Clinical and Informatics Research on Large Clinical Databases

National Library Of Medicine

Investigators

Linked publications, trials & patents

Abstract

A. Association between Female Hormone replacement therapy (HRT) and longevity, cardiovascular diseases, and cancers HRT is an effective treatment for the typical menopause-related symptoms (such as hot flashes, night sweats, irregular periods, etc.) and long-term health problems associated with menopause (the risk of osteoporosis, cardiovascular disease, and stroke). Reports of some studies have trumpeted negative effects of HRT on outcomes such as cardiovascular diseases, cancers, and all-cause mortality. However, the evidence behind them is weak or has been reversed. In this study, we traced about 1.5 million female Medicare beneficiaries from Medicare Part D entry to the onset of each outcome, death, switching to capitated plan, disenrollment from Medicare, or end of data availability whichever comes first and then we compared each risk among women treated with HRT of various kinds with to those not treated, and we treated almost all covariates as time time-dependent in a Cox proportional hazard regression analysis. Estrogen use, but not combined estrogen+progestin use, was associated with a lower risk of breast and other studied cancers and a significant reduction in mortality risk. B. Evaluating the risk of fractures among elderly women enrolled in Medicare Osteoporosis, characterized by progressive deterioration of bone structure due to decreased bone mineral density (BMD), is closely associated with fractures. There are several pharmacotherapies available for the prevention and treatment of postmenopausal osteoporosis, including bisphosphonates, estrogen, raloxifene, denosumab, and more. However, their beneficial and/or detrimental effect on fractures is not well addressed. We are conducting a nationwide cohort study of patients with osteoporosis to compare risks of any, hip, and atypical femur fractures among patients treated with any of the drugs. C. Risk and benefit profiles of Testosterone replacement therapy among senior hypogonadal males Clinical guidelines recommend testosterone replacement therapy (TRT) for adult men with late-onset testosterone deficiency (TD), intending to improve symptoms and elevate testosterone levels into the normal reference range. Benefits are clearly established for sexual function, increases in lean muscle mass and strength, mood, and cognitive function, with possible reduction in