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Clinical manifestations correlated to the prevalence of autoantibodies in a large (n=321) cohort of patients with primary Sjögren's syndrome: a comparison of patients initially diagnosed according to the Copenhagen classification criteria with the American-European consensus criteria.

In this study we imposed the recently described American-European consensus criteria for primary Sjögren's syndrome (pSS) on a large cohort of patients originally classified according to the Copenhagen set of criteria. Of the 321 patients fulfilling the Copenhagen criteria, 205 conformed to the Consensus criteria. When comparing clinical manifestations and laboratory findings between the two groups defined by different standards we found only small variations. Thus, the consequence of using the Consensus criteria in daily clinical practice will lead to the exclusion of a considerable proportion of patients with classical features of pSS. The main reason for this discrepancy is probably the absolute requirement of a positive test for anti-Ro/La or a characteristic lymphocytic infiltration in the labial gland biopsy. The sensitivity and specificity of testing for autoantibodies to Ro-52, Ro-60, and La were calculated for each set of criteria. Antibodies to La but not to Ro-52 or Ro-60 were strongly correlated to internal organ (kidney, lung, liver) dysfunction in pSS (OR 6; 95% CI 3-12), p<0.0001. Although presence of ANA was slightly more prevalent among patients with internal organ involvement it did not reach statistical significance. The fine speckled ANA pattern was most often found followed by the homogeneous and centromere pattern. Individual ANA patterns did not correlate with any particular organ manifestation.

Autoantibodies↗

GERD 2004: issues from the past and a consensus for the future.

In the early 1900's, gastroesophageal reflux disease (GERD) was an almost unknown entity with less than 200 cases reported worldwide. Currently the disease is regarded as almost endemic with as much as 25% of the population in some countries exhibiting signs or symptoms of reflux. Early therapies directed at chemical neutralization (milk drip, antacids) were of modest effect and required constant administration for efficacy. The introduction of histamine 2 receptor antagonists in the 1970's dramatically improved the management of GERD, but was limited by problems of tachyphylaxis and adverse events. The advent of the PPI class of drugs revolutionized medical care of GERD, given their efficacy and safety profile. As a consequence, the surgical approach with its pronounced dependence on individual operator skill and its high morbidity and even mortality has fallen into disregard. Thus, modest surgical outcome results as compared to the efficacy of PPIs has led to the widespread recognition that pharmacological therapy for GERD represents the platinum standard of care and the current consensus is that the PPI class of drugs provide the safest and most effective form of therapy for GERD. Furthermore, it is apparent based on acid suppression, symptom relief and healing rates, that all PPIs are on a milligram for milligram basis similarly efficacious for the management of GERD. While a consensus exists in regard to the current management of GERD with PPIs there is little agreement as to the management of the associated mucosal metaplastic process. At this time there is inadequate understanding of the biological basis of the mucosal transformation and minimal information about the mechanistic regulation of this event and its perpetuation. A future consensus thus requires the identification of the appropriate tools to detect Barrett's early, identify the specific molecular markers associated with neoplastic transformation and establish a definitive therapeutic algorithm.

Barrett Esophagus↗

Interobserver agreement and consensus over the esthetic evaluation of conservative treatment for breast cancer.

Twenty-four experts from 13 different countries were asked to evaluate photographs taken of 60 women following conservative breast cancer treatment. The esthetic result of each case was classified as poor, fair, good or excellent. Agreement was evaluated using the kappa (k) and weighted kappa (wk) statistics, for all observers, male and female participants, those younger and older than 50 years, those seeing more than 250 cases a year, and those with previous publications in this area. Consensus was obtained by way of a modified Delphi approach, when more than 50% of participants provided the same classification. In a second round, consensual cases were disclosed and a revised opinion was asked in non-consensual ones. Agreement between all participants was fair (k=0.24, wk=0.37) and remained within the same range (k=0.20-0.31, wk=0.31-0.45) in the subgroups analyzed. First round consensus was obtained in 46 out of 60 cases (77%) and in the second round in 59 out of 60 cases (98%). Evaluation of the esthetic results of conservative treatment for breast cancer is only fairly reproducible when performed by experts working in different geographical areas. Consensus is obtainable if a relatively low threshold of agreement is considered acceptable.

Adult↗

Computation of semantic similarity within an ontology of breast pathology to assist inter-observer consensus.

