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Biomedical subjects

R S Hayward

Publications and source records attributed to R S Hayward.

At least 19 recordsLinked to original sources

Practice guidelines. What are internists looking for?

To determine features of the presentation of clinical practice guidelines that may enhance their use by internists, we conducted a cross-sectional survey to which 1,513 (60%) of 2,513 eligible internists responded. Endorsements by respected colleagues and by major organizations were identified as very important by 72% and 69% of respondents, respectively. Respondents preferred short pamphlets and manuals summarizing a number of guidelines and felt that concise recommendations (86%), synopsis of supporting evidence (85%), and quantification of benefit (77%) were important in guideline presentation. We conclude that guideline developers should gain the endorsement of major organizations and present key aspects in brief, easily assimilated formats.

Attitude of Health Personnel

A Clinical Informatics Network (CLINT) to support the practice of evidence-based health care.

CLINT, which stands for Clinical Informatics NeTwork, is one of the clinical informatics initiatives in development at McMaster University's Health Information Research Unit. CLINT is a microcomputer-based system of over 60 workstations providing 24 hour availability of a set of clinical information resources to clinicians throughout our teaching hospital. CLINT encompasses three domains: (1) a user adaptable clinician-computer interface, (2) unique evidence-based health care content, and (3) automated data collection and viewing tools. An objective of the CLINT project is to determine CLINT's impact on the practice of health care. Early analysis of our data has revealed that over the past year, there has been widespread use of CLINT by clinicians from all clinical domains. Our next task is to evaluate CLINT's usefulness.

Clinical Medicine

A hybrid sigma subunit directs RNA polymerase to a hybrid promoter in Escherichia coli.

Most of the sigma (transcriptional initiation specificity) subunits of RNA polymerase, from a wide range of eubacteria, show strong elements of amino acid sequence similarity. There is evidence that two of the "conserved" regions, 2.4 and 4.2, are involved in recognition of the consensus DNA sequences centred near -10 and -35, respectively, which define promoter sites for the initiation of transcription. Since all the alternative sigma subunits of the above type function by binding to a common core polymerase enzyme in a given bacterium, it can be predicted that a hybrid sigma might be functional, and if so should permit RNA polymerase to initiate only at a correspondingly hybrid promoter. To test these predictions, a hybrid gene encoding the amino-proximal 529 amino acids of the major Escherichia coli sigma protein, sigma 70 (including region 2.4) followed by the last 82 amino acids of the heat-shock sigma protein, sigma 32 (including region 4.2) was constructed and fused to Plac on a plasmid. Major-consensus, heat-shock and hybrid promoters were fused to a chloramphenicol acetyl transferase (CAT) reporter gene on a compatible plasmid. CAT assays showed that, as predicted, a promoter with a "heat-shock" -35 consensus and a "major" -10 consensus sequence (PHM) required Plac-dependent production of the hybrid sigma (sigma 70-32) for activity in vivo. PHM then became a strong promoter. The hybrid sigma gene has potential advantages over its parents for structure-function studies.

Amino Acid Sequence

The practice guidelines development cycle: a conceptual tool for practice guidelines development and implementation.

PURPOSE: To develop a conceptual tool for the systematic development of cancer treatment practice guidelines. MATERIALS AND METHODS: The guidelines development tool, the Practice Guidelines Development Cycle, was derived from observing an evidence-based practice guidelines initiative at a comprehensive cancer center in Ontario, Canada, and from a literature review that uncovered barriers to guidelines development and implementation. Based on the literature findings and direct observations of how clinicians struggled with evidence-based guidelines development, we evolved a framework to incorporate clinical and administrative factors (eg, costs) into evidence-based guidelines. Use of the Practice Guidelines Development Cycle is illustrated with a clinical example (the use of adjuvant systemic therapy in good-risk, node-negative premenopausal breast cancer patients). RESULTS: The result is the Practice Guidelines Development Cycle, which consists of eight sequential steps, from topic selection to policy formulation. Independent validation of guidelines is included. The cycle products are the evidence-based recommendation, the practice guideline, and the practice policy. The main features of the cycle are emphasis on scientific evidence, acknowledgment of the roles of clinical experience and nonclinical (administrative) factors through consensus, and explicit separation of clinical and cost considerations in guidelines development. Twenty guidelines are currently in development. CONCLUSION: Attention to the barriers of guidelines development and the sociocultural nature of clinical practice, and respect for clinical experience, can lead to improved strategies for guidelines development.

