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Consensus guidelines for radiation therapy of benign diseases: a multicenter approach in Germany.

PURPOSE: To overcome the lack of written guidelines for radiation therapy (RT) of benign diseases, the German Working Group on Radiotherapy of Benign Diseases initiated a consensus process in 1999 to warrant continuous quality assurance and outcome research in this field. METHODS: An expert panel was convened to define key issues and develop written guidelines for RT of benign diseases. Pertinent information and data from published literature were reviewed, and data of most importance were identified. In addition, a patterns of care study was conducted to obtain a nationwide survey on the current status and treatment standards. RESULTS: From the data gathered, the expert panel prepared a first consensus statement that was open to propositions and comments from all participating institutions. After completion of the multicenter discussion, a final written consensus statement was compiled, discussed, and finally agreed on during a national conference of radiation therapists. For each individual nonmalignant disease, the accepted RT concepts were documented. Finally, specific evaluation tools and recommendations for follow-up examinations were defined. CONCLUSIONS: For the first time, written consensus guidelines for RT of nonmalignant diseases have been developed by the interaction of all institutions involved. These guidelines may serve as a starting point for quality assessment, prospective clinical trials, and outcome research.

Germany↗

Generality of a functional initiator consensus sequence.

Transcriptional initiator (Inr) elements, like TATA boxes, are found in the core promoters of many eukaryotic protein-coding genes. To facilitate the dissection of transcription initiation mechanisms, and to identify Inr elements within known and newly-discovered genes, the precise DNA sequence requirements for Inr activity must be defined. Previously, we reported a preliminary Inr consensus sequence based on an extensive mutant analysis carried out in HeLa cell extracts. This analysis was limited, however, because it was performed only with an in vitro transcription assay and with the mutants in only one promoter context. In this study, we have assessed the general validity of the functional Inr consensus sequence by analyzing a selected set of mutants in additional promoter contexts and with both in vivo and in vitro assays. In addition, we analyzed the evolutionary conservation of the Inr consensus sequence by determining the sequence requirements for Inr function in Drosophila embryo extracts. The results demonstrate the generality and strict conservation among vertebrates and invertebrates of the Inr consensus sequence, Py Py A+1 N T/A Py Py.

Animals↗

Interpreting quality-of-life data: methods for community consensus in asthma.

BACKGROUND: Change in health-related quality of life (HRQoL) is an important outcome in asthma treatment. Patient and provider consensus on how to determine thresholds for identifying important improvements and declines, however, has not been achieved. OBJECTIVE: To search for consensus in clinically important difference (CID) thresholds for HRQoL change from 3 points of view: (1) an expert panel of physicians who treat patients with asthma and measure the HRQoL of their patients, (2) asthmatic patients, and (3) the primary care physicians (PCPs) of these asthmatic patients. METHODS: The expert panel used Delphi and consensus methods to agree on CID levels for the Asthma Quality of Life Questionnaire and the Medical Outcomes Study 36-Item Short-Form Health Survey, version 2.0. A total of 396 patients attending midwestern primary care clinic sites completed these interviews bimonthly for 1 year. The 46 PCPs treating these patients completed baseline assessments on each patient's asthma and then evaluated the change in each patient's condition at subsequent office visits during the next year. RESULTS: The patient-perceived estimates were consistent with results of previous studies but were notably lower than those derived from the expert panel and the PCPs. The Short-Form Health Survey generally did not provide sufficient sensitivity to detect important changes. CONCLUSIONS: Although consensus on the interpretation of change in HRQoL measures was not achieved, this evidence-based approach demonstrates the value of patient and physician perspectives and the need for improved dialogue and understanding to optimize the HRQoL of patients with asthma.

Adult↗

Format and conduct of consensus development conferences. Multi-nation comparison.

