Search PubMed⌕ Search

Biomedical subjects

C D Naylor

Publications and source records attributed to C D Naylor.

At least 145 records · Page 8Linked to original sources
PubMed1994

Can there be a more patient-centred approach to determining clinically important effect sizes for randomized treatment trials?

Sample sizes for treatment trials with categorical outcomes are conventionally derived by balancing three elements: a difference between alternative treatments in the event rates for the outcomes of interest (commonly termed the clinically important difference), the alpha error tolerance (false positive risk) and the beta error tolerance (false negative risk). Clinically important differences used to plan trials are chosen in part based on earlier experience with similar interventions (i.e. biological or clinical plausibility). Methodological conventions and clinicians' perceptions will also affect choices. Lastly, practical concerns about the feasibility of accruing large numbers of subjects may drive trialists to specify bigger differences as clinically important, with a view to containing sample size requirements. We suggest that patients or other members of the public be given an active role in determining the magnitude of the clinically important treatment effect for trial planning. Probability trade-offs could be constructed to enable patients and/or healthy volunteers to indicate the degree of benefit they would want from a "new" treatment, given the potential side-effects of the same treatment. This method has the advantage of respecting patient autonomy and principles of informed consent. It provides an additional consideration when plausible effect sizes and error tolerances on hypothesis tests are balanced against feasibility of accruing various sample sizes. Its primary disadvantage is inconvenience, as it adds another step to trial design. On the other hand, if patient-based clinically important differences are generated for a variety of disease states and types of treatments, specific trade-off exercises may be needed only for unusual trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1994

Variation in hospital length of stay for acute myocardial infarction in Ontario, Canada.

Unexplained variation in length of stay (LOS) following acute myocardial infarction (AMI) has been observed among American hospitals. We explored this phenomenon in the universal hospital care system of Ontario, Canada's largest province, analyzing general hospital discharge abstracts for all patients with a primary diagnosis of AMI. Case homogeneity was increased by excluding inter-hospital transfers, in-hospital deaths, patients with revascularization during the index admission and patients with severe comorbid conditions. This left 11,411 records of patients in 187 hospitals from April 1, 1990 to March 31, 1991. The mean length of stay was 9.9 days with standard deviation of 3.8. Available patient and hospital characteristics explained only 12% of the individual variation in LOS. Interinstitutional variation remained highly significant after controlling for patients' characteristics within the 87 hospitals admitting more than 50 cases per annum; these hospitals accounted for 84% of the eligible provincial admissions. The grand mean length of stay for 87 hospitals was 10 days, ranging from 6.6 to 12.9 days. Stepwise multiple linear regression analyses showed that lower caseload was associated with an increased length of hospitalization. Thus, despite Ontario's uniform system of hospital funding and medical insurance, a large amount of unexplained variation in length of stay exists for patients hospitalized with AMI, affecting thousands of bed-days per annum.

Adult↗
PubMed1994

Effects of thrombolytic therapy administered 6 to 24 hours after myocardial infarction on the signal-averaged ECG. Results of a multicenter randomized trial. LATE Ancillary Study Investigators. Late Assessment of Thrombolytic Efficacy.

BACKGROUND: Thrombolytic therapy reduces mortality after acute myocardial infarction, even when treatment is initiated relatively late after onset of symptoms. The mechanism underlying this survival benefit is incompletely understood. METHODS AND RESULTS: In a prospectively designed ancillary study of a randomized, placebo-controlled trial of late thrombolytic therapy (LATE), the signal-averaged (SA) ECG was recorded before hospital discharge in an effort to assess the effect of thrombolytic therapy on arrhythmia substrate. Three hundred ten patients were enrolled at 23 participating sites; 160 patients received placebo, and 150 patients received recombinant tissue-type plasminogen activator (rTPA) therapy 6 to 24 hours after onset of symptoms. Compared with placebo, rTPA tended to reduce the frequency of SAECG abnormality (filtered QRS duration > 120 milliseconds) by 37% (95% CI, -64%, +6%; P = .087) and the filtered QRS duration (105.7 +/- 13.8 versus 108.8 +/- 14.6 milliseconds, P = .05). In the prespecified subgroup of 185 patients with ST elevation on the qualifying ECG, rTPA resulted in a 52% reduction (95% CI, 4% to 77%, P = .011) of SAECG abnormality and a shorter filtered QRS duration (105.7 +/- 10.9 versus 110.7 +/- 15.9 milliseconds, P = .01). No benefit was seen in patients without ST elevation on ECG. CONCLUSIONS: Late thrombolytic therapy produced a more stable electrical substrate, which probably represents an important mechanism of mortality benefit.

