Biomedical subjects
Publications and source records attributed to J I Williams.
A short formal synthesis of squalamine is described, utilizing the biotransformation product 2, which is available in one step from commercially available 3-keto-23,24-bisnorchol-4-en-22-ol (1). Regioselective C-22 oxidation and C-24 sulfation of the corresponding alcohols in the presence of a free C-7 alcohol make for an efficient preparation of squalamine intermediate 11.
BACKGROUND: Previous studies suggest that, for some conditions, women receive fewer health care interventions than men. We estimated the potential need for arthroplasty and the willingness to undergo the procedure in both men and women and examined whether there were differences between the sexes. METHODS: All 48,218 persons 55 years of age or older in two areas of Ontario, Canada, were surveyed by mail and telephone to identify those with hip or knee problems. In these subjects, we assessed the severity of arthritis and the presence of coexisting conditions by questionnaire, documented arthritis by examination and radiography, and conducted interviews to evaluate the subjects' willingness to undergo arthroplasty. The potential need for arthroplasty was defined by the presence of severe symptoms and disability, the absence of any absolute contraindications to surgery, and clinical and radiographic evidence of arthritis. The estimates of need were then adjusted for the subjects' willingness to undergo arthroplasty. RESULTS: The overall response rates were at least 72 percent for the questionnaires and interviews. As compared with men, women had a higher prevalence of arthritis of the hip or knee (age-adjusted odds ratio, 1.76; P<0.001) and had worse symptoms and greater disability, but women were less likely to have undergone arthroplasty (adjusted odds ratio, 0.78; P<0.001). Despite their equal willingness to have the surgery, fewer women than men had discussed the possibility of arthroplasty with a physician (adjusted odds ratio, 0.63). The numbers of people with a potential need for hip or knee arthroplasty were 44.9 per 1000 among women and 20.8 per 1000 among men. After adjustment for willingness to undergo the procedure, the numbers were 5.3 per 1000 for women and 1.6 per 1000 for men. CONCLUSIONS: There is underuse of arthroplasty for severe arthritis in both sexes, but the degree of underuse is more than three times as great in women as in men.
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The Activities Scale for Kids (ASK) is a self-report measure of childhood physical disability, that has excellent reliability (ICC = 0.97). The purpose of this study was to assess further the ASK's measurement properties. ASK questionnaires were completed by 200 children with musculoskeletal limitations (mean age, 10.1 years). Rasch analyses confirmed that all items measured the same construct and supported aggregation of a summary score. Validity of the ASK was demonstrated by a correlation of 0.81 (P<0.0001) with parent-reported Childhood Health Assessment Questionnaire scores; a significant difference in scores according to clinicians' global ratings of disability (P<0.0001), and a correlation of 0.92 (P<0.0001) with clinician-observation. The ASK showed minimal ceiling effects, no floor effects, and changed by 1.73 standard deviation units after clinically important change. The ASK is a valid and responsive outcome measure that permits 5- to 15-year-old children physical functioning in the community to be assessed accurately by mail. The quality of this measure will enable clinical studies to measure outcome not only in a way that is relevant to patients, but also in a way that is sensitive to small amounts of change and is practical and inexpensive.
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PURPOSE: Modalities for inhibiting neovascularization may be one avenue to the development of effective therapies for retinopathy. The effect of squalamine, an antiangiogenic amino sterol, on oxygen-induced retinopathy (OIR) was assessed in a mouse model. METHODS: OIR was induced in C57BL6 mice by a 5-day exposure to 75% oxygen from postnatal day (P)7 through P12. Squalamine (25 mg/kg, subcutaneous)treated animals received either daily doses for five days from P12 to P16 or one dose just after removal from oxygen on P12. Each set of animals was killed at P17 to P21. Retinopathy was assessed with a retinopathy scoring system evaluation of retinal wholemounts and by quantification of neovascular nuclei on retinal sections. RESULTS: Animals receiving 5 days of squalamine after a 5-day exposure to oxygen had total retinopathy scores (expressed as median score with 25th and 75th quartiles in parentheses) of 4(3, 5) versus oxygen-only-reared animals with scores of 8(7, 9; P < 0.001). Animals reared in room air and animals exposed to squalamine only had similar retinopathy scores: 1(1, 2) and 1(0, 2). Oxygen-reared animals receiving single-dose squalamine also showed improvement, with a median retinopathy score of 4(4, 6.75) versus oxygen-only-reared animals with median retinopathy score of 9(7, 10; P < 0.001). There was a decreased number of neovascular nuclei extending beyond the inner limiting membrane on retinal sections in animals treated with 5 days (P < 0.01) and 1 day (P < 0.001) of squalamine. CONCLUSIONS: Squalamine significantly improved retinopathy and may be a novel agent for effective treatment of ocular neovascularization.
