Sunnybrook Health Sciences Centre

About: Sunnybrook Health Sciences Centre is a healthcare organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Medicine. The organization has 7689 authors who have published 15236 publications receiving 523019 citations. The organization is also known as: Sunnybrook.

Vascular Dysfunction in Women With a History of Preeclampsia and Intrauterine Growth Restriction Insights Into Future Vascular Risk

Abstract: Background—Women with a history of placental disease are at increased risk for the future development of vascular disease. It is unknown whether preexisting endothelial dysfunction underlies both the predisposition to placental disease and the later development of vascular disease. The aim of this study was to assess vascular function in postpartum women and to determine whether differences emerged depending on the presentation of placental disease. Methods and Results—Women with a history of early-onset preeclampsia (n=15), late-onset preeclampsia (n=9), intrauterine growth restriction without preeclampsia (n=9), and prior normal pregnancy (n=16) were studied 6 to 24 months postpartum. Flow-mediated vasodilatation and flow-independent (glyceryl trinitrate–induced) vasodilatation were studied through the use of high-resolution vascular ultrasound examination of the brachial artery. Arterial stiffness was assessed by pulse-wave analysis (augmentation index). Laboratory assessment included circulating angio...

Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study

Abstract: Summary Background Enzalutamide is an oral androgen-receptor inhibitor that has been shown to improve survival in two placebo-controlled phase 3 trials, and is approved for patients with metastatic castration-resistant prostate cancer. The objective of the TERRAIN study was to compare the efficacy and safety of enzalutamide with bicalutamide in patients with metastatic castration-resistant prostate cancer. Methods TERRAIN was a double-blind, randomised phase 2 study, that recruited asymptomatic or minimally symptomatic men with prostate cancer progression on androgen-deprivation therapy (ADT) from academic, community, and private health-care provision sites across North America and Europe. Eligible patients were randomly assigned (1:1) via an interactive voice response system to receive enzalutamide 160 mg/day or bicalutamide 50 mg/day, both taken orally, in addition to ADT, until disease progression. Patients were stratified by a permutated block method (block size of four), by whether bilateral orchiectomy or receipt of luteinising hormone-releasing hormone agonist or antagonist therapy started before or after the diagnosis of metastases, and by study site. Participants, investigators, and those assessing outcomes were masked to group assignment. The primary endpoint was progression-free survival, analysed in all randomised patients. Safety outcomes were analysed in all patients who received at least one dose of study drug. The open-label period of the trial is in progress, wherein patients still on treatment at the end of the double-blind treatment period were offered open-label enzalutamide at the discretion of the patient and study investigator. This trial is registered with ClinicalTrials.gov, number NCT01288911. Findings Between March 22, 2011, and July 11, 2013, 375 patients were randomly assigned, 184 to enzalutamide and 191 to bicalutamide. 126 (68%) and 168 (88%) patients, respectively, discontinued their assigned treatment before study end, mainly due to progressive disease. Median follow-up time was 20·0 months (IQR 15·0–25·6) in the enzalutamide group and 16·7 months (10·2–21·9) in the bicalutamide group. Patients in the enzalutamide group had significantly improved median progression-free survival (15·7 months [95% CI 11·5–19·4]) compared with patients in the bicalutamide group (5·8 months [4·8–8·1]; hazard ratio 0·44 [95% CI 0·34–0·57]; p vs 38 [20%] of 189 in the bicalutamide group), back pain (35 [19%] vs 34 [18%]), and hot flush (27 [15%] vs 21 [11%]); those occurring more frequently with bicalutamide were nausea (26 [14%] vs 33 [17%]), constipation (23 [13%] vs 25 [13%]), and arthralgia (18 [10%] vs 30 [16%]). The most common grade 3 or worse adverse events in the enzalutamide or bicalutamide treatment groups, respectively, were hypertension (13 [7%] vs eight [4%]), hydronephrosis (three [2%] vs seven [4%]), back pain (five [3%] vs three [2%]), pathological fracture (five [3%] vs two [1%]), dyspnoea (four [2%] vs one [1%]), bone pain (one [1%] vs four [2%]), congestive cardiac failure (four [2%] vs two [1%]), myocardial infarction (five [3%] vs none), and anaemia (four [2%] vs none]). Serious adverse events were reported by 57 (31%) of 183 patients and 44 (23%) of 189 patients in the enzalutamide and bicalutamide groups, respectively. One of the nine deaths in the enzalutamide group was thought to be possibly related to treatment (due to systemic inflammatory response syndrome) compared with none of the three deaths in the bicalutamide group. Interpretation The data from the TERRAIN trial support the use of enzalutamide rather than bicalutamide in patients with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer. Funding Astellas Pharma, Inc and Medivation, Inc.

Long-term Outcomes of Stereotactic Body Radiotherapy for Low-Risk and Intermediate-Risk Prostate Cancer.