Cancer Care Facilities

CLINT: a clinical informatics system for an internal medicine ward.

This paper describes a clinical informatics system that provides access to electronic information management tools for clinicians. The Clinical Informatics Network (CLINT) provides a variety of tools for accessing information on an internal medicine ward. Evaluations based on the use of the tools will provide insight to clinicians' information needs, and how these needs can be addressed using electronic information management tools. Better access to information could enhance the quality of patient care.

Computer Graphics

GAP: a computer-assisted design tool for the development and analysis of evidence-based automated questionnaires.

This paper describes the design and use of a computer-assisted design tool for developing evidence-based automated questionnaires that may assist health practitioners to implement clinical practice guidelines. The Guideline Application Program (GAP) facilitates the design, development, testing, customization, and implementation of interactive patient-computer questionnaires, the analysis of patient-derived information, and the clinical application of practice guidelines that require knowledge of multiple patient-specific characteristics. GAP is being used to create a variety of software applications for HealthQuiz and Microsoft Windows-compatible computers. GAP-generated applications are presently used to support preventive care guideline implementation in primary care settings, preoperative screening in anesthesia clinics, student health screening in Universities, hormone replacement counseling for peri-menopausal women, and patient-reported data collection in various clinical research projects.

Algorithms

Internists' attitudes about clinical practice guidelines.

OBJECTIVE: To assess internists' familiarity with, confidence in, and attitudes about practice guidelines issued by various organizations. DESIGN: Cross-sectional, self-administered survey. PARTICIPANTS: Questionnaires were mailed to a stratified random sample of 2600 members of the American College of Physicians (ACP) in 1992. Of the 2513 internists who met our eligibility criteria, 1513 responded (60%). MEASUREMENTS AND RESULTS: Familiarity with guidelines varied from 11% of responders for the ACP guideline on exercise treadmill testing to 59% of responders for the National Cholesterol Education Program guideline. Confidence was reported in ACP guidelines by 82% of responders but by only 6% for Blue Cross and Blue Shield guidelines. Subspecialists had greatest confidence in guidelines developed by their own subspecialty organizations. It was thought that guidelines would improve the quality of health care by 70% of responders, increase health care costs by 43%, be used to discipline physicians by 68%, and make practice less satisfying by 34%. More favorable attitudes were held by internists who were paid a fixed salary, saw patients for less than 20 hours per week, had recently graduated from medical school, or were not in private practice. CONCLUSIONS: Although most ACP members studied recognized the potential benefits of practice guidelines, many were concerned about possible effects on clinical autonomy, health care costs, and satisfaction with clinical practice.

Attitude of Health Personnel

Role of the sigma 70 subunit of Escherichia coli RNA polymerase in transcription activation.