Double-Blind Method↗
PubMed1994

Drug prices and third party payment: do they influence medication selection?

The growing burden of prescription drug costs has focused attention on factors which influence physicians' prescribing decisions. We hypothesised that third party coverage of prescription costs would elicit selection of expensive drugs, but that this tendency could be moderated by price reminders. In a mailed survey, primary care physicians throughout Ontario (n = 1072) were provided with the clinical scenario of a patient with an infectious exacerbation of chronic obstructive pulmonary disease, and asked to select diagnostic tests as well as 1 of 6 antibiotics. Two antibiotics were expensive (ciprofloxacin and cefaclor; average price $Can52.23), and 4 inexpensive {amoxicillin, cotrimoxazole (trimethoprim/sulfamethoxazole), erythromycin and tetracycline; average price $Can2.80}. Neither expensive drug is considered first line therapy for the condition described. Questionnaires differed in the presence or absence of drug benefit coverage and price information. The response rate was 71%. With third party cost coverage and prices shown, 18% of respondents selected an expensive antibiotic. This increased to 38% when the prices were omitted {odds ratio 2.72; 95% confidence interval (CI) 1.61, 4.60; p less than 0.001}, and decreased to 8% when the patient was said to have no drug benefits coverage (odds ratio 0.40; 95% CI 0.19, 0.84; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1994

Cardiopulmonary bypass, temperature, and central nervous system dysfunction.

BACKGROUND: Neurological injury is an important cause of morbidity and mortality after cardiac surgery. With the advent of warm heart surgery, the neuroprotective role of hypothermic cardiopulmonary bypass (CPB) has come under increasing scrutiny. Preliminary work by us in the area found no increased risk of neurological morbidity with normothermic CPB in a small group of patients and suggested a possible benefit. The purpose of the present study is to compare the incidence of neurological and neuropsychological dysfunction in a larger number of patients randomized to warm or cold aortocoronary bypass surgery. METHODS AND RESULTS: With the approval of the institutional research ethics committee, 201 aortocoronary bypass patients were randomized to normothermic or moderate hypothermic CPB and subjected to neurological and neuropsychological evaluation. These subjects were a subset of patients enrolled in a large multicenter trial comparing warm versus cold heart surgery. The examinations took place preoperatively, 5 days after operation, and a 3-month follow-up. The examination consisted of a clinical neurological examination and a brief neuropsychological test battery. The neuropsychological tests included the Buschke selective reminding procedure, the Wechsler memory scale-revised visual reproduction subtest, the trial making test (parts A and B), the Wechsler adult intelligence scale-revised digit symbol subtest, and the grooved pegboard test. The examiner and subjects were unaware of the CPB temperature allocation (warm, > 34 degrees C; cold, < or = 28 degrees C). Statistical analysis was performed using the SAS statistical software package. Two hundred one patients were enrolled in the study. Of these, 155 patients completed the entire protocol and were included in the final analysis (warm group, n = 78; cold group, n = 77). One patient in the warm group died perioperatively from a massive hemispheric stroke. Another warm group patient was unable to complete neuropsychological evaluation because of a perioperative stroke. Thus, 153 patients completed the entire series of neuropsychological tests. A total of 6 patients (warm group, n = 2; cold group, n = 4; P = NS) suffered from perioperative focal neurological deficits. There was a consistent deterioration in scores from tests of psychomotor speed/coordination (trial making, digit symbol, pegboard) in the early postoperative period, which resolved by the 3-month follow-up. Tests of memory (Buschke, Wechsler memory scale) showed no evidence of patient deterioration in the postoperative period. No difference was seen between the warm and cold groups. CONCLUSIONS: In this randomized trial of normothermic versus hypothermic CPB, we found deterioration in scores of tests of psychomotor speed but not of memory in the early postoperative period. We were unable to demonstrate any neuroprotective effect from moderate hypothermia in this patient population.

