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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
PubMed2000

Aromatic amino acids in region 2.3 of Escherichia coli sigma 70 participate collectively in the formation of an RNA polymerase-promoter open complex.

Formation of an initiation-competent RNA polymerase-promoter complex involves DNA melting over a region of about 12 base-pairs, which includes the start site of transcription, thus enabling the template strand to base-pair with the initiating nucleoside triphosphates. By studying the effects of alanine substitutions, we have investigated the role of the aromatic amino residues in the Escherichia coli sigma(70) conserved region 2.3 in promoter strand separation. The resulting mutants were assessed for their activity in vivo in the context of a sigma(70)/sigma(32) hybrid sigma factor that could be targeted to a specific hybrid promoter in the cell. All substitutions lead to an at least twofold reduction in expression of the hybrid promoter-driven reporter gene. The in vitro assay of single substitutions indicated cold sensitivity similar to that previously observed with analogous substitutions in Bacillus subtilis sigma(A). Kinetic assays showed that these substitutions slowed the rate of open complex formation at 37 degrees C as well. RNA polymerase reconstituted with a sigma(70) containing multiple alanine substitutions readily binds to promoter DNA, but then proceeds slowly beyond the first intermediate complex on the pathway to formation of the transcription-competent complex. These data demonstrate that together the aromatic residues in region 2.3 of E. coli sigma(70) ensure that DNA strand separation proceeds efficiently, even if no individual residue may be essential for accomplishment of the process.

Alanine↗
PubMed1997

Canadian physicians' attitudes about and preferences regarding clinical practice guidelines.

OBJECTIVE: To assess Canadian physicians' confidence in, attitudes about and preferences regarding clinical practice guidelines. DESIGN: Cross-sectional, self-administered mailed survey. PARTICIPANTS: Stratified random sample of 3000 Canadian physicians; 1878 (62.6%) responded. SETTING: Canada. OUTCOME MEASURES: Physicians' use of various information sources; familiarity with and confidence in guidelines; attitudes about guidelines and their effect on medical care; rating of importance of guidelines and other sources of information in clinical decision-making; rating of importance of various considerations in deciding whether to adopt a set of guidelines; and rating of usefulness of different formats for presenting guidelines. MAIN RESULTS: In all, 52% of the respondents reported using guidelines at least monthly, substantially less frequently than traditional information sources. Most of the respondents expressed confidence in guidelines issued by various physician organizations, but 51% to 77% were not confident in guidelines issued by federal or provincial health ministries or by health insurance plans. The respondents were generally positive about guidelines (e.g., over 50% strongly agreed that they are a convenient source of advice and good educational tools); however, 22% to 26% had concerns about loss of autonomy, the rigidity of guidelines and decreased satisfaction with medical practice. Endorsement by respected colleagues or major organizations was identified as very important by 78% and 62% of the respondents respectively in deciding whether to adopt a set of guidelines in their practice. User friendliness of the guidelines format was thought to be very important by 62%; short pamphlets, manuals summarizing a number of guidelines, journal articles and pocket cards summarizing guidelines were the preferred formats (identified as most useful by 50% to 62% of the respondents). CONCLUSIONS: Canadian physicians, although generally positive about guidelines and confident in those developed by clinicians, have not yet integrated the use of guidelines into their practices to a large extent. Our results suggest that respected organizations and opinion leaders should be involved in the development of guidelines and that the acceptability of any proposed format and medium for guidelines presentation should be pretested.

Attitude of Health Personnel↗
PubMed1997

Clinical practice guidelines in general practice: a national survey of recall, attitudes and impact.

OBJECTIVE: To determine Australian general practitioners' (GPs') views about and recall of clinical practice guidelines. DESIGN: Self-administered questionnaire survey. SUBJECTS: Randomly selected Australian GPs. RESULTS: 286 of 373 GPs returned questionnaires (77% response rate). GPs' recall of each of nine guidelines ranged from 52% to 94%; 49% considered that their practice had changed as a result of a guideline. While 92% of respondents agreed that guidelines were "good educational tools", 85% indicated that guidelines were "developed by experts who don't understand general practice". Factors most frequently identified as important in deciding whether to follow the guideline recommendations were whether the guideline was based on evidence and credible endorsement. CONCLUSIONS: Australian GPs have positive views about the purpose of clinical practice guidelines and an evidence-based approach to guidelines development. However, respondents rating of the perceived impact of available guidelines in everyday practice was low. The dissemination of specific guidelines is patchy and there is little evidence of systematic implementation.

Adult↗
PubMed1997

Future directions for clinical practice guidelines: needs, lead agencies and potential dissemination strategies identified by Australian general practitioners.

There has been an increasing interest in developing clinical practice guidelines for general practitioners as a means of improving health outcomes. We conducted a survey of a national random sample of Australian general practitioners in May 1995 to determine their needs, preferred formats and dissemination strategies and to identify potential lead agencies for guidelines development. Of 373 eligible general practitioners, 286 (77 per cent) returned completed questionnaires. At least 50 per cent of respondents considered guidelines in angina, psychotic illness, skin cancer and attention deficit disorder as 'extremely' or 'very' useful. However, three other topics identified as areas for future guidelines development in Better health outcomes for Australians were so rated by less than half of the general practitioners surveyed. The Australian Cancer Society and the Australian Medical Association outranked nine other organisations in terms of credibility in guidelines development. Innovative formats, including computerised medical records or text, were not highly rated, consistent with our finding that only 27 respondents (9 per cent) had Internet access. Strategies nominated as likely to increase the adoption of a guideline included a personal visit by a trained nurse, a lecture about its content or a Medicare rebate being available when a patient was managed in accordance with the guideline. Public health practitioners and nominated lead agencies are encouraged to respond to these findings and recognise potential strategies to enhance the effective dissemination of guidelines. Interventional studies are required to demonstrate and allow understanding of changes in clinical practice attributable to guidelines.

Adult↗
PubMed1997

Automated direct-from-patient information collection for evidence-based diabetes care.

BACKGROUND: Computer-based clinical decision support tools can improve physician performance in ambulatory care settings. Acquiring and entering the patient-specific information necessary to take advantage of this technology, however, can often be a major impediment. OBJECTIVE: To develop and evaluate a self-administered electronic questionnaire for acquiring patient-specific information to be used for generating diabetes-related evidence-based care recommendations. METHODS: An initial paper questionnaire was developed that evaluated current diabetes management, complications, and screening interventions. This was then coded for electronic presentation using software that can also analyze patient responses and produce personal feedback. To evaluate the electronic questionnaire, 47 patients completed it using a small laptop computer and also responded to a personal interview that assessed similar topics. RESULTS: Patients required between 7-29 minutes to complete the questionnaire (mean: 15 min.). For 21 of the 23 topic assessed, the agreement between the electronic questionnaire and the personal interview was 80% or higher. CONCLUSIONS: An electronic, self-administered questionnaire can be used to acquire information for generating patient-specific care recommendations.

Data Collection↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