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[Consensus statement of an interdisciplinary group of French experts on modalities of diagnosis and medical treatment of Alzheimer's disease at a treatable stage].

A group of French expert met on the 7th and 8th of February 1998 in order to establish a consensus attitude for Alzheimer's disease diagnosis and treatment. Members were drawn from primary care, geriatrics, neurology and psychiatry. They used the consensus statement of the American Association for Geriatrics, the Alzheimer's Association and the American Geriatrics Society published in JAMA, in October 1997 as a source of data for further consideration. Alzheimer's disease in the most common etiology of dementia. Main clinical features are cognitive impairment and psycho-behavioral disorders. Diagnosis must be one of inclusion and not exclusion. It is based on interviews of informants and family members and office-based clinical assessment. After a physical examination, cognitive function must be evaluated using the Mini-Mental State Examination. A laboratory evaluation should include a complete blood cell count, blood chemistry and determination of thyroid-stimulating hormone. In addition, noncontrast computed tomography head scans are adequate in most cases. Available pharmacologic treatments are not curative but are given to improve quality of life and enhance cognition and behavior. Two cholinesterases inhibitors, tacrine and donepezil, are the only agents officially authorized for treatment of the cognitive impairment in Alzheimer's disease. Mood and behaviour disorder also have to be treated by both pharmacologic and nonpharmacologic strategies. Only pharmacologic treatments will be detailed here. The consensus statements established by this group of experts will be reevaluated each year, considering the new available data on Alzheimer's disease.

Aged↗

Prevention of chemotherapy- and radiotherapy-induced emesis: results of Perugia Consensus Conference. Antiemetic Subcommittee of the Multinational Association of Supportive Care in Cancer (MASCC).

BACKGROUND: The need to review and summarize the evidence concerning preventive treatment of cancer chemotherapy- and radiotherapy-induced emesis. DESIGN: After a survey among experts the Antiemetic Subcommittee of the MASCC planned and held a Consensus Conference on antiemetic therapy. Recommendations were provided on the basis of scientific confidence and the level of consensus among the participating experts. RESULTS AND CONCLUSIONS: A 5-HT3 antagonist plus dexamethasone is the regimen of choice in the prevention of acute emesis induced by single high, and low and repeated doses of cisplatin, and of acute emesis induced by moderately-high emetogenic chemotherapy (i.e., cyclophosphamide, doxorubicin, epirubicin, carboplatin, used alone or in combination) in both adults and children. In the prevention of delayed emesis induced by cisplatin the most efficacious choice is a combination of dexamethasone with either metoclopramide or a 5-HT3 antagonist, while in moderately-high emetogenic chemotherapy dexamethasone alone or a 5-HT3 antagonist alone or their combination should be used. No evidence or consensus exists regarding antiemetic treatment for patients receiving low emetogenic chemotherapy, or about the optimal rescue treatment for patients failing antiemetic prophylaxis. The best treatment for anticipatory emesis is the best possible control of acute and delayed emesis. Although 5-HT3 antagonists have some efficacy in the prevention of acute emesis induced by high-dose chemotherapy, more studies should be carried out to determine the best preventive treatment. For prevention of acute emesis induced by highly/moderately emetogenic radiotherapy (TBI, irradiation of the upper part of the abdomen or of the whole abdomen/radiotherapy of the thorax, pelvis and lower body half) a 5-HT3 antagonist is the best choice.

Adult↗

Need for consensus development in prehospital emergency medicine: effect of an expert panel approach.

The objective of this study was to look at the need for consensus development in prehospital emergency medicine, and to determine the effect of an expert panel approach. The study took place in Euregio Scheldemond, comprising Sealand Flanders, The Netherlands, and Belgian Flanders, Belgium. Firstly, seven experts rated in organized mailings 153 (random selection out of 505) existing cases of acute or critically ill patients, situated in Dutch Sealand-Flanders. Experts were asked to decide whether assistance from neighbouring Belgian Flanders, consisting of a trauma team with or without the use of a highly equipped ambulance/helicopter, was needed or not in Dutch Sealand-Flanders, at: (1) the site of the incident, and (2) for transport to the hospital. They also had to decide on: (3) the required type of destination hospital (Belgian centre/university, versus Dutch regional). In a subsequent meeting using a modified nominal group technique 23 'worst' cases from the postal rounds with the lowest agreement were discussed and re-rated. We present a framework for the consensus measurement and development procedures. Agreement among experts was poor with multiple rater (Fleiss) kappa values for all 153 postal cases for the first, second and third decisions of 0.32, 0.08 and 0.45, respectively. After group discussions of the 23 'worst' postal cases, kappa values increased significantly and substantially; for the first, second and third decisions from 0.08 to 0.51, from -0.08 to 0.39 and from 0.16 to 0.62, respectively (all p < 0.001). Agreement increased significantly for medical cases, but not for trauma cases. It is concluded that consensus development for prehospital emergency medicine is needed. An expert panel approach seems fruitful in achieving more agreement, which forms a basis for guideline or protocol development.

