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PubMed2001

Consensus development of a histopathological classification system for chronic prostatic inflammation.

OBJECTIVE: To develop a standardized histopathological classification system for chronic prostatitis (standardized description of prostatic inflammatory infiltrates) based on a literature review, extensive prospective evaluations in two recognized prostatitis research centres and widespread consensus of international urological centres identified as having major expertise or interest in chronic prostatitis. METHODS: Relevant articles for review were identified by a Medline search undertaken by the Cochrane Review Group in Prostate Diseases and Urologic Malignancies, and cross-checking bibliographies of retrieved studies, reviews, book chapters and abstracts of the American Urological Association and International Prostatitis Collaborative Network Annual Meetings. Initial drafts were based on classification systems independently developed by the Prostatitis Research Centers at Queen's University in Canada and University of Washington in the USA. A collaborative draft was distributed to 20 urological/pathological clinical centres who participated in the North American Chronic Prostatitis Collaborative Research Network and First International Prostatitis Collaborative Network. A consensus classification system was then distributed to the participating panel for acceptance. RESULTS: The literature review identified a reasonably consistent description of inflammatory infiltrate locations and patterns that were further incorporated into the draft based on the Queen's University and University of Washington proposals. Eighteen (90%) of the identified Prostatitis Centers participated in the revision of the draft and the final consensus process. The final consensus document classifies prostatic inflammation according to its extent and grade/severity in each tissue compartment (location). Conclusion The consensus of the expert panel was that this classification system can be used in the evaluation of prostatic inflammation in prostate biopsies, transurethral resected prostate chips or prostatectomy specimens. A standardized accepted framework to describe histopathological prostate inflammation will prove useful in evaluating prostate disease.

Chronic Disease↗
PubMed1995

Analysis of the short consensus repeats of human complement factor B by site-directed mutagenesis.

Human factor B is required for the initiation and propagation of the complement alternative pathway. It also participates in the amplification of the complement classical pathway. Alone, factor B is a zymogen with little known biochemical activity, but in the context of the alternative pathway convertases, the factor B serine protease is activated in a process that first involves the association with C3b and subsequently the cleavage of factor B into two fragments, Ba and Bb. Ba, the NH2-terminal fragment, is composed mainly of three tandem short consensus repeats, globular domains found in other complement proteins. It dissociates from the convertase during assembly, leaving the active C3 convertase, C3bBb. Previous reports suggest that the Ba region may be instrumental in convertase assembly. This hypothesis was tested using site-directed mutagenesis of recombinant factor B and monoclonal antibody epitope mapping to evaluate the relative importance of specific short consensus repeat amino acid residues. Three sites of interest were identified. Site 1 is a stretch of 19 contiguous amino acids in short consensus repeat 1 that form the epitope of a monoclonal antibody that effectively blocks factor B function. Site 2, composed of 6 contiguous amino acids in short consensus repeat 2, and site 3, consisting of 7 contiguous amino acids in short consensus repeat 3, were defined by mutations that reduce factor B hemolytic activity to 3% or less. Further analyses indicated that sites 2 and 3 contribute to factor B-C3b interactions.

Amino Acid Sequence↗
PubMed2001

From consensus sequence peptide to high affinity ligand, a "library scan" strategy.

A wide variety of proteins have been shown to recognize and bind to specific amino acid sequences on other proteins. These sequences can be readily identified using combinatorial peptide libraries. However, peptides containing these preferred sequences ("consensus sequence peptides") typically display only modest affinities for the consensus sequence-binding site on the intact protein. In this report, we describe a parallel synthesis strategy that transforms consensus sequence peptides into high affinity ligands. The work described herein has focused on the Lck SH2 domain, which binds the consensus peptide acetyl-Tyr(P)-Glu-Glu-Ile-amide with a K(D) of 1.3 micrometer. We employed a strategy that creates a series of spatially focused libraries that challenge specific subsites on the target protein with a diverse array of functionality. The final lead compound identified in this study displayed a 3300-fold higher affinity for the Lck SH2 domain than the starting consensus sequence peptide.

Amino Acid Sequence↗
PubMed1996

Cell surface binding characteristics correlate with consensus type I interferon enhanced activity.