Blood↗
PubMed1994

Sex differences in the use of invasive coronary procedures in Ontario.

OBJECTIVE: To determine whether sex differences exist in the use of coronary angiography, coronary artery bypass surgery (CABS) or percutaneous transluminal coronary angioplasty (PTCA) among persons recently diagnosed with an acute myocardial infarction (AMI) in Canada. BACKGROUND: A growing body of literature suggests that coronary artery disease in males is treated differently from females. Specifically, recent studies have indicated that sex may influence decisions about the use of invasive diagnostic and therapeutic coronary procedures in patients with suspected or proven coronary artery disease. PATIENTS AND METHODS: The study design is a population-based inception cohort study. The data source is hospital discharges from all acute care hospitals in Ontario. The study population consisted of 6949 men and women discharged with a principal diagnosis of AMI between April 1 and September 30, 1990, and followed through record linkage until March 31, 1991 to determine whether any invasive coronary procedures were performed after their AMI. Odds ratio estimates (OR) and 95% confidence intervals (95% CI) for use of coronary angiography, CABS and PTCA in men were compared with those in women. RESULTS: The adjusted OR for coronary angiography was 1.4 (95% CI 1.2 to 1.6), indicating that males were more likely to undergo angiography than females. A similar finding was seen for CABS (OR = 1.6, 95% CI 1.2 to 2.1), but for PTCA, the sex difference was less pronounced (OR = 1.3, 95% CI 1.0 to 1.7). Cox proportional hazards regression also was used to test the hypothesis and showed similar results. CONCLUSIONS: Women suffering AMI undergo coronary angiography and CABS at a significantly lower rate than men in Ontario, with similar trends evident in use of PTCA.

Adult↗
PubMed1993

Waiting for coronary revascularization in Toronto: 2 years' experience with a regional referral office.

OBJECTIVES: To determine the frequency of major adverse events among patients awaiting coronary revascularization; to assess the match between referring physicians' estimates of urgency, a computer-generated multifactorial urgency rating score and actual waiting times; to determine the changes in waiting times as capacity for bypass surgery increased; and to evaluate the influence of choice of procedure or operator on waiting times. DESIGN: Consecutive case series. SETTING: Greater Toronto region. SUBJECTS: All 571 patients referred to an organized referral office by cardiologists at hospitals without on-site revascularization facilities between Jan. 3, 1989, and June 30, 1991. MAIN OUTCOME MEASURES: Preoperative fatal or nonfatal myocardial infarction; proportions of patients waiting longer than the maximum period recommended for their urgency rating; mean waiting times for various subgroups; and correlations among referring physicians' urgency ratings, computer-generated multifactorial urgency scores and waiting times. RESULTS: Of the 496 patients accepted for a procedure 5 had fatal cardiac events and 3 nonfatal myocardial infarction. Events occurred three times more often in patients with left mainstem disease than in those in other anatomic categories (relative risk [RR] 3.05, 95% confidence interval [CI] 1.48 to 6.27, p = 0.03). Both the computer-generated scores and the referring physicians' scores were correlated with the actual waiting time (r = 0.46 and 0.57 respectively). Waiting times and the proportion of patients with excessive waiting times fell during the study period (p < 0.0001). However, urgent cases were much less likely to be done "on time" than those with a recommended waiting time of more than 2 weeks (RR 0.16, 95% CI 0.11 to 0.25, p < 0.0001). The mean wait for coronary artery bypass grafting (CABG) was 22.73 days if the referral office was allowed to find a surgeon or interventional cardiologist and 35.31 days if one was requested (p = 0.002 after adjustment for urgency scores). CONCLUSIONS: Death of a patient on the waiting list is uncommon in an organized referral system. Patients with left main-stem disease are at higher risk of death than those in other anatomic categories. There were significant correlations between referring physicians' ratings of urgency, multifactorial urgency scores and actual waiting times. Expansion of capacity for CABG led to shorter waiting times, but patients with unstable symptoms continued to wait longer than recommended. Requests for a specific surgeon caused significantly longer delays.