The role of the sigma 70 subunit of Escherichia coli RNA polymerase in transcription activation by positive transcription factors was investigated. For this purpose, we constructed a nested set of E. coli rpoD deletion mutants generating carboxy-terminally truncated sigma 70 subunits of RNA polymerase in a high-expression plasmid. The purified mutant sigma 70 subunits were reconstituted into holoenzymes and examined in vitro for their promoter selectivity. As expected, since the -35 recognition helix of sigma 70 was deleted in all cases, the mutant enzymes were unable to initiate at factor-independent promoters, except for the special case of perfect "extended minus 10" promoters, at which the need for -35 sequence recognition by RNA polymerase is replaced by recognition of additional base-pairs in the -10 region. However, two factor-dependent promoters, PhoB-dependent PpstS and cAMP receptor protein (CRP)-dependent P1gal, could be activated for transcription by different subsets of the mutant holoenzymes, although these promoters do not contain the perfect extended -10 sequences. These results establish that -35 DNA recognition by sigma 70 is not essential for these cases. Presumably it is replaced by protein-protein contacts between RNA polymerase and the activator, which in both cases is bound to the DNA in a position overlapping the -35 region. Further, the detailed results support the view that the contact and/or activation sites for these two factors may lie on the sigma 70 subunit, within a "contact site II", which extends at least from conserved region 3.2 to the upstream end of region 4.2. Moreover, as in the case of contact site I on the alpha subunit, it appears that contact site II contains various different subsites for interaction with specific class II activators, and that PhoB and CRP require distinct subsites.

Base Sequence

Perceived risk of cancer and practice of cancer prevention behaviors among employees in an oncology center.

METHODS: A survey of oncology center employees was conducted to determine those factors associated with perceived risk of cancer and compliance with preventive care guidelines. Five hundred six employees participated in the survey. RESULTS: The average perceived absolute risk of developing cancer in the next 20 years was 29%. Perceived risk for cancer was higher among women than men. Among men, only current smoking and duration of employment, adjusting for age, were significantly associated with the perceived risk of developing cancer. For women, in addition to smoking, personal experience with cancer among family and friends and perceived health status were significantly associated with the perceived risk of cancer. The practice of cancer preventive behaviors was unrelated to personal risk perception. Less than one-fourth of participants age 40 years and older had a sigmoidoscopy in the last 3 years and less than one-third reported having had their stool checked for blood. The majority of women had a pap smear in the past 10 years; 89% had a pap smear in the past 3 years. Eighty-eight percent of women over 40 and 94% of women over 50 had ever had a mammogram; the majority of these women had had mammograms in the past two years. CONCLUSION: Perceived risk of developing cancer was significantly higher than in projected probabilities based on the incidence of cancer in the United States. Despite the high perceived risk of developing cancer, the practice of colon cancer screening was low. Factors other than perception of personal risk of cancer may be important in encouraging participation in screening programs.

Adult

Guidelines, practice policies, and parameters: the case for geriatrics.

OBJECTIVE: As the population ages, the care of older persons becomes more important. At the same time, practice guidelines that provide recommendations for appropriate care are being published in greater numbers. The purpose of this work is to determine the proportion of guidelines that contain specific information about older persons. DESIGN: Through a random sample of published guidelines listed in the AMA Directory of Practice Parameters, 1992 Edition, we determined the proportion of guidelines that contain specific age-related information. We also determined if, over time, there was a difference in the proportion of practice guidelines containing information about older persons. RESULTS: 45.9% (95% CI, range 33.4-58.4) of guidelines that could conceivably pertain to older persons contain no age information; 24.6% (95% CI, range 13.8-35.4) of guidelines contain information only about persons less than 65 years of age; 29.5% (95% CI, range 18.1-41.0) of guidelines contain specific information about older persons. Moreover, there were no secular trends in the proportion of guidelines pertaining to older persons. CONCLUSIONS: Only a minority of practice guidelines contain information about older persons. Possible causes and solutions to this shortfall are discussed.

Age Factors

The minus 35-recognition region of Escherichia coli sigma 70 is inessential for initiation of transcription at an "extended minus 10" promoter.