Health expectancy measures are becoming a common method of combining information on mortality and health-related quality of life into one summary population health measure. However, health expectancy measures are infrequently measured at the local level, despite a shift toward health service planning to that level. Using a modified Sullivan method, we calculated health-adjusted life expectancy (HALE) for the 42 public health units in Ontario using life tables that were derived from mortality and population data for 1988-1992 and the Health Utilities Index from the 1990 Ontario Health Survey. There were large variations among health units in HALE at age 15 for both men (range: 51.3-58.2 years) and women (range: 56.6-62.9 years). Generally, rural and northern areas had the lowest HALE. Local differences in male HALE were greater than for life expectancy (7.1 versus 6.0 years). Despite a relatively large health survey (45,583 respondents, range: 729-1,746 per health unit), few HALE differences deviated significantly from the Ontario mean, raising concerns about the feasibility of estimating local health expectancy measures with adequate precision. Nevertheless, the wider local differences and different geographic distribution of local HALE compared with mortality measures, along with the additional benefit of being able to model the complex interaction of mortality and morbidity, suggest that HALE may be a useful population health measure.
BACKGROUND: Structured feedback of information can produce change in physician behaviour. The objective of this study was to assess the effectiveness of 2 educational interventions for improving the quality of care provided by family physicians in Ontario: the Practice Assessment Report (PAR) and the Continuing Medical Education Plan (CMEP) with a follow-up visit by a mentor. METHODS: The study was a randomized controlled trial. Physicians in the control group received only the PAR, whereas those in the experimental group received the PAR, CMEP and mentor interventions. The participants were 56 family physicians and general practitioners (27 in the PAR group and 29 in the CMEP group) in southern Ontario who agreed to participate in the interventions and provide data. A total of 2395 patients randomly sampled from the practices returned questionnaires and consented to have their medical records abstracted. The outcome measures were global scores in 4 areas--quality of care, charting, prevention and overall use of medications--and patient ratings of satisfaction with care and preventive practices. The measures were applied at the beginning (phase 1) and end (phase 2) of the study. RESULTS: The mean global scores at the end of the study for the PAR group were 70.1% for quality of care, 84.7% for prevention, 77.7% for charting and 82.2% for overall use of medications. The corresponding scores for the CMEP group were 68.3%, 82.1%, 76.4% and 83.2%. In the patient satisfaction component, the personal care scores at phase 2 were 93.6% for the PAR group and 94.6% for the CMEP group. Examples of the scores for prevention for the PAR group were 98.3% for children's current immunization, 96.6% for blood pressure measured within the previous 5 years, 79.4% for referral of women of the appropriate age for mammography within the previous 2 years, and 58.4% for discussion about alcohol use. The corresponding scores for the CMEP group were 95.8%, 97.6%, 77.6% and 64.6%. The changes in mean scores between phase 1 and phase 2 ranged from -1.9 to 2.3 points. There were no significant differences between the 2 groups in phase 1 or phase 2 scores or in change in scores. A total of 64.3% of the physicians rated the PAR as useful, 26.5% found the CMEP to be useful, and 41.0% considered the mentor strategy to be a useful form of continuing medical education. Although changes in practice related to the PAR, CMEP or mentor were reported by some physicians, they were not related to chart audit or patient scores. INTERPRETATION: Educational interventions based on quality-of-care assessments and directed to global improvements in quality of care did not result in improvements in the outcome measures. Educational interventions may have to be targeted to specific areas of the practice, with physicians being monitored and receiving ongoing feedback on their performance.
