Comparison of international guideline programs to evaluate and update the Dutch program for clinical guideline development in physical therapy

<p>Abstract</p> <p>Background</p> <p>Clinical guidelines are considered important instruments to improve quality in health care. Since 1998 the Royal Dutch Society for Physical Therapy (KNGF) produced evidence-based clinical guidelines, based on a standardized program. New developments in the field of guideline research raised the need to evaluate and update the KNGF guideline program.</p> <p>Purpose of this study is to compare different guideline development programs and review the KNGF guideline program for physical therapy in the Netherlands, in order to update the program.</p> <p>Method</p> <p>Six international guideline development programs were selected, and the 23 criteria of the AGREE Instrument were used to evaluate the guideline programs. Information about the programs was retrieved from published handbooks of the organizations. Also, the Dutch program for guideline development in physical therapy was evaluated using the AGREE criteria. Further comparison the six guideline programs was carried out using the following elements of the guideline development processes: Structure and organization; Preparation and initiation; Development; Validation; Dissemination and implementation; Evaluation and update.</p> <p>Results</p> <p>Compliance with the AGREE criteria of the guideline programs was high. Four programs addressed 22 AGREE criteria, and two programs addressed 20 AGREE criteria. The previous Dutch program for guideline development in physical therapy lacked in compliance with the AGREE criteria, meeting only 13 criteria.</p> <p>Further comparison showed that all guideline programs perform systematic literature searches to identify the available evidence. Recommendations are formulated and graded, based on evidence and other relevant factors. It is not clear how decisions in the development process are made. In particular, the process of translating evidence into practice recommendations can be improved.</p> <p>Conclusion</p> <p>As a result of international developments and consensus, the described processes for developing clinical practice guidelines have much in common. The AGREE criteria are common basis for the development of guidelines, although it is not clear how final decisions are made. Detailed comparison of the different guideline programs was used for updating the Dutch program. As a result the updated KNGF program complied with 22 AGREE criteria. International discussion is continuing and will be used for further improvement of the program.</p

Hodgkin's lymphoma presenting with markedly elevated IgE: a case report

<p>Abstract</p> <p>Background</p> <p>Markedly elevated IgE as a manifestation of a lymphoproliferative disorder has been only rarely reported.</p> <p>Case Presentation</p> <p>We present the case of a 22 year old female referred to the adult Allergy & Clinical Immunology clinic for an extremely elevated IgE level, eventually diagnosed with Hodgkin's lymphoma. She had no history of atopy, recurrent infections, eczema or periodontal disease; stool was negative for ova & parasites. Chest X-ray revealed large bilateral anterior mediastinal masses that demonstrated prominent uptake on gallium scan. Mediastinal lymph node biopsy was consistent with Hodgkin's lymphoma, nodular sclerosing subtype, grade I/II.</p> <p>Conclusion</p> <p>Although uncommon, markedly elevated IgE may be a manifestation of a malignant process, most notably both Hodgkin's and Non-Hodgkin's lymphomas. This diagnosis should be considered in evaluating an otherwise unexplained elevation of IgE.</p

Prozone effect of serum IgE levels in a case of plasma cell leukemia

We describe a case of multiple myeloma (MM) and secondary plasma cell leukemia (PCL) secreting IgE-kappa immunoglobulin. To our knowledge, only 2 cases of IgE-producing secondary PCL have been reported in the medical literature. In our patient, the only tumor marker available for monitoring the therapeutic response to chemotherapy and allogeneic stem cell transplantation was the quantitative M component at serum protein electrophoresis (SPEP), because serum free light chains were in the normal range, Bence-Jones proteinuria was absent, and quantitative serum IgE levels provided inaccurate and erratic results, due to the prozone effect. This is a laboratory phenomenon that occurs when antigen excess interferes with antibody-based methods requiring immune complex formation for detection. It is important to recognize the presence of a prozone effect, because it can produce falsely normal results, and therefore it could lead clinicians to incorrect assessment of the response to therapy

Incorporating a gender perspective into the development of clinical guidelines: a training course for guideline developers

<p>Abstract</p> <p>Background</p> <p>Dutch guideline-developing organizations do not focus systematically on differences between men and women when developing guidelines, even though there is increasing evidence that being male or female may have an effect on health and health outcomes. In collaboration with two prominent Dutch guideline-developing organizations, we designed a training course to encourage systematic attention to sex differences in guideline development procedures.</p> <p>Methods</p> <p>The course is targeted towards guideline developers. Its aims are to improve awareness concerning the relevance of considering sex differences in the guideline development process, as well as the competence and skills necessary for putting this into practice. The design and teaching methods of the course are based on adult learning styles and principles of changing provider behaviour. It was adjusted to the working methods of guideline organizations. The course was taught to, and evaluated by, a group of staff members from two guideline organizations in the Netherlands.</p> <p>Results</p> <p>The course consists of five modules, each of which corresponds to a key step in the guideline development process. The participants rated the training course positively on content, programme, and trainers. Their written comments suggest that the course met its objectives.</p> <p>Conclusion</p> <p>The training course is the first to address sex differences in guideline development. Results from the pilot test suggest that the course achieved its objectives. Because its modules and teaching methods of the course are widely transferable, the course could be useful for many organizations that are involved in developing guidelines. Follow-up studies are needed to assess the long-term effect of the course on the actions of guideline developers and its utility in other settings.</p

