Characterisation of Clinical Practice Guideline Changes

Sub-Saharan Africa is facing a double crisis of high disease burden and shortage of healthcare resources. To cope with this challenge, many countries have adopted the practice of task-shifting with clinical practice guidelines (CPGs) as a key component. It is not unusual for CPGs to be revised or proved wrong, spurring frequent updates of state-mandated CPGs. This negatively affects maintainability of healthcare applications using those CPGs. Therefore, it is essential that the types of CPG changes are understood in order to develop clinical decision support systems that are maintainable through adequate support for CPGs. We take a bottom-up approach to analyse successive sets of CPGs so as to elucidate and characterise types of CPG changes overtime. The identified 10 type of changes in decisions, actions, and recommendations are exhaustive and affect fine-grained structural components of a CPG. We also determined their occurrences using Malawi’s HIV CPGs of 2008, 2011, and 2014 as case study. The results showed that the number of changes, as well as the type of changes that occur in successive versions, varies widely

Guidelines for the use of cell lines in biomedical research

Cell-line misidentification and contamination with microorganisms, such as mycoplasma, together with instability, both genetic and phenotypic, are among the problems that continue to affect cell culture. Many of these problems are avoidable with the necessary foresight, and these Guidelines have been prepared to provide those new to the field and others engaged in teaching and instruction with the information necessary to increase their awareness of the problems and to enable them to deal with them effectively. The Guidelines cover areas such as development, acquisition, authentication, cryopreservation, transfer of cell lines between laboratories, microbial contamination, characterisation, instability and misidentification. Advice is also given on complying with current legal and ethical requirements when deriving cell lines from human and animal tissues, the selection and maintenance of equipment and how to deal with problems that may arise

Guidelines for the recording and evaluation of pharmaco-EEG data in man: the International Pharmaco-EEG Society (IPEG)

The International Pharmaco-EEG Society (IPEG) presents updated guidelines summarising the requirements for the recording and computerised evaluation of pharmaco-EEG data in man. Since the publication of the first pharmaco-EEG guidelines in 1982, technical and data processing methods have advanced steadily, thus enhancing data quality and expanding the palette of tools available to investigate the action of drugs on the central nervous system (CNS), determine the pharmacokinetic and pharmacodynamic properties of novel therapeutics and evaluate the CNS penetration or toxicity of compounds. However, a review of the literature reveals inconsistent operating procedures from one study to another. While this fact does not invalidate results per se, the lack of standardisation constitutes a regrettable shortcoming, especially in the context of drug development programmes. Moreover, this shortcoming hampers reliable comparisons between outcomes of studies from different laboratories and hence also prevents pooling of data which is a requirement for sufficiently powering the validation of novel analytical algorithms and EEG-based biomarkers. The present updated guidelines reflect the consensus of a global panel of EEG experts and are intended to assist investigators using pharmaco-EEG in clinical research, by providing clear and concise recommendations and thereby enabling standardisation of methodology and facilitating comparability of data across laboratories

Project Retrosight. Understanding the returns from cardiovascular and stroke research: Methodology Report

Copyright @ 2011 RAND Europe. All rights reserved. The full text article is available via the link below.This project explores the impacts arising from cardiovascular and stroke research funded 15-20 years ago and attempts to draw out aspects of the research, researcher or environment that are associated with high or low impact. The project is a case study-based review of 29 cardiovascular and stroke research grants, funded in Australia, Canada and UK between 1989 and 1993. The case studies focused on the individual grants but considered the development of the investigators and ideas involved in the research projects from initiation to the present day. Grants were selected through a stratified random selection approach that aimed to include both high- and low-impact grants. The key messages are as follows: 1) The cases reveal that a large and diverse range of impacts arose from the 29 grants studied. 2) There are variations between the impacts derived from basic biomedical and clinical research. 3) There is no correlation between knowledge production and wider impacts 4) The majority of economic impacts identified come from a minority of projects. 5) We identified factors that appear to be associated with high and low impact. This report presents the key observations of the study and an overview of the methods involved. It has been written for funders of biomedical and health research and health services, health researchers, and policy makers in those fields. It will also be of interest to those involved in research and impact evaluation.This study was initiated with internal funding from RAND Europe and HERG, with continuing funding from the UK National Institute for Health Research, the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada and the National Heart Foundation of Australia. The UK Stroke Association and the British Heart Foundation provided support in kind through access to their archives

General Practitioners' perceptions of the route to evidence-based medicine: a questionnaire survey

Objectives: To determine the attitude of general practitioners towards evidence based medicine and their related educational needs. Design: A questionnaire study of general practitioners. Setting: General practice in the former Wessex region, England. Subjects: Randomly selected sample of 25% of all general practitioners (452), of whom 302 replied. Main outcome measures: Respondents' attitude towards evidence based medicine, ability to access and interpret evidence, perceived barriers to practising evidence based medicine, and best method of moving from opinion based to evidence based medicine. Results: Respondents mainly welcomed evidence based medicine and agreed that its practice improves patient care. They had a low level of awareness of extracting journals, review publications, and databases (only 40% knew of the Cochrane Database of Systematic Reviews), and, even if aware, many did not use them. In their surgeries 20% had access to bibliographic databases and 17% to the world wide web. Most had some understanding of the technical terms used. The major perceived barrier to practising evidence based medicine was lack of personal time. Respondents thought the most appropriate way to move towards evidence based general practice was by using evidence based guidelines or proposals developed by colleagues. Conclusion: Promoting and improving access to summaries of evidence, rather than teaching all general practitioners literature searching and critical appraisal, would be the more appropriate method of encouraging evidence based general practice. General practitioners who are skilled in accessing and interpreting evidence should be encouraged to develop local evidence based guidelines and advice