The binding characteristics of a genetically engineered consensus interferon with unusually high biologic activity were compared to the characteristics of recombinant interferon-alpha 2. Both interferon-alpha 2 and the consensus interferon produced typical biphasic Scatchard plots, indicating multiple independent binding sites. The consensus interferon, which exhibited a biologic potency more than 10-fold greater than all other type I interferons, also exhibited binding site affinities greater than those for IFN-alpha 2b. In addition, a larger number of high, and low-affinity cell surface sites were recognized by the consensus interferon, resulting in equivalent numbers of sites at reduced molar concentrations compared to IFN-a2b. Thus, at any given biologic activity, similar numbers of sites were bound by the consensus interferon and IFN-alpha 2, despite differences in their molar concentrations. No differences in internalization kinetics were identified between the two interferons, indicating that the differences in cell surface binding may be sufficient to produce the differences in biologic activity.

Cell Line↗
PubMed1993

A consensus program for molecular sequences.

Although molecular biologists often calculate consensus sequences from aligned DNA or protein sequences, relatively little is known about the properties of many of the consensus methods being used. Consequently, we wrote a program, CONSENSUS, to analyze and compare methods of calculating a consensus result (a base, an ambiguity code or a subset of codes) at a position in an aligned set of molecular sequences. The program supports alphabets of up to four symbols (e.g. [R,Y] or [A,C,G,T]). The program's output makes it suitable for exploratory data analysis or for selecting values of thresholds or confidence levels in consensus methods having such parameters.

Base Sequence↗
PubMed2003

Generating consensus sequences from partial order multiple sequence alignment graphs.

MOTIVATION: Consensus sequence generation is important in many kinds of sequence analysis ranging from sequence assembly to profile-based iterative search methods. However, how can a consensus be constructed when its inherent assumption-that the aligned sequences form a single linear consensus-is not true? RESULTS: Partial Order Alignment (POA) enables construction and analysis of multiple sequence alignments as directed acyclic graphs containing complex branching structure. Here we present a dynamic programming algorithm (heaviest_bundle) for generating multiple consensus sequences from such complex alignments. The number and relationships of these consensus sequences reveals the degree of structural complexity of the source alignment. This is a powerful and general approach for analyzing and visualizing complex alignment structures, and can be applied to any alignment. We illustrate its value for analyzing expressed sequence alignments to detect alternative splicing, reconstruct full length mRNA isoform sequences from EST fragments, and separate paralog mixtures that can cause incorrect SNP predictions. AVAILABILITY: The heaviest_bundle source code is available at http://www.bioinformatics.ucla.edu/poa

Algorithms↗
PubMed1992

Critical comparison of consensus methods for molecular sequences.

Consensus methods are recognized as valuable tools for data analysis, especially when some sort of data aggregation is desired. Although consensus methods for sequences play a vital role in molecular biology, researchers pay little heed to the features and limitations of such methods, and so there are risks that criteria for constructing consensus sequences will be misused or misunderstood. To understand better the issues involved, we conducted a critical comparison of nine consensus methods for sequences, of which eight were used in papers appearing in this journal. We report the results of that comparison, and we make recommendations which we hope will assist researchers when they must select particular consensus methods for particular applications.

Algorithms↗
PubMed2005

Correcting errors in synthetic DNA through consensus shuffling.

Although efficient methods exist to assemble synthetic oligonucleotides into genes and genomes, these suffer from the presence of 1-3 random errors/kb of DNA. Here, we introduce a new method termed consensus shuffling and demonstrate its use to significantly reduce random errors in synthetic DNA. In this method, errors are revealed as mismatches by re-hybridization of the population. The DNA is fragmented, and mismatched fragments are removed upon binding to an immobilized mismatch binding protein (MutS). PCR assembly of the remaining fragments yields a new population of full-length sequences enriched for the consensus sequence of the input population. We show that two iterations of consensus shuffling improved a population of synthetic green fluorescent protein (GFPuv) clones from approximately 60 to >90% fluorescent, and decreased errors 3.5- to 4.3-fold to final values of approximately 1 error per 3500 bp. In addition, two iterations of consensus shuffling corrected a population of GFPuv clones where all members were non-functional, to a population where 82% of clones were fluorescent. Consensus shuffling should facilitate the rapid and accurate synthesis of long DNA sequences.

Adenosine Triphosphatases↗
PubMed2000

The Texas Children's Medication Algorithm Project: Report of the Texas Consensus Conference Panel on Medication Treatment of Childhood Attention-Deficit/Hyperactivity Disorder. Part I. Attention-Deficit/Hyperactivity Disorder.

