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Biomedical subjects

R Grad

Publications and source records attributed to R Grad.

At least 19 recordsLinked to original sources
PubMed2001

Teaching evidence-based medical care: description and evaluation.

BACKGROUND AND OBJECTIVES: This paper describes and evaluates several years of a seminar series designed to stimulate residents to seek evidence-based answers to their clinical questions and incorporate this evidence into practice. METHODS: At the first session, 86 of 89 (97%) residents completed a baseline needs assessment questionnaire. Post-course self-assessment questionnaires measured change from the first to the final seminar session in six domains of interest and skill, as well as residents' preferred sources of information for clinical problem solving up to 2 years after the course. RESULTS: Before the seminars, 48% of residents reported that textbooks were their most important source of information for solving clinical problems. A total of 58 of 75 (77%) residents completed the first post-course questionnaire. Residents reported significant increases in skill at formulating clinical questions and searching for evidence-based answers, appraising reviews, and deciding when and how to incorporate new findings into practice. Use of secondary sources of information such as "Best Evidence," moved up in importance from before the course to after the course. CONCLUSIONS: First-year family practice residents who completed our seminar series have reported increased skill at blending consideration of a clinical problem with the use of secondary sources of information to access evidence to support their health care decisions.

Clinical Competence↗
PubMed1999

Risk of a new benzodiazepine prescription in relation to recent hospitalization.

OBJECTIVE: To determine if recent hospital admission was associated with new outpatient prescribing of benzodiazepines among community-dwelling older people. DESIGN: Nested case-control study using administrative data sets of the provincial health insurance board. SETTING: Province of Quebec. PARTICIPANTS: Cases were 4127 community-dwelling older people who were newly dispensed a benzodiazepine during an 8-month period in 1990. Controls were 16,486 community-dwelling older people who were dispensed any drug (except a benzodiazepine) on the same day as the case-defining index prescription. EXPOSURE AND OUTCOME MEASURES: Admission to an acute care hospital within a 30-day period before a new dispensing of a benzodiazepine. Other variables measured were patient age, gender, number of ambulatory physician visits, healthcare region, Chronic Disease Score (CDS), and use of drugs for depression and psychosis. RESULTS: Cases were more than three times as likely as controls to have been hospitalized in the 30-day period before the index date (adjusted odds ratio (OR) 3.09; 95% CI, 2.78-3.45). The use of prescription drugs for physical health problems modified this association in that cases who used more medication were also more likely to receive a new benzodiazepine prescription following a recent hospital admission (adjusted OR 4.09; 95% CI, 3.59-4.65 when the CDS was equal to 5 vs adjusted OR 1.96; 95% CI, 1.66-2.31 when the CDS was equal to 0). CONCLUSIONS: Recent hospitalization confers an increased risk of a new outpatient benzodiazepine prescription among community-dwelling older people in Quebec. Those who use more medication, and who may be more vulnerable to drug-related adverse events, are more likely to be newly dispensed a benzodiazepine following a recent, acute-care hospital admission.

Aged↗
PubMed1998

Where do family practice patients go in case of emergency?

OBJECTIVE: To determine the annual incidence of patient-defined emergencies and patients' use of emergency services at a family medicine teaching unit. DESIGN: Cross-sectional survey. SETTING: Hospital-based family medicine teaching unit in Montreal. PARTICIPANTS: Registered patients attending a family medicine teaching unit during 11 consecutive weekdays. MAIN OUTCOME MEASURES: Annual incidence of patient-defined medical emergencies and use of emergency services at the unit. RESULTS: Eligible patients made 815 visits during the study period; 584 usable questionnaires were returned for a response rate of 71.7%. In the previous 12 months, 37% of patients reported at least one medical emergency. For their last emergency, 42% reported using at least one of the emergency services offered by the clinic. Only 19% of patients with after-hours emergencies reported using our on-call system. Although socioeconomic and clinical variables did not predict the incidence of patient-defined emergencies, multivariate analysis revealed three significant predictors for use: patients with the practice for 5 or more years were more likely to use our services, while patients 75 and older and those with emergencies after hours were less likely to use our services. CONCLUSIONS: In an urban group family practice, annual incidence of medical emergencies among registered patients was 37%. Those whose most recent emergency occurred after hours used the clinics' emergency on-call services disappointingly little.