Belgium↗

National Depressive and Manic-Depressive Association consensus statement on the use of placebo in clinical trials of mood disorders.

A consensus conference on the use of placebo in mood disorder studies consisted of expert presentations on bioethics, biostatistics, unipolar depression, and bipolar disorder. Work groups considered evidence and presented statements to the group. Although it was not possible to write a document for which there was complete agreement on all issues, the final document incorporated input from all authors. There was consensus that placebo has a definite role in mood disorder studies. Findings of equivalence between a new drug and standard treatment in active control studies is not evidence of efficacy unless the new drug is also significantly more effective than placebo. Add-on studies in which patients are randomized to standard therapy plus the investigational drug or standard therapy plus placebo are especially indicated for high-risk patients. Mood disorders in elderly and pediatric patients are understudied, and properly designed trials are urgently needed. Research is needed on the ethical conduct of studies to limit risks of medication-free intervals and facilitate poststudy treatment. Patients must fully understand the risks and lack of individualized treatment involved in research.

Bipolar Disorder↗

Antenatal corticosteroids revisited: repeat courses - National Institutes of Health Consensus Development Conference Statement, August 17-18, 2000.

OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data regarding the benefits and risks of repeat courses of antenatal corticosteroids. PARTICIPANTS: A non-Federal, non-advocate, 16-member panel representing the fields of obstetrics and gynecology, pediatrics, maternal and fetal medicine, neonatology, medical ethics, community health, pharmacology, psychology, and reproductive biology. In addition, 13 experts in these same fields presented data to the panel and to a conference audience of approximately 200. EVIDENCE: The literature was searched using MEDLINE and an extensive bibliography of references was provided to the panel. Experts prepared abstracts of their conference presentations with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience. CONSENSUS PROCESS: The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in open forum and the scientific literature. The panel composed a draft statement that was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately following its release at the conference and was updated with the panel's final revisions. CONCLUSIONS: The collective international data continue to support unequivocally the use and efficacy of a single course of antenatal corticosteroids using the dosage and interval of administration specified in the 1994 Consensus Development Conference report. The current benefit and risk data are insufficient to support routine use of repeat or rescue courses of antenatal corticosteroids in clinical practice. Clinical trials are in progress to assess potential benefits and risks of various regimens of repeat courses. Until data establish a favorable benefit-to-risk ratio, repeat courses of antenatal corticosteroids, including rescue therapy, should be reserved for patients enrolled in clinical trials.

Adrenal Cortex Hormones↗

Analytic sensitivities of hybrid-capture, consensus and type-specific polymerase chain reactions for the detection of human papillomavirus type 16 DNA.

Human papillomavirus type 16 (HPV-16) DNA is detected commonly in cervical carcinomas; in this study, we have determined the analytical sensitivities of Hybrid Capture, HPV-consensus PCR, and three HPV-16-specific polymerase chain reactions (PCRs) for the detection of HPV-16 DNA. Samples investigated included a cervical cancer cell line, cervical scrapes from 20 patients attending colposcopy clinics, and buccal swabs from eight immunosuppressed children. HPV-16 E7 and E5-nested PCRs [Cavuslu et al. (1996): Journal of Virological Methods, in press] produced positive signals from samples containing fewer than ten HPV-16 genomes per reaction. HPV-consensus PCR [Manos et al. (1989): Cancer Cells 7:209-214] and HPV-16 PCR using primers of van den Brule et al. [(1990): Journal of Clinical Microbiology 25:2739-2743] were of intermediate sensitivity (i.e., produced positive signals from samples containing 250 and 2,500 HPV-16 genoms/reaction, respectively) and Hybrid Capture could detect just 50,000 HPV-16 genomes/reaction. Highest rates of positivity for cervical samples were detected with HPV-16 E7 or E5-nested PCRs [50% (10 of 20 samples) and 60% (12 of 20 samples) positive, respectively], intermediate rates with HPV-consensus PCR and PCRs using the primers of van den Brule et al. [both 35% (7 of 20 samples)], and lowest rates of positivity [25% (5 of 20 samples)] with Hybrid Capture. None of eight buccal swab samples from immunosuppressed children were positive by Hybrid Capture, yet three (37.5%) were positive by HPV-16 E5-nested PCR. These data indicate that HPV-16 type-specific PCRs should be used for the investigation of specimens that may contain low amounts of HPV-16 DNA.