OBJECTIVES: Expert consensus methodology was used to develop evidence-based, consensually agreed-upon medication treatment algorithms for attention-deficit/hyperactivity disorder (ADHD) in the public mental health sector. Although treatment algorithms for adult mental disorders have been developed, this represents one of the first attempts to develop similar algorithms for childhood mental disorders. Although these algorithms were developed initially for the public sector, the goals of this approach are to increase the uniformity of treatment and improve the clinical outcomes of children and adolescents with ADHD in a variety of treatment settings. METHOD: A consensus conference of academic clinicians and researchers, practicing clinicians, administrators, consumers, and families was convened to develop evidence-based consensus algorithms for the pharmacotherapy of childhood ADHD. After a series of presentations of current research evidence and panel discussion, the consensus panel met and drafted the algorithms along with guidelines for implementation. RESULTS: The panel developed consensually agreed-upon algorithms for ADHD with and without specific comorbid disorders. The algorithms consist of systematic strategies for psychopharmacological interventions and tactics to ensure successful implementation of the strategies. While the algorithms focused on the medication management of ADHD, the conference emphasized that psychosocial treatments are often a critical component of the overall management of ADHD. CONCLUSIONS: Medication algorithms for ADHD can be developed with consensus. A companion article will discuss the implementation of these algorithms.

Adrenergic alpha-Agonists↗
PubMed2005

Consensus development in acute renal failure: The Acute Dialysis Quality Initiative.

PURPOSE OF REVIEW: Although acute renal failure is both common and highly lethal in the intensive care unit, our understanding of the epidemiology and pathophysiology of acute renal failure is limited, and treatment for acute renal failure is extremely variable around the world. The general lack of consensus with regard to definitions, prevention, and treatment of acute renal failure has limited progress in this field. RECENT FINDINGS: Consensus in acute renal failure requires establishing a framework in which intensivists, nephrologists, pharmacologists, and others who care for critically ill patients with or at risk for acute renal failure can reach consensus and develop evidence-based practice guidelines. The Acute Dialysis Quality Initiative seeks to provide an objective, dispassionate distillation of the literature and description of the current state of practice of dialysis and related therapies as they are applied to acutely ill patients. The purposes of Acute Dialysis Quality Initiative are first, to develop a consensus of opinion, with evidence where possible, on best practice; and second, to articulate a research agenda to focus on important unanswered questions. SUMMARY: Broad consensus in the diagnosis and management of acute renal failure and in the use of blood purification in nonrenal critical illness is achievable. Standardization of definitions, practice, and research methodology is urgently needed, and specific proposals have been made by an international, interdisciplinary group.

Acute Kidney Injury↗
PubMed2004

To strengthen consensus, consult the stakeholders.

CIOMS has been criticised for not adequately consulting stakeholders about its revised ethical guidelines regarding medical research. Political and logistical issues that arise in democratic processes and open exchange of information probably contributed to this exclusion. What might CIOMS have done to be more inclusive and attain broader consensus on its proposed revisions? Consensus is dynamic, and evolves as a community digests new information and perspectives. Engaging the public (and particularly the stakeholders) in discussion about the revisions would have generated broader consensus. It would have encouraged more stakeholders (i.e. researchers, potential research participants, research institutions, or governments) to buy in. CIOMS needs a process to encourage dialogue and stakeholder input. The CIOMS guidelines themselves promote stakeholder consultation and capacity building, but CIOMS has done relatively little to distribute or promote its own guidelines. CIOMS should do more to promote its revised guidelines, and engage stakeholders in dialogue. This paper explores the bioethics debate about universal and relative values to illustrate the value of consultation and consensus building. It concludes that like research sponsors, CIOMS and similar organisations have an ethical responsibility to facilitate capacity building in less developed areas, and to participate more actively in consensus building.

Community Participation↗
PubMed2003

Immediate/early loading of dental implants: a report from the Sociedad Española de Implantes World Congress consensus meeting in Barcelona, Spain, 2002.

BACKGROUND: Immediate/early loading protocols are becoming frequently used in implant dentistry, but the prerequisites for achieving good results and the limitations of such protocols are not fully known. Moreover, the terminology used in immediate/early loading is still confusing. PURPOSE: The purpose of this article is to present the outcome of a consensus meeting on immediate/early loading. MATERIALS AND METHODS: A consensus meeting was organized during the Sociedad Española de Implantes World Congress in Barcelona on May 23, 2002, with the objective to present and discuss the experiences from immediate/early loading protocols in dental implant treatment. The purpose was also to discuss definitions of the terminology used in immediate/early loading. The consensus meeting agenda included presentations from invited experts, followed by a consensus discussion. RESULTS: A consensus statement was agreed on. CONCLUSIONS: Multiple independent investigators have demonstrated that immediate/early loading of implants is possible in many clinical situations; however, additional documentation is required.

