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PubMed2000

An agenda for research into uterine artery embolization: results of an expert panel conference.

PURPOSE: To develop a research agenda for uterine artery embolization (UAE) for the treatment of symptomatic leiomyomata. MATERIALS AND METHODS: An expert panel was convened to examine data and develop a consensus for UAE research. Panelists reviewed data from articles about UAE and data on hysterectomy and myomectomy, which were abstracted into evidence tables. A modified Delphi process was used to rate the importance of measuring specific outcomes and a nominal group process was used to develop ideas for study designs. RESULTS: Panelists agreed that UAE studies would have to examine certain key measures. Outcomes identified as either "important to measure" or "essential to measure" were death, reoperation, operative injury, menorrhagia, premature menopause, recurrence of myomata, and satisfaction. The panel proposed four areas for research: randomized trial, prospective registry, disease-specific quality-of-life instrument, and cost analysis. CONCLUSIONS: Symptomatic uterine leiomyomata are a major health concern for women. New techniques that promise to provide symptom relief deserve careful consideration. Traditionally, surgical procedures have been poorly studied until after they have been widely used. If the process described in this article can guide the acquisition of knowledge in this field, it may serve as a model for evaluating other new technologies before they become widely adopted.

Costs and Cost Analysis↗

PubMed1998

Economic analysis of epilepsy treatment: a cost minimization analysis comparing carbamazepine and lamotrigine in the UK.

New anti-epileptic drugs differ from existing standard therapies not in their clinical efficacy, but in their side-effects profiles. To determine the relative economic value of these agents, one must compare drug costs, costs of resources employed in the management of adverse events, and costs associated with therapeutic switching. In this economic analysis, carbamazepine (CBZ) and lamotrigine (LTG) are evaluated in monotherapy treatment of partial and/or general tonic-clonic seizures in the UK. Adverse event and tolerability data are obtained from a published randomized controlled trial of CBZ vs. LTG. A Delphi panel of clinicians advised treatment patterns for adverse events. Cost data are obtained from public sources. Results show that CBZ therapy costs about one-third of LTG therapy (pound sterling 179 for CBZ vs. pound sterling 522 for LTG) even after the costs associated with the management of adverse events and therapeutic switching are considered.

Anticonvulsants↗

PubMed2006

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↗

PubMed2003

Clinically important differences in health-related quality of life for patients with asthma: an expert consensus panel report.

BACKGROUND: Standards for change in health-related quality of life (HRQoL) measures used among asthmatic patients have been established by considering only patient preferences to determine important differences and may not reflect an informed clinical evaluation of change. OBJECTIVE: To establish clinically important difference (CID) standards through the consensus of an expert physician panel for the Juniper Asthma Quality of Life Questionnaire (AQLQ) and Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36, version 2) when used to measure HRQoL among asthmatic patients. METHODS: We organized an 8-person panel of physicians familiar with measuring HRQoL among asthmatic patients with the AQLQ and the SF-36. This expert panel participated in 2 rounds of a modified Delphi process before attending an in-person consensus meeting to establish the CID standards for small, moderate, and large changes in the AQLQ and the SF-36. After the consensus meeting, the panel used an iterative improvement process to cooperatively complete their final report. RESULTS: The expert panel's thresholds for detecting CIDs in the domains of the AQLQ were much higher than previously established levels using patient-perceived changes. CIDs for asthma were also ascertained on the scales of the SF-36, version 2, which were markedly greater than previously cited cross-sectional differences between patient groups. CONCLUSIONS: The CID standards established by this expert panel elucidate a potential distinction between patient and physician perspectives of important HRQoL changes. The many stakeholders of HRQoL difference standards should consider this distinction when adopting standards to evaluate patient change.

Asthma↗

PubMed2000

Docking of sulfonamides to carbonic anhydrase II and IV.

