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Cardiovascular disease is a common cause of death in prostate cancer patients. Low testosterone is associated with increased cardiovascular risk in the general male population. We investigated the relationship between serum testosterone, cardiovascular disease and risk factors in androgen-deprivation therapy-naïve prostate cancer patients.We performed a cross-sectional analysis of a subgroup of 1,326 androgen-deprivation therapy-naïve men from RADICAL-PC (Role of Androgen-Deprivation Therapy In CArdiovascular Disease-A Longitudinal Prostate Cancer study) in whom serum testosterone was measured at baseline. RADICAL-PC is a prospective multicenter cohort study of men (2,565) enrolled within 1 year of prostate cancer diagnosis, or within 6 months of commencing androgen-deprivation therapy for the first time. Cardiovascular risk factors, cancer characteristics and total serum testosterone were collected at baseline. Low testosterone was defined as total serum testosterone11 nmol/L (320 ng/dL). A Framingham cardiovascular risk score ≥15 was considered high risk for future cardiovascular events. We performed logistic regression to calculate odds ratios for the association between testosterone and cardiovascular risk.Among 1,326 participants (median age 67 years, range 45-93), 553 (42%) had low testosterone. Low testosterone was associated with existing cardiovascular disease, diabetes, elevated hemoglobin A1c, obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, hypertension and Framingham score15. Among patients with low testosterone, the odds ratio for high cardiovascular risk was 1.33 (1.02-1.73) after adjusting for ethnicity, education, alcohol use, cancer characteristics, physical activity and body mass index.Among androgen-deprivation therapy-naïve prostate cancer patients, low testosterone is common and associated with increased cardiovascular risk factors.

Objective To evaluate the power of responder analyses in a randomized controlled trial. Study design and setting Simulations were based on the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST), which compared sertraline to placebo for the treatment of depression in kidney disease. Baseline disease severity, placebo response, effect size, and the proportion of responders were varied across 72 scenarios. Power was assessed using a t-test for change scores, and the chi-square test for dichotomized outcomes of the minimal important difference (MID), improvement and remission in 10,000 datasets with a fixed sample size of 193. Results The t-test had >80% power except for scenarios with the lowest sertraline effect size. The chi-square test using the MID had 80% power only at higher effect sizes and/or when the proportion of responders was highest at 0.5. The chi-square test for improvement had marginal power increases compared to the t-test (4/72 scenarios = 5.6%) and that for remission did not outperform the t-test in any scenario. Conclusions The t-test outperforms the chi-square test for dichotomized outcomes regardless of baseline disease severity, placebo response, effect size and the proportion of responders to the intervention.

The Management of Myocardial Injury after Non-Cardiac Surgery (MANAGE) trial demonstrated that dabigatran 110 mg twice daily was more effective than placebo in preventing the primary composite outcome of vascular mortality, non-fatal myocardial infarction, non-hemorrhagic stroke, peripheral arterial thrombosis, amputation and symptomatic venous thromboembolism in patients with myocardial injury after non-cardiac surgery (MINS). The cost implications of dabigatran for this population are unknown but are important given the significant clinical implications. Hospitalized events, procedures, and study and non-study medications were documented. We applied Canadian unit costs to healthcare resources consumed for all patients in the trial, and calculated the average cost per patient in Canadian dollars for the duration of the study (median follow-up of 16 months). A sensitivity analysis was performed using only Canadian patients, and subgroup analyses were also conducted. The total study cost for the dabigatran group was $9985 per patient, compared with $10,082 for placebo, a difference of − $97 (95% confidence interval [CI] − $2128 to $3672). Savings arising from fewer clinical events and procedures in the dabigatran 110 mg twice-daily group were enough to offset the cost of the study drug. In Canadian patients, the difference was $250 (95% CI −$2848 to $4840). Both differences were considered cost neutral. Dabigatran 110 mg twice daily was cost saving or cost neutral in many subgroups that were considered. Dabigatran 110 mg twice daily was cost neutral for patients in the MANAGE trial. Our cost findings support the use of dabigatran 110 mg twice daily in patients with MINS. ClinicalTrials.gov identifier number NCT01661101.