The consensus development conference method developed by the National Institutes of Health in the United States has been adopted and modified by a number of countries. Based on published articles and communication with representatives from each country, we examined whether the organization and conduct of these conferences in nine countries (United States, Canada, Denmark, Finland, the Netherlands, Norway, Sweden, Switzerland, and the United Kingdom) enhanced or detracted from achieving the stated conference goals and objectives. We conclude that improvements in the process by which consensus conferences are conducted may be warranted. More scientific methods for synthesizing literature, such as meta-analysis, should be used in developing inputs for the conference panel. Formalizing the decision-making processes through polling or other methods that allow for structured disagreement with parts of a consensus statement would potentially expand the range and type of issues that can be addressed in such conferences. Finally, countries should consider having the consensus statement written over a longer period of time than the traditional overnight session, which seems unlikely to promote clear thinking.

Consensus Statements as Topic↗

Evaluation of the consensus conference program in Sweden. Its impact on physicians.

The impact of consensus conferences on physicians was studied in 1985 for the first four conferences Sweden held in 1982-1985. For each conference a main target group was defined as hospital-based physicians in supervisory positions within relevant clinics. Data were collected through a postal survey of all 1,668 members of the four different target groups. The total response rate was 86%. Reported awareness of a particular consensus conference as well as professed knowledge of a single conference statement was high--roughly 90%--for all four conferences. The consensus statement evoked changes in clinical practice according to 7%-10% of the respondents and changes were proportionally higher for physicians in smaller hospitals. Most of the respondents (61%-83%) reported no change, claiming that the consensus statement reflected clinical practices established prior to the conference. The validity of self-reported data is discussed.

Consensus Statements as Topic↗

Stylistic variations in National Institutes of Health consensus statements, 1979-1983.

This paper describes a content analysis of the statements of 24 Consensus Development Conferences conducted by the Office of Medical Applications of Research (OMAR) of the National Institutes of Health in the years 1979-1983. The goal was to understand the potential influence of the consensus statements by identifying characteristics that might determine whether and how physicians become aware of their findings and adopt their recommendations. Three characteristics emerged, each suggestive of a different style of consensus statement: discursiveness, didacticism, and scholarliness. Variations in style among consensus statements may affect their acceptance by the medical profession.

Consensus Statements as Topic↗

Impact of perceived consensus on stereotypes about obese people: a new approach for reducing bias.

In 3 experiments, the authors tested the effect of perceived social consensus on attitudes toward obese people. Participants completed self-report measures of attitudes toward obese people prior to and after manipulated consensus feedback depicting attitudes of others. In Study 1 (N=60), participants decreased negative and increased positive stereotypes after learning that others held more favorable attitudes toward obese people. In Study 2 (N=55), participants improved attitudes when they learned about favorable attitudes of obese people from an in-group versus an out-group source. In Study 3 (N=200), a consensus approach was compared with other stigma reduction methods. Social consensus feedback influenced participants' attitudes and beliefs about causes of obesity. Providing information about the uncontrollable causes of obesity and supposed scientific prevalence of traits also improved attitudes.

Adolescent↗

Comparison of clinical treatment decisions with US National Institutes of Health consensus indications for lower third molar removal.

Treatment decisions about lower third molar surgery have important clinical and cost implications. Although indications for surgery have been the subject of a National Institutes of Health (NIH) consensus conference at which several unambiguous criteria were agreed, no prospective investigations have been carried out to compare clinic treatment decisions with these consensus criteria. Treatment decisions made by six Hospital Service oral surgeons were therefore evaluated for 72 consecutive patients (28 men, 44 women) aged 15-44 years (mean age 25 years), referred for lower third molar assessment. The presence of local disease; recurrent pericoronitis; caries not amenable to restorative measures; follicular cyst formation; internal/external resorption and periodontal disease was recorded by an independent observer immediately after treatment planning had been completed. Of the 139 third molars present, 55 were unerupted, 79 partially erupted and 5 fully erupted. Thirty patients had been scheduled for surgery under general anaesthesia (GA), 36 under local anaesthesia and six patients had not been scheduled for surgery. A total of 42 teeth, according to NIH consensus criteria, had no indications for removal, of which 27 had been scheduled for surgery. These excluded disease-free contralateral teeth that had been scheduled for removal under GA. When a single episode of pericoronitis was excluded as a valid indication, 39 teeth did not meet criteria for removal but had been scheduled for surgery. It was concluded that two-thirds of lower third molars not meeting NIH consensus criteria for surgery had been scheduled for removal. The reasons for this, which may include inappropriate criteria, require further research.