Aged↗
PubMed1993

Sex-related differences in coronary revascularization practices: the perspective from a Canadian queue management project.

OBJECTIVE: To assess sex-related differences in coronary revascularization practices in a Canadian setting. DESIGN: Prospective analytic cohort study. SETTING: Regional referral office in Toronto. PATIENTS: A selected but consecutive group of 131 women and 440 men referred by cardiologists for revascularization procedures between Jan. 3, 1989, and June 30, 1991. INTERVENTIONS: Coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA). Nurse-coordinators placed the referral with a surgeon or interventional cardiologist at one of three hospitals, who then communicated directly with the referring cardiologist. MAIN OUTCOME MEASURES: Symptom status at referral, procedures requested and performed, and time from referral to procedure. RESULTS: Although the women were more likely than the men to have unstable angina at the time of referral (odds ratio [OR] 2.28, 95% confidence interval [CI] 1.38 to 3.79, p = 0.0006), more women than men (16.8% v. 12.1%) were turned down for a procedure. Significant sex-related differences in practice patterns (p < 0.001) persisted after controlling for age or for the referring cardiologists' perception of expected procedural risk. A stepwise multivariate model showed that anatomy was the main determinant of case management; sex was the only other significant variable (p = 0.016). The referring physicians requested CABG more often for men than for women (p = 0.009), and the men accepted for a procedure were much more likely to undergo CABG than the women (OR 2.40, CI 1.47 to 3.93, p = 0.0002). Although the women undergoing CABG waited shorter periods than the men (p = 0.0035), this difference was attributable to their more severe symptoms. CONCLUSIONS: In this selected group women had more serious symptoms before referral but were turned down for revascularization more often than men. Reduced use of CABG rather than PTCA largely accounted for the sex-related differences in revascularization. Once accepted for a procedure women had shorter waiting times, which was appropriate given their more severe symptoms.

Age Factors↗
PubMed1993

Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis.

PURPOSE: To determine whether alpha-interferon is effective in terminating viral replication and in eradicating the carrier state in patients with chronic hepatitis B virus (HBV) infection. DATA SOURCES: Randomized controlled studies published in the English literature between January 1966 and June 1992 were identified through a MEDLINE computer search. STUDY SELECTION: Fifteen randomized controlled studies with a total of 837 adult chronic HBV carriers who were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were identified. Studies were included if patients were treated for at least 3 months and followed for at least 6 months after cessation of therapy. RESULTS: Overall, the loss of HBsAg occurred 6% more often in interferon-treated patients than the natural seroconversion seen in controls (7.8% compared with 1.8%, P = 0.001), and the loss of viral replication occurred approximately 20% more often in treated patients than in controls (33% compared with 12% for loss of HBeAg and 37% compared with 17% for the loss of HBV DNA, P = 0.0001) if patients received interferon for 3 to 6 months and were followed for 6 to 12 months. Interferon also had a significant treatment effect on the development of antibodies to HBsAg (anti-HBs), antibodies to HBeAg (anti-HBe), and on the normalization of alanine aminotransferase levels. CONCLUSIONS: Alpha-interferon is effective in terminating viral replication and in eradicating the carrier state in patients with chronic HBV infection who are HBeAg positive when these patients are treated for 3 to 6 months and followed for 6 to 12 months after cessation of therapy. Follow-up studies are required to determine whether interferon reduces the risk for developing cirrhosis or hepatocellular carcinoma.

Adolescent↗
PubMed1993

Pulmonary artery catheterization. Can there be an integrated strategy for guideline development and research promotion?