Starting with a known active site of a protein and a database of compounds, one would like to quickly identify a few compounds that "dock" into the active site and obtain "good" binding free energies. The main goal of current automated docking procedures is to predict the "best" substrate-enzyme complex while other programs such as UHBD and DelPhi can be used to compute binding free energies. In this paper, we will focus on the application of docking methods and parameters to study substrate-enzyme interactions of a metalloenzyme system. Specifically, we report on the docking of sulfonamides to carbonic anhydrase II and IV, which are of interest due to their application in glaucoma therapy. Using a standard docking protocol, it is possible to correctly predict not only the orientation of inhibitors to a specific isozyme, but also determine the qualitative affinity for a group of inhibitor for an isozyme.

Algorithms↗

PubMed1997

External and internal electrostatic potentials of cholinesterase models.

The electrostatic potentials for the three-dimensional structures of cholinesterases from various species were calculated, using the Delphi algorithm, on the basis of the Poisson-Boltzmann equation. We used structures for Torpedo californica and mouse acetylcholinesterase, and built homology models of the human, Bungarus fasciatus, and Drosophila melanogaster acetylcholinesterases and human butyrylcholinesterase. All these structures reveal a negative external surface potential, in the area around the entrance to the active-site gorge, that becomes more negative as the rim of the gorge is approached. Moreover, in all cases, the potential becomes increasingly more negative along the central axis running down the gorge, and is largest at the base of the gorge, near the active site. Ten key acidic residues conserved in the sequence alignments of AChE from various species, both in the surface area near the entrance of the active-site gorge and at its base, appear to be primarily responsible for these potentials. The potentials are highly correlated among the structures examined, down to sequence identities as low as 35%. This indicates that they are a conserved property of the cholinesterase family, could serve to attract the positively charged substrate into and down the gorge to the active site, and may play other roles important for cholinesterase function.

Amino Acid Sequence↗

PubMed2001

EULAR recommendations for the management of knee osteoarthritis. Report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials.

UNLABELLED: A task force for the EULAR standing committee for clinical trials determined the methodological and logistical approach required for the development of evidence-based guidelines for treatment of knee osteoarthirits (OA). METHODS: The first stage was the selection of treatment modalities to be considered. The second stage comprised a search of the databases of all European-language publications. All of the relevant studies were quality scored. The third stage involved determination of key clinical propositions by expert consensus employing a Delphi approach. The final stage involved ranking of these propositions according to the available evidence. A second set of propositions relating to a future research agenda was determined by expert consensus. RESULTS: Seven hundred and forty-four studies presented outcome data of the effects of specific treatments on knee OA. Quantitative analysis of treatment effect was possible in only 61 studies. Recommendations for the management of knee OA based on currently available data and expert opinion are presented. Proposals for a future research agenda are highlighted. CONCLUSIONS: These are the first clinical guidelines on knee OA to combine an evidence-based approach and a consensus approach across a wide range of treatment modalities. It is apparent that only certain clinical propositions are supported by substantial research-based evidence. There is thus an urgent need for future well-designed trials to address key clinical questions.

Adult↗

PubMed1998

Multimedia system based on programmed instruction in medical genetics: construction and evaluation.

A multimedia system used as an auxiliary didactic tool for teaching medical genetics, HGEN, is based on non-linear programmed instruction and multimedia. HGEN was implemented in layers for PC compatible using MULTIMEDIA TOOLBOOK and DELPHI. It includes basic medical genetics concepts (inheritance patterns and cytogenetics) and it is based on multiple choice questions with images, diagrams and animations. The student-program interaction occurs by choosing an alternative in a question and receiving a specific answer as feedback and additional information. Links send the students to a glossary, to short descriptions of diseases used as examples, or to references for further studies. In order to evaluate the performance of the HGEN the authors used two questionnaires: (a) about the students' background in using computers; and (b) the system efficiency as a didactic tool, the software quality and user satisfaction. HGEN was used by 63 students from three medical schools and it was considered efficient as a learning tool (100%). Furthermore the implementation of a navigation map for frequencies analysis of followed path enable the study to detect structure and content inadequacies that could be correct for version 1.1 and proved to be an efficient tool to optimize a didactic software.