Computer-assisted consensus in medical imaging involves automatic comparison of morphological abnormalities observed by physicians in images. We built an ontology of morphological abnormalities in breast pathology to assist inter-observer consensus. Concepts of morphological abnormalities extracted from existing terminologies, published grading systems and medical reports were organized in an taxonomic hierarchy and furthermore linked by the relation "is a diagnostic criterion of" according to diagnostic meaning. We implemented position-based, content-based and mixed semantic similarity measures between concepts in this ontology and compared the results with experts' judgment. The position-based similarity measure using both taxonomic and non-taxonomic relations performed as well as the other measures and was used for automatic comparison of morphological abnormalities within the IDEM computer-assisted consensus platform.

Breast↗

The rational use of albumin in patients with cirrhosis and ascites. A Delphi study for the attainment of a consensus on prescribing standards.

BACKGROUND: Ascites is one of the most frequent severe complications in patients with liver cirrhosis. The treatment of this chronic disease usually requires the prolonged use of albumin, frequently continued even after patients' discharge from the hospital. AIMS: Aim of the study was to define a consensus among Italian physicians with regard to the use of albumin in patients with decompensated cirrhosis and ascites. METHODS: The study adopted the Delphi technique to conduct the consensus activities. All controversial issues related to the use of albumin were identified by the experts' board and proposed to the 68 participating hepatology centres through two subsequent questionnaires. The questionnaires, returned by the specialists involved, were collected and the answers classified to verify the elements on which a consensus was reached. RESULTS: The home use of albumin can help to improve the patient's general conditions and well-being. About 77% of the experts involved considered likely that albumin administration could shorten hospital stays or could reduce the number of hospital admissions. The results of the study, along with a socioeconomic analysis, were presented to the Italian Drug Commission, which subsequently removed the specific hypoalbuminemia level as a prerequisite for having the drug reimbursed by the National Health Service. CONCLUSIONS: For an outpatient prescription, the hypoalbuminemia limit of 2.5 g/dl or less is not sufficient, while the decision whether to administer the drug requires the evaluation of patient's overall clinical conditions as an essential criterion for the prescription of a home treatment with albumin.

Albumins↗

Consensus scoring for protein-ligand interactions.

This article reviews the application of consensus scoring for cases when the target 3D structure is known. Comparing the performance of different methods is not a trivial task, and it appears that consensus scoring usually substantially improves virtual screening performance, contributing to better enrichments. It also seems to improve--albeit less dramatically--the prediction of bound conformations and poses. The prediction of binding energies is still rather inaccurate and although consensus scoring generally improves these predictions, more development is required before it can be used for this purpose in routine lead optimization.

Binding Sites↗

Alu's dimeric consensus sequence destabilizes its transcripts.

The effect that different regions of the Alu consensus sequence have upon the stability and accumulation of its RNA polymerase III (Pol III) directed transcripts was determined by transiently overexpressing Alu deletion and chimeric constructs in human 293 cells. Transcripts of the left Alu monomer are more stable than those of the full-length consensus sequence and any additional 3' sequence beyond the left monomer destabilizes the resulting transcript. Neither the middle A-rich region nor the 3' A-rich tail specifically affect the stability of Alu transcripts. However, the right monomer is inherently less stable than corresponding left monomer transcripts. Alu's dimeric structure and sequences peculiar to the right monomer each limit the stability and steady state accumulation of its transcripts. A host requirement to rapidly metabolize Alu RNA or restrict its abundance may have selected for these two features of the Alu consensus sequence.

Alu Elements↗

Defining research criteria to characterize medical necessity in emergency medical services: a consensus among experts at the Neely Conference.

OBJECTIVE: Researchers interested in ensuring appropriate use of emergency medical services (EMS) resources have attempted to define safe and effective protocols for triage either at the time of dispatch or after on-scene evaluation. Published work in this area is difficult to evaluate because protocols and outcome criteria vary from study to study. The goal of the Neely Conference was to bring together EMS experts to define a set of criteria to be used in research studies evaluating dispatch triage and field triage systems. METHODS: Thirty-one experts in EMS systems and research attended a day-long workshop to assess the current literature regarding dispatch triage and field triage, and make recommendations to standardize methods used to evaluate future triage protocols. Participants were surveyed during the workshop; consensus analysis techniques were used to determine if a formal consensus was reached. A Bayesian posterior probability of 0.99 was required to consider responses a "consensus." RESULTS: Participants considered current evidence regarding the usefulness of EMS triage criteria to be "weak." However, respondents agreed on a set of research criteria that could define the need for an EMS response and/or EMS transport. Field triage criteria were considered more plausible than dispatch criteria. Valid outcome criteria for assessing the effectiveness of triage protocols included ED assessment and the need for immediate surgery. Hospital admission, final diagnosis, and expert opinion were not considered adequate outcome measures. CONCLUSION: EMS experts agreed on a standard set of triage criteria and outcome measures for evaluating triage protocols supporting alternative forms of transport and care.

