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1.
Br J Clin Pharmacol ; 87(4): 1801-1813, 2021 04.
Article in English | MEDLINE | ID: mdl-32986870

ABSTRACT

AIMS: Aldosterone has been found to influence cancer cell growth, cell cycle regulation and cell migration, including in prostate cancer cells. Spironolactone is an aldosterone antagonist used for managing chronic heart failure (HF) with known antiandrogenic effects. We examined the effect of spironolactone exposure amongst men with HF on the incidence of prostate cancer. METHODS: This retrospective cohort study utilized provincial clinical and administrative databases from the Manitoba Centre for Health Policy. Incident cases of prostate cancer were identified from the provincial cancer registry, and spironolactone exposure was quantified from pharmacare databases. A multivariable proportional hazards model was used to assess the time-dependent impact of spironolactone exposure on prostate cancer incidence. RESULTS: A total of 18 562 men with newly diagnosed HF from 2007 to 2015 with a median age of 72 years (interquartile range: 61-81) and a median follow-up from HF diagnosis to prostate cancer incidence of 2.7 years (interquartile range: 1.1-4.9) were included. A time-dependent multivariable analysis of spironolactone exposure following HF diagnosis found a reduced the risk of prostate cancer hazard ratio 0.55 (95% confidence interval 0.31-0.98, P = .043). CONCLUSION: Spironolactone exposure significantly reduced the incidence of prostate cancer amongst men with HF. These findings support the plausibility of aldosterone as a promoter of prostate cancer growth and development. Prospective clinical trials are warranted to further assess the role of spironolactone or other mineralocorticoid receptor antagonists as a means to prevent prostate cancer development or as an adjunctive measure to prostate cancer treatments.


Subject(s)
Heart Failure , Prostatic Neoplasms , Aged , Aged, 80 and over , Heart Failure/epidemiology , Humans , Incidence , Male , Middle Aged , Mineralocorticoid Receptor Antagonists/adverse effects , Prospective Studies , Prostatic Neoplasms/epidemiology , Retrospective Studies , Spironolactone/adverse effects , Treatment Outcome
2.
Am J Clin Oncol ; 43(12): 865-871, 2020 12 01.
Article in English | MEDLINE | ID: mdl-32976179

ABSTRACT

OBJECTIVES: Androgen deprivation therapy (ADT) is the standard of care for men with nonmetastatic hormone-sensitive prostate cancer (nmHSPC) after treatment failure. Although intermittent ADT (iADT) is noninferior to continuous ADT for prostate cancer outcomes, with superior quality of life and cost-to-benefit ratio, little is known regarding its real-world utilization. The authors aimed to determine the utilization of iADT in a Canadian Provincial Cancer Program for relapsed nmHSPC and identified risk factors associated with the nonreceipt of iADT. MATERIALS AND METHODS: This retrospective population-based cohort study used linked administrative databases to identify all patients with relapsed nmHSPC from 2012 to 2016 and quantified ADT prescription history. Patients were defined as iADT eligible if prostate-specific antigen (PSA) was <4 ng/mL and trending downwards on ≥2 sequential PSAs after ≥6 months of ADT. Univariable and multivariable logistic regression analyses were performed to determine factors associated with nonreceipt of iADT. RESULTS: A total of 601 men with relapsed, nmHSPC were included with a median age at relapse of 73 (range, 46 to 96), pre-ADT PSA of 12.2 ng/mL, and a median pre-ADT PSA doubling time of 7.8 months. 80.9% of the cohort were eligible to receive iADT and 74.4% were treated with iADT. On multivariable analysis, patients originally treated with surgery (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.08-0.46) or having a Gleason Score ≥8 (OR, 0.30; 95% CI, 0.12-0.78) had decreased odds of receipt of iADT. Patients with longer PSA doubling times were more likely to receive iADT (OR, 2.71; 95% CI, 1.17-6.31). CONCLUSIONS: The utilization of iADT was relatively common for men in Manitoba during the study period, however, the uptake of iADT can be improved among identified subgroups.


Subject(s)
Adenocarcinoma/drug therapy , Androgen Antagonists/therapeutic use , Antineoplastic Agents, Hormonal/therapeutic use , Prostatic Neoplasms/drug therapy , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Aged , Aged, 80 and over , Humans , Kallikreins/blood , Male , Manitoba/epidemiology , Marital Status , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Prostate-Specific Antigen/blood , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathology , Prostatic Neoplasms/therapy , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Radiation Oncologists , Retrospective Studies , Survival Analysis
3.
Stud Health Technol Inform ; 257: 184-188, 2019.
Article in English | MEDLINE | ID: mdl-30741193

ABSTRACT

BACKGROUND: Early reports in the literature describe using student-generated questions as a method of student learning as well as augmenting question exam banks. Reports on the performance of student-generated questions versus faculty-generated questions, however, remain limited. This study aims to compare the question performance of student-generated versus faculty-generated multiple-choice questions (MCQ). OBJECTIVES: To determine if student-generated questions using mobile audience response systems and online discussion boards have similar item discrimination scores as faculty-generated questions. METHODS: A team-based learning session was used to create 113 student-generated multiple-choice questions (SGQs). A 20 question MCQ quiz was presented to a second year medical school class made of 10 randomly selected SGQs and 10 randomly selected faculty-generated multiple-choice questions (FGQs). Item analysis was performed on the test results. RESULTS: The data showed no statistical difference in the point-biserial scores between the two groups (average point-biserial 0.31 students vs 0.36 faculty, p=0.14), with 90% of student-generated and 100% of faculty-generated questions meeting a cut-off of point-biserial score >0.2. Interestingly, student-generated questions were statistically more difficult than the faculty-generated questions (Item Difficulty score 0.46 students vs 0.69 faculty, p=0.003). CONCLUSIONS: This study suggests that student-generated compared to faculty-generated MCQs have similar item discrimination scores, but are perhaps more difficult questions.


Subject(s)
Computer-Assisted Instruction , Schools, Medical , Students, Medical , Computer-Assisted Instruction/standards , Educational Measurement , Faculty , Humans , Learning
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