Many recent epidemiological studies have linked health effects with short-term exposure to air pollution levels commonly found in North America. The association of ozone and fine particulate matter with mortality and hospital admissions in 12 Canadian cities was explored in a time-series study. City-specific estimates were obtained by Poisson regression models adjusting for the confounding effects of seasonality and temperature. Estimates were then pooled across cities using the inverse variance method. Results suggest significant associations across all outcomes except cardiovascular hospital admissions. Generally, stronger associations were found among the elderly. Effect estimates were robust to adjustment for seasonality confounding but were sensitive to lag structures. Considering the large population exposed to air pollution, reductions in ozone and particulate matter would lead to considerable health benefits.

Patients with insulin-dependent diabetes mellitus (IDDM) must adhere to a complex treatment regimen. Adherence is often poor during adolescence, when the regimen behaviours may interact negatively with many of the developmental tasks. In a randomized controlled outcome study, 15 adolescents and their families participated in a family-based intervention for improving adherence to the diabetic regimen. Fourteen comparison group adolescents with IDDM spent a comparable amount of time learning stress management techniques. Adolescents in both groups attended a diabetes management review session with the clinic nurse. Inclusion criteria included mean glycosylated hemoglobin (HbAlc) levels $>$9.0% over the previous nine months. At a 6-month follow-up, adolescents in the family intervention group were testing blood glucose levels more regularly (p $$1% (0% vs. 29%, $\chi\sp2$ = 6.32, p =.05). Methodological issues were discussed.

The human prostate is a secondary sexual organ that requires an uninterrupted supply of androgens to maintain structural and functional integrity of androgen dependent epithelial cells. Eventual failure of hormonal therapies for prostate cancer is often attributed to the presence of androgen independent epithelial cells in the tumor. Using the rat ventral prostate as a model of the human prostate, we have isolated and characterized an androgen independent epithelial cell population present in the normal rat ventral prostate. These cells grow very quickly and have been termed Rapidly-Dividing Epithelial (RDE) cells. The RDE cells are completely independent of androgens for cell survival and do not secrete the androgen dependent secretory proteins, secretory acid phosphatase and prostate steroid binding protein. The epithelial cell origin of RDE cells was confirmed by cytokeratin expression, testosterone metabolism patterns and by purification parameters. Culture with various differentiation-inducing agents resulted in major morphological changes and structures reminiscent of those in the mature prostate but not in the expression of androgen-dependent secretory products. RDE cells demonstrate a very high in-vitro propensity for transformation yet no tumor growth in-vivo. None of the ten common "immortalizing" proto-oncogenes tested were expressed. RDE cells appear to be the rat counterpart to androgen-independent epithelial cells which cause renewed tumor growth in prostate cancer patients treated by hormonal therapies.

Background. About 5--15% of the North American and European populations pass a urinary stone in their lifetime. The most accurate way of detecting degree of urinary obstruction is with a radiograph called an intravenous pyelogram or IVP. Objectives. (1) To assess the feasibility of developing a clinical decision rule that would identify the clinical factors that are sensitive in predicting which patients with suspected ureteral calculi have severe obstruction and require urgent pyelography by: (i) defining severe obstruction; (ii) determining the incidence of severe obstruction; (iii) identifying potential predictor variables; and (iv) calculating a sample size for the definitive decision rule study. (2) To prospectively assess clinical predictors of complications from urinary calculi after discharge from the ED by: (i) determining the incidence of complications; (ii) identifying preliminary predictor variables; (iii) calculating a sample size for the definitive study. (Abstract shortened by UMI.)

Context. Subarachnoid haemorrhage is a type of haemorrhagic stroke with an annual incidence of 1 per 10,000 people and accounts for 1% of emergency department visits for acute headache. Objectives. (1) Phase 0: To determine patient characteristics, association of predictor variables with subarachnoid haemorrhage, mean length of stay determined by investigation(s) performed, and an estimate of the incidence of subarachnoid haemorrhage in alert patients with headache and normal neurological examination at the Ottawa Hospital. (2) Phase 1: To develop and pre-test standardized clinical assessments in alert patients with possible subarachnoid haemorrhage and apply these standardized clinical assessments to alert patients with possible subarachnoid haemorrhage. With these clinical assessments, determine the statistical association between the clinical findings and the diagnosis of subarachnoid haemorrhage, and develop a preliminary decision rule to determine which patients require investigation to rule out subarachnoid haemorrhage. (Abstract shortened by UMI.)