BACKGROUND: The use of the prostate-specific antigen (PSA) test has been increasing rapidly in Canada since its introduction in 1988. The reasons for using the PSA test in patients without known prostate cancer are unclear. This paper reports on the first study in Canada to use physician records to assess the use of PSA testing. METHODS: A questionnaire was mailed to physicians attending 475 patients without diagnosed prostate cancer. The patients were randomly selected from 2 laboratory databases of PSA test records in the greater Toronto area during 1995. The physicians were asked to consult their patient records to avoid recall bias. Information obtained included physician's specialty, patient's age at time of PSA test and reason(s) for the test. RESULTS: There were 264 responses (56%), of which 240 (91%) were usable. Of these 240, 63% (95% confidence interval [Cl] 58%-70%) indicated that the test was conducted to screen for prostate cancer, 40% (95% Cl 34%-47%) said it was to investigate urinary symptoms, and 33% (95% Cl 27%-40%) responded that it was a follow-up to a medical procedure or drug therapy. More than one reason was permitted. Of 151 responses indicating screening as one reason for testing, 64% (95% Cl 56%-72%) stated that it was initiated by the patient, and 73% (95% Cl 65%-80%) stated that it was part of a routine examination. For 19%, both investigation of symptoms and screening asymptomatic patients were given as reasons for testing, and for another 19% both follow-up of a medical procedure and screening were given as reasons. Screening was recorded as a reason for testing far more commonly for patients seen by family physicians and general practitioners than for patients seen by urologists (67% v. 29%, p < 0.001). In contrast, the use of PSA testing to diagnose urinary symptoms was more common for patients seen by urologists than for those seen by family physicians and general practitioners (52% v. 37%, p = 0.044). No significant difference was found between physician groups in the use of PSA testing as a follow-up of a medical procedure (42% for urologists and 31% for family physicians and general practitioners). About 24% of the PSA test records were for patients younger than 50 and older than 70 years. PSA testing initiated by patients was more common in the practices of family physicians and general practitioners than in the practices of urologists (44% v. 13%, p < 0.001). INTERPRETATION: Screening for prostate cancer was the most common reason for PSA testing in our study group; it occurred most commonly in the family and general practice setting and was usually initiated by the patient. Differences in reasons for testing were identified by practice specialty. Although PSA screening for prostate cancer is sometimes recommended for men between 50 and 70 years of age, it is being conducted in men outside this age group.
BACKGROUND AND PURPOSE: As survival following stroke improves, individuals are more likely to live with the aftermath of stroke rather than immediately die from it. The purpose of this study was to examine the consequences of stroke on the life activities of survivors in the social realm (stroke handicap) using the framework of the World Health Organization's International Classification of Impairments, Disabilities and Handicaps. METHODS: Multivariate analysis of variance was applied to cross-sectional data from a clinical study to investigate the correlates of handicap in a cohort of hemispheric stroke survivors at 3 months (n = 145) and at 1 year (n = 135) after stroke onset. Handicap was assessed with the Reintegration to Normal Living Index, impairment by the Adams' Hemispheric Stroke Scale and Zung Depression Scale, and disability by the Functional Independence Measure. Environmental variables in the model included marital status and receipt of rehabilitation therapy. RESULTS: Physical disability and post-stroke depressive symptoms were associated with handicap at both follow-up periods (p < 0.05). Cognitive disability and impairments from a previous stroke were also associated with handicap (p < 0.01), but only at 1 year. The presence of a spouse was found to benefit male survivors at 1 year. CONCLUSIONS: Disability and depressive symptoms restrict the meaningful life activities of stroke survivors in the first year of recovery. Social supports may be influential in reducing their impact.
