Clinical practice guidelines: towards better quality guidelines and increased international collaboration

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A constructive study of the module structure of rings of partial differential operators

The purpose of this paper is to develop constructive versions of Stafford's theorems on the module structure of Weyl algebras A n (k) (i.e., the rings of partial differential operators with polynomial coefficients) over a base field k of characteristic zero. More generally, based on results of Stafford and Coutinho-Holland, we develop constructive versions of Stafford's theorems for very simple domains D. The algorithmization is based on the fact that certain inhomogeneous quadratic equations admit solutions in a very simple domain. We show how to explicitly compute a unimodular element of a finitely generated left D-module of rank at least two. This result is used to constructively decompose any finitely generated left D-module into a direct sum of a free left D-module and a left D-module of rank at most one. If the latter is torsion-free, then we explicitly show that it is isomorphic to a left ideal of D which can be generated by two elements. Then, we give an algorithm which reduces the number of generators of a finitely presented left D-module with module of relations of rank at least two. In particular, any finitely generated torsion left D-module can be generated by two elements and is the homomorphic image of a projective ideal whose construction is explicitly given. Moreover, a non-torsion but non-free left D-module of rank r can be generated by r+1 elements but no fewer. These results are implemented in the Stafford package for D=A n (k) and their system-theoretical interpretations are given within a D-module approach. Finally, we prove that the above results also hold for the ring of ordinary differential operators with either formal power series or locally convergent power series coefficients and, using a result of Caro-Levcovitz, also for the ring of partial differential operators with coefficients in the field of fractions of the ring of formal power series or of the ring of locally convergent power series. © 2014 Springer Science+Business Media

Impacts des vers de terre sur les composants et la dynamique du sol (synthèse bibliographique)

Impacts of earthworms on soil components and dynamics. A review. Earthworm populations are important decomposers contributing to aggregate formation and nutrient cycling processes involving nitrogen cycles, phosphorus and carbon. They are known to influence soil fertility by participating to important processes in soil such as soil structure regulation and organic matter dynamics. Earthworms also modify the microbial communities through digestion, stimulation and dispersion in casts. Consequently, changes in the activities of earthworm communities, as a result of soil management practices, can also be used as indicators of soil fertility and quality. It is therefore important to understand how earthworm communities affect soil dynamics. This review adresses the current state of knowledge on earthworm's impacts on soil structure and soil organic matter (carbon, nitrogen, and phosphorus) dynamics, with special emphasis on the effects of land management practices on earthworm communities

Dislocation loops in overheated free-standing smectic films

Static and dynamic phenomena in overheated free-standing smectic-A films are studied using a generalization of de Gennes' theory for a confined presmectic liquid. A static application is to determine the profile of the film meniscus and the meniscus contact angle, the results being compared with those of a recent study employing de Gennes' original theory. The dynamical generalization of the theory is based on on a time-dependent Ginzburg-Landau approach. This is used to compare two modes for layer-thinning transitions in overheated films, namely "uniform thinning" vs. nucleation of dislocation loops. Properties such as the line tension and velocity of a moving dislocation line are evaluated self-consistently by the theory.Comment: 16 pages, 8 figure

Current practices and challenges in adaptation of clinical guidelines : A qualitative study based on semistructured interviews

Funding YS is funded by China Scholarship Council (No 201707040103).Altres ajuts: CSC/201707040103Objective This study aims to better understand the current practice of clinical guideline adaptation and identify challenges raised in this process, given that published adapted clinical guidelines are generally of low quality, poorly reported and not based on published frameworks. Design A qualitative study based on semistructured interviews. We conducted a framework analysis for the adaptation process, and thematic analysis for participants' views and experiences about adaptation process. Setting Nine guideline development organisations from seven countries. Participants Guideline developers who have adapted clinical guidelines within the last 3 years. We identified potential participants through published adapted clinical guidelines, recommendations from experts, and a review of the Guideline International Network Conference attendees' list. Results We conducted ten interviews and identified nine adaptation methodologies. The reasons for adapting clinical guidelines include developing de novo clinical guidelines, implementing source clinical guidelines, and harmonising and updating existing clinical guidelines. We identified the following core steps of the adaptation process (1) selection of scope and source guideline(s), (2) assessment of source materials (guidelines, recommendations and evidence level), (3) decision-making process and (4) external review and follow-up process. Challenges on the adaptation of clinical guidelines include limitations from source clinical guidelines (poor quality or reporting), limitations from adaptation settings (lacking resources or skills), adaptation process intensity and complexity, and implementation barriers. We also described how participants address the complexities and implementation issues of the adaptation process. Conclusions Adaptation processes have been increasingly used to develop clinical guidelines, with the emergence of different purposes. The identification of core steps and assessment levels could help guideline adaptation developers streamline their processes. More methodological research is needed to develop rigorous international standards for adapting clinical guidelines

