for Research Methodology; Medical Research Council, UK Department of Health; Chief Scientist OfficeNot peer reviewedPublisher PD

Overexpression of the oncostatin-M receptor in cervical squamous cell carcinoma is associated with epithelial-mesenchymal transition and poor overall survival.

BACKGROUND: Copy-number gain of the oncostatin-M receptor (OSMR) occurs frequently in cervical squamous cell carcinoma (SCC) and is associated with adverse clinical outcome. We previously showed that OSMR overexpression renders cervical SCC cells more sensitive to the major ligand oncostatin-M (OSM), which increases migration and invasion in vitro. We hypothesised that a major contribution to this phenotype would come from epithelial-mesenchymal transition (EMT). METHODS: We performed a comprehensive integrated study, involving in vitro cell line studies, in vivo animal models and numerous clinical samples from a variety of anatomical sites. RESULTS: In independent sets of cervical, head/neck and lung SCC tissues, OSMR expression levels correlated with multiple EMT-associated phenotypic markers and transcription factors. OSM treatment of OSMR overexpressing cervical SCC cells produced consistent EMT changes and increased tumour sphere formation in suspension culture. In a mouse model, OSMR overexpressing SCC cells treated with OSM showed significant increases in lung colonisation. The biological effects of exogenous OSM were mirrored by highly significant adverse overall survival in cervical SCCs with OSMR overexpression (N=251). CONCLUSIONS: OSM:OSMR interactions are able to induce EMT, increased cancer stem cell-like properties and enhanced lung colonisation in SCC cells. These changes are likely to contribute to the highly significant adverse outcome associated with OSMR overexpression in cervical SCCs.This work was supported by Cancer Research UK (Programme Grant A13080).This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Nature Publishing Group