Computer-Assisted Instruction↗

PubMed2003

Adverse drug reaction risk factors in older outpatients.

BACKGROUND: Adverse drug reactions (ADRs) are common in older (age >or=65 years) outpatients (prevalence, 5%-35%), but there is no consensus on factors that put these patients at high risk for ADRs. Identifying a uniform set of risk factors would be helpful to develop risk models for ADRs for older outpatients and to implement targeted interventions for those patients at high risk for ADRs. OBJECTIVE: The aim of this study was to identify potential risk factors for ADRs in older outpatients through a survey of geriatric experts and to determine their prevalence. METHODS: A comprehensive literature search was conducted to find published articles on ADRs in older patients. Forty-four potential risk factors were identified through the literature search and 6 additional factors were suggested by the expert panel. Through a modified 2-round survey, based on the Delphi consensus method, of an expert panel of 5 physicians and 5 pharmacists, the probability that each of these 50 potential factors could contribute independently to placing an older outpatient at high risk for an ADR was rated on a 5-point Likert scale. After the survey responses were received, means and 95% Cls were calculated. Consensus was defined as a lower 95% confidence limit >or=4.0. Potential risk factors that reached consensus were then applied to a sample of older outpatients to determine their prevalence. RESULTS: After 2 rounds, the expert panel reached consensus on 21 factors, including 12 medication-related factors and 9 patient characteristics. The most prevalent medication-related risk factors were opioid analgesics; warfarin; non-acetylsalicylic acid, non-cyclooxygenase-2 nonsteroidal anti-inflammatory drugs; anticholinergics; and benzodiazepines. The most prevalent patient characteristics included polypharmacy, multiple chronic medical problems, prior ADR, and dementia. CONCLUSIONS: An expert panel was able to reach a consensus on potential risk factors that increase the risk for ADRs in older outpatients. Many risk factors were common in a sample of older outpatients. Future research is needed to determine the predictive validity of these risk factors for ADRs in older outpatients.

Aged↗

PubMed2005

PoInTree: a polar and interactive phylogenetic tree.

PoInTree (Polar and Interactive Tree) is an application that allows to build, visualize and customize phylogenetic trees in a polar interactive and highly flexible view. It takes as input a FASTA file or multiple alignment formats. Phylogenetic tree calculation is based on a sequence distance method and utilizes the Neighbor Joining (NJ) algorithm. It also allows displaying precalculated trees of the major protein families based on Pfam classification. In PoInTree, nodes can be dynamically opened and closed and distances between genes are graphically represented. Tree root can be centered on a selected leaf. Text search mechanism, color-coding and labeling display are integrated. The visualizer can be connected to an Oracle database containing information on sequences and other biological data, helping to guide their interpretation within a given protein family across multiple species. The application is written in Borland Delphi and based on VCL Teechart Pro 6 graphical component (Steema software).

Algorithms↗

PubMed1977

Pholeter anterouterus Fischthal & Nasir, 1974 (Digenea: Opisthorchiidae) redescribed, together with remarks on the genera Pholeter Odhner, 1914 and Phocitrema Goto & Ozaki, 1930 and their relationship to the centrocestine heterophyids.

Photoleter anterouterus Fischthal & Nasir, 1974, from Pelecanus occidentalis Linnaeus and Pelecanus erythrorhynchos Gmelin from Florida, USA and the ventro-genital complexes of Photeleter gastrophilus (Kossack, 1910) from Delphinus delphis Linnaeus from Queensland, Australia and of Phocitrema fusiforme Goto & Ozaki, 1930 from Alopex lagopus (Linnaeus) and Phoca vitulina Linnaeus from Alaska are redescribed. The genus Photoleter Odhner, 1914 is emended and compared with Phocitrema Goto & Ozaki, 1930 and both genera are compared with members of, and as a result transferred from the family Opisthorchiidae Looss, 1899 to, the subfamily Centrocestinae Looss, 1899, family Heterophyidae Odhner, 1914.

Animals↗

PubMed1985

Priorities for research on mental health in primary care settings.