Abstract: Importance Stereotactic body radiotherapy harnesses improvements in technology to allow the completion of a course of external beam radiotherapy treatment for prostate cancer in the span of 4 to 5 treatment sessions. Although mounting short-term data support this approach, long-term outcomes have been sparsely reported. Objective To assess long-term outcomes after stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer. Design, Setting, and Participants This cohort study analyzed individual patient data from 2142 men enrolled in 10 single-institution phase 2 trials and 2 multi-institutional phase 2 trials of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer between January 1, 2000, and December 31, 2012. Statistical analysis was performed based on follow-up from January 1, 2013, to May 1, 2018. Main Outcomes and Measures The cumulative incidence of biochemical recurrence was estimated using a competing risk framework. Physician-scored genitourinary and gastrointestinal toxic event outcomes were defined per each individual study, generally by Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events scoring systems. After central review, cumulative incidences of late grade 3 or higher toxic events were estimated using a Kaplan-Meier method. Results A total of 2142 men (mean [SD] age, 67.9 [9.5] years) were eligible for analysis, of whom 1185 (55.3%) had low-risk disease, 692 (32.3%) had favorable intermediate-risk disease, and 265 (12.4%) had unfavorable intermediate-risk disease. The median follow-up period was 6.9 years (interquartile range, 4.9-8.1 years). Seven-year cumulative rates of biochemical recurrence were 4.5% (95% CI, 3.2%-5.8%) for low-risk disease, 8.6% (95% CI, 6.2%-11.0%) for favorable intermediate-risk disease, 14.9% (95% CI, 9.5%-20.2%) for unfavorable intermediate-risk disease, and 10.2% (95% CI, 8.0%-12.5%) for all intermediate-risk disease. The crude incidence of acute grade 3 or higher genitourinary toxic events was 0.60% (n = 13) and of gastrointestinal toxic events was 0.09% (n = 2), and the 7-year cumulative incidence of late grade 3 or higher genitourinary toxic events was 2.4% (95% CI, 1.8%-3.2%) and of late grade 3 or higher gastrointestinal toxic events was 0.4% (95% CI, 0.2%-0.8%). Conclusions and Relevance In this study, stereotactic body radiotherapy for low-risk and intermediate-risk disease was associated with low rates of severe toxic events and high rates of biochemical control. These data suggest that stereotactic body radiotherapy is an appropriate definitive treatment modality for low-risk and intermediate-risk prostate cancer.

Spinal cord tolerance for stereotactic body radiotherapy.

Abstract: Purpose Dosimetric data are reported for five cases of radiation-induced myelopathy after stereotactic body radiotherapy (SBRT) to spinal tumors. Analysis per the biologically effective dose (BED) model was performed. Methods and Materials Five patients with radiation myelopathy were compared to a subset of 19 patients with no radiation myelopathy post-SBRT. In all patients, the thecal sac was contoured to represent the spinal cord, and doses to the maximum point, 0.1-, 1-, 2-, and 5-cc volumes, were analyzed. The mean normalized 2-Gy-equivalent BEDs (nBEDs), calculated using an α/β value of 2 for late toxicity with units Gy 2/2, were compared using the t test and analysis of variance test. Results Radiation myelopathy was observed at the maximum point with doses of 25.6 Gy in two fractions, 30.9 Gy in three fractions, and 14.8, 13.1, and 10.6 Gy in one fraction. Overall, there was a significant interaction between patient subsets and volume based on the nBED (p = 0.0003). Given individual volumes, a significant difference was observed for the mean maximum point nBED (p = 0.01). Conclusions The maximum point dose should be respected for spine SBRT. For single-fraction SBRT 10 Gy to a maximum point is safe, and up to five fractions an nBED of 30 to 35 Gy 2/2 to the thecal sac also poses a low risk of radiation myelopathy.

Identification of Physician-Diagnosed Alzheimer's Disease and Related Dementias in Population-Based Administrative Data: A Validation Study Using Family Physicians' Electronic Medical Records

Abstract: BACKGROUND Population-based surveillance of Alzheimer's and related dementias (AD-RD) incidence and prevalence is important for chronic disease management and health system capacity planning. Algorithms based on health administrative data have been successfully developed for many chronic conditions. The increasing use of electronic medical records (EMRs) by family physicians (FPs) provides a novel reference standard by which to evaluate these algorithms as FPs are the first point of contact and providers of ongoing medical care for persons with AD-RD. OBJECTIVE We used FP EMR data as the reference standard to evaluate the accuracy of population-based health administrative data in identifying older adults with AD-RD over time. METHODS This retrospective chart abstraction study used a random sample of EMRs for 3,404 adults over 65 years of age from 83 community-based FPs in Ontario, Canada. AD-RD patients identified in the EMR were used as the reference standard against which algorithms identifying cases of AD-RD in administrative databases were compared. RESULTS The highest performing algorithm was "one hospitalization code OR (three physician claims codes at least 30 days apart in a two year period) OR a prescription filled for an AD-RD specific medication" with sensitivity 79.3% (confidence interval (CI) 72.9-85.8%), specificity 99.1% (CI 98.8-99.4%), positive predictive value 80.4% (CI 74.0-86.8%), and negative predictive value 99.0% (CI 98.7-99.4%). This resulted in an age- and sex-adjusted incidence of 18.1 per 1,000 persons and adjusted prevalence of 72.0 per 1,000 persons in 2010/11. CONCLUSION Algorithms developed from health administrative data are sensitive and specific for identifying older adults with AD-RD.