부산대학교 도서관

Proton pump inhibitors (PPIs);were initially intended for short-term usage (<8 weeks); however, population-level data demonstrate that long-term, off-label use of PPIs continues to worsen (6-10% of all Americans).;Initially thought to have anti-tumor effects via regulation of cancer cell apoptosis, metastasis, and autophagy,;recent evidence suggests that;PPI use may be associated with increased prostate cancer (PCa);risk. An Icelandic population-based, case-control study demonstrated that 'ever' PPIs use was associated with 12% increased odds of a PCa diagnosis,;and a population-level analysis of 20,000 Ontario men;with a history of a single negative prostate biopsy demonstrated that PPI use was associated with a 40% increase in PCa mortality rate.The objective of this study was to longitudinally evaluate the association of cumulative PPI use with PCa diagnosis and adverse outcomes in a population-based cohort of men with no prior PCa diagnosis or diagnostic work up. This is a population-based study, using provincewide-linked administrative data from Ontario, Canada. We identified all;Ontario men age ≥66 years with no prior PCa diagnosis, work-up (prostate biopsy and/or TRUS),;or treatment, and no PPI/H2-blocker prescriptions within the year preceding study inclusion (Ontario Drug Benefit coverage starts at age 65).;The study inclusion period was January 2003 to December 2018. Men were;followed until death, administrative censoring, or March 31st, 2020.The primary exposure was cumulative PPI use. H2-blocker and glaucoma eye drop use were included as 'positive' and 'negative' controls, respectively.;The primary outcome was time to PCa diagnosis. Secondary outcomes included time to first PSA value ≥4 ng/ml, PSA velocity >0.75 ng/ml/year, clinically significant PCa, high-grade PCa, PSADT;≤6 months, and ADT;prescription/bilateral orchiectomy. Associations between;study exposure and time-to-event outcomes were evaluated using multivariable complementary log-log logistic regression. The median follow-up was 10.1 years. Median age was 66 years. Any PPI use was observed in 26.1% of men. Annual PPI use increased from 0.9% to 15% between 2003 and 2019. On multivariable modeling, adjusted for age, income quintile and comorbidities, cumulative PPI exposure was associated with significantly increased rates of PCa diagnosis (HR=4.10, 95% CI:3.97-4.23). This association persisted following further adjustment for frequency of general practitioner visits and PSA testing (HR=2.87, p<0.001). Cumulative PPI exposure was also associated with increased rates of clinically significant (HR=4.42, 95% CI:4.11-4.75) and high-grade PCa (HR=3.78, 95% CI:3.37-4.24), time to first ADT prescription/bilateral orchiectomy (HR=2.93, 95% CI:2.77-3.09), and PSA doubling time ≤6 months (HR=3.12, 95% CI:2.98-3.27). Compared to PPI use, the associations between H2-blocker use and study outcomes were of significantly lower magnitudes of effect. In a population-based cohort of elderly men with no prior PCa work-up, diagnosis, or treatment and no known prior PPI exposure, cumulative PPI intake was associated with clinically significant increases in the rates of PCa diagnosis, independent of PSA testing frequency and/or general practitioner;visits, as well as adverse PCa-related outcomes. In lieu of prospective data, these results should be used to counsel long-term PPI users regarding the long-term risks of adverse PCa outcomes. [ABSTRACT FROM AUTHOR]