In pursuit of certainty: Can the systematic review process deliver?

Background: There has been increasing emphasis on evidence-based approaches to improve patient outcomes through rigorous, standardised and well-validated approaches. Clinical guidelines drive this process and are largely developed based on the findings of systematic reviews (SRs). This paper presents a discussion of the SR process in providing decisive information to shape and guide clinical practice, using a purpose-built review database: the Cochrane reviews; and focussing on a highly prevalent medical condition: hypertension. Methods. We searched the Cochrane database and identified 25 relevant SRs incorporating 443 clinical trials. Reviews with the terms 'blood pressure' or 'hypertension' in the title were included. Once selected for inclusion, the abstracts were assessed independently by two authors for their capacity to inform and influence clinical decision-making. The inclusions were independently audited by a third author. Results: Of the 25 SRs that formed the sample, 12 provided conclusive findings to inform a particular treatment pathway. The evidence-based approaches offer the promise of assisting clinical decision-making through clarity, but in the case of management of blood pressure, half of the SRs in our sample highlight gaps in evidence and methodological limitations. Thirteen reviews were inconclusive, and eight, including four of the 12 conclusive SRs, noted the lack of adequate reporting of potential adverse effects or incidence of harm. Conclusions: These findings emphasise the importance of distillation, interpretation and synthesis of information to assist clinicians. This study questions the utility of evidence-based approaches as a uni-dimensional approach to improving clinical care and underscores the importance of standardised approaches to include adverse events, incidence of harm, patient's needs and preferences and clinician's expertise and discretion. © 2013 Saltman et al; licensee BioMed Central Ltd

Sound field planarity characterized by superdirective beamforming

The ability to replicate a plane wave represents an essential element of spatial sound field reproduction. In sound field synthesis, the desired field is often formulated as a plane wave and the error minimized; for other sound field control methods, the energy density or energy ratio is maximized. In all cases and further to the reproduction error, it is informative to characterize how planar the resultant sound field is. This paper presents a method for quantifying a region's acoustic planarity by superdirective beamforming with an array of microphones, which analyzes the azimuthal distribution of impinging waves and hence derives the planarity. Estimates are obtained for a variety of simulated sound field types, tested with respect to array orientation, wavenumber, and number of microphones. A range of microphone configurations is examined. Results are compared with delay-and-sum beamforming, which is equivalent to spatial Fourier decomposition. The superdirective beamformer provides better characterization of sound fields, and is effective with a moderate number of omni-directional microphones over a broad frequency range. Practical investigation of planarity estimation in real sound fields is needed to demonstrate its validity as a physical sound field evaluation measure. © 2013 Acoustical Society of America

Impact of Viral Status on Survival in Patients Receiving Sorafenib for Advanced Hepatocellular Cancer: A Meta-Analysis of Randomized Phase III Trials

Purpose: Following the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP) trial, sorafenib has become the standard of care for patients with advanced unresectable hepatocellular carcinoma, but the relation between survival advantage and disease etiology remains unclear. To address this, we undertook an individual patient data meta-analysis of three large prospective randomized trials in which sorafenib was the control arm. Methods: Of a total of 3,256 patients, 1,643 (50%) who received sorafenib were available. The primary end point was overall survival (OS). A Bayesian hierarchical approach for individual patient data meta-analyses was applied using a piecewise exponential model. Results are presented in terms of hazard ratios comparing sorafenib with alternative therapies according to hepatitis C virus (HCV) or hepatitis B virus (HBV) status. Results: Hazard ratios show improved OS for sorafenib in patients who are both HBV negative and HCV positive (log [hazard ratio], −0.27; 95% CI, −0.46 to −0.06). Median unadjusted survival is 12.6 (11.15 to 13.8) months for sorafenib and 10.2 (8.88 to 12.2) months for “other” treatments in this subgroup. There was no evidence of improvement in OS for any other patient subgroups defined by HBV and HCV. Results were consistent across all trials with heterogeneity assessed using Cochran’s Q statistic. Conclusion: There is consistent evidence that the effect of sorafenib on OS is dependent on patients’ hepatitis status. There is an improved OS for patients negative for HBV and positive for HCV when treated with sorafenib. There was no evidence of any improvement in OS attributable to sorafenib for patients positive for HBV and negative for HCV

Systematic Review and Meta-analysis of Long-term survival After Elective Infrarenal Abdominal Aortic Aneurysm Repair 1969-2011: 5 Year Survival Remains Poor Despite Advances in Medical Care and Treatment Strategies.