Comparability: manufacturing, characterization and controls, report of a UK Regenerative Medicine Platform Pluripotent Stem Cell Platform Workshop, Trinity Hall, Cambridge, 14–15 September 2015

This paper summarizes the proceedings of a workshop held at Trinity Hall, Cambridge to discuss comparability and includes additional information and references to related information added subsequently to the workshop. Comparability is the need to demonstrate equivalence of product after a process change; a recent publication states that this ‘may be difficult for cell-based medicinal products’. Therefore a well-managed change process is required which needs access to good science and regulatory advice and developers are encouraged to seek help early. The workshop shared current thinking and best practice and allowed the definition of key research questions. The intent of this report is to summarize the key issues and the consensus reached on each of these by the expert delegates

ERIGrid Holistic Test Description for Validating Cyber-Physical Energy Systems

Smart energy solutions aim to modify and optimise the operation of existing energy infrastructure. Such cyber-physical technology must be mature before deployment to the actual infrastructure, and competitive solutions will have to be compliant to standards still under development. Achieving this technology readiness and harmonisation requires reproducible experiments and appropriately realistic testing environments. Such testbeds for multi-domain cyber-physical experiments are complex in and of themselves. This work addresses a method for the scoping and design of experiments where both testbed and solution each require detailed expertise. This empirical work first revisited present test description approaches, developed a newdescription method for cyber-physical energy systems testing, and matured it by means of user involvement. The new Holistic Test Description (HTD) method facilitates the conception, deconstruction and reproduction of complex experimental designs in the domains of cyber-physical energy systems. This work develops the background and motivation, offers a guideline and examples to the proposed approach, and summarises experience from three years of its application.This work received funding in the European Community’s Horizon 2020 Program (H2020/2014–2020) under project “ERIGrid” (Grant Agreement No. 654113)

Gla-rich protein (GRP) as an early and novel marker of vascular calcification and kidney dysfunction in diabetic patients with CKD: a pilot cross-sectional study

Vascular calcification (VC) is one of the strongest predictors of cardiovascular risk in chronic kidney disease (CKD) patients. New diagnostic/prognostic tools are required for early detection of VC allowing interventional strategies. Gla-rich protein (GRP) is a cardiovascular calcification inhibitor, whose clinical utility is here highlighted. The present study explores, for the first time, correlations between levels of GRP in serum with CKD developmental stage, mineral metabolism markers, VC and pulse pressure (PP), in a cohort of 80 diabetic patients with mild to moderate CKD (stages 2-4). Spearman's correlation analysis revealed a positive association of GRP serum levels with estimated glomerular filtration rate (eGFR) and α-Klotho, while a negative correlation with phosphate (P), fibroblast growth factor 23 (FGF-23), vascular calcification score (VCS), PP, calcium (x) phosphate (CaxP) and interleukin 6 (IL-6). Serum GRP levels were found to progressively decrease from stage 2 to stage 4 CKD. Multivariate analysis identified low levels of eGFR and GRP, and high levels of FGF-23 associated with both the VCS and PP. These results indicate an association between GRP, renal dysfunction and CKD-mineral and bone disorder. The relationship between low levels of GRP and vascular calcifications suggests a future, potential utility for GRP as an early marker of vascular damage in CKD.Portuguese Society of Nephrology (SPN) ; Portuguese national funds from FCT-Foundation for Science and Technology through the transitional provision DL57/2016/CP1361/CT0006 UIDB/04326/2020info:eu-repo/semantics/publishedVersio

The clinical meaning of histamine skin reactivity

The definition of the “atopic state”, i.e. subjects presenting at least one skin wheal with a minimum diameter of 3 mm induced by an allergen skin-prick test (ASPT), is based on the assumption that wheal size depends entirely on the amount of histamine produced in the antigen-antibody reaction. Several epidemiological studies have, however, demonstrated that an ASPT-elicited wheal is heavily modulated by “histamine skin reactivity” (HSR), i.e. the size of the wheal induced by a prick test performed with a given solution of histamine. HSR not only varies widely depending on the individual characteristics and geographical setting, but also changes over time; these differences in HSR markedly influence the amount of specific IgE required to produce a wheal of at least 3 mm in an ASPT. We should therefore ideally conceive the existence of two types of” atopic patients”: one type in whom “atopy” is mainly the result of an increased level of specific IgE antibodies, and another type in whom positive ASPTs are mainly the result of marked skin reactivity to even small amounts of histamine. If hyper-reactivity to histamine occurs not only in the skin but in parallel also in other parts of the organism, especially at the mucosal level, “normal” histamine production may cause chronic or recurrent clinical symptom