BACKGROUND Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to >= 70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations. METHODS We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery. High-sensitivity cardiac troponin I measurements (upper reference limit, 26 ng per liter) were obtained 3 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We performed Cox analyses using a regression spline that explored the relationship between peak troponin measurements and 30-day mortality, adjusting for scores on the European System for Cardiac Operative Risk Evaluation II (which estimates the risk of death after cardiac surgery on the basis of 18 variables, including age and sex). RESULTS Of 13,862 patients included in the study, 296 (2.1%) died within 30 days after surgery. Among patients who underwent isolated coronary-artery bypass grafting or aortic-valve replacement or repair, the threshold troponin level, measured within 1 day after surgery, that was associated with an adjusted hazard ratio of more than 1.00 for death within 30 days was 5670 ng per liter (95% confidence interval [CI], 1045 to 8260), a level 218 times the upper reference limit. Among patients who underwent other cardiac surgery, the corresponding threshold troponin level was 12,981 ng per liter (95% CI, 2673 to 16,591), a level 499 times the upper reference limit. CONCLUSIONS The levels of high-sensitivity troponin I after cardiac surgery that were associated with an increased risk of death within 30 days were substantially higher than levels currently recommended to define clinically important periprocedural myocardial injury. (Funded by the Canadian Institutes of Health Research and others; VISION Cardiac Surgery ClinicalTrials.gov number, NCT01842568.)

Our study purpose was to determine the prevalence of metabolically healthy obesity (MHO) and examine factors associated with MHO in children with obesity. This cross-sectional study was a secondary, exploratory analysis of data that included 2-17 years old with a body mass index (BMI) ≥85th percentile from the CANadian Pediatric Weight management Registry. Children were classified as having MHO or metabolically unhealthy obesity (MUO) using consensus-based criteria. Those with MHO had normal triglycerides, high-density lipoprotein cholesterol, blood pressure, and fasting glucose. Logistic regression was used to examine factors associated with MHO, which included calculating odds ratios (ORs) and 95% confidence intervals (CIs). In total, 945 children were included (mean age: 12.3 years; 51% female). The prevalence of MHO was 31% (n = 297), with lower levels across increasing age categories (2-5 years [n = 18; 43%], 6-11 years [n = 127; 35%], 12-17 years [n = 152; 28%]). Children with MHO were younger, weighed less, and had lower BMI z-scores than their peers with MUO (all p

Background There are few concise tools to evaluate dietary habits in men with prostate cancer in Canada. Objective The aim was to develop a short food-frequency questionnaire (SFFQ) in a cohort of prostate cancer patients. Methods A total of 130 men with prostate cancer completed the SFFQ and a validated comprehensive food-frequency questionnaire (CFFQ). Both questionnaires were administered at baseline and 6 mo later. Results We found good correlation between the SFFQ and the CFFQ for seafood, dairy, egg, fruits, potatoes, grains, soft drinks, and processed meat (Spearman rank correlation >0.5). Moderate correlation was found for meat, sweets, vegetables, protein, and carbohydrates (Spearman rank correlation: 0.3–0.5). We found a weaker correlation for total fat measured by SFFQ and CFFQ (Spearman rank correlation