OBJECTIVE: To determine family physicians' attitudes and practices regarding documentation of informed consent for antipsychotic medication. DESIGN: Pilot cross-sectional study. SETTING: Teaching and non-teaching hospitals in Toronto, Ont. PARTICIPANTS: Thirty family physicians were selected in equal numbers from teaching and non-teaching hospitals with no more than five physicians from a given hospital. Participants were treating at least 10 patients with antipsychotic medication. Participants' mean age was 44.3 years; 83% were men. MAIN OUTCOME MEASURES: Documentation of consent and of disclosure of consent for antipsychotic medication in patients' charts. RESULTS: Documentation was found in only 13% of charts. Whether it was there or not did not correlate with information disclosed, score on an attitude scale, or demographics. Physicians who found documentation time-consuming were less likely to document. Most physicians disclosed reasons for antipsychotic medication, but less than half described tardive dyskinesia, a potentially irreversible movement disorder that affects about 25% of patients on long-term treatment. CONCLUSIONS: The low rate of documentation observed in this sample was consistent with reports of similar samples and might indicate that family physicians are unaware of recommendations for documentation or simply do not have time to keep abreast of current recommendations. Many physicians thought signed consent forms unnecessary for psychotic patients, and even more believed seeking consent for antipsychotic medications would increase patient anxiety.
OBJECTIVE: To evaluate the complication rates after conversion of hip and knee fusions to total joint replacements in the Province of Ontario. DESIGN: A retrospective cohort study. PATIENTS: Those who had undergone an elective conversion of a hip or knee fusion to a total joint replacement during fiscal year 1993 through 1996, as captured in the Canadian Institute for Health Information and Ontario Health Insurance Plan databases. OUTCOME MEASURES: Inhospital complications and length of initial hospital stay, revision, infection, amputation and repeat fusion rates within 4 years. RESULTS: Conversion of hip and knee fusion to total joint arthroplasty was generally performed by high-volume surgeons in high-volume hospital settings. Forty hip and 18 knee replacements involved conversion of a previous fusion. Conversion of a hip fusion was associated with a 10% infection rate, a 10% revision rate and a 5% resection arthroplasty rate due to infection within 4 years of the conversion. Conversion of a knee fusion was associated with an 11% infection rate, and a more than 5% revision rate at 4 years. Over 16% of patients who underwent conversion of a knee fusion required removal of the components (for various reasons) within the first 4 years. CONCLUSIONS: There is a high rate of complications after conversion of a hip or knee fusion to a total joint arthroplasty. These issues must be carefully considered and discussed with the patient before any conversion procedure.
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The Short Form 36, The Toronto Extremity Salvage Score, and the 1987 and 1993 Musculoskeletal Tumor Society Rating Scales were compared as measures of functional status for patients with lower extremity sarcoma. The study included 97 patients with lower extremity sarcoma and evaluated each measure on the following measurement properties: conceptual framework; statement of the purpose; feasibility; breadth of content; depth of measurement; cross sectional and longitudinal reliability; and validity and responsiveness. The Short Form 36 represents patients' perceptions of their physical and mental health and is practical to use. However, the validity of the measure is questionable for the patients with sarcoma because the subscale structure could not be reproduced in the current data. The Toronto Extremity Salvage Score meets all standards of measurement with the exception of breadth of content as it measures only physical function. The 1987 and 1993 Musculoskeletal Tumor Society scales do not meet the standards of measurement. In choosing an outcome measure for the extremity sarcoma population, the Toronto Extremity Salvage Score has superior measurement properties when compared with the Short Form 36 or the 1987 and 1993 Musculoskeletal Tumor Society scales. The Toronto Extremity Salvage Score is a reliable and efficient measure for monitoring patients and for use in clinical trials.
The novel aminosterol, squalamine, inhibits angiogenesis and tumor growth in multiple animal models. This effect is mediated, at least in part, by blocking mitogen-induced proliferation and migration of endothelial cells, thus preventing neovascularization of the tumor. Squalamine has no observable effect on unstimulated endothelial cells, is not directly cytotoxic to tumor cells, does not alter mitogen production by tumor cells, and has no obvious effects on the growth of newborn vertebrates. Squalamine was also found to have remarkable effects on the primitive vascular bed of the chick chorioallantoic membrane, which has striking similarities to tumor capillaries. Squalamine may thus be well suited for treatment of tumors and other diseases characterized by neovascularization in humans.