Perceived barriers to guideline adherence: A survey among general practitioners

Contains fulltext : 97209.pdf (publisher's version ) (Open Access)BACKGROUND: Despite considerable efforts to promote and support guideline use, adherence is often suboptimal. Barriers to adherence vary not only across guidelines but also across recommendations within guidelines. The aim of this study was to assess the perceived barriers to guideline adherence among GPs by focusing on key recommendations within guidelines. METHODS: We conducted a cross-sectional electronic survey among 703 GPs in the Netherlands. Sixteen key recommendations were derived from four national guidelines. Six statements were included to address the attitudes towards guidelines in general. In addition, GPs were asked to rate their perceived adherence (one statement) and the perceived barriers (fourteen statements) for each of the key recommendations, based on an existing framework. RESULTS: 264 GPs (38%) completed the questionnaire. Although 35% of the GPs reported difficulties in changing routines and habits to follow guidelines, 89% believed that following guidelines leads to improved patient care. Perceived adherence varied between 52 and 95% across recommendations (mean: 77%). The most perceived barriers were related to external factors, in particular patient ability and behaviour (mean: 30%) and patient preferences (mean: 23%). Lack of applicability of recommendations in general (mean: 22%) and more specifically to individual patients (mean: 25%) were also frequently perceived as barriers. The scores on perceived barriers differed largely between recommendations [minimum range 14%; maximum range 67%]. CONCLUSIONS: Dutch GPs have a positive attitude towards the NHG guidelines, report high adherence rates and low levels of perceived barriers. However, the perceived adherence and perceived barriers varied largely across recommendations. The most perceived barriers across recommendations are patient related, suggesting that current guidelines do not always adequately incorporate patient preferences, needs and abilities. It may be useful to provide tools such as decision aids, supporting the flexible use of guidelines to individual patients in practice

Structure-Function Analysis of Diacylglycerol Acyltransferase Sequences from 70 Organisms

<p>Abstract</p> <p>Background</p> <p>Diacylglycerol acyltransferase families (DGATs) catalyze the final and rate-limiting step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. Understanding the roles of DGATs will help to create transgenic plants with value-added properties and provide clues for therapeutic intervention for obesity and related diseases. The objective of this analysis was to identify conserved sequence motifs and amino acid residues for better understanding of the structure-function relationship of these important enzymes.</p> <p>Results</p> <p>117 DGAT sequences from 70 organisms including plants, animals, fungi and human are obtained from database search using tung tree DGATs. Phylogenetic analysis separates these proteins into DGAT1 and DGAT2 subfamilies. These DGATs are integral membrane proteins with more than 40% of the total amino acid residues being hydrophobic. They have similar properties and amino acid composition except that DGAT1s are approximately 20 kDa larger than DGAT2s. DGAT1s and DGAT2s have 41 and 16 completely conserved amino acid residues, respectively, although only two of them are shared by all DGATs. These residues are distributed in 7 and 6 sequence blocks for DGAT1s and DGAT2s, respectively, and located at the carboxyl termini, suggesting the location of the catalytic domains. These conserved sequence blocks do not contain the putative neutral lipid-binding domain, mitochondrial targeting signal, or ER retrieval motif. The importance of conserved residues has been demonstrated by site-directed and natural mutants.</p> <p>Conclusions</p> <p>This study has identified conserved sequence motifs and amino acid residues in all 117 DGATs and the two subfamilies. None of the completely conserved residues in DGAT1s and DGAT2s is present in recently reported isoforms in the multiple sequences alignment, raising an important question how proteins with completely different amino acid sequences could perform the same biochemical reaction. The sequence analysis should facilitate studying the structure-function relationship of DGATs with the ultimate goal to identify critical amino acid residues for engineering superb enzymes in metabolic engineering and selecting enzyme inhibitors in therapeutic application for obesity and related diseases.</p

The European Society of Human Reproduction and Embryology guideline for the diagnosis and treatment of endometriosis: an electronic guideline implementability appraisal