Dental Implantation, Endosseous↗
PubMed1998

A MADS box protein consensus binding site is necessary and sufficient for activation of the opaque-phase-specific gene OP4 of Candida albicans.

The majority of strains of Candida albicans can switch frequently and reversibly between two or more general phenotypes, a process now considered a putative virulence factor in this species. Candida albicans WO-1 switches frequently and reversibly between a white and an opaque phase, and this phenotypic transition is accompanied by the differential expression of white-phase-specific and opaque-phase-specific genes. In the opaque phase, cells differentially express the gene OP4, which encodes a putative protein 402 amino acids in length that contains a highly hydrophobic amino-terminal sequence and a carboxy-terminal sequence with a pI of 10.73. A series of deletion constructs fused to the Renilla reniformis luciferase was used to functionally characterize the OP4 promoter in order to investigate how this gene is differentially expressed in the white-opaque transition. An extremely strong 17-bp transcription activation sequence was identified between -422 and -404 bp. This sequence contained a MADS box consensus binding site, most closely related to the Mcm1 binding site of Saccharomyces cerevisiae. A number of point mutations generated in the MADS box consensus binding site as well as a complete deletion of the consensus site further demonstrated that it was essential for the activation of OP4 transcription in the opaque phase. Gel mobility shift assays with the 17-bp activation sequence identified three specific complexes which formed with both white- and opaque-phase cell extracts. Competition with a putative MADS box consensus binding site from the promoter of the coordinately regulated opaque-phase-specific gene PEP1 (SAP1) and the human MADS box consensus binding site for serum response factor demonstrated that one of the three complexes formed was specific to the OP4 sequence.

Base Sequence↗
PubMed2003

International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis.

OBJECTIVE: To obtain an international consensus about the use of anti-tumour necrosis factor alpha (anti-TNF alpha) for treating patients with ankylosing spondylitis (AS). METHODS: These recommendations were developed by a review of published reports in combination with expert opinion, including a Delphi exercise, and a consensus meeting of the ASsessments in AS (ASAS) Working Group. RESULTS: The final consensus comprises the following requirements: (1) For the initiation of anti-TNF alpha therapy: (a) a diagnosis of definitive AS; (b) presence of active disease for at least four weeks as defined by both a sustained Bath AS Disease Activity Index (BASDAI) of at least 4 and an expert opinion based on clinical features, acute phase reactants, and imaging modalities; (c) presence of refractory disease defined by failure of at least two non-steroidal anti-inflammatory drugs during a single three month period, failure of intra-articular steroids if indicated, and failure of sulfasalazine in patients with peripheral arthritis; (d) application and implementation of the usual precautions and contraindications for biological therapy. (2) For the monitoring of anti-TNF alpha therapy: both the BASDAI and the ASAS core set for clinical practice should be followed regularly. (3) For the discontinuation of anti-TNF alpha therapy: in non-responders, consideration should be made after 6-12 weeks' treatment. Response is defined as improvement of (a) at least 50% or 2 units (on a 0-10 scale) of the BASDAI, (b) expert opinion that treatment should be continued. CONCLUSION: This consensus statement on anti-TNF alpha treatment in AS may be used for guidance in clinical decision making and as the basis for the development of guidelines. Evaluation of the healthcare consequences of this consensus is subject to further research by the ASAS group.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMedDate not supplied

[Avoidable mortality: a consensus list of causes to update the indicator in Spain].

OBJECTIVE: Mortality indicators could reflect the effect of health services interventions on the population's health, although there is no agreement about which indicator would be the most appropriate. The objective of this study was to obtain a consensus list of causes of avoidable mortality that could be used as a reference in Spain. METHODS: Based on existing publications and participants' knowledge, a process of consensus among medical practitioners, producers and users of health indicators was carried out. The degree of agreement on the different items was assessed. RESULTS: Agreement was reached on a final list of 34 causes of avoidable mortality as well as on the interventions that could avoid death. The level of consensus was high or intermediate in most categories (consensus was low in only 4 categories) and was high for the list and sublists (medical care or health policy interventions) as a whole. Agreement was higher on the avoidable causes of death than on the kind of interventions that can avoid it. Discrepancy was greater for the kind of medical interventions than for intersectorial policy measures. CONCLUSIONS: The reflection and discussion involved in reaching a consensus on the avoidable mortality list, as well as the dissemination of the criteria and the procedures followed, provide added value. The list will improve data comparisons and facilitate benchmarking among the various regional health systems. We recommend its use in the Spanish context.