Adolescent↗
PubMed1997

Use of standardized patients to assess between-physician variations in resource utilization.

CONTEXT: As medical costs are increasingly being scrutinized, there is heightened interest in defining variations in physician behavior in clinical settings. OBJECTIVE: To evaluate if standardized patient (SP) technology is a reliable and feasible method of studying interphysician variations in test ordering, referral requests, prescribing behavior, and visit costs. DESIGN: The study was conducted with blinded SP visits to family medicine and internal medicine residents, university-affiliated family physicians, and community-based family physicians. Resource utilization and visit costs were assessed using test requisitions, consult requests, and prescriptions that were collected by the SPs. SETTING: Physicians' offices in ambulatory care, hospital-based clinics and in the community. PARTICIPANTS: Four persons (aged 57-77 years) trained to simulate having osteoarthritis of the hip. In one simulation, the patient had gastropathy due to nonsteroidal anti-inflammatory drug use, and in the other, the patient sought therapy for hip discomfort. MAIN OUTCOME MEASURES: Reliability of cost estimates of physician services, tests, consultations, prescriptions, and total visits and test-ordering behavior for nonsteroidal anti-inflammatory gastropathy. RESULTS: Overall, 112 (63%) of the physicians who were sent invitations to the study agreed to participate. Of 312 total SP visits conducted over a 1-year period, unblinding due to SP detection occurred on 36 occasions (11.5%). Reliable cost estimates of physician services, tests, and consultations, and moderately reliable estimates of total visit costs, were obtained with 4 visits per practicing physician and with 2 visits per resident. There were extreme variations in total visit costs generated by the study physicians. A small number of physicians had a major impact on this variability. CONCLUSION: Standardized patient technology provides a reliable, feasible method to assess variations in resource utilization between physicians.

Diagnosis-Related Groups↗
PubMed1997

Unnecessary prescribing of NSAIDs and the management of NSAID-related gastropathy in medical practice.

BACKGROUND: Use of nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk for hospitalization and death from gastrointestinal bleeding and perforation. OBJECTIVES: To 1) estimate the extent to which NSAIDs are prescribed unnecessarily and NSAID-related side effects are inaccurately diagnosed and inappropriately managed and 2) identify the physician and visit characteristics associated with suboptimal use of NSAIDs. DESIGN: Prospective cohort study. SETTING: Montreal, Canada. PARTICIPANTS: 112 physicians representing academically affilliated general practitioners, community-based general practitioners, and residents in family medicine and internal medicine. INTERVENTIONS: Blinded, office-based assessment of the management of two clinical cases (chronic hip pain due to early osteoarthritis and NSAID-related gastropathy) using elderly standardized patients. MEASUREMENTS: Quality of drug management and potential predictors of suboptimal drug management. RESULTS: Unnecessary prescriptions for NSAIDs or other drugs were written during 41.7% of visits. Gastropathy related to NSAID use was correctly diagnosed in 93.4% of visits and was acceptably managed in 77.4% of visits. The risk for an unnecessary NSAID prescription was greater when the contraindications to NSAID therapy were incompletely assessed (odds ratio, 2.3 [95% CI, 1.0 to 5.2]) and when the case was managed by residents in internal medicine (odds ratio, 4.1 [CI, 1.2 to 14.7]). The risk for suboptimal management of NSAID-related side effects was increased by incorrect diagnosis (odds ratio, 16.6 [CI, 3.6 to 76.5]) and shorter visits. CONCLUSIONS: Unnecessary NSAID prescribing and suboptimal management of NSAID-related side effects were sufficiently common to raise questions about the appropriateness of NSAID use in the general population. If these results reflect current practice, prescribing patterns may contribute to avoidable gastrointestinal morbidity in elderly persons.