The Management of Myocardial Injury after Non-Cardiac Surgery (MANAGE) trial demonstrated that dabigatran 110 mg twice daily was more effective than placebo in preventing the primary composite outcome of vascular mortality, non-fatal myocardial infarction, non-hemorrhagic stroke, peripheral arterial thrombosis, amputation and symptomatic venous thromboembolism in patients with myocardial injury after non-cardiac surgery (MINS). The cost implications of dabigatran for this population are unknown but are important given the significant clinical implications.Hospitalized events, procedures, and study and non-study medications were documented. We applied Canadian unit costs to healthcare resources consumed for all patients in the trial, and calculated the average cost per patient in Canadian dollars for the duration of the study (median follow-up of 16 months). A sensitivity analysis was performed using only Canadian patients, and subgroup analyses were also conducted.The total study cost for the dabigatran group was $9985 per patient, compared with $10,082 for placebo, a difference of - $97 (95% confidence interval [CI] - $2128 to $3672). Savings arising from fewer clinical events and procedures in the dabigatran 110 mg twice-daily group were enough to offset the cost of the study drug. In Canadian patients, the difference was $250 (95% CI -$2848 to $4840). Both differences were considered cost neutral. Dabigatran 110 mg twice daily was cost saving or cost neutral in many subgroups that were considered.Dabigatran 110 mg twice daily was cost neutral for patients in the MANAGE trial. Our cost findings support the use of dabigatran 110 mg twice daily in patients with MINS.ClinicalTrials.gov identifier number NCT01661101.

Chronic obstructive pulmonary disease (COPD) poses a significant but heterogeneous burden to individuals and healthcare systems. Policymakers develop targeted policies to minimize this burden but need personalized tools to evaluate novel interventions and target them to subpopulations most likely to benefit. We developed a platform to identify subgroups that are at increased risk of emergency department visits, hospitalizations and mortality and to provide stratified patient input in economic evaluations of COPD interventions. We relied on administrative and survey data from Ontario, Canada and applied a combination of microsimulation and multi-state modeling methods. We illustrated the functionality of the platform by quantifying outcomes across smoking status (current, former, never smokers) and by estimating the effect of smoking cessation on resource use and survival, by comparing outcomes of hypothetical cohorts of smokers who quit at diagnosis and smokers that continued to smoke post diagnosis. The cumulative incidence of all-cause mortality was 37.9% (95% CI: 34.9, 41.4) for never smokers, 34.7% (95% CI: 32.1, 36.9) for current smokers, and 46.4% (95% CI: 43.6, 49.0) for former smokers, at 14 years. Over 14 years, smokers who did not quit at diagnosis had 16.3% (95% CI: 9.6, 38.4%) more COPD-related emergency department visits than smokers who quit at diagnosis. In summary, we combined methods from clinical and economic modeling to create a novel tool that policymakers and health economists can use to inform future COPD policy decisions and quantify the effect of modifying COPD risk factors on resource utilization and morality.

OBJECTIVES (1) To explore individual and family characteristics related to anthropometric and cardiometabolic health indicators and (2) examine whether characteristics that correlate with cardiometabolic health indicators differ across severity of obesity at time of entry to Canadian pediatric weight management clinics. METHODS We conducted a cross-sectional analysis of 2-17 year olds with overweight or obesity who registered in the CANadian Pediatric Weight Management Registry (CANPWR) between May 2013 and October 2017 prior to their first clinic visit. Individual modifiable health behaviors included dietary intake, physical activity, screen time, and sleep. Family characteristics included parental BMI, family medical history, socioeconomic status and family structure. Linear mixed effects stepwise regression analysis was performed to determine which characteristics were related to each health indicator: BMI z-score; waist circumference; waist to height ratio; blood pressure; glycemia; HDL cholesterol; non-HDL cholesterol; triglycerides. RESULTS This study included 1296 children (mean age ± standard deviation: 12.1 ± 3.5 years; BMI z-score: 3.55 ± 1.29; 95.3% with obesity). Hours spent sleeping (estimated β = -0.10; 95% CI [-0.15, -0.05], p = 0.0001), hours per week of organized physical activity (estimated β = -0.32; 95% CI [-0.53, -0.11], p = 0.0026), daily sugared drink intake (estimated β = 0.06; 95% CI [0.01, 0.10], p = 0.0136) and maternal BMI (estimated β = 0.03; 95% CI [0.02, 0.04], p

INTRODUCTION AND OBJECTIVE:Cardiovascular disease (CVD) is the second most common cause of death in prostate cancer (PC) patients, yet the prevalence of CVD and its risk factors have been incomplet...