Adolescent↗

The first international consensus conference on continuous renal replacement therapy.

BACKGROUND: Management of acute renal failure (ARF) in the critically ill is extremely variable and there are no published standards for the provision of renal replacement therapy in this population. We sought to review the available evidence, make evidence-based practice recommendations, and delineate key questions for future study. METHODS: We undertook an evidence-based review of the literature on continuous renal replacement therapy (CRRT) using MEDLINE searches. We determined a list of key questions and convened a 2-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated practice guidelines and/or directions for future research. RESULTS: Of the 46 questions considered, we found consensus for 20. We found inadequate evidence for 21 questions and for the remaining five we found data but no consensus. Full versions of workgroup findings are available on the Internet at http://www.ADQI.net. CONCLUSIONS: Despite limited data, broad areas of consensus exist for use of CRRT and guideline development appears feasible. Equally broad areas of disagreement also exist and additional basic and applied research in acute renal failure is needed.

Acute Kidney Injury↗

[Consensus double reading of mammograms in private practice].

PURPOSE: To evaluate retrospectively the results of consensus double reading of mammograms in a private practice for a period of 1.5 years (November 2001 to March 2003). MATERIALS AND METHOD: Two independent experts with dedicated training read all mammograms on a weekly basis. All mammograms including sonographic examinations were evaluated independently and categorized using the BI-RADS classification. The achieved consensus included a possible recommendation for recall or therapy. A total of 3936 mammograms and 1912 sonography studies were evaluated. All cases with BI-RADS 4 and 5 categories were compared with the histologic results. For a period of three months, the acceptance of double reading including a delay of the final report by one week was tested with a questionnaire and informed consent sheet. RESULTS: BI-RADS categories 4 and 5 were found in 57 cases, with 41 consensus results by two independent readers and 26 carcinomas verified by histology. No consensus could be reached in 16 patients, of which 10 had a final histologic result, with 5 benign lesions and 5 carcinomas of less than 1 cm in diameter. Clinical symptoms or alterations were absent in all patients. The 5 carcinomas were discovered by the double reading procedure. The result of the questionnaire (695 questionnaires) showed a refusal rate of 0.7 %, with only 5 women refusing the opportunity of double reading their mammograms. CONCLUSION: Double reading of mammograms by independent experts is feasible, shows a measurable increase in quality and is accepted by almost all women.

Breast↗

Combined evidence-based literature analysis and consensus guidelines for stocking of emergency antidotes in the United States.

STUDY OBJECTIVE: To develop guidelines for the stocking of antidotes at hospitals that accept emergency admissions using combined evidence-based and consensus methods. METHODS: Study participants were 12 medical care providers from disciplines that are affected by insufficient stocking of emergency antidotes (clinical pharmacology, critical care, clinical pharmacy, emergency medicine, hospital pharmacy, internal medicine, managed care pharmacy, clinical toxicology, pediatrics, poison control centers, pulmonary medicine, regulatory medicine). Selection of individuals for the study panel was based on evidence of previous antidote research or perspective regarding the purchase and use of antidotes. The literature regarding each antidote was systematically amassed using pre-1966 literature files, current MEDLINE searches, the reference lists of major medical textbooks, and citations solicited from the consensus panel. Articles relevant to 4 defined core questions were included. These articles formed the basis of an evidence-based analysis performed by the principal investigator. After literature analysis, a literature summary and proposed guidelines for antidote stocking were submitted to the panel. Consensus was formed by electronic iterative presentation of alternatives to each panel member using a modified Delphi method. All panel members participated in 5 rounds of guideline analysis of 20 antidotes. RESULTS: Of the 20 antidotes, 16 antidotes were ultimately recommended for stocking (N -acetylcysteine, atropine, Crotalid snake antivenin, calcium gluconate and chloride, cyanide antidote kit, deferoxamine, digoxin immune Fab, dimercaprol, ethanol, fomepizole, glucagon, methylene blue, naloxone, pralidoxime, physostigmine, sodium bicarbonate), 2 were not recommended for stocking (black widow antivenin, ethylenediamine tetraacetic acid), and consensus could not be reached for 2 antidotes (flumazenil, physostigmine). CONCLUSION: These guidelines provide a tool to be used in revising or creating policies and procedures with regard to the stocking of antidotes in hospitals that accept emergency patients.

