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        Comparison of First-Line Dual Combination Treatments in Hypertension: Real-World Evidence from Multinational Heterogeneous Cohorts

        Seng Chan You,Sungjae Jung,Joel N. Swerdel,Patrick B. Ryan,Martijn J. Schuemie,Marc A. Suchard,Seongwon Lee,Jaehyeong Cho,George Hripcsak,Rae Woong Park,Sungha Park 대한심장학회 2020 Korean Circulation Journal Vol.50 No.1

        Background and Objectives: 2018 ESC/ESH Hypertension guideline recommends 2-drug combination as initial anti-hypertensive therapy. However, real-world evidence for effectiveness of recommended regimens remains limited. We aimed to compare the effectiveness of first-line anti-hypertensive treatment combining 2 out of the following classes: angiotensin-converting enzyme (ACE) inhibitors/angiotensin-receptor blocker (A), calcium channel blocker (C), and thiazide-type diuretics (D). Methods: Treatment-naïve hypertensive adults without cardiovascular disease (CVD) who initiated dual anti-hypertensive medications were identified in 5 databases from US and Korea. The patients were matched for each comparison set by large-scale propensity score matching. Primary endpoint was all-cause mortality. Myocardial infarction, heart failure, stroke, and major adverse cardiac and cerebrovascular events as a composite outcome comprised the secondary measure. Results: A total of 987,983 patients met the eligibility criteria. After matching, 222,686, 32,344, and 38,513 patients were allocated to A+C vs. A+D, C+D vs. A+C, and C+D vs. A+D comparison, respectively. There was no significant difference in the mortality during total of 1,806,077 person-years: A+C vs. A+D (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.97−1.20; p=0.127), C+D vs. A+C (HR, 0.93; 95% CI, 0.87−1.01; p=0.067), and C+D vs. A+D (HR, 1.18; 95% CI, 0.95−1.47; p=0.104). A+C was associated with a slightly higher risk of heart failure (HR, 1.09; 95% CI, 1.01−1.18; p=0.040) and stroke (HR, 1.08; 95% CI, 1.01−1.17; p=0.040) than A+D. Conclusions: There was no significant difference in mortality among A+C, A+D, and C+D combination treatment in patients without previous CVD. This finding was consistent across multi-national heterogeneous cohorts in real-world practice.

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        Pomegranate Juice and Extracts Provide Similar Levels of Plasma and Urinary Ellagitannin Metabolites in Human Subjects

        Navindra P. Seeram,Yanjun Zhang,Rodney McKeever,Susanne M. Henning,Ru-po Lee,Marc A. Suchard,Zhaoping Li,Steve Chen,Gail Thames,Alona Zerlin,Martha Nguyen,David Wang,Mark Dreher,David Heber 한국식품영양과학회 2008 Journal of medicinal food Vol.11 No.2

        Pomegranate juice (PJ), a rich source of polyphenols including ellagitannins, has attracted much attention dueto its reported health benefits. This has resulted in the consumption of liquid and powder pomegranate extracts as alternativesto PJ. Therefore establishing the bioavailability of polyphenols from these extract preparations is necessary. Sixteen healthyvolunteers sequentially consumed, with a 1-week washout period between treatments, PJ (8 ounces, Wonderful fruit variety),a pomegranate polyphenol liquid extract (POMxl, 8 ounces), and a pomegranate polyphenol powder extract (POMxp, 1,000mg). The three interventions provided 857, 776, and 755 mg of polyphenols as gallic acid equivalents, respectively. Plasmabioavailability, judged based on ellagic acid levels over a 6-hour period, did not show statistical differences in area under thecurve for the three interventions: 0.14. 0.05, 0.11. 0.03, and 0.11. 0.04 .mol.hour/L for PJ, POMxl, and POMxp, re-spectively. The time of maximum concentration was delayed for POMxp (2.58. 0.42 hours) compared to PJ (0.65. 0.23hours) and POMxl (0.94. 0.06 hours). Urolithin-A glucuronide, a urinary metabolite of ellagic acid, was not significantlydifferent with the three interventions, reaching levels of approximately 1,000 ng/mL. This study demonstrates that ellagitan-nin metabolites, delivered from pomegranate fruits, as PJ, POMxl, and POMxp, reach equivalent levels with a delay in timeof maximum concentration of POMxp compared to PJ and POMxl.

      • Characterizing treatment pathways at scale using the OHDSI network

        Hripcsak, George,Ryan, Patrick B.,Duke, Jon D.,Shah, Nigam H.,Park, Rae Woong,Huser, Vojtech,Suchard, Marc A.,Schuemie, Martijn J.,DeFalco, Frank J.,Perotte, Adler,Banda, Juan M.,Reich, Christian G.,S National Academy of Sciences 2016 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.113 No.27

        <P>Observational research promises to complement experimental research by providing large, diverse populations that would be infeasible for an experiment. Observational research can test its own clinical hypotheses, and observational studies also can contribute to the design of experiments and inform the generalizability of experimental research. Understanding the diversity of populations and the variance in care is one component. In this study, the Observational Health Data Sciences and Informatics (OHDSI) collaboration created an international data network with 11 data sources from four countries, including electronic health records and administrative claims data on 250 million patients. All data were mapped to common data standards, patient privacy was maintained by using a distributed model, and results were aggregated centrally. Treatment pathways were elucidated for type 2 diabetes mellitus, hypertension, and depression. The pathways revealed that the world is moving toward more consistent therapy over time across diseases and across locations, but significant heterogeneity remains among sources, pointing to challenges in generalizing clinical trial results. Diabetes favored a single first-line medication, metformin, to a much greater extent than hypertension or depression. About 10% of diabetes and depression patients and almost 25% of hypertension patients followed a treatment pathway that was unique within the cohort. Aside from factors such as sample size and underlying population (academic medical center versus general population), electronic health records data and administrative claims data revealed similar results. Large-scale international observational research is feasible.</P>

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