<p>Abstract</p> <p>Background</p> <p>Clinical guidelines are intended to improve healthcare. However, even if guidelines are excellent, their implementation is not assured. In subfertility care, the European Society of Human Reproduction and Embryology (ESHRE) guidelines have been inventoried, and their methodological quality has been assessed. To improve the impact of the ESHRE guidelines and to improve European subfertility care, it is important to optimise the implementability of guidelines. We therefore investigated the implementation barriers of the ESHRE guideline with the best methodological quality and evaluated the used instrument for usability and feasibility.</p> <p>Methods</p> <p>We reviewed the ESHRE guideline for the diagnosis and treatment of endometriosis to assess its implementability. We used an electronic version of the guideline implementability appraisal (eGLIA) instrument. This eGLIA tool consists of 31 questions grouped into 10 dimensions. Seven items address the guideline as a whole, and 24 items assess the individual recommendations in the guideline. The eGLIA instrument identifies factors that influence the implementability of the guideline recommendations. These factors can be divided into facilitators that promote implementation and barriers that oppose implementation. A panel of 10 experts from three European countries appraised all 36 recommendations of the guideline. They discussed discrepancies in a teleconference and completed a questionnaire to evaluate the ease of use and overall utility of the eGLIA instrument.</p> <p>Results</p> <p>Two of the 36 guideline recommendations were straightforward to implement. Five recommendations were considered simply statements because they contained no actions. The remaining 29 recommendations were implementable with some adjustments. We found facilitators of the guideline implementability in the quality of decidability, presentation and formatting, apparent validity, and novelty or innovation of the recommendations. Vaguely defined actions, lack of facilities, immeasurable outcomes, and inflexibility within the recommendations formed barriers to implementation. The eGLIA instrument was generally useful and easy to use. However, assessment with the eGLIA instrument is very time-consuming.</p> <p>Conclusions</p> <p>The ESHRE guideline for the diagnosis and treatment of endometriosis could be improved to facilitate its implementation in daily practice. The eGLIA instrument is a helpful tool for identifying obstacles to implementation of a guideline. However, we recommend a concise version of this instrument.</p

Evolutionary view of acyl-CoA diacylglycerol acyltransferase (DGAT), a key enzyme in neutral lipid biosynthesis

<p>Abstract</p> <p>Background</p> <p>Triacylglycerides (TAGs) are a class of neutral lipids that represent the most important storage form of energy for eukaryotic cells. DGAT (acyl-CoA: diacylglycerol acyltransferase; EC 2.3.1.20) is a transmembrane enzyme that acts in the final and committed step of TAG synthesis, and it has been proposed to be the rate-limiting enzyme in plant storage lipid accumulation. In fact, two different enzymes identified in several eukaryotic species, DGAT1 and DGAT2, are the main enzymes responsible for TAG synthesis. These enzymes do not share high DNA or protein sequence similarities, and it has been suggested that they play non-redundant roles in different tissues and in some species in TAG synthesis. Despite a number of previous studies on the DGAT1 and DGAT2 genes, which have emphasized their importance as potential obesity treatment targets to increase triacylglycerol accumulation, little is known about their evolutionary timeline in eukaryotes. The goal of this study was to examine the evolutionary relationship of the DGAT1 and DGAT2 genes across eukaryotic organisms in order to infer their origin.</p> <p>Results</p> <p>We have conducted a broad survey of fully sequenced genomes, including representatives of Amoebozoa, yeasts, fungi, algae, musses, plants, vertebrate and invertebrate species, for the presence of DGAT1 and DGAT2 gene homologs. We found that the DGAT1 and DGAT2 genes are nearly ubiquitous in eukaryotes and are readily identifiable in all the major eukaryotic groups and genomes examined. Phylogenetic analyses of the DGAT1 and DGAT2 amino acid sequences revealed evolutionary partitioning of the DGAT protein family into two major DGAT1 and DGAT2 clades. Protein secondary structure and hydrophobic-transmembrane analysis also showed differences between these enzymes. The analysis also revealed that the MGAT2 and AWAT genes may have arisen from DGAT2 duplication events.</p> <p>Conclusions</p> <p>In this study, we identified several DGAT1 and DGAT2 homologs in eukaryote taxa. Overall, the data show that DGAT1 and DGAT2 are present in most eukaryotic organisms and belong to two different gene families. The phylogenetic and evolutionary analyses revealed that DGAT1 and DGAT2 evolved separately, with functional convergence, despite their wide molecular and structural divergence.</p

An integrated bioinformatics analysis reveals divergent evolutionary pattern of oil biosynthesis in high- and low-oil plants

Seed oils provide a renewable source of food, biofuel and industrial raw materials that is important for humans. Although many genes and pathways for acyl-lipid metabolism have been identified, little is known about whether there is a specific mechanism for high-oil content in high-oil plants. Based on the distinct differences in seed oil content between four high-oil dicots (20~50%) and three low-oil grasses (<3%), comparative genome, transcriptome and differential expression analyses were used to investigate this mechanism. Among 4,051 dicot-specific soybean genes identified from 252,443 genes in the seven species, 54 genes were shown to directly participate in acyl-lipid metabolism, and 93 genes were found to be associated with acyl-lipid metabolism. Among the 93 dicot-specific genes, 42 and 27 genes, including CBM20-like SBDs and GPT2, participate in carbohydrate degradation and transport, respectively. 40 genes highly up-regulated during seed oil rapid accumulation period are mainly involved in initial fatty acid synthesis, triacylglyceride assembly and oil-body formation, for example, ACCase, PP, DGAT1, PDAT1, OLEs and STEROs, which were also found to be differentially expressed between high- and low-oil soybean accessions. Phylogenetic analysis revealed distinct differences of oleosin in patterns of gene duplication and loss between high-oil dicots and low-oil grasses. In addition, seed-specific GmGRF5, ABI5 and GmTZF4 were predicted to be candidate regulators in seed oil accumulation. This study facilitates future research on lipid biosynthesis and potential genetic improvement of seed oil content