Ambulances↗

Recent developments in the way forward for alternative methods: formation of national consensus platforms in Europe.

Ecopa, the European Consensus Platform on 3R-Alternatives, is an international not-for-profit organization that wants to stimulate the development of 3R-alternatives, increase awareness among the public, scientists and regulatory bodies, and help their implementation into the different national legislations. This is done by networking and bringing together National Consensus Platforms on 3R-alternatives. Consensus means that all parties concerned are represented, namely, animal welfare, industry, academia, and governmental institutions. Actually, 14 Member State Platforms exist. Fully complying with the criteria, set by ecopa, are the platforms of Austria, Belgium, the Czech Republic, Finland, Germany, Italy, the Netherlands, Spain, Sweden, Switzerland, and the United Kingdom. Under development are the platforms of Denmark, Norway, and Poland. To reach its goals, ecopa uses conventional scientific tools such as workshops and meetings but it also makes scientific-political statements. A recent realization in particular is the involvement of ecopa in several European projects of the Sixth Framework Programme, either as coordinator, research partner, or board member.

Animal Testing Alternatives↗

Antigenicity and immunogenicity of HIV-1 consensus subtype B envelope glycoproteins.

"Centralized" (ancestral and consensus) HIV-1 envelope immunogens induce broadly cross-reactive T cell responses in laboratory animals; however, their potential to elicit cross-reactive neutralizing antibodies has not been fully explored. Here, we report the construction of a panel of consensus subtype B (ConB) envelopes and compare their biologic, antigenic, and immunogenic properties to those of two wild-type Env controls from individuals with early and acute HIV-1 infection. Glycoprotein expressed from full-length (gp160), uncleaved (gp160-UNC), truncated (gp145), and N-linked glycosylation site deleted (gp160-201N/S) versions of the ConB env gene were packaged into virions and, except for the fusion defective gp160-UNC, mediated infection via the CCR5 co-receptor. Pseudovirions containing ConB Envs were sensitive to neutralization by patient plasma and monoclonal antibodies, indicating the preservation of neutralizing epitopes found in contemporary subtype B viruses. When used as DNA vaccines in guinea pigs, ConB and wild-type env immunogens induced appreciable binding, but overall only low level neutralizing antibodies. However, all four ConB immunogens were significantly more potent than one wild-type vaccine at eliciting neutralizing antibodies against a panel of tier 1 and tier 2 viruses, and ConB gp145 and gp160 were significantly more potent than both wild-type vaccines at inducing neutralizing antibodies against tier 1 viruses. Thus, consensus subtype B env immunogens appear to be at least as good as, and in some instances better than, wild-type B env immunogens at inducing a neutralizing antibody response, and are amenable to further improvement by specific gene modifications.

AIDS Vaccines↗

Occupational prestige for registered nurses in the Asia-Pacific region: status consensus.

Occupational prestige for nurses may result in improved job satisfaction, enhanced abilities in health promotion activities, and autonomy in decision-making related to patient care. Regional consensus in the ascription of professional occupational status and consequent prestige, between health workers and within registered nurses, has been investigated within the Asia-Pacific region and other countries. Consensus for registered nurses and medical officers at the level of professional was supported for 66% of countries. Australia, although rapid and complete in its transition to degree level education, still reflects a paraprofessional status compared with the professional status of medical officers. Registered nurses from Thailand and the Philippines led the region in within-group consensus with 80% of registered nurses holding a degree as their minimum educational qualification. Findings highlight the need to promote professional status for all registered nurses within the Asia-Pacific region and outline areas for potential disjuncture between status and prestige achievement.

Asia↗

Structural characterization of recombinant consensus interferon-alpha.

Recombinant consensus interferon-alpha is derived from genetically modified Escherichia coli containing a synthetic gene constructed from a consensus of interferon sequences. The purified and biologically active protein has been subjected to detailed structural characterization including sequence determination and peptide isolation and identification. The homogeneous consensus interferon-alpha preparation contains two chromatographically indistinguishable homologous polypeptides with one containing an extra methionyl residue at the amino terminus. The delineated amino acid sequence of the protein is identical to that expected from the coding sequence of the gene. Correct oxidation of the molecule has been confirmed with two intramolecular disulfide linkages observed at Cys(1)-Cys(99) and Cys(29)-Cys(139).