Adolescent↗

Conformational studies of an undecapeptide reproducing the consensus sequence around the cleavage site of the RXVRG endoprotease from Xenopus laevis skin.

Two synthetic fragments, corresponding to the 4-9 and 4-14 sequences of a tetradecapeptide used as a model to test the RXVRG-endoprotease activity from Xenopus laevis skin, have been studied by two-dimensional nmr spectroscopies, correlated spectroscopy, and nuclear Overhauser effect (NOE) spectroscopy. Both peptides wore the 5-9 consensus sequence found in several hormonal precursors. The nmr data for the 4-9 hexapeptide did not indicate any particular organization, either in water or in dimethylsulfoxide (DMSO), whereas, the 4-14 undecapeptide, a substrate for the RXVRG endoprotease, showed, in DMSO solution, significant trends of structural organization involving the amino acids pertaining to the consensus domain. From variations of integrated NOE peaks with temperature, the apparent interproton correlation times tau c were estimated and the maxima observed with Val7, the central residue in the consensus sequence. A defined tertiary structure in that domain was also supported by medium- and long-range NOEs between Asp6 and Arg8, Glu4 and Gly9, and by the likely involvement of Arg8 and Gly9 NHs in intramolecular hydrogen bonds. Most of these observations could be rationalized by an equilibrium between a 5-8 beta-turn and a 9 > 4 H-bonded loop. The predominance of one rotamer for the C alpha-C beta bond was established in four residues. Finally, the average phi and psi angles were derived from two models taking, or not, into account variations in the correlation times along the sequence. This allowed us to discuss the artefacts generated by using an average correlation time through the whole molecule.

Amino Acid Sequence↗

How many raters? Toward the most reliable diagnostic consensus.

When faced with a decision whether or not to treat a patient, to enter or to withdraw a patient from a clinical trial, or any other such binary decision, based on diagnosis with unsatisfactory reliability, can a consensus diagnosis be used to improve reliability? If so, exactly how? That is the question I address here. I draw comparisons and contrasts between the known results with an interval consensus and those with a binary consensus and suggest tactics for use in a pilot study to answer the above questions.

Clinical Trials as Topic↗

Analysis of DNA sequences homologous with the ARS core consensus in Saccharomyces cerevisiae.

We have previously identified an autonomously replicating segment (ARS) near the 3' end of the histone H4 gene at the copy-I H3-H4 locus. We have now searched for additional autonomously replicating segments and sequences homologous with the ARS core consensus sequence near the copy-II histone H4 gene and both of the histone H3 genes. No new ARS elements were identified by functional cloning assays. However, several matches to the ARS core consensus element were found within the DNA sequences of the copy-I and copy-II genes. An exact match to the ARS core consensus was identified in the region downstream from the copy-I histone H3 gene and a set of sequences with weak homology was also located within the copy-II region. However, restriction fragments including these sequences did not demonstrate ARS activity on a plasmid in transformed cells.

Base Sequence↗

Rat beta 1-adrenergic receptor regulatory region containing consensus AP-2 elements recognizes novel transactivator proteins.