TP53 and MDM2 single nucleotide polymorphisms influence survival in non-del(5q) myelodysplastic syndromes

Abstract:P53 is a key regulator of many cellular processes and is negatively regulated by the human homolog of murine double minute-2 (MDM2) E3 ubiquitin ligase. Single nucleotide polymorphisms (SNPs) of either gene alone, and in combination, are linked to cancer susceptibility, disease progression, and therapy response. We analyzed the interaction of TP53 R72P and MDM2 SNP309 SNPs in relationship to outcome in patients with myelodysplastic syndromes (MDS). Sanger sequencing was performed on DNA isolated from 208 MDS cases. Utilizing a novel functional SNP scoring system ranging from +2 to -2 based on predicted p53 activity, we found statistically significant differences in overall survival (OS) (p = 0.02) and progression-free survival (PFS) (p = 0.02) in non-del(5q) MDS patients with low functional scores. In univariate analysis, only IPSS and the functional SNP score predicted OS and PFS in non-del(5q) patients. In multivariate analysis, the functional SNP score was independent of IPSS for OS and PFS. These data underscore the importance of TP53 R72P and MDM2 SNP309 SNPs in MDS, and provide a novel scoring system independent of IPSS that is predictive for disease outcome

Holonomic functions of several complex variables and singularities of anisotropic Ising n-fold integrals

Lattice statistical mechanics, often provides a natural (holonomic) framework to perform singularity analysis with several complex variables that would, in a general mathematical framework, be too complex, or could not be defined. Considering several Picard-Fuchs systems of two-variables "above" Calabi-Yau ODEs, associated with double hypergeometric series, we show that holonomic functions are actually a good framework for actually finding the singular manifolds. We, then, analyse the singular algebraic varieties of the n-fold integrals $\chi^{(n)}$, corresponding to the decomposition of the magnetic susceptibility of the anisotropic square Ising model. We revisit a set of Nickelian singularities that turns out to be a two-parameter family of elliptic curves. We then find a first set of non-Nickelian singularities for $\chi^{(3)}$ and $\chi^{(4)}$, that also turns out to be rational or ellipic curves. We underline the fact that these singular curves depend on the anisotropy of the Ising model. We address, from a birational viewpoint, the emergence of families of elliptic curves, and of Calabi-Yau manifolds on such problems. We discuss the accumulation of these singular curves for the non-holonomic anisotropic full susceptibility.Comment: 36 page

Quality and methods of developing practice guidelines

BACKGROUND: It is not known whether there are differences in the quality and recommendations between evidence-based (EB) and consensus-based (CB) guidelines. We used breast cancer guidelines as a case study to assess for these differences. METHODS: Five different instruments to evaluate the quality of guidelines were identified by a literature search. We also searched MEDLINE and the Internet to locate 8 breast cancer guidelines. These guidelines were classified in three categories: evidence based, consensus based and consensus based with no explicit consideration of evidence (CB-EB). Each guideline was evaluated by three of the authors using each of the instruments. For each guideline we assessed the agreement among 14 decision points which were selected from the NCCN (National Cancer Comprehensive Network) guidelines algorithm. For each decision point we recorded the level of the quality of the information used to support it. A regression analysis was performed to assess if the percentage of high quality evidence used in the guidelines development was related to the overall quality of the guidelines. RESULTS: Three guidelines were classified as EB, three as CB-EB and two as CB. The EB guidelines scored better than CB, with the CB-EB scoring in the middle among all instruments for guidelines quality assessment. No major disagreement in recommendations was detected among the guidelines regardless of the method used for development, but the EB guidelines had a better agreement with the benchmark guideline for any decision point. When the source of evidence used to support decision were of high quality, we found a higher level of full agreement among the guidelines' recommendations. Up to 94% of variation in the quality score among guidelines could be explained by the quality of evidence used for guidelines development. CONCLUSION: EB guidelines have a better quality than CB guidelines and CB-EB guidelines. Explicit use of high quality evidence can lead to a better agreement among recommendations. However, no major disagreement among guidelines was noted regardless of the method for their development