Aged↗
PubMed1997

A molecular mechanics and dynamics study of the minor adduct between DNA and the carcinogen 2-(acetylamino)fluorene (dG-N2-AAF).

Experimental studies involving the carcinogenic aromatic amine 2-(acetylamino)fluorene (AAF) have afforded two acetylated DNA adducts, the major one bound to C8 of guanine and a minor adduct bound to N2 of guanine. The minor adduct may be important in carcinogenesis because it persists, while the major adduct is rapidly repaired. Primer extension studies of the minor adduct have indicated that it blocks DNA synthesis, with some bypass and misincorporation of adenine opposite the lesion [Shibutani, S., and Grollman, A.P. (1993) Chem. Res. Toxicol. 6, 819-824]. No experimental structural information is available for this adduct. Extensive minimized potential energy searches involving thousands of trials and molecular dynamics simulations were used to study the conformation of this adduct in three sequences: I, d(C1-G2-C3-[AAF]G4-C5-G6-C7).d(G8-C9-G10-C11-G12-C13-G14+ ++); II, the sequence of Shibutani and Grollman, d(C1-T2-A3-[AAF]G4-T5-C6-A7).d(T8-G9-A10-C11-T12-A13-G14); and III, which is the same as II but with a mismatched adenine in position 11, opposite the lesion. AAF was located in the minor groove in the low-energy structures of all sequences. In the lowest energy form of the C3-[AAF]G4-C5 sequence I, the fluorenyl rings point in the 3' direction along the modified strand and the acetyl in the 5' direction. These orientations are reversed in the second lowest energy structure of this sequence, and the energy of this structure is 1.4 kcal/mol higher. Watson Crick hydrogen bonding is intact in both structures. In the two lowest energy structures of the A3-[AAF]G4-T5 sequence II, the AAF is also located in the minor groove with Watson-Crick hydrogen bonding intact. However, in the lowest energy form, the fluorenyl rings point in the 5' direction and the acetyl in the 3' direction. The energy of the structure with opposite orientation is 5.1 kcal/mol higher. In sequence III with adenine mismatched to the modified guanine, the lowest energy form also had the fluorenyl rings oriented 5' in the minor groove with intact Watson-Crick base pairing. However, the mispaired adenine adopts a syn orientation with Hoogsteen pairing to the modified guanine. These results suggest that the orientation of the AAF in the minor groove may be DNA sequence dependent. Mobile aspects of favored structures derived from molecular dynamics simulations with explicit solvent and salt support the essentially undistorting nature of this lesion, which is in harmony with its persistence in mammalian systems.

2-Acetylaminofluorene↗
PubMed1997

Does knowledge of drug prescribing predict drug management of standardized patients in office practice?

Drug prescribing for the elderly is an important area of medical knowledge since inappropriate prescribing may lead to significant adverse drug events. The objective of this study was to evaluate the association between knowledge of drug use and quality of drug management by general practitioners in practice. A cross-sectional study design was used to evaluate a sample of 37 GPs in practice. A set of common musculoskeletal problems was chosen to evaluate doctors' knowledge of non-steroidal anti-inflammatory drug use, while performance in practice was assessed using elderly standardized patients. The reliability of knowledge test scores was evaluated using measures of internal consistency. The relationship between knowledge of drug use and quality of therapeutic management in practice was evaluated by rank order and linear correlation analysis. Demographic characteristics of participating and non-participating doctors were similar. The reliability of the knowledge test was 0.55. The reliability of performance scores was 0.66. The correlation between overall performance on the standardized patient cases and total knowledge test score was 0.22 (95% confidence interval = 0-0.63). Knowledge test scores were poorly correlated with quality of therapeutic management in office practice. This indicates that knowledge tests alone cannot predict quality of performance with regard to drug prescribing for the elderly in primary care office practice.