beta 1-Adrenergic receptors (beta1-ARs) serve as important regulators of central nervous system (CNS)-mediated behavior and several neural functions, including mood, memory, neuroendocrine control, and stimulation of autonomic function. Using beta 1-AR-luciferase reporter recombinants, we have previously determined that important beta 1-AR genetic elements controlling expression within the C6 glioma cell line are contained within the region -396 to -299, relative to the translational start site. By conducting progressive internal deletions of the rat beta 1-AR 5' flanking region and with the use of beta 1-AR-luciferase recombinants, we have verified that this region contains the primary beta 1-AR promoter and/or major regulatory elements. To begin the identification of protein factors involved in beta 1-AR transcriptional activity conferred by this beta 1-AR region and flanking sequences, we conducted electrophoretic mobility shift assays using defined beta 1-AR DNA subregion probes. One probe (GS-1), encompassing the region -396 to -367, was found to produce two major and two minor mobility shift complexes when bound to nuclear extracts from the beta 1-AR expresser C6 cell line. UV-crosslinking of DNA-protein complexes, coupled with DNase I digestion, indicated that this beta 1-AR region interacts with one major protein of approximately 117 kDa molecular weight and additional minor proteins. GS-1 DNA-protein complexes were observed using beta 1-AR expresser tissues in the CNS, including cortex, hippocampus, and olfactory bulb. No DNA-protein complexes were observed when using nuclear extracts from beta 1-AR nonexpresser tissues; in some cases, using L6 cells, previously characterized to express little or no beta1-ARs, a reduction in intensities of the DNA-protein complexes was observed. Competition experiments indicate that nuclear protein binds to one of two subregions within the GS-1 sequence that contain AP-2-like consensus elements. Recombinant AP-2 protein will bind to both the beta 1-AR GS-1 promoter fragment and commercially available AP-2 consensus element control probes. Interestingly, using antibody supershift and immunoblotting experiments, no supershifts were observed and the major 117-kDa protein was not immunoreactive to antibodies recognizing either AP-2 alpha or AP-2 beta. These results support our contention that this beta 1-AR regulatory region contains AP-2 consensus elements that recognize novel transactivator proteins.

Animals↗

European standards for antibiotic susceptibility testing: towards a theoretical consensus.

Six different systems for antimicrobial susceptibility testing are used in Europe (BSAC, DIN, SFM, SIR, NCCLS and WRG). Breakpoints defining susceptibility or resistance of bacteria to antimicrobial agents remain the subject of discussion. Nevertheless, it is possible to establish a theoretical consensus standard list of breakpoints such that more than 95% of the breakpoints proposed by the different systems differ from the consensus standard by no more than one dilution. In general, the BSAC and DIN systems recommend lower breakpoints, and the SFM and NCCLS systems higher breakpoints than the consensus standard. Two-thirds of the discrepancies are related to the breakpoints defining susceptibility. The breakpoint for susceptibility should reflect the intrinsic susceptibility of the isolate (absence of mechanisms of resistance), and the breakpoint for resistance the pharmacological potential of the drug. The scientific validation of breakpoints requires clinical verification.

Anti-Bacterial Agents↗

AIDS policy response in New Zealand: consensus in crisis.

Typically, Western governments have aimed to construct consensus over HIV/AIDS policy. The history of policy formation in New Zealand is examined, and is found to reflect the general pattern. There was a deliberate strategy designed to establish the broadest possible consensus. However, partly because of this breadth, the consensus was nevertheless fraught with contradiction and tension.

Acquired Immunodeficiency Syndrome↗

Citizen Involvement in Waste Management: An Application of The STOPER Model via an Informed Consensus Approach.

/ Waste management planning and implementation is not only a technological issue, but a social and political one as well. In this paper, we discuss a proposal to rethink certain aspects about waste management planning and implementation. Specifically, we present a framework whereby the ordinary citizen can proactively and constructively participate in the decision-making process. After briefly discussing the STOPER research team and certain limits inherent in current waste-management practices, we propose a mode of consultation known as the informed consensus approach. We assert that this approach incorporates social perceptions of key intervenors such as experts, decision makers, interest groups, and ordinary citizens and that this can enrich the decision-making process concerning complex environmental issues such as waste management. We focus our presentation on the results of the application of an informed consensus approach to waste management strategies in the municipality of Sherbrooke (Québec, Canada). KEY WORDS: Informed consensus; Public participation; Decision-making process; Social acceptability; Waste management

Journal Article↗

Guidelines for autologous blood and marrow stem cell transplantation in multiple sclerosis: a consensus report written on behalf of the European Group for Blood and Marrow Transplantation and the European Charcot Foundation. BMT-MS Study Group.