Antidotes↗

DNA affinity cleaving analysis of homeodomain-DNA interaction: identification of homeodomain consensus sites in genomic DNA.

We have incorporated the DNA-cleaving moiety o-phenanthroline-copper at amino acid 10 of the Msx-1 homeodomain, and we have analyzed site-specific DNA cleavage by the resulting Msx-1 derivative. We show that amino acid 10 of the Msx-1 homeodomain is close to the 5' end of the consensus DNA site 5'-(C/G)TAATTG-3' in the Msx-1-DNA complex. Our results indicate that the orientation of the Msx-1 homeodomain relative to DNA is analogous to the orientation of the engrailed and Antennapedia homeodomains. We show further that DNA affinity cleaving permits identification of consensus DNA sites for Msx-1 in kilobase DNA substrates. The specificity of the approach enabled us to identify an Msx-1 consensus DNA site within the transcriptional control region of the developmental regulatory gene Wnt-1. We propose that incorporation of o-phenanthroline-copper at amino acid 10 of a homeodomain may provide a generalizable strategy to determine the orientation of a homeodomain relative to DNA and to identify homeodomain consensus DNA sites in genomic DNA.

Animals↗

Identification of an UP element consensus sequence for bacterial promoters.

The UP element, a component of bacterial promoters located upstream of the -35 hexamer, increases transcription by interacting with the RNA polymerase alpha-subunit. By using a modification of the SELEX procedure for identification of protein-binding sites, we selected in vitro and subsequently screened in vivo for sequences that greatly increased promoter activity when situated upstream of the Escherichia coli rrnB P1 core promoter. A set of 31 of these upstream sequences increased transcription from 136- to 326-fold in vivo, considerably more than the natural rrnB P1 UP element, and was used to derive a consensus sequence: -59 nnAAA(A/T)(A/T)T(A/T)TTTTnnAAAAnnn -38. The most active selected sequence contained the derived consensus, displayed all of the properties of an UP element, and the interaction of this sequence with the alpha C-terminal domain was similar to that of previously characterized UP elements. The identification of the UP element consensus should facilitate a detailed understanding of the alpha-DNA interaction. Based on the evolutionary conservation of the residues in alpha responsible for interaction with UP elements, we suggest that the UP element consensus sequence should be applicable throughout eubacteria, should generally facilitate promoter prediction, and may be of use for biotechnological applications.

Base Sequence↗

Site-directed mutagenesis within an ectoplasmic ATPase consensus sequence abrogates the cell aggregating properties of the rat liver canalicular bile acid transporter/ecto-ATPase/cell CAM 105 and carcinoembryonic antigen.