Development and Validation of a Tool to Assess the Quality of Clinical Practice Guideline Recommendations

Clinical practice guidelines (CPGs) may lack rigor and suitability to the setting in which they are to be applied. Methods to yield clinical practice guideline recommendations that are credible and implementable remain to be determined. To describe the development of AGREE-REX (Appraisal of Guidelines Research and Evaluation-Recommendations Excellence), a tool designed to evaluate the quality of clinical practice guideline recommendations. A cross-sectional study of 322 international stakeholders representing CPG developers, users, and researchers was conducted between December 2015 and March 2019. Advertisements to participate were distributed through professional organizations as well as through the AGREE Enterprise social media accounts and their registered users. Between 2015 and 2017, participants appraised 1 of 161 CPGs using the Draft AGREE-REX tool and completed the AGREE-REX Usability Survey. Usability and measurement properties of the tool were assessed with 7-point scales (1 indicating strong disagreement and 7 indicating strong agreement). Internal consistency of items was assessed with the Cronbach, and the Spearman-Brown reliability adjustment was used to calculate reliability for 2 to 5 raters. A total of 322 participants (202 female participants [62.7%]; 83 aged 40-49 years [25.8%]) rated the survey items (on a 7-point scale). All 11 items were rated as easy to understand (with a mean [SD] ranging from 5.2 [1.38] for the alignment of values item to 6.3 [0.87] for the evidence item) and easy to apply (with a mean [SD] ranging from 4.8 [1.49] for the alignment of values item to 6.1 [1.07] for the evidence item). Participants provided favorable feedback on the tool's instructions, which were considered clear (mean [SD], 5.8 [1.06]), helpful (mean [SD], 5.9 [1.00]), and complete (mean [SD], 5.8 [1.11]). Participants considered the tool easy to use (mean [SD], 5.4 [1.32]) and thought that it added value to the guideline enterprise (mean [SD], 5.9 [1.13]). Internal consistency of the items was high (Cronbach = 0.94). Positive correlations were found between the overall AGREE-REX score and the implementability score (r = 0.81) and the clinical credibility score (r = 0.76). This cross-sectional study found that the AGREE-REX tool can be useful in evaluating CPG recommendations, differentiating among them, and identifying those that are clinically credible and implementable for practicing health professionals and decision makers who use recommendations to inform clinical policy.

Assessment of the quality of recommendations from 161 clinical practice guidelines using the Appraisal of Guidelines for Research and Evaluation-Recommendations Excellence (AGREE-REX) instrument shows there is room for improvement

To assess the quality of recommendations from 161 clinical practice guidelines (CPGs) using AGREE-REX-D (Appraisal of Guidelines REsearch and Evaluation-Recommendations Excellence Draft). International CPG community. Three hundred twenty-two international CPG developers, users, and researchers. Participants were assigned to appraise one of 161 CPGs selected for the study using the AGREE-REX-D tool Main outcome measures: AGREE-REX-D scores of 161 CPGs (7-point scale, maximum 7). Recommendations from 161 CPGs were appraised by 322 participants using the AGREE-REX-D. CPGs were developed by 67 different organizations. The total overall average score of the CPG recommendations was 4.23 (standard deviation (SD) = 1.14). AGREE-REX-D items that scored the highest were (mean; SD): evidence (5.51; 1.14), clinical relevance (5.95; SD 0.8), and patients/population relevance (4.87; SD 1.33), while the lowest scores were observed for the policy values (3.44; SD 1.53), local applicability (3,56; SD 1.47), and resources, tools, and capacity (3.49; SD 1.44) items. CPGs developed by government-supported organizations and developed in the UK and Canada had significantly higher recommendation quality scores with the AGREE-REX-D tool (p < 0.05) than their comparators. We found that there is significant room for improvement of some CPGs such as the considerations of patient/population values, policy values, local applicability and resources, tools, and capacity. These findings may be considered a baseline upon which to measure future improvements in the quality of CPGs