It is known that Escherichia coli promoters having the major minus 10 consensus sequence TATAAT, but lacking significant resemblance to consensus in the minus 35 region, allow transcriptional initiation in vivo and in vitro if they have an additional TGn motif immediately upstream of minus 10. To determine whether region 4.2 of sigma 70, whose normal role is sequence recognition at minus 35, is unnecessary for initiation of transcription at such "extended minus 10" promoters, we modified the sigma 70 gene so as to generate a carboxy-truncated polypeptide lacking the last 84 amino acids and therefore missing region 4.2. Our results show that both the intact and truncated sigma 70 allow purified RNA polymerase to initiate efficiently and specifically at an extended minus 10 promoter, whereas only the intact sigma 70 permits efficient initiation at normal promoters (defined by minus 35 and minus 10 hexamer sequences).

Bacterial Proteins

More informative abstracts of articles describing clinical practice guidelines.

UNLABELLED: Recommendations are proposed for preparing more informative abstracts of articles describing clinical practice guidelines. Information about the development and content of guidelines should be summarized with the following structure. OBJECTIVE: a succinct statement of the objective of the guideline, including the targeted health problem, the targeted patients and providers, and the main reason for developing recommendations concerning this problem for this population. OPTIONS: principal practice options that were considered in formulating the guideline. OUTCOMES: significant health and economic outcomes identified as potential consequences of the practice options. EVIDENCE: Methods used to gather, select, and synthesize evidence, and the date of the most recent evidence obtained. VALUES: persons and methods used to assign values (relative importance) to potential outcomes of alternative practice options. BENEFITS, HARMS, AND COSTS: the type and magnitude of the main benefits, harms, and costs that are expected to result from guideline implementation. RECOMMENDATIONS: a brief and specific list of key recommendations. VALIDATION: the results of any external review, comparison with guidelines developed by other groups, or clinical testing of guideline use. SPONSORS: key persons or groups that developed, funded, or endorsed the guideline. Abstracts adhering to these recommendations could enhance readers' ability to appraise the applicability, importance, and validity of guidelines for specific providers, patients, and settings. More informative abstracts could also promote the use of more explicit methods of guideline development, more consistent reporting of guideline documents, and the more appropriate use of guidelines by clinicians.

Abstracting and Indexing

Hypersymmetry in a transcriptional terminator of Escherichia coli confers increased efficiency as well as bidirectionality.

Rho-independent transcriptional terminators in Escherichia coli usually consist of a GC-rich region encoding a sequence which allows the nascent transcript to form a stem-loop structure, and thereby apparently causes the RNA polymerase to pause; followed by an A-rich region on the DNA template strand, whose weak pairing to the consequently U-rich 3'-tail of the transcript is believed to aid release of the RNA. Quite commonly there is additional symmetry encoding, in the RNA, an A-rich sequence complementary to the 'tail', just upstream of the GC-rich motif. It has been pointed out by others that this should allow the termination of transcription in both directions. We hypothesized that it might also increase the efficiency of termination, for example by competing with the template DNA strand so as to help 'unzip' the 3'-end of the RNA from its complementary DNA. We have tested this hypothesis by deletion analysis of the hypersymmetric alpha-operon terminator, tL17. The results show that efficiency as well as bidirectionality is indeed adversely affected by deletion of the upstream A-rich sequence.

Base Sequence

Can patients use an automated questionnaire to define their current health status?

Patient management decisions rarely incorporate standardized health status assessments, since accurate and reliable measures are difficult and expensive to obtain. In prior research with various methods for obtaining health data from patients, it was found that physicians' acceptance of a method was improved if it provided an individualized printout. It was also determined that patients will readily complete a health status questionnaire on a computer when the computer does not look like a computer. Patients' acceptance was greatest when they were presented with a single line of large, pressure-sensitive buttons with which they could respond to questions about their health histories. Using such an instrument, the HealthQuiz, the current study found the same discrepancy rate (3%) between patients' responses to health questions presented on HealthQuiz and during interview as between their responses to questions asked during two separate interviews. Further, to ascertain health status, rules determined by an expert panel were applied to patients' responses to health questions presented on the HealthQuiz screen. It was found that the numerical health status derived from answers to the automated presentation of questions was similar to numerical health status derived by a physician after a patient-physician interview.

Aged