Objective To determine if virtual care with remote automated monitoring (RAM) technology versus standard care increases days alive at home among adults discharged after non-elective surgery during the covid-19 pandemic. Design Multicentre randomised controlled trial. Setting 8 acute care hospitals in Canada. Participants 905 adults (≥40 years) who resided in areas with mobile phone coverage and were to be discharged from hospital after non-elective surgery were randomised either to virtual care and RAM (n=451) or to standard care (n=454). 903 participants (99.8%) completed the 31 day follow-up. Intervention Participants in the experimental group received a tablet computer and RAM technology that measured blood pressure, heart rate, respiratory rate, oxygen saturation, temperature, and body weight. For 30 days the participants took daily biophysical measurements and photographs of their wound and interacted with nurses virtually. Participants in the standard care group received post-hospital discharge management according to the centre’s usual care. Patients, healthcare providers, and data collectors were aware of patients’ group allocations. Outcome adjudicators were blinded to group allocation. Main outcome measures The primary outcome was days alive at home during 31 days of follow-up. The 12 secondary outcomes included acute hospital care, detection and correction of drug errors, and pain at 7, 15, and 30 days after randomisation. Results All 905 participants (mean age 63.1 years) were analysed in the groups to which they were randomised. Days alive at home during 31 days of follow-up were 29.7 in the virtual care group and 29.5 in the standard care group: relative risk 1.01 (95% confidence interval 0.99 to 1.02); absolute difference 0.2% (95% confidence interval −0.5% to 0.9%). 99 participants (22.0%) in the virtual care group and 124 (27.3%) in the standard care group required acute hospital care: relative risk 0.80 (0.64 to 1.01); absolute difference 5.3% (−0.3% to 10.9%). More participants in the virtual care group than standard care group had a drug error detected (134 (29.7%) v 25 (5.5%); absolute difference 24.2%, 19.5% to 28.9%) and a drug error corrected (absolute difference 24.4%, 19.9% to 28.9%). Fewer participants in the virtual care group than standard care group reported pain at 7, 15, and 30 days after randomisation: absolute differences 13.9% (7.4% to 20.4%), 11.9% (5.1% to 18.7%), and 9.6% (2.9% to 16.3%), respectively. Beneficial effects proved substantially larger in centres with a higher rate of care escalation. Conclusion Virtual care with RAM shows promise in improving outcomes important to patients and to optimal health system function. Trial registration ClinicalTrials.gov NCT04344665 .

We develop tests of goodness of fit of the exponential model against some over/under dispersion family of distributions. In particular, we develop 3 score test statistics and 3 likelihood ratio statistics. These are (S1, L1), (S2, L2), and (S3, L3) based on a general over-dispersed family of distributions, two specic over/under dispersed exponential models, namely, the gamma and the Weibull distributions, respectively. A simulation study shows that the statistics S3 and L3 have best overall performance, in terms of both, level and power. However, the statistic L3 can be liberal in some instances and it needs the maximum likelihood estimates of the parameters of the Weibull distribution as opposed to the statistic S3 which is very simple to use. So, our recommendation is to use the statistic S3 to test the fit of an exponential distribution over any over/under-dispersed exponential distribution.

We describe the cardiovascular risk profile in a representative cohort of patients with prostate cancer treated with or without androgen deprivation therapy.We prospectively characterized in detail 2,492 consecutive men (mean age 68 years) with prostate cancer (newly diagnosed or with a plan to prescribe androgen deprivation therapy for the first time) from 16 Canadian sites. Cardiovascular risk was estimated by calculating Framingham risk scores.Most men (92%) had new prostate cancer (intermediate risk 41%, high risk 50%). The highest level of education achieved was primary school in 12%. Most (58%) were current or former smokers, 22% had known cardiovascular disease, 16% diabetes, 45% hypertension, 31% body mass index 30 kg/mTwo-thirds of men with prostate cancer are at high cardiovascular risk. There is a positive association between a plan to use androgen deprivation therapy and baseline cardiovascular risk factors. However, this association is explained by confounding factors.

