Appraisal Tools for Clinical Practice Guidelines: A Systematic Review

Introduction

Clinical practice guidelines can improve healthcare processes and patient outcomes, but are often of low quality. Guideline appraisal tools aim to help potential guideline users in assessing guideline quality. We conducted a systematic review of publications describing guideline appraisal tools in order to identify and compare existing tools.

Methods

Among others we searched MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews from 1995 to May 2011 for relevant primary and secondary publications. We also handsearched the reference lists of relevant publications.On the basis of the available literature we firstly generated 34 items to be used in the comparison of appraisal tools and grouped them into thirteen quality dimensions. We then extracted formal characteristics as well as questions and statements of the appraisal tools and assigned them to the items.

Results

We identified 40 different appraisal tools. They covered between three and thirteen of the thirteen possible quality dimensions and between three and 29 of the possible 34 items. The main focus of the appraisal tools were the quality dimensions “evaluation of evidence” (mentioned in 35 tools; 88%), “presentation of guideline content” (34 tools; 85%), “transferability” (33 tools; 83%), “independence” (32 tools; 80%), “scope” (30 tools; 75%), and “information retrieval” (29 tools; 73%). The quality dimensions “consideration of different perspectives” and “dissemination, implementation and evaluation of the guideline” were covered by only twenty (50%) and eighteen tools (45%) respectively.

Conclusions

Most guideline appraisal tools assess whether the literature search and the evaluation, synthesis and presentation of the evidence in guidelines follow the principles of evidence-based medicine. Although conflicts of interest and norms and values of guideline developers, as well as patient involvement, affect the trustworthiness of guidelines, they are currently insufficiently considered. Greater focus should be placed on these issues in the further development of guideline appraisal tools.     

Activity-dependent shedding of the NMDA receptor glycine binding site by matrix metalloproteinase 3: a PUTATIVE mechanism of postsynaptic plasticity

Functional and structural alterations of clustered postsynaptic ligand gated ion channels in neuronal cells are thought to contribute to synaptic plasticity and memory formation in the human brain. Here, we describe a novel molecular mechanism for structural alterations of NR1 subunits of the NMDA receptor. In cultured rat spinal cord neurons, chronic NMDA receptor stimulation induces disappearance of extracellular epitopes of NMDA receptor NR1 subunits, which was prevented by inhibiting matrix metalloproteinases (MMPs). Immunoblotting revealed the digestion of solubilized NR1 subunits by MMP-3 and identified a fragment of about 60 kDa as MMPs-activity-dependent cleavage product of the NR1 subunit in cultured neurons. The expression of MMP-3 in the spinal cord culture was shown by immunoblotting and immunofluorescence microscopy. Recombinant NR1 glycine binding protein was used to identify MMP-3 cleavage sites within the extracellular S1 and S2-domains. N-terminal sequencing and site-directed mutagenesis revealed S542 and L790 as two putative major MMP-3 cleavage sites of the NR1 subunit. In conclusion, our data indicate that MMPs, and in particular MMP-3, are involved in the activity dependent alteration of NMDA receptor structure at postsynaptic membrane specializations in the CNS.     

The two faces of the purple membrane: Structural differences revealed by metal decoration

The two faces of the purple membrane are unambiguously distinguishable from each other in the electron microscope after metal decoration. Crystalline order is revealed on one of the two surfaces of the membrane. Membrane cracking and fragmentation upon drying is strongest on hydrophilic supports and becomes less severe with increasing hydrophobicity of the support. This behaviour is almost unaffected by the presence of low molecular weight, aqueous “sustains”, such as glucose or sucrose, and demonstrates the importance of surface interactions for the preservation of thin macromolecular assemblies in vacuo.     

The rhizosheath – a potential trait for future agricultural sustainability occurs in orders throughout the angiosperms

Aims

Phosphorus (P) is frequently limiting crop production in agroecosystems. Large progress was achieved in understanding root traits associated with P acquisition efficiency (PAE, i.e. P uptake achieved under low P conditions). Most former studies were performed in controlled environments, and avoided the complexity of soil-root interactions. This may lead to an oversimplification of the root-soil relations. The aim of the present study was, therefore, to identify the dominant root and rhizosphere-related traits determining PAE, in contrasting soil conditions in the field.

Methods

Twenty-three maize hybrids were grown at two contrasting P levels of a long-term P-fertilizer trial in two adjacent soil types: alkaline and neutral. Bulk soil, rhizosphere and root parameters were studied in relation to plant P acquisition.

Results

Soil type had robust effect on PAE. Hybrids’ performance in one soil type was not related to that in the other soil type. In the neutral soil, roots exhibited higher specific root length, higher root/shoot ratio but lower PAE. Best performing hybrids in the neutral soil were characterized by top soil exploration, i.e., greater root surface and topsoil foraging. In contrast, in the alkaline soil, PAE and foraging traits were not correlated, P availability in the rhizosphere was greater than the bulk soil and phosphatase activity was higher, suggesting a ‘mining strategy’ in that case (i.e. traits that facilitate elevated P availability).

Conclusions

These results indicate the key role of environmental factors for roots traits determining high PAE. The study highlights the need to consider soil properties when breeding for high PAE, as various soil types are likely to require different crop ideotypes.

     

Experimental modal analysis on fresh-frozen human hemipelvic bones employing a 3D laser vibrometer for the purpose of modal parameter identification

To provide a close-to-reality simulation model, such as for improved surgery planning, this model has to be experimentally verified. The present article describes the use of a 3D laser vibrometer for determining modal parameters of human pelvic bones that can be used for verifying a finite elements model. Compared to previously used sensors, such as acceleration sensors or strain gauges, the laser vibrometric procedure used here is a non-contact and non-interacting measuring method that allows a high density of measuring points and measurement in a global coordinate system. Relevant modal parameters were extracted from the measured data and provided for verifying the model. The use of the 3D laser vibrometer allowed the establishment of a process chain for experimental examination of the pelvic bones that was optimized with respect to time and effort involved. The transfer functions determined feature good signal quality. Furthermore, a comparison of the results obtained from pairs of pelvic bones showed that repeatable measurements can be obtained with the method used.     

Comparative suitability of CFDA‐SE and rhodamine 6G for in vivo assessment of leukocyte‐endothelium interactions

Intravital fluorescence microscopy (IVM) is a predestined tool for investigating the fate of leukocytes during the process of leukocyte recruitment. In the present study, the commonly used dye for this purpose, rhodamine 6G, and carboxyfluorescein diacetate succinimidyl ester (CFDA‐SE) were compared for leukocytes labelling with respect to suitability for IVM studies. Their potential in labelling different leukocytes subpopulations as well as their fluorescence intensities were assessed by flow cytometry revealing distinct differences between both dyes. These differences had a profound impact on their application for in vivo imaging of leukocyte‐endothelium interactions. In summary, CFDA‐SE revealed superior in labelling leukocytes for in vivo microscopy with respect to image quality. In addition, we could show the efficiency of CFDA‐SE also under disease condition in an animal model of sepsis. (© 2014 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)