BACKGROUND: Improved critical care, pre-operative optimization, and the advent of endovascular surgery (EVAR) have improved 30 day mortality for elective abdominal aortic aneurysm (AAA) repair. It remains unknown whether this has translated into improvements in long-term survival, particularly because these factors have also encouraged the treatment of older patients with greater comorbidity. The aim of this study was to quantify how 5 year survival after elective AAA repair has changed over time. METHODS: A systematic review was performed identifying studies reporting 5 year survival after elective infrarenal AAA repair. An electronic search of the Embase and Medline databases was conducted to January 2014. Thirty-six studies, 60 study arms, and 107,814 patients were identified. Meta-analyses were conducted to determine 5 year survival and to report whether 5 year survival changed over time. RESULTS: Five-year survival was 69% (95% CI 67 to 71%, I(2) = 87%). Meta-regression on study midpoint showed no improvement in 5 year survival over the period 1969-2011 (log OR -0.001, 95% CI -0.014-0.012). Larger average aneurysm diameter was associated with poorer 5 year survival (adjusted log OR -0.058, 95% CI -0.095 to -0.021, I(2) = 85%). Older average patient age at surgery was associated with poorer 5 year survival (adjusted log OR -0.118, 95% CI -0.142 to -0.094, I(2) = 70%). After adjusting for average patient age, an improvement in 5 year survival over the period that these data spanned was obtained (adjusted log OR 0.027, 95% CI 0.012 to 0.042). CONCLUSION: Five-year survival remains poor after elective AAA repair despite advances in short-term outcomes and is associated with AAA diameter and patient age at the time of surgery. Age-adjusted survival appears to have improved; however, this cohort as a whole continues to have poor long-term survival. Research in this field should attempt to improve the life expectancy of patients with repaired AAA and to optimise patient selection

iRFP is a real time marker for transformation based assays in high content screening

Anchorage independent growth is one of the hallmarks of oncogenic transformation. Here we show that infrared fluorescent protein (iRFP) based assays allow accurate and unbiased determination of colony formation and anchorage independent growth over time. This protocol is particularly compatible with high throughput systems, in contrast to traditional methods which are often labor-intensive, subjective to bias and do not allow further analysis using the same cells. Transformation in a single layer soft agar assay could be documented as early as 2 to 3 days in a 96 well format, which can be easily combined with standard transfection, infection and compound screening setups to allow for high throughput screening to identify therapeutic targets

Improving evidence based practice in postgraduate nursing programs: A systematic review: Bridging the evidence practice gap (BRIDGE project)

© 2018 Background: The nursing profession has a significant evidence to practice gap in an increasingly complex and dynamic health care environment. Objective(s): To evaluate effectiveness of teaching and learning strategies related to a capstone project within a Masters of Nursing program that encourage the development of evidence based practice capabilities. Design: Systematic review that conforms to the PRISMA statement. Sample: Master's Nursing programs that include elements of a capstone project within a university setting. Data Sources/Review Methods: MEDLINE, CINAHL, Cochrane Database of Systematic Reviews, ERIC and PsycInfo were used to search for RCT's or quasi experimental studies conducted between 1979 and 9 June 2017, published in a peer reviewed journal in English. Results: Of 1592 studies, no RCT's specifically addressed the development of evidence based practice capabilities within the university teaching environment. Five quasi-experimental studies integrated blended learning, guided design processes, small group work, role play and structured debate into Masters of Nursing research courses. All five studies demonstrated some improvements in evidence based practice skills and/or research knowledge translation, with three out of five studies demonstrating significant improvements. Conclusions: There is a paucity of empirical evidence supporting the best strategies to use in developing evidence based practice skills and/or research knowledge translation skills for Master's Nursing students. As a profession, nursing requires methodologically robust studies that are discipline specific to identify the best approaches for developing evidence-based practice skills and/or research knowledge translation skills within the university teaching environment. Provision of these strategies will enable the nursing profession to integrate the best empirical evidence into nursing practice

Rating and ranking the role of bibliometrics and webometrics in nursing and midwifery