Recent studies of the rat liver canalicular bile acid transporter/ecto-ATPase/cell CAM 105 (CBATP), a member of the carcinoembryonic antigen (CEA) supergene family, indicate that it is a multifunctional protein possessing bile acid efflux, ecto-ATPase, and intercellular aggregating properties. Cheung et al. (Cheung, P. H., Luo, W., Qiu, Y., Zhang, K. E., Millron, P., Lin, S. H. (1993) J. Biol. Chem. 268, 24303-24310) have shown that the amino-terminal Ig V-like domain of this protein is required for its aggregating properties, much like the homologous amino-terminal domain of CEA is required for its aggregating properties. The amino-terminal domains of both CBATP and CEA include a consensus ATPase sequence. Site-directed mutagenesis within this ATPase consensus sequence completely eliminates the ecto-ATPase activity of CBATP (Sippel, C. J., McCollum, M., Perlmutter, D. H. (1994) J. Biol. Chem. 269, 2820-2826). In this study we examined the possibility that it is this ATPase consensus sequence which is required for the cell aggregating properties of CBATP and CEA and whether there is a relationship between ATPase, aggregating, and bile acid efflux activities. For this we used a baculovirus vector to express in Sf9 cells wild type as well as mutant and chimeric CBATP and CEA molecules. The results indicate that Arg-98 in the ATPase consensus sequence of CBATP and the corresponding residue of CEA are essential for the aggregating properties of these molecules. Moreover Arg-98 is essential for CBATP to interact with itself, CEA to interact with itself, and CBATP to interact with CEA. However, the role of Arg-98 in aggregation is distinct from its role in ecto-ATPase activity and the aggregating properties cannot be attributed to a change in ATP metabolism in the pericellular milieu.

Adenosine Triphosphatases↗

Intronic enhancer activity of the eosinophil-derived neurotoxin (RNS2) and eosinophil cationic protein (RNS3) genes is mediated by an NFAT-1 consensus binding sequence.

The eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are both small, cationic ribonuclease toxins that are stored in and secreted by activated human eosinophilic leukocytes. We have previously shown that optimal expression of the EDN gene is dependent on an interaction between an intronic enhancer element or elements and the 5' promoter region. Here we present evidence demonstrating that the gene encoding ECP is regulated in an analogous fashion and that an intronic enhancer element functioning in both genes is a consensus binding sequence for the transcription factor NFAT-1. Our initial results demonstrate that one or more nuclear proteins isolated from human promyelocytic leukemia (HL-60) cells bind specifically at this consensus site (5'-GGAGAA-3') within the intron of the EDN gene and that disruption of this sequence reduced the characteristic 20-30-fold increase in reporter gene activity observed with the tandem EDN promoter/exon 1/intron construct to background levels. The NFAT-1 consensus site in the ECP gene differs from that found in the EDN gene by a single nucleotide (5'-GGAGAG-3'); the conversion of the 3' G to an A resulted in a further enhancement of the reporter gene activity supported by the ECP promoter/exon 1/intron construct. Interestingly, no "supershift" was observed in gel shift assays performed in the presence of anti-NFAT-1 antiserum, suggesting that a nuclear protein other than NFAT-1 may be acting at this consensus site.

Base Sequence↗

Multiple chemical sensitivity: a 1999 consensus.

Consensus criteria for the definition of multiple chemical sensitivity (MCS) were first identified in a 1989 multidisciplinary survey of 89 clinicians and researchers with extensive experience in, but widely differing views of, MCS. A decade later, their top 5 consensus criteria (i.e., defining MCS as [1] a chronic condition [2] with symptoms that recur reproducibly [3] in response to low levels of exposure [4] to multiple unrelated chemicals and [5] improve or resolve when incitants are removed) are still unrefuted in published literature. Along with a 6th criterion that we now propose adding (i.e., requiring that symptoms occur in multiple organ systems), these criteria are all commonly encompassed by research definitions of MCS. Nonetheless, their standardized use in clinical settings is still lacking, long overdue, and greatly needed--especially in light of government studies in the United States, United Kingdom, and Canada that revealed 2-4 times as many cases of chemical sensitivity among Gulf War veterans than undeployed controls. In addition, state health department surveys of civilians in New Mexico and California showed that 2-6%, respectively, already had been diagnosed with MCS and that 16% of the civilians reported an "unusual sensitivity" to common everyday chemicals. Given this high prevalence, as well as the 1994 consensus of the American Lung Association, American Medical Association, U.S. Environmental Protection Agency, and the U.S. Consumer Product Safety Commission that "complaints [of MCS] should not be dismissed as psychogenic, and a thorough workup is essential," we recommend that MCS be formally diagnosed--in addition to any other disorders that may be present--in all cases in which the 6 aforementioned consensus criteria are met and no single other organic disorder (e.g., mastocytosis) can account for all the signs and symptoms associated with chemical exposure. The millions of civilians and tens of thousands of Gulf War veterans who suffer from chemical sensitivity should not be kept waiting any longer for a standardized diagnosis while medical research continues to investigate the etiology of their signs and symptoms.