Amino Acid Sequence↗

Day surgery--how much is possible? A Delphi consensus among surgeons.

Although day surgery (DS) has been performed for many years, it has only relatively recently become a popular and acceptable method of treating many common surgical conditions. With considerable pressure to maximise resource usage DS has been seized upon as a way of stretching scarce resources further. A review of the amount of DS undertaken within the West Midlands region revealed that the current workload showed considerable variation both between districts and between consultants. In an effort to gain clinical commitment to increasing generally the amount of DS undertaken, and obtaining more uniform coverage of DS across the region, a consensus conference was held. The two aims of the conference were to set targets as to the amount of DS considered feasible at a procedural level, and to seek clinicians' views as to the obstacles to developing the service. Targets for 43 procedures at one and/or five years were obtained by the use of a modified Delphi consensus. The groups showed a high level of consensus in the targets reached. A variety of obstacles were discussed. We have shown that it is possible to involve a large number of doctors in the decision-making/target-setting process by using a modified Delphi technique. It remains to be seen whether those targets are met in clinical practice. Surprisingly, obstacles to development were mainly concerned with management and personnel issues rather than capital investment.

Ambulatory Surgical Procedures↗

Cutaneous manifestations of Crohn's disease, its spectrum, and its pathogenesis: intracellular consensus bacterial 16S rRNA is associated with the gastrointestinal but not the cutaneous manifestations of Crohn's disease.

The classic pathology of skin disease discontinuous from the inflamed gastrointestinal (GI) tract in patients with Crohn's disease (CD) includes pyoderma gangrenosum (PG), erythema nodosum (EN), and so-called metastatic Crohn's disease. The purpose of this study was two-fold: First, we explored the full spectrum of cutaneous lesions associated with Crohn's disease, and second, we sought to explore a potential molecular basis of the skin lesions in patients with CD. In this regard, we analyzed skin and GI tract biopsies from affected patients for the consensus bacterial SrRNA to determine whether direct bacterial infection was associated with either condition. Formalin-fixed, paraffin-embedded sections were studied and correlated to clinical presentation and histories from 33 patients with CD. Consensus bacterial RNA sequences were analyzed using an RT in situ PCR assay on both skin biopsy and GI biopsy material. The GI tract material included biopsies from 3 patients who had skin lesions and from 7 patients in whom there were no known skin manifestations. There were 8 cases of neutrophilic dominant dermal infiltrates, including pyoderma gangrenosum, 6 cases of granuloma annulare/necrobiosis lipoidica-like lesions, 5 cases of sterile neutrophilic folliculitis, 5 cases of panniculitis, 4 cases of vasculitis, 2 cases of psoriasis, 2 cases of lichenoid and granulomatous inflammation, and 1 case of classic metastatic CD. Intracellular bacterial 16S rRNA was detected in 8 of 10 tissues of active CD in the GI tract, of which 3 of the cases tested were from patients who also developed skin lesions at some point in their clinical course; in contrast, none of the skin biopsies had detectable bacterial RNA. The dermatopathological manifestations of CD discontiguous from the involved GI tract mucosa have in common a vascular injury syndrome, typically with a prominent extravascular neutrophilic and/or histiocytic dermal infiltrate. In addition, this study, the first to document in situ intracellular consensus bacterial SrRNA in the GI tract in CD, suggests that hematogenous dissemination of viable microbes is not associated with the cutaneous manifestations of this disease. Bacteria do, however, appear to play a role in bowel lesions of patients with CD.

Adolescent↗

Ranking of laboratory tests by consensus analysis.

A new analytical technique (consensus analysis) was devised to assess the performance of laboratory tests that are commonly used to monitor the acute and chronic phases of inflammatory disease. On thirty-one tests carried out monthly for 7 months in seventeen patients with rheumatoid arthritis, the consensus analysis procedure ranked plasma viscosity and erythrocyte sedimentation rate in a tie for first place. Measurement of the acute-phase serum protein orosomucoid ranked third. Consensus analysis has the potential to reduce laboratory costs by identifying the most useful tests; it also promises to be helpful in the design of new laboratory tests that are more sensitive and specific.

Adult↗

[Management of erysipelas in French hospitals: a post-consensus conference study].

