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Biomedical subjects

Carey Levinton

Publications and source records attributed to Carey Levinton.

4 recordsLinked to original sources

Validation of a decision model for preventive pharmacological strategies in postmenopausal women.

BACKGROUND: Benefits and risks of a combined hormone replacement therapy (HRT) based on randomized clinical trial emerged on various disease endpoints in 2002. The Women's Health Initiative (WHI) provides an important health answer for healthy postmenopausal women, such as do not use combined HRT to prevent chronic disease, because of the elevated risk of coronary artery disease (CHD), stroke and venous thromboembolism. In March 2004, the NIH stopped the drugs in the estrogen-alone trial after finding an increase risk of stroke and no effect, neither an increase or a decrease, on risk of CHD after an average of 7 years in the trial. On the other hand, raloxifene, which does not seem to significantly increase the risk of cardiovascular events and could retain skeletal benefits without stimulating endometrial and breast tissue, requires decision-makers since no current data on these disease clinical endpoints have been published. OBJECTIVE: To construct a multi-disease model based on patient-specific risk factor profiles, and to validate the multi-disease model with several tools of internal and external validities. METHODS: A Markov state model was developed. The risks of these various diseases (including coronary artery disease, stroke, hip fracture and breast cancer) are derived from published hazards proportional models which take into account significant risk factors. Canadian-specific rates and data sources for these transition probabilities are derived from published studies and Canadian Health Statistics. The validation of our model were based on several tools of internal and external validities, such as Canadian life expectancy, population-based incidence rate of diseases, clinical trials and other published life expectancy models. RESULTS: First, presumably, small changes in the lifetime probability of dying support the hypothesis that the disease states operate in a largely independent fashion. For instance, the difference in the probability of dying from a particular disease by the complete elimination of a selected disease, such as CHD, stroke or breast cancer, ranged from 0.2 to 2.2% of difference in the lifetime probability of dying of these diseases. Second, we demonstrated that the model adequately predicted the Canadian population lifetable and disease-incidence rates from population-based data among women from 45 to 75 years old. The predictions of the model were cross-checked from non-source data, such as predicted outcomes versus observed outcomes from results of clinical trials. Predicted relative risks of CHD event, breast cancer and hip fracture fell in the reported 95% confidence interval of clinical trials. Finally, predicted treatment benefits are comparable with those of published life expectancy models. CONCLUSIONS: The results of the study demonstrated that this multi-disease model, including coronary artery disease, stroke, hip fracture and breast cancer, is a valid model to predict the impact on life expectancy or number of events prevented for preventive pharmacological interventions.

Aged↗

Developing an efficient model to select emergency department patient satisfaction improvement strategies.

STUDY OBJECTIVE: Patient satisfaction is an important performance measure for emergency departments (EDs), but the most efficient ways of improving satisfaction are unclear. This study uses optimization techniques to identify the best possible combination of predictors of overall patient satisfaction to help guide improvement efforts. METHODS: The results of a satisfaction survey from 20,500 patients who visited 123 EDs were used to develop ordinal logistic regression models for overall quality of care, overall medical treatment, willingness to recommend the ED to others, and willingness to return to the same ED. Originally, 68,981 surveys were mailed, and 20,916 were returned, representing an overall response rate of 30.3%. We then incorporated these regressions into an optimization model to select the most efficient combination of predictors necessary to increase the 4 overall satisfaction measures by 5%. A sensitivity analysis was also conducted to explore differences across hospital peer groups and regions. RESULTS: Results differ slightly for each of the 4 overall satisfaction measures. However, 4 predictors were common to all of these measures: "perceived waiting time to receive treatment," "courtesy of the nursing staff," "courtesy of the physicians," and "thoroughness of the physicians." The selected predictors were not necessarily the strongest predictors identified through regression models. The optimization model suggests that most of these predictors must be improved by 15% to increase the overall satisfaction measures by 5%. CONCLUSION: This study introduces the use of optimization techniques to study ED patient satisfaction and highlights an opportunity to apply this technique to widely collected data to help inform hospitals' improvement strategies. The results suggest that hospitals should focus most of their improvement efforts on the 4 predictors mentioned above.

Adolescent↗

Phase I/II trial of the safety and efficacy of AE-941 (Neovastat) in the treatment of non-small-cell lung cancer.

AE-941 (Neovastat), an antiangiogenic component extracted from cartilage, selectively competes for the binding of vascular endothelial growth factor to its receptor, inhibits matrix metalloproteinases, stimulates tissue plasminogen activator enzymatic activities, and induces apoptotic activities in endothelial cells. A phase I/II study was conducted to obtain information on its safety and efficacy in patients with advanced cancer refractory to treatment or for which no standard treatments were available. Eighty patients with histologically confirmed lung cancer were enrolled in a multicenter, open-label, dose-escalation study of AE-941 (30, 60, 120, or 240 mL/day) administered orally b.i.d. as monotherapy. No dose-limiting toxicity was reported. The most frequent adverse events were nausea (9%), pruritus (5%), anorexia (4%), and vomiting (4%). All adverse events were grade 1/2 except grade 3 constipation (n = 1). A survival analysis was conducted in the 48 patients with unresectable stage IIIA, IIIB, or IV non-small-cell lung cancer. A significant survival advantage was observed for patients receiving doses > 2.6 mL/kg/day (which correspond to approximately 180 mL/day in a 70-kg patient) compared to patients receiving lower doses (median, 6.1 months vs. 4.6 months; P = 0.026). No tumor responses were observed. On the other hand, 26% of the patients in the high-dose group had stable disease compared to 14% in the low-dose group. AE-941 is well tolerated in patients with advanced lung cancer. The higher dose of AE-941 explored in this phase I/II trial may confer a survival benefit.

Journal Article↗

The risk of diabetes during olanzapine use compared with risperidone use: a retrospective database analysis.

BACKGROUND: The relative risk of diabetes among patients undergoing risperidone treatment was compared with that of patients receiving olanzapine. METHOD: A cohort was formed of 33,946 patients with at least 1 prescription for either olanzapine (N = 19,153) or risperidone (N = 14,793) between January 1, 1997, and December 31, 1999, recorded in the Régie de l'Assurance Maladie du Québec database. Patients were excluded if clozapine was dispensed to them during the study period or if they were diagnosed with diabetes before beginning antipsychotic therapy. New diabetes diagnoses made after the first antipsychotic prescription during the period were tabulated until December 31, 1999; censoring occurred at this date or at the last service date, if there was no record of using services during the last 6 months of follow-up. Crude hazard ratio and proportional hazard analyses were carried out. RESULTS: 319 patients developed diabetes on olanzapine treatment, and 217 developed diabetes on risperidone treatment; a crude hazard ratio of 1.08 (95% CI = 0.89 to 1.31, p =.43) was determined. When age, gender, and haloperidol use were controlled for using proportional hazard analysis, there was a 20% increased risk of diabetes with olanzapine relative to risperidone (95% CI = 0% to 43%, p =.05). Proportional hazard analyses adjusted for duration of olanzapine exposure indicated that the first 3 months of olanzapine treatment was associated with an increased risk of diabetes of 90% (95% CI = 40% to 157%, p <.0001), after adjusting for age, gender, and haloperidol use. CONCLUSION: Compared with risperidone, olanzapine was associated with an increased risk of developing diabetes. More studies are required to further investigate this association.

Aged↗