OBJECTIVES: To review the evidence regarding indications for pulmonary artery catheterization (PAC) in critically ill patients, and to propose a guideline-generating process that would encourage randomized controlled trials of PAC. DATA SOURCES: Computerized and manual search for randomized trials involving PAC as an integral part of the protocol, published as of October 1992. Manual search for guidelines endorsed by specialty societies and/or proposed by expert panels following an explicit group process. DATA SYNTHESIS: Four trials suggest benefit from PAC for pre- or perioperative management of high-risk surgical patients. Two others indicate that PAC for low-risk aortic aneurysm surgery confers no advantages. Use of PAC to guide therapy aimed at improved mixed venous oxygen saturation was beneficial compared with usual care with PAC in two small trials among patients with septic shock and severe trauma. Other PAC indications are either untested or inadequately tested by small trials. Large trials are needed, but trials to date have been impeded by clinicians' uncertainty about PAC and unwillingness to randomize critically ill patients. No published guidelines for PAC have used a formal group process and/or a hierarchical review of evidence to demarcate proven from unproven indications. CONCLUSIONS: We propose a research-promoting expert panel on indications for PAC. Aided by a critical literature review, experts would rate case scenarios on the need for routine PAC with or without a specified intervention strategy. Future trials should test indications where there is either consensus about the uncertainty of need for PAC, or interpanelist disagreement owing to inconclusive evidence. This process could facilitate practice guideline development, utilization management, and large trials of PAC and related interventions.

Cardiac Catheterization↗
PubMed1993

Trends in coronary artery bypass grafting in Ontario from 1981 to 1989.

OBJECTIVES: To determine the trends in overall and age-specific rates of coronary artery bypass grafting (CABG) in Ontario from 1981 to 1989 and to assess whether relative resource scarcity, as manifested in waiting lists, resulted in obvious age-related or sex-related changes in utilization. DESIGN: Computerized compilation of hospital discharge abstracts from the Hospital Medical Records Institute. All separations for every other year from Apr. 1, 1981, to Mar. 31, 1990, were included. Procedures rather than patients were the unit of analysis (repeat procedures were double-counted if associated with separate hospital admissions). SETTING: Ontario acute care hospitals offering CABG. PATIENTS: People aged 20 years and over who underwent one or more CABG procedures. RESULTS: The overall rate of CABG increased by 31% in the study period, plateauing only between 1983 and 1985. By 1989-90 the rate was 66.03 per 100,000. The highest annual increase in the rate was among people aged 65 to 74 years, at 17.61 procedures per 100,000, as compared with 4.64 per 100,000 among people 75 years and over. In 1989-90 those aged 65 and over represented 37% of the total caseload. The overall male:female ratio did not change significantly throughout the study period. CONCLUSIONS: Since the CABG utilization rate continues to increase in Ontario, recent waiting lists must be due to a disproportionate growth in demand. There was no convincing evidence of age-related or sex-related discrimination in allocating this limited resource. Supply-demand mismatch was driven above all by the continued increase in CABG use among elderly people.

Adult↗
PubMed1993

Queueing for coronary surgery during severe supply-demand mismatch in a Canadian referral centre: a case study of implicit rationing.

Queues for in-patient surgery are commonplace in universal health care systems. Clinicians and hospitals usually manage these waiting lists with informal criteria for determining patient priority--a form of implicit rationing. To understand the workings of implicit rationing by queue, we took advantage of a natural experiment in the Canadian province of Ontario. Unprecedentedly severe supply-demand mismatch led to long waiting lists for coronary surgery [CABS] in Ontario during 1987-88. The crisis was resolved by increased funding and widespread adoption of a multifactorial clinical index for patient priority that was developed by an expert panel in 1989. Thus, we audited randomly chosen charts of patients who underwent coronary angiography at four Toronto hospitals during the crisis period, and calculated urgency scores for each case based on the multifactorial index. From 413 charts, 193 eligible patients were identified who proceeded to CABS. Waiting times did correlate with urgency ratings (r = 0.42, P < 0.0001). However, mean wait from catheterization to CABS varied among hospitals by as much as 8 weeks (P < 0.0001 after controlling for urgency scores). At the hospital with shortest queues, waiting times were twice as long for patients catheterized by cardiologists off-site vs those referred by on-site practitioners (P < 0.0001, after controlling for urgency scores); a similar form of bias was found at a second coronary surgery centre (P = 0.056, after controlling for urgency scores). Over half the patients waited longer than the maximum suggested for their category by the expert panel.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiology Service, Hospital↗