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PubMed1998

[Management of chronic obstructive pulmonary disease: is there really more consensus, or just more consensus statements?].

Advances in the knowledge of chronic obstructive pulmonary disease pathophysiology have introduced chantes in the treatment of this disease, that have been presented in several guidelines published at a national or supranational level. In this paper some of these changes are analysed, together with significant aspects of these guidelines and items that remain unclear.

Humans↗
PubMed2006

Biological assay using T cell response for Cry-consensus peptide designed for the peptide-based immunotherapy of Japanese cedar pollinosis.

INTRODUCTION: Cry-consensus peptide is a linearly linked peptide of T-cell epitopes for the management of Japanese cedar (JC) pollinosis and is expected to become a new drug for immunotherapy. However, the mechanism of T-cell epitopes in allergic diseases is not well understood, and thus, a simple in vitro procedure for evaluation of its biological activity is desired. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated from 27 JC pollinosis patients and 10 healthy subjects, and cultured in vitro for 4 days in the presence of Cry-consensus peptide and (3)H-thymidine. The relationship between growth stimulation (stimulation index; SI) and antigen-specific IgE levels in serum was also investigated in JC pollinosis patients. Moreover, to confirm the importance of the primary sequence in Cry-consensus peptide, heat-treated Cry-consensus peptide and a mixture of the amino acids of which Cry-consensus peptide is composed, and their (3)H-thymidine uptake was compared with Cry-consensus peptide. Finally, whether Cry-consensus peptide stimulates PBMCs from healthy subjects was investigated. RESULTS: The mean SI of JC patients showed a good correlation with Cry-consensus peptide concentration in the culture medium; however, the SI was independent of the anti-Cry j 1 IgE level. Heat-denatured Cry-consensus peptide retained a PBMC proliferation stimulatory effect comparable to the original Cry-consensus peptide, while the mixture of amino acids constituting Cry-consensus peptide did not stimulate PBMC proliferation. PBMCs from healthy subjects did not respond to Cry-consensus peptide at all. DISCUSSION: These data indicate that the PBMC response of patients suffering from JC pollinosis to Cry-consensus peptide is specific for the sequence of T cell epitopes thereof and may be useful for the evaluation of the efficacy of Cry-consensus peptide in vivo.

Adult↗
PubMed2006

PS80 interferes with the antiallergic effect of Cry-consensus peptide, a novel recombinant peptide for immunotherapy of Japanese cedar pollinosis, at very low concentration through modulation of Th1/Th2 balance.

Polysorbate 80 (PS80 or Tween-80) is often used as an additive to promote the rapid solubilization of pharmaceuticals in aqueous solutions. We investigated whether coinjection of a minimal amount of PS80 had a modulatory effect on the immunotherapeutic effects of Cry (Cryptomeria)-consensus peptide, a novel peptide developed for the therapeutic management of Japanese cedar pollinosis, using a Cry j 1-sensitized mouse model with experimental allergic rhinitis. Subcutaneous challenge with Cry-consensus peptide plus 50 microg/ml of PS80 did not affect the antigen-specific proliferation of splenocytes, but decreased the potency of Cry-consensus peptide to inhibit antigen-specific interleukin (IL)-5 production by the cells significantly in comparison with challenge with Cry-consensus peptide alone. However, there was no significant difference between the effect of Cry-consensus peptide administration on interferon (IFN)-gamma production in the presence and absence of PS80, indicating that PS80 interfered with the T helper 1 (Th1)-dominant T helper balance induced by Cry-consensus peptide challenge. Moreover, the increase in the level of antigen-specific immunoglobulin G2a (IgG2a) induced by Cry-consensus peptide challenge was inhibited slightly but unambiguously by PS80 coinjection. These in vitro experiments indicated that PS80 induces Th2-type differentiation of T helper cells through preferential inhibition of IFN-gamma expression relative to IL-5 expression in splenocytes in a concentration-dependent manner. In naïve mice, sensitization by Cry-consensus peptide with PS80 induced antigen-specific IL-5 production more potently than sensitization by Cry-consensus peptide alone, and when PS80 was added to bone marrow-derived dendritic cells, the endocytosis of fluorescence-labelled Cry-consensus peptide was dramatically inhibited in a concentration-dependent manner. Therefore, we conclude that PS80 has an immunomodulatory effect on the antigen-specific response resulting in a shift towards Th2 predominance with respect to the antigen recognition stage. Taken together, our findings suggest that PS80 might decrease the efficacy of Cry-consensus peptide through modulation of the efficiency of antigen endocytosis and/or of the direction of successive T helper cell differentiation.

Allergens↗
PubMed1995

Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consensus Development Panel on the Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes.