BACKGROUND: Previous studies of hospital utilization have not taken into account the use of acute care beds for subacute care. The authors determined the proportion of patients who required acute, subacute and nonacute care on admission and during their hospital stay in general hospitals in Ontario. From this analysis, they identified areas where the efficiency of care delivery might be improved. METHODS: Ninety-eight of 189 acute care hospitals in Ontario, at 105 sites, participated in a review that used explicit criteria for rating acuity developed by Inter-Qual Inc., Marlborough, Mass. The records of 13,242 patients who were discharged over a 9-month period in 1995 after hospital care for 1 of 8 high-volume, high-variability diagnoses or procedures were randomly selected for review. Patients were categorized on the basis of the level of care (acute, subacute or nonacute) they required on admission and during subsequent days of hospital care. RESULTS: Of all admissions, 62.2% were acute, 19.7% subacute and 18.1% nonacute. The patients most likely to require acute care on admission were those with acute myocardial infarction (96.2% of 1826 patients) or cerebrovascular accident (84.0% of 1596 patients) and those admitted for elective surgery on the day of their procedure (73.4% of 3993 patients). However, 41.1% of patients awaiting hip or knee replacement were admitted the day before surgery so did not require acute care on admission. The proportion of patients who required acute care on admission and during the subsequent hospital stay declined with age; the proportion of patients needing nonacute care did not vary with age. After admission, acute care was needed on 27.5% of subsequent days, subacute care on 40.2% and nonacute care on 32.3%. The need for acute care on admission was a predictor of need for acute care during subsequent hospital stay among patients with medical conditions. The proportion of patients requiring subacute care during the subsequent hospital stay increased with age, decreased with the number of inpatient beds in each hospital and was highest among patients with congestive heart failure, chronic obstructive pulmonary disease and pneumonia. INTERPRETATION: In 1995, inpatients requiring subacute care accounted for a substantial proportion of nonacute care days in Ontario's general hospitals. These findings suggest a need to evaluate the efficiencies that might be achieved by introducing a subacute category of care into the Canadian health care system. Generally, efforts are needed to reduce the proportion of admissions for nonacute care and of in-hospital days for other than acute care.
We assessed patients on the waiting lists of a purposive sample of orthopaedic surgeons in Ontario, Canada, to determine patients' attitudes towards time waiting for hip or knee replacement. We focused on 148 patients who did not have a definite operative date, obtaining complete information on 124 (84%). Symptom severity was assessed with the Western Ontario/McMaster Osteoarthritis Index and a disease-specific standard gamble was used to elicit patients' overall utility for their arthritic state. Next, in a trade-off task, patients considered a hypothetical choice between a 1-month wait for a surgeon who could provide a 2% risk of post-operative mortality, or a 6-month wait for joint replacement with a 1% risk of post-operative mortality. Waiting times were then shifted systematically until the patient abandoned his/her initial choice, generating a conditional maximal acceptable wait time. Patients were divided in their attitudes, with 57% initially choosing a 6-month wait with a 1% mortality risk. The overall distribution of conditional maximum acceptable wait time scores ranged from 1 to 26 months, with a median of 7 months. Utility values were independently but weakly associated with patients' tolerance of waiting times (adjusted R-square = 0.059, P = 0.004). After splitting the sample along the median into subgroups with a relatively 'low' and 'high' tolerance for waiting, the subgroup with the apparently lower tolerance for waiting reported lower utility scores (z = 2.951; P = 0.004) and shorter times since their surgeon first advised them of the need for surgery (z = 3.014; P = 0.003). These results suggest that, in the establishment and monitoring of a queue management system for quality-of-life-enhancing surgery, patients' own perceptions of their overall symptomatic burden and ability to tolerate delayed relief should be considered along with information derived from clinical judgements and pre-weighted health status instruments.