Background. Bibliometrics are an essential aspect of measuring academic and organizational performance. Aim. This review seeks to describe methods for measuring bibliometrics, identify the strengths and limitations of methodologies, outline strategies for interpretation, summarise evaluation of nursing and midwifery performance, identify implications for metric of evaluation, and specify the implications for nursing and midwifery and implications of social networking for bibliometrics and measures of individual performance. Method. A review of electronic databases CINAHL, Medline, and Scopus was undertaken using search terms such as bibliometrics, nursing, and midwifery. The reference lists of retrieved articles and Internet sources and social media platforms were also examined. Results. A number of well-established, formal ways of assessment have been identified, including h- and c-indices. Changes in publication practices and the use of the Internet have challenged traditional metrics of influence. Moreover, measuring impact beyond citation metrics is an increasing focus, with social media representing newer ways of establishing performance and impact. Conclusions. Even though a number of measures exist, no single bibliometric measure is perfect. Therefore, multiple approaches to evaluation are recommended. However, bibliometric approaches should not be the only measures upon which academic and scholarly performance are evaluated. © 2014 Patricia M. Davidson et al

Temporal and spatial drivers of the structure of macroinvertebrate assemblages associated with <em>Laminaria </em><em>hyperborea </em>detritus in the northeast Atlantic

\ua9 2024Kelp forests occur on more than a quarter of the world\u27s coastlines, serving as foundation species supporting high levels of biodiversity. They are also a major source of organic matter in coastal ecosystems, with the majority of primary production released and exported as detritus. Kelp detritus also provides food and shelter for macroinvertebrates, which comprise important components of inshore food-webs. Hitherto, research on kelp detritus-associated macroinvertebrate assemblages remains relatively limited. We quantified spatiotemporal variability in the structure of detritus-associated macroinvertebrate assemblages within Laminaria hyperborea forests and evaluated the influence of putative drivers of the observed variability in assemblages across eight study sites within four regions of the United Kingdom in May and September 2015. We documented 5167 individuals from 106 taxa with Malacostraca, Gastropoda, Isopoda and Bivalvia the most abundant groups sampled. Assemblage structure varied across months, sites, and regions, with highest richness in September compared to May. Many taxa were unique to individual regions, with few documented in all regions. Finally, key drivers of assemblage structure included detritus tissue nitrogen content, depth, sea surface temperature, light intensity, as well as L. hyperborea canopy density and canopy biomass. Despite their dynamic composition and transient existence, accumulations of L. hyperborea detritus represent valuable repositories of biodiversity and represent an additional kelp forest component which influences secondary productivity, and potentially kelp forest food-web dynamics

Transglutaminase 2 limits the extravasation and the resultant myocardial fibrosis associated with factor XIII-A deficiency

Background and aims Transglutaminase (TG) 2 and Factor (F) XIII-A have both been implicated in cardiovascular protection and repair. This study was designed to differentiate between two competing hypotheses: that TG2 and FXIII-A mediate these functions in mice by fulfilling separate roles, or that they act redundantly in this respect. Methods Atherosclerosis was assessed in brachiocephalic artery plaques of fat-fed mixed strain apolipoprotein (Apo)e deficient mice that lacked either or both transglutaminases. Cardiac fibrosis was assessed both in the mixed strain mice and also in C57BL/6J Apoe expressing mice lacking either or both transglutaminases. Results No difference was found in the density of buried fibrous caps within brachiocephalic plaques from mice expressing or lacking these transglutaminases. Cardiac fibrosis developed in both Apoe/F13a1 double knockout and F13a1 single knockout mice, but not in Tgm2 knockout mice. However, concomitant Tgm2 knockout markedly increased fibrosis, as apparent in both Apoe/Tgm2/F13a1 knockout and Tgm2/F13a1 knockout mice. Amongst F13a1 knockout and Tgm2/F13a1 knockout mice, the extent of fibrosis correlated with hemosiderin deposition, suggesting that TG2 limits the extravasation of blood in the myocardium, which in turn reduces the pro-fibrotic stimulus. The resulting fibrosis was interstitial in nature and caused only minor changes in cardiac function. Conclusions These studies confirm that FXIII-A and TG2 fulfil different roles in the mouse myocardium. FXIII-A protects against vascular leakage while TG2 contributes to the stability or repair of the vasculature. The protective function of TG2 must be considered when designing clinical anti-fibrotic therapies based upon FXIII-A or TG2 inhibition