Cause of Death↗
PubMedDate not supplied

A critique of the ACCP consensus conference on mechanical ventilation. American College of Chest Physicians.

The American College of Chest Physicians recently published a statement summarizing the results of the Consensus Conference on Mechanical Ventilation (Chest 1993; 104:1833-1859). In this statement, the physiology of mechanical ventilation was extensively reviewed, and 5 principles and 38 guidelines or recommendations on which consensus was reached were presented. The following critique (1) summarizes the findings of the conference; (2) comments on selected principles, recommendations, and physiological concepts presented in the statement; and (3) discusses the strengths and the limitations of the consensus conference format, as well as the errors and biases inherent in the policy-making process. The Consensus Conference statement is one of the clearest, most complete reviews of physiology and techniques of mechanical ventilation I have yet encountered. The suggested guidelines and recommendations clearly follow from the physiological principles discussed. Unfortunately, numerous problems with the consensus conference format and the almost total lack of controlled randomized studies limit the confidence with which these suggestions can be accepted. Our experts in respiratory care are remiss for not providing outcome-based or preference-based data, and the pulmonary and critical care community is remiss for not demanding that they do so before changing our approaches on the basis of their suggestions.

Bias↗
PubMed2006

A systematic review of factors affecting the judgments produced by formal consensus development methods in health care.

OBJECTIVES: Formal consensus development methods are ways of obtaining and synthesising views of experts, opinion leaders and other stakeholders, and are increasingly being used to develop clinical practice guidelines. Our objective was to examine the impact that the characteristics of individual participants, groups and the consensus process have on the judgments produced by formal consensus development methods in health care. METHODS: Studies were identified from an earlier methodological review and a search of five bibliographic databases for the period January 1996 to December 2004. Studies were eligible if they involved formal consensus development methods and reported differences in judgments between groups or participants. For studies comparing two or more groups overall percentage agreement, the kappa coefficient and the odds ratio for differences in judgments were calculated. RESULTS: There were 22 studies comparing the impact of the characteristics of individual participants within groups and 30 studies comparing the results produced by two or more groups. Practitioners who perform a procedure tend to emphasise the appropriateness of the procedure compared with non-performing practitioners, and individuals from groups that were subject to performance criteria are more critical of those criteria than individuals from other groups. There was no clear pattern for the differences in judgments produced by participants and groups from different countries. CONCLUSIONS: Except for participant specialty there is little general evidence for how the characteristics of participants and groups influence the judgments produced in formal consensus development methods. Multi-specialty groups are preferable to single-specialty groups because of their potential for taking account of a wider range of opinions.

Consensus↗
PubMed2006

A comparison of formal consensus methods used for developing clinical guidelines.

OBJECTIVES: To compare two consensus development methods commonly used for developing clinical guidelines in terms of the judgments produced, closeness of consensus, amount of change between rounds, concordance with research evidence and reliability. METHODS: In all, 213 general practitioners and mental health professionals from England participated in four Delphi and four nominal groups. They rated the appropriateness of four treatments (cognitive behavioural therapy [CBT], behavioural therapy [BT], brief psychodynamic interpersonal therapy [BPIT] and antidepressants) for three conditions. First, participants rated the appropriateness of interventions independently, using a postal questionnaire. For nominal groups, the ratings were fed back and discussed at a meeting, and then group members privately completed the questionnaire again. For Delphi groups, there was feedback but no discussion, and the entire process was conducted by postal questionnaire. RESULTS: The effect of consensus method on final ratings varied with therapeutic intervention, with nominal groups rating CBT and antidepressants more favourably than Delphi groups. Consensus was closer in the nominal than in the Delphi groups in both rounds. There was no overall difference between groups in their concordance with research evidence (odds ratio 1.13, 95% confidence interval 0.79-1.61). In this study, the Delphi method was more reliable (kappa coefficients 0.88 and 0.89 compared with 0.41 and 0.65 for nominal groups). CONCLUSIONS: The advantages of nominal groups (more consensus; greater understanding of reasons for disagreement) could be combined with the greater reliability of the Delphi approach by developing a hybrid method.

Chronic Disease↗