A Delphi study was conducted with a multi-disciplinary group of experts attending a conference on mental illness in primary care settings. Respondents' priorities for research which could maximize benefits for service developments in this field were elicited by asking them to distribute hypothetical annual research budgets among (a) 6 mental health priority areas, and (b) 7 subjects 'needing' investigation within the primary care priority area. The respondents' three top-ranked priority areas for research were: (1) primary care; (2) the elderly mentally ill; and (3) chronically disabling mental illness. Their three top-ranked subjects for investigation within the primary care priority area were: (1) the effectiveness of treatment measures; (2) the problems of mental health presenting to primary care services; and (3) the training requirements for family doctors in psychiatric skills. The results are discussed with reference to the method used and to the economic concepts of programme budgeting and marginal analysis.

Adult↗

PubMed2000

Impact of quality items on study outcome. Treatments in acute lateral ankle sprains.

OBJECTIVE: This study investigates the influence of different aspects of methodologic quality on the conclusions of a systematic review concerning treatments of acute lateral ankle sprain. METHOD: A data set of a systematic review of 44 trials was used, of which 22 trials could be included in this study. Quality assessment of the individual studies was performed using the Delphi list. We calculated effect sizes of the main outcome measure in each study in order to evaluate the relationship between overall quality scores and outcome. Next, we investigated the impact of design attributes on pooled effect sizes by subgroup analysis. RESULTS: The quality of most studies (82%) was low; only 4 of 22 trials were of high quality. Studies with proper randomization and blinding procedure produce a slightly higher (not statistically significant) effect estimate compared to the other studies. CONCLUSION: Previous research has suggested that methodologically poorly designed studies tend to over-estimate the effect estimate. Our study does not confirm these conclusions.

Ankle Injuries↗

PubMed2006

A low cost decision support tool for the diagnosis of endemic bovine infectious diseases in the mixed crop-livestock production system of sub-Saharan Africa.

Diagnosis and treatment of endemic infectious disease is crucial for productivity of cattle in rural sub-Saharan Africa, but shortages of trained veterinary professionals necessitate support for less well-trained cadres of animal health worker. A Delphi survey of veterinary experts provided quantitative information on key clinical signs associated with eight endemic bovine diseases, then heuristics and dendrogram analysis identified a reduced sign set to be incorporated in a diagnostic decision support tool implemented as a simple colour-banded card. One hundred and seventy disease-sign questionnaire returns were obtained from 32 veterinary research scientists and 14 veterinary practitioners. Preliminary validation of the decision support tool for 16 prototypical cases resulted in 'correct' diagnosis over 90% of the time. The card potentially serves as a training aid and aide-mémoire, and could improve the diagnostic competence of animal healthcare providers.

Africa South of the Sahara↗

PubMed1993

Contribution of long-range electrostatic interactions to the stabilization of the catalytic transition state of the serine protease subtilisin BPN'.

The possible role of long-range electrostatic interactions on the catalytic activity of the serine protease subtilisin BPN' is investigated using protein engineering techniques. Charged residues on the surface of the enzyme some 13-15 A from the active site were mutated to either neutral or oppositely charged residues. The effect of these mutations on the stability of a complex formed between subtilisin BPN' and Z-Ala-Ala-Pro-Phe-trifluoromethyl ketone, a transition-state inhibitor of the enzyme, was measured. The values of Ki for the complex between the trifluoromethyl ketone and wild-type and mutant subtilisins were used to study the possible contribution of long-range electrostatics in stabilizing the charge distribution in the complex and thus, by analogy, on the transition state of hydrolysis for subtilisin BPN'. Measurement of kon, koff, and Ki for the inhibition of wild-type and mutant subtilisins showed that charged mutations distant from the active site can affect koff and Ki but have little effect on kon. The experimental results show that there is a small, 0.10-0.46 kcal mol-1, but significant contribution to the binding energy from distant surface charges, at low ionic strength. The experimental results were compared to theoretical results, calculated using the DelPhi program for different charge distributions in the complex. The experimental results were found to be most consistent with a complex in which an ion pair is formed between the protonated active site histidine and the ionized oxyanion. Both experimental and theoretical results suggest that long-range electrostatic interactions do play a role in stabilizing the transition-state complex formed between enzyme and inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacillus↗

PubMed1977

The complete amino acid sequence of the major component myoglobin from the arctic minke whale, Balaenoptera acutorostrata.