OBJECTIVE: To develop a consensus on the use of antenatal corticosteroids for fetal maturation in preterm infants. PARTICIPANTS: A nonfederal, nonadvocate, 16-member consensus panel including representatives from neonatology, obstetrics, family medicine, behavioral medicine, psychology, biostatistics, and the public; 19 experts in neonatology, obstetrics, and pharmacology presented data to the consensus panel and a conference audience of approximately 500. EVIDENCE: An extensive bibliography of references was produced for the consensus panel and the conference audience using a variety of on-line databases including MEDLINE. The consensus panel met several times prior to the conference to review the literature. It also commissioned an updated meta-analysis, a neonatal registry review, and an economic analysis that were presented at the conference. The experts prepared abstracts for distribution at the conference, presented data, and answered questions from the panel and audience. The panel evaluated the strength of the scientific evidence using the grading system developed by the Canadian Task Force on the Periodic Health Examination and adapted by the US Preventive Services Task Force. CONSENSUS: The consensus panel, answering predefined consensus questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. CONSENSUS STATEMENT: The consensus panel composed a draft statement that was read in its entirety at the conference for comment. The panel released a revised statement at the end of the conference and finalized the revisions a few weeks after the conference. CONCLUSIONS: Antenatal corticosteroid therapy is indicated for women at risk of premature delivery with few exceptions and will result in a substantial decrease in neonatal morbidity and mortality, as well as substantial savings in health care costs. The use of antenatal corticosteroids for fetal maturation is a rare example of a technology that yields substantial cost savings in addition to improving health.

Betamethasone↗
PubMed2003

Should consensus be 'the commission method' in the US? The perspective of the Federal Advisory Committee Act, regulations, and case law.

This paper examines the drive for consensus from the perspective of the good government framework for federal advisory commissions in the United States. Specifically, the paper examines the Federal Advisory Committee Act (FACA)--the statute, its regulations, and case law. It shows that the FACA was intended to be an antidote to abuses in consensus-making processes, including the failure to fully include competing views on commissions. The index of suspicion in the FACA scheme rises when a group work product--including a consensus report--is to be the basis of recommendations to federal officials. Once FACA's requirements regarding committee composition are satisfied, the index of suspicion drops and FACA is indifferent to consensus-making; but the conditions for informed, meaningful participation apply to members who dissent from, as well as those who participate in, consensus. In negotiated rulemaking, the push for consensus and closure creates unacceptable tension with the good government goals of openness and accountability. Proponents of consensus-only bioethics commissions can learn from FACA-related legislative, agency, and judicial insights that consensus-seeking is not always desired by government officials; is rarely cost free; and that diversity and dissent enhance openness, accountability, and fairness. The burden of proof is therefore on proponents of a consensus-only standard for bioethics commissions to demonstrate that a drive for consensus furthers sound decision-making by government officials more than it sets back openness and accountability to a diverse public.

Advisory Committees↗
PubMed1997

A consensus approach to diagnosing coronary artery disease based on clinical and exercise test data.

OBJECTIVE: To demonstrate that a consensus approach for combining prediction equations based on clinical and exercise test variables derived from different populations can stratify patients referred for possible coronary artery disease (CAD) into low-, intermediate-, and high-risk groups. DESIGN: Retrospective analysis of consecutive patients with complete data from exercise testing and coronary angiography referred for evaluation of possible CAD. After derivation of a logistic equation in our own training set of patients, this equation, along with two other equations developed independently by other investigators, was validated in a test set. The validation strategy for the consensus approach included the following: (1) calculation of probability scores for each patient using each logistic equation independently; (2) determination of probability thresholds in the training set to divide the patients into three groups-low risk (prevalence CAD <5%), intermediate risk (5 to 70%), and high risk (>70% prevalence of CAD); (3) using agreement among at least two of three of the prediction equations to generate "consensus" for each patient; and (4) application of the consensus approach thresholds to the test set of patients. SETTINGS: Two university-affiliated Veteran's Affairs medical centers. PATIENTS: We studied 718 consecutive men between 1985 and 1995 who had coronary angiography within 3 months of an exercise treadmill test for suspected CAD. The population was randomly divided into a training set of 429 patients and a test set of 289 patients. Patients with previous myocardial infarction or coronary artery bypass surgery, valvular heart disease, left bundle branch block, or any Q waves present on their resting ECG were excluded from the study. MEASUREMENTS: Recording of clinical and exercise test data along with visual interpretation of the ECG recordings on standardized forms and abstraction of visually interpreted angiographic data from clinical catheterization reports. RESULTS: We demonstrated that by using simple clinical and exercise test variables, we could improve on the standard use of ECG criteria during exercise testing for diagnosing CAD. Using the consensus approach divided the test set into populations with low, intermediate, and high risk for CAD. Since the patients in the intermediate group would be sent for further testing and would eventually be correctly classified, the sensitivity of the consensus approach is 94% and the specificity is 92%. The consensus approach controls for varying disease prevalence, missing data, inconsistency in variable definition, and varying angiographic criterion for stenosis severity. The percent of correct diagnoses increased from the 67% for standard exercise ECG analysis and from the 80% for multivariable predictive equations alone to >90% correct diagnoses for the consensus approach. CONCLUSIONS: The consensus approach has made population-specific logistic regression equations portable to other populations. Excellent diagnostic characteristics can be obtained using simple data and measurements. The consensus approach is best applied utilizing a programmable calculator or a computer program to simplify the process of calculating the probability of CAD using the three equations.