In this paper, we develop estimation procedure for the parameters of a zero-inflated over-dispersed/under-dispersed count model in the presence of missing responses. In particular, we deal with a zero-inflated extended negative binomial model in the presence of missing responses. A weighted expectation maximization algorithm is used for the maximum likelihood estimation of the parameters involved. Some simulations are conducted to study the properties of the estimators. Robustness of the procedure is shown when count data follow other over-dispersed models, such as the log-normal mixture of the Poisson distribution or even from a zero-inflated Poisson model. An illustrative example and a discussion leading to some conclusions are given. Copyright © 2016 John Wiley & Sons, Ltd.

364 Background: Cardiovascular disease (CVD) is the second most common cause of death in prostate cancer (PC) patients, yet the prevalence of CVD and its risk factors have been incompletely described in this population. Androgen deprivation therapy (ADT) is a risk factor for CVD. The objective of this study were to describe the CVD characteristics and risk factors in PC patients and the relationship between CVD risk and how ADT is used in real-world practice. Methods: RADICAL-PC (Role of Androgen Deprivation Therapy in CArdiovascular Disease – A Longitudinal Prostate Cancer Study) is an ongoing prospective cohort study. We recruited 2395 consecutive men (mean age 68 years) with newly diagnosed PC or with a plan to prescribe ADT for the first time. Cardiovascular risk was estimated by calculating Framingham risk scores. A Framingham score >17 (corresponding with a predicted 10-year CVD risk of >30%) was considered high-risk. Multivariable logistic regression was performed with ADT use as the outcome variable and CVD risk factors as the exposures of interest. Results: The prevalence of known CVD for the entire cohort was 22% and 35% had a Framingham risk score >17. Most participants (58%) were current or former smokers; 16% had diabetes; 45% had hypertension and 23% had high blood pressure but had not received a diagnosis of hypertension; 31% were obese (BMI ≥30kg/m2); 24% had low levels of physical activity. There was a positive relationship between each major cardiovascular risk factor and the use of ADT. However, after adjustment for age, education, alcohol use, BMI and time from PC diagnosis to eligibility assessment, these associations were significantly attenuated. Participants in whom ADT was planned had higher Framingham risk scores than those not intending to receive ADT. This risk was abolished after adjustment for confounders. Conclusions: One in three men with PC is at high cardiovascular risk. Men receiving ADT are a priori at higher CVD risk than PC patients whose treatment strategy does not include ADT. These differences are explained by confounding factors. Clinical trial information: NCT03127631.

Introduction The "gold standard" diagnostic test for assessing in vitro platelet function, light transmission aggregometry (LTA), has limitations to application because of sample requirements. Whole blood or multiple electrode aggregometry (MEA) using the Multiplate® analyzer (Roche Diagnostics) requires smaller blood volumes and less sample manipulation than LTA, making it an attractive clinical testing option. Direct comparisons of MEA with LTA for diagnosis of platelet aggregation abnormalities are few. Methods Ninety-nine patients (66 F/33 M; median age 26 [range 2-86] years), referred for initial laboratory evaluation of mucocutaneous bleeding, had parallel MEA/LTA testing. Concentrations of ADP, arachidonic acid (AA), collagen, and thrombin receptor-activating peptide (TRAP) that produced threshold responses in normal controls were used for testing patients. Results Twenty-nine of the 99 patients (30%) had at least one abnormal agonist response by LTA; 15 of these patients had >1 abnormal agonist response. Thirty-six patients (36%) had at least one abnormal agonist response by MEA; 27 had >1 abnormal agonist response. Sensitivity/specificity of MEA relative to LTA: ADP, 0.70/0.72; AA, 0.71/0.85; collagen, 0.85/0.71; TRAP 0.25/0.84. Negative predictive values (NPVs) for MEA relative to LTA: ADP, 0.90; AA, 0.93; collagen, 0.97; TRAP, 0.96. Conclusions Specific abnormal results of MEA testing did not adequately predict specific abnormalities in LTA testing using threshold agonist concentrations. However, favorable NPVs suggest that MEA may be useful in screening patients for platelet aggregation abnormalities; those with normal MEA results not requiring further diagnostic testing by LTA.