Introduction. Optimal management of paroxysmal atrial fibrillation (PAF), a common presenting complaint in emergency departments (EDs), remains undetermined. Methods. Six month prospective observational study at three EDs. Patients had clinically stable PAF for less than 48 hours. Conservative (rate control) and aggressive (pharmacologic and/or electrical cardioversion) treatment were analyzed. Results. 169 patients were analyzed, 32 treated conservatively and 137 aggressively. 83.9% of aggressively treated patients converted in the ED, 8.0% were admitted, and 52.3% stayed in sinus rhythm for four weeks. The corresponding proportions for conservative treatment were 34.4%, 37.5%, and 30.0%. There were 15 ED complications (2 rate control, 4 pharmacologic, and 9 electrical), two required admission (one pharmacologic and one electrical). No thromboembolism occurred by four-week follow-up. Conclusions. The results of this study---the first prospective study of ED treatment of PAF---will be used to plan a randomized controlled trial which will compare the two treatments.

Introduction. The treatment of cellulitis with intravenous antibiotics administered in Emergency Departments is a new phenomenon with significant inter-physician variation. A clinical trial will address many of the questions surrounding this practice. Previous trials have been flawed because of the absence of a validated objective outcome measure. Methods. Eligible patients with cellulitis were prospectively recruited for an observational cohort study and underwent daily measurements of their infection. These measurements were evaluated for their feasibility, inter-rater reliability and criterion validity (compared with the primary outcome of treatment failure versus clinical response; a classification based on physician treatment decisions) Results. Only the infection size and change in size over time performed well, obtaining statistical significance in all domains. Conclusions. The change in size of infection over time is a valid and reliable reflection of clinical decisions for patients with cellulitis, and should be used as the primary outcome for clinical trials of cellulitis therapy.

This thesis demonstrates the application of a feedforward backpropagation-trained artificial neural network using the weight-elimination cost function to the estimation of in-hospital mortality for coronary artery bypass grafting patients from the San Francisco Heart Institute in Daly City, California, USA. The highly-skewed a priori statistics due to the low mortality rate present difficulties for modelling this data. Artificial training and test datasets with higher mortality rates were developed to improve the classification performance of the artificial neural networks. Sensitivity was considered the most important measure of performance for this work. Given that current mortality risk models are unable to accurately identify high-risk patients (those who do not survive the surgery), focussing on increasing the sensitivity rate will indicate when more of the patients who are difficult to classify are correctly identified. The final result was an increase in sensitivity when training with a dataset with a higher mortality rate than the test set. This dataset modification approach resulted in only small changes for other performance measures (specificity, predictive positive value, predictive negative value, and correct classification rate), and thus helped to achieve the main goal of the study.

There are no available guidelines for the diagnosis of meniscal tears in patients with osteoarthritis of the knee. The goal of the present study was to prospectively study a cohort of such patients referred for arthroscopy and develop a clinical prediction rule to select patients who would benefit from arthroscopy. Patients with osteoarthritis of the knee refractory to conservative medical treatment were selected for arthroscopic evaluation. A standardized assessment protocol was administered to each patient and repeated by a second observer when feasible to permit calculation of the kappa coefficient ($\kappa$) for interobserver agreement. Arthroscopic determination of unstable meniscal tears was recorded by one observer who reviewed a video recording and was blinded to preoperative data based on objective criteria. Those variables which had the highest interobserver agreement and the strongest association with meniscal tear by univariable methods were then entered into a logistic regression model. This study underscored the difficulty in using clinical variables to predict unstable medial meniscal tears which were addressed at arthroscopy. (Abstract shortened by UMI.)

Introduction. Surrogate marker responses are imperfect indicators of response to antiretroviral therapy in HIV. It is proposed that the area under the curve of surrogate marker response will be superior to peak response, or to that measured after a period of therapy. Methods. The database from a study of ritonavir in advanced HIV was used. Using logistic regression, the specificity of the surrogate marker level at baseline, change between baseline and at time points to week 16, peak response, and area under the curve of the response to week 16 and week 40 were determined. The predictive values, likelihood ratios and receiver operating characteristic curves were determined for those of highest specificity. Results. Specificities increased from baseline to week 16. Peak responses were inferior to time period surrogate marker changes, whereas the areas under the curve were comparable or better than the time period surrogate marker changes. The highest specificity at any time point was for the CD4 change at week 8 (55.90%), whereas the highest overall specificity was for the 16 week AUC for the CD4% (69.63%). However, the PPV, NPV, likelihood ratios and ROC curves demonstrated poor performance overall for these surrogate markers. Too few subjects had viral load testing for this marker to be assessed. Discussion. Within the limits of this study, it was demonstrated that the CD4 and CD4% were the surrogate markers most associated with clinical outcome, with the CD4% AUC to 16 weeks having the highest overall specificity and the week 8 CD4 having the greatest specificity for clinical use. However, all surrogate markers had specificities below 70%.