INTRODUCTION: A prospective hospital-based survey on the management of bacterial dermal-hypodermal infections was conducted before the consensus conference "How should Erysipelas-Necrotic Fasciitis be managed?". The results of the survey were circulated early in 2001. To assess the eventual impact of the guidelines from the conference on hospital practices with regard to erysipelas, we conducted a new prospective survey at the end of 2002. PATIENTS AND METHODS: The questionnaire used was identical to that of the 2001 survey. It collected, anonymously, data on the clinical characteristics, supplementary examinations conducted (bacteriology, imaging), initial treatment and outcome. The questionnaire was mailed to the departments of dermatology, internal and/or infectious diseases and intensive care that had replied to the first survey (n = 124). The patients eligible for inclusion were those hospitalized between 09/01/2002 and 11/30/2002. Statistical analysis compared the results with those of the preceding survey. RESULTS: The files of 245 patients were collected that came from 41 departments (15 from university hospitals, 23 from general hospitals and 3 from military hospitals) and 235 of whom had erysipelas. For those with erysipelas, the mean age was of 65 +/- 2.5 years, the M/F sex ratio was of 0.66 and the localization was the leg in 89.5 p. 100 of cases. A Doppler of the legs was performed in 33 p. 100 of cases. The initial antibiotherapy was penicillin G in 38 p. 100 of cases and pristinamycine in 18 p. 100 (others: 44 p. 100). The route of administration was initially intravenous in 73 p. 100 of cases. An anti-coagulant was associated in 60 p. 100. The outcome was favorable in 94 p. 100 of cases, with a mean duration of hospitalization of 11.2 +/- 1.2 days and antibiotics of 17.7 +/- 1.3 days. Dopplers and the blood cultures were performed more frequently than before the consensus conference, but no difference was found in the antibiotics or adjuvant therapies. DISCUSSION: The follow-up survey showed the stability of hospital practices concerning erysipelas, notably with regard to treatment. In contrast, the clear tendency in limiting the supplementary examinations is in agreement with the consensus conference.

Age of Onset↗

Heterogeneous nature of the genome of the ARILVAX yellow fever 17D vaccine revealed by consensus sequencing.

Consensus sequencing of the genome of the ARILVAX live attenuated yellow fever (YF) 17D vaccine was performed directly on reconstituted virus from a vial of the vaccine secondary seed (without plaque-purification or cloning of cDNA). The genome of ARILVAX was identical in organization and size (10,862 nucleotides (nt)) to other published YF 17D sequences. A total of 12 nt heterogeneities were detected indicating that the vaccine is a heterogeneous population. Some of these indicated the presence of quasispecies with residues not reported previously for other sequenced YF 17D strains. A number of nts clearly differed from some YF vaccine strain sequences but coincided with the others, which could be due to the use of consensus sequencing approach in this study. Most (but not all) of the heterogeneities and nt differences were silent (i.e. did not result in an amino acid change). The differences are inconsequential to safety and effectiveness of ARILVAX. Other YF 17D vaccines are undoubtedly also heterogeneous and need to be re-examined using the consensus approach.

5' Untranslated Regions↗

US EPA's IRIS pilot program: establishing IRIS as a centralized, peer-reviewed data base with agency consensus. Integrated Risk Information System.

The US EPA's Integrated Risk Information System (IRIS) contains Agency consensus scientific positions and quantitative values on cancer and noncancer health effects that may result from lifetime oral or inhalation exposure to specific chemical substances in the environment. Combined with specific exposure assessment information, the summary health information in IRIS may be used as a source in evaluating potential public health risks from environmental contaminants. IRIS is available to the public via EPA's Internet server at http://www.epa.gov/iris. Originally developed for internal EPA use, IRIS usage has broadened since being made publicly available in 1988 to include the private and public sectors nationally and internationally. Up to 1995, IRIS summaries were generated from within various EPA Offices and Regions and reviewed by Agency Workgroups, one for cancer and one for noncancer endpoints, before entry onto IRIS. In response to the increasing usage and recognition of IRIS and suggestions for improvement, an IRIS Pilot program was initiated in 1995. The purpose of the Pilot was 3-fold: To improve efficiency in getting information on to IRIS; to improve documentation for the positions reported in IRIS summaries, including applying new methodologies and guidance; and to improve opportunity for public input including external peer review. A new infrastructure was put in place, consisting of a cross-Agency team of 'Chemical Managers', a Pilot Program Manager, and a set of Agency 'Consensus Reviewers'. Cancer and noncancer assessments were prepared in an integrated fashion for Pilot chemical substances, documented in 'Toxicological Reviews' and derivative IRIS summaries. Public input was emphasized via an initial data call and rigorous external peer review. A final step was Agency-wide consensus review by senior staff scientists representing EPA's Offices and Regions. EPA's experience with the Pilot is forming the basis for designing operational aspects of the long-term IRIS program.

Benchmarking↗