Clinical Competence↗
PubMed1996

Prediction of the three-dimensional structure of the rap-1A protein from its homology to the ras-gene-encoded p21 protein.

rap-1A, an anti-oncogene-encoded protein, is a ras-p21-like protein whose sequence is over 80% homologous to p21 and which interacts with the same intracellular target proteins and is activated by the same mechanisms as p21, e.g., by binding GTP in place of GDP. Both interact with effector proteins in the same region, involving residues 32-47. However, activated rap-1A blocks the mitogenic signal transducing effects of p21. Optimal sequence alignment of p21 and rap-1A shows two insertions of rap-1A at ras positions 120 and 138. We have constructed the three-dimensional structure of rap-1A bound to GTP by using the energy-minimized three-dimensional structure of ras-p21 as the basis for the modeling using a stepwise procedure in which identical and homologous amino acid residues in rap-1A are assumed to adopt the same conformation as the corresponding residues in p21. Side-chain conformations for homologous and nonhomologous residues are generated in conformations that are as close as possible to those of the corresponding side chains in p21. The entire structure has been subjected to a nested series of energy minimizations. The final predicted structure has an overall backbone deviation of 0.7 A from that of ras-p21. The effector binding domains from residues 32-47 are identical in both proteins (except for different side chains of different residues at position 45). A major difference occurs in the insertion region at residue 120. This region is in the middle of another effector loop of the p21 protein involving residues 115-126. Differences in sequence and structure in this region may contribute to the differences in cellular functions of these two proteins.

Algorithms↗
PubMed1993

Vitamin A pretreatment and bleomycin induced rat lung injury.

Possible antioxidant effects of pretreatment with vitamin A on bleomycin-induced rat lung injury were studied. Intratracheal bleomycin was administered to rats pretreated with vitamin A (50,000 IU/day) or vehicle control. Analysis of bronchoalveolar lavage fluid (BAL) total and differential cell counts, lung weight, lung pathology, and alveolar macrophage superoxide anion production were performed before and at various time points after the instillation of bleomycin. Bleomycin with vehicle raised total BAL cell count and the per cent of BAL neutrophils at day 7 post injury. The percent of lung involved with pneumonitis, the lung wet weight/body weight ratio and the alveolar macrophage superoxide anion production were also increased after bleomycin alone compared to the group pretreated with vitamin A. Rats pretreated with vitamin A demonstrated a statistically significant reduction in total BAL cell count and in alveolar macrophage superoxide anion production 7 days after bleomycin compared with vehicle control. Lung wet weight/body weight ratio 7 days after bleomycin was reduced in the vitamin A treated rats. There was a trend to less pneumonitis in the vitamin A pretreated group. These data suggest that vitamin A attenuates bleomycin induced pulmonary damage by a mechanism which involves inhibition of bleomycin-induced alveolar macrophage superoxide anion production.

Animals↗
PubMed1993

Safety of continuous nebulized albuterol for bronchospasm in infants and children.

OBJECTIVE: To determine the incidence of cardiotoxicity in infants and children who receive continuous nebulized albuterol (CNA) for bronchospasm. DESIGN: Prospective, case series. SETTING: A university pediatric intensive care and pediatric subacute units. PATIENTS: Nineteen infants and children who received CNA for at least 24 hours. INTERVENTIONS: None. MEASUREMENTS: Creatinine phosphokinase (CK) was measured at the time of admission and then at 12, 24, 48, and 72 hours while the patient received CNA. Isoenzyme CK-MB fractions were measured if CK concentration was > or = 250 IU/L. One electrocardiogram was obtained for each patient during CNA treatment. All patients had continuous cardiac monitoring during continuous nebulization therapy. MAIN RESULTS: Creatinine phosphokinase levels remained within normal limits for 16 patients during CNA treatment. Three patients had elevated CK and in two CK-MB fractions were elevated at one measurement. None of the electrocardiograms showed evidence of ischemia and no arrhythmias were noted during CNA therapy, even in the patients with elevated CK-MB fractions. CONCLUSIONS: Continuous albuterol therapy appears to be safe in our patient population as there was no significant evidence of cardiotoxicity. The significance of the transient elevation of CK-MB without other evidence of cardiotoxicity remains to be determined.

Acute Disease↗