California↗

Two-dimensional 1H NMR study of a tetradecapeptide with the consensus sequence Arg5-Asp-Val-Arg-Gly9: structural effects of the outside substitution Ser12 by Ala12.

Conformation of a tetradecapeptide with a RXVRG consensus sequence, Arg5-Asp-Val-Arg-Gly9, found in several precursors of antibacterian peptides, was investigated in dimethylsulfoxide solution by proton NMR spectroscopy. Complete resonance assignments and conformational parameters were obtained through correlated (COSY) and nuclear Overhauser (NOESY) techniques. The 3J(alpha H, beta H) coupling constants and the intramolecular NOE, NH...beta H, were used to analyse the conformers around the C alpha-C beta bond and, in four cases, to obtain stereospecific assignments. Use of restraints derived from NOE connectivities and 3J(NH, alpha H) coupling constants allows the determination of a range of phi and psi dihedral angles for all the residues in the sequence. The present NMR results provide favourable evidence for the formation of two bends in the consensus sequence of the tetradecapeptide. The first one has most of the features of a Glu4-Val7 beta-turn (low temperature coefficient of the Val7NH chemical shift, Arg5 alpha H...Val7NH and Asp6NH...Val7NH NOE correlations). The second one exhibits only the Asp6 alpha H...Arg7NH and Val7NH...Arg8NH NOE interactions. These consensus sequence organizations proposed were confirmed by molecular modeling based on low potential energy structure on the [4-9] fragment with high agreement of NOE data. Overall, the substitution of Ser12 by Ala12 shifts the conformation of the hydrophobic moiety [10-14] towards a quite random coil structure in this fragment and strongly destabilizes the folded structures of the consensus domain where only one NH (Val7) is solvent-shielded opposed to three (Asp6 to Arg8) in the [Ser12] tetradecapeptide. These conformational changes could be related to the processing enzyme activities on these model oligopeptides.

Alanine↗

Solutions for engaging priority populations in HIV cure research: a hybrid Delphi consensus-building process.

BACKGROUND: To achieve consensus on barriers and strategies to improve the engagement of three priority populations - Black and Latino/a/x individuals, cisgender women, and transgender women in HIV cure research. METHODS: We assembled a panel of 54 experts assigned to six groups in a hybrid Delphi process: (1) HIV community members, (2) biomedical researchers, (3) medical providers, (4) funders and private industry members, (5) bioethicists and regulators, and (6) social scientists. Over 18 months, we conducted four iterative survey rounds and three group discussions to identify barriers and strategies to arrive at a consensus on how to engage these priority populations in HIV cure research. RESULTS: For Black and Latino/a/x populations, the panellists identified inadequate outreach and a lack of accessible educational information as primary barriers and emphasised community-driven engagement and partnerships with trusted leaders as key strategies. For cisgender women, logistical hurdles, caregiving responsibilities and time constraints were identified as major barriers, with flexible trial designs and equitable compensation proposed as solutions. For transgender women, the lack of transgender-focused research design, including misrepresentation and exclusion, was identified as a key barrier, while centring transgender-specific needs in study design achieved consensus as the most effective strategy. CONCLUSION: Among all four priority populations, investment in outreach, engagement along the research process, better integration of health needs with research, and enhanced incentives are not novel ideas, but remain obviously ignored in a way that has led to underrepresentation of people in HIV cure research, who carry the greatest burden of HIV in the U.S. SUMMARY: This paper uses a hybrid Delphi process to identify and reach consensus on key barriers and strategies to engage underrepresented groups: Black and Latino/a/x individuals, cisgender women, and transgender women in HIV cure research across the United States.

Humans↗