The complete primary structure of the major component myoglobin from the Arctic minke whale, Balaenoptera acutorostrata, was determined by specific cleavage of the protein to obtain large peptides which are readily degraded by the automatic sequencer. Over 80% of the amino acid sequence was established from the three peptides resulting from the cleavage of the apomyoglobin at the two methionine residues with cyanogen bromide along with the four peptides resulting from the cleavage of the methylacetimidated apomyoglobin at the three arginine residues with trypsin. The further digestion of the central cyanogen bromide peptide with trypsin and S. aureus strain V8 protease enabled the determining of the remainder of the covalent structure. This myoglobin differs from that of the dwarf sperm whale, Kogia simus, at 16 positions, and the common dolphin, Delphinus delphis, at 14 positions, from that of the common porpoise, Phocaena phocaena, and the bottlenosed dolphin, Tursiops truncatus at 13 positions, from that of the Amazon River dolphin, Inia geoffrensis, at 10 positions, and from that of California gray whale, Eschrichtius gibbosus, at 3 positions- All of the substitutions observed in this sequence fit easily into the three-dimensional structure of the sperm whale myoglobin.

Amino Acid Sequence↗

PubMed1976

Complete primary structure of the major component myoglobin of California gray whale (Eschrichtius gibbosus).

The complete primary structure of the major component myoglobin from the California gray whale, Eschrichtius gibbosus, was determined by specific cleavage of the protein to obtain large peptides for degradation by the automatic sequenator. Cleavage at the two methionine residues of the apomyoglobin with cyanogen bromide and at the three arginine residues of the methyl acetimidated protein with trypsin resulted in three and four easily separable peptides, respectively, which when sequenced accounted for 85% of the primary structure. The remainder of the covalent structure was obtained by further digestion of the central cyanogen bromide peptide with trypsin and S. aureus strain V8 protease. This protein differs from that of the sperm whale, Physeter catodon, at 12 positions, from that of the common porpoise, Phocoena phocoena, and the Black Sea dolphin, Delphinus delphis, at 14 positions, and from that of the Amazon River dolphin, Inia geoffrensis, at 7 positions. All substitutions observed in this sequence fit easily into the tertiary structure of sperm whale myoglobin.

Amino Acid Sequence↗

PubMed1976

Complete amino acid sequence of the myoglobin from the Atlantic bottlenosed dolphin, Tursiops truncatus.

The complete amino acid sequence of the major component myoglobin from the Atlantic bottlenosed dolphin, Tursiops truncatus, was determined by specific cleavage of the protein to obtain large peptides that are readily degraded by the automatic sequencer. Three easily separable peptides were obtained by cleaving the protein with cyanogen bromide at the 2 methionine residues and 4 peptides were obtained by cleaving the methyl acetimidated protein with trypsin at the 3 arginine residues. By subjecting 4 of these peptides and the apomyoglobin to automatic Edman degradation, over 80% of the covalent structure of the protein was obtained. The remainder of the primary structure was determined by further digestion of the central cyanogen bromide peptide with trypsin and staphylococcal protease. This myoglobin differs from that of the sperm whale, Physter catodon, at 15 positions, from that of the California gray whale, Eschrichtius gibbosus, at 14 positions, from that of the common porpoise, Phocoena phocoena, at 6 positions, and from the myoglobin of the Black Sea dolphin, Delphinus delphis and the Amazon River dolphin, Inia goeffrensis, at 5 and 7 positions, respecitvely. All substitutions observed in this sequence fit easily into the tertiary structure of sperm whale myoglobin.

Amino Acid Sequence↗