Recent reports suggest the possible beneficial effects of haemopoietic stem cell transplantation (HSCT) in autoimmune diseases such as multiple sclerosis (MS). The definition of the risk/benefit ratio for such a treatment is perceived as a major issue for the neurological community worldwide. The First Consensus Conference on Bone Marrow Transplantation in Patients with Multiple Sclerosis was held in Milan, Italy on 21 February 1998. Participants from 16 European, North American, and South American countries discussed the guidelines for performing HSCT in MS. This conference was organized in order to: (a) define criteria for patient selection; (b) define transplantation procedures to maximize efficacy of the treatment and minimize its toxicity; (c) standardize patient outcome evaluation; and (d) establish an international working group to evaluate the efficacy and safety of HSCT in MS and to study the immunological changes related to HSCT in MS patients. During the meeting in Milan agreement was reached on: (a) the preparation and distribution of a consensus report on HSCT in MS and (b) the design of an open trial for an initial assessment of the safety and efficacy of HSCT in MS. The consensus reached during the meeting and the design of the clinical trial are summarized in this contribution.

Blood Transfusion, Autologous↗

High rate of sustained response to consensus interferon plus ribavirin in chronic hepatitis C patients resistant to alpha-interferon and ribavirin: a pilot study.

BACKGROUND: The aim of this study was to evaluate an alternative treatment (consensus interferon plus ribavirin) for chronic hepatitis C patients resistant to combined therapy. METHODS: Fourteen patients previously resistant to interferon alpha plus ribavirin were consecutively assigned to receive 15 microg of consensus interferon plus ribavirin (1000 mg) daily for 4 weeks, and 9-15 microg every other day plus daily ribavirin for the following 44 weeks. Alanine aminotransferase and hepatitis C virus (HCV) RNA (Amplicor Monitor; Roche) levels were monitored during therapy and for 24 weeks after its completion. RESULTS: A rapid and marked decrease of HCV RNA viremia of more than 2 logs was observed in 10 (71%) of 14 patients at week 2 of treatment. At the end of therapy, 10 (71%) of 14 patients had undetectable HCV RNA. The end-of-treatment response rates were 6 of 9 (67%) patients for genotype 1 and 4 of 5 (80%) for other genotypes. Sustained response was observed in 4 (36%) of 11 patients who completed 24 weeks of follow-up. CONCLUSIONS: A marked and rapid decrease of viral load was observed during therapy with high doses of consensus interferon plus ribavirin in patients previously resistant to combined therapy, even in those infected with genotype 1. Of 11 patients who completed the post-treatment follow-up, 36% presented a sustained response.

Adult↗

Critical study of consensus analysis.

Consensus analysis has been proposed as a statistical method by which the efficacy of clinical and laboratory tests of inflammatory activity can be assessed. This technique is claimed to overcome the need for an external "gold standard" as a reference method; instead, the consensus of all tests is used as the gold standard. We have evaluated the reliability of consensus analysis using data collected from patients with Crohn's disease. Our results demonstrate that the technique depends strongly on the correlation structure underlying the set of measures of disease used for analysis. This observation was supported by a series of conventional cluster analyses of the same set of variables. Furthermore, slight modifications of the algorithm had profound effects on the final result. We conclude that for the evaluation of tests of inflammatory activity, an external reference method, albeit an imperfect one, remains indispensable.

Clinical Laboratory Techniques↗

A report of the consensus workshop panel on the treatment of brain metastases.

The consensus workshop on management of brain metastases focused on several broad issues concerning the patient with brain metastases. These issues included: What are the goals of treatment? Who should not be treated with radiation? What are the optimal treatment regimens? What are the areas of controversy where future investigations may be useful? The brain consensus panel attempted to develop guidelines for radiation oncologists through use of a decision tree format. Existing data to support management decisions, particularly those regarding radiation treatment, were reviewed. Data regarding cost of treatment as well as data regarding explicit quality of life measures were felt to be very important but were largely not available and therefore played little scientific role in the guideline development. Areas where controversy existed and where consensus could not be reached were identified.

Brain Neoplasms↗

The consensus sequence of ice nucleation proteins from Erwinia herbicola, Pseudomonas fluorescens and Pseudomonas syringae.

The consensus sequence of three bacterial ice nucleation proteins was determined by extrapolation from the nucleotide (nt) sequences of three ice nucleation-encoding genes, iceE (presented here), inaW and inaZ. The three proteins possess considerable similarity, so that a preferred amino acid is shown in most positions of the consensus. The corresponding genes show considerable divergence in the third nt positions of synonymous codons, suggesting that the proteins' conserved features have been maintained by selection. Therefore, the consensus sequence is likely to represent the components of primary structure most important to the ice nucleation function.

Amino Acid Sequence↗