Coronary Angiography↗
PubMed2005

Identifying performance indicators for family practice: assessing levels of consensus.

OBJECTIVE: To identify performance indicators for family practice that focus on organizational structures and clinical processes of care, to review evidence linking indicators to patient outcomes, to have providers select indicators they consider important for performance assessment, and to obtain provider views on challenges to developing a performance assessment system. DESIGN: Review of published and unpublished literature and contact with international experts resulted in a list of 131 structure and process indicators and associated evidence. This information was used in a two-round modified Delphi consensus process, which was followed by interviews with each of the 12 consensus panel members. SETTING: Ontario family practices. PARTICIPANTS: Eleven family physicians and one nurse practitioner from Ontario. MAIN OUTCOME MEASURES: Survey package with 131 indicators and associated evidence was mailed to panel members who rated each of the indicators on a Likert scale from 1 (not at all important for performance assessment) to 9 (essential for performance assessment). Interviews were conducted with panel members to discuss indicator feasibility and data sources. Consensus score and median importance score for each indicator were main outcome measures; interviews identified barriers to performance assessment. RESULTS: Fifty-one indicators achieved high consensus, 19 moderate consensus, and 38 low consensus. Clinical indicators that reached a high level of consensus were generally supported by grade A or B recommendations and level I to III evidence. Clinical indicators that achieved moderate consensus often had fair support in the literature. Low consensus was mainly associated with fair or equivocal evidence. During follow-up interviews, consensus panel members voiced frustration with inconsistencies in the evidence and practice guidelines upon which indicators are often based, and with poor transfer of patient information between health care providers. Lack of detail in patient care documentation and inconsistent documentation were mentioned frequently as threats to data quality. CONCLUSION: Despite challenges to performance measurement noted by the panel, study results support the continued development, refinement, and testing of primary care performance indicators.

Consensus↗
PubMed2001

Consensus change, conflict, and relationship satisfaction in romantic relationships.

In this cross-sectional study of 92 romantic relationships, both the S. S. Hendrick (1988) Relationship Assessment Scale and a 16-item negative conflict scale were independently associated with the consensus items of the Short Marital Adjustment Test (H. J. Locke & K. M. Wallace, 1959), but not with change from initial to present consensus. However, consensus change was significantly correlated with relationship satisfaction and negative conflict in those reporting decreased consensus or no change but not increased consensus. Furthermore, relationship satisfaction was accounted for solely by negative conflict in the increased consensus group and by present consensus in the decreased consensus group. These results suggest that the association of relationship satisfaction with consensus and negative conflict may differ according to perceived consensus change.

Conflict, Psychological↗
PubMed1990

Mutational analysis of the consensus sequence of a replication origin from yeast chromosome III.

Yeast autonomously replicating sequence (ARS) elements contain an 11-base-pair core consensus sequence (5'-[A/T]TTTAT[A/G]TTT[A/T]-3') that is required for function. The contribution of each position within this sequence to ARS activity was tested by creating all possible single-base mutations within the core consensus sequence of ARS307 (formerly called the C2G1 ARS) and testing their effects on high-frequency transformation and on plasmid stability. Of the 33 mutations, 22 abolished ARS function as measured by high-frequency transformation, 7 caused more than twofold reductions in plasmid stability, and 4 had no effect on plasmid stability. Mutations that reduced or abolished ARS activity occurred at each position in the consensus sequence, demonstrating that each position of this sequence contributes to ARS function. Of the four mutations that had no effect on ARS activity, three created alternative perfect matches to the core consensus sequence, demonstrating that the alternate bases allowed by the consensus sequence are, indeed, interchangeable. In addition, a change from T to C at position 6 did not perturb wild-type efficiency. To test whether the essential region extends beyond the 11-base-pair consensus sequence, the effects on plasmid stability of point mutations one base 3' to the T-rich strand of the core consensus sequence (position 12) and deletion mutations that altered bases 5' to the T-rich strand of the core consensus sequence were examined. An A at position 12 or the removal of three T residues 5' to the core consensus sequence severely diminished ARS efficiency, showing that the region required for full ARS efficiency extends beyond the core consensus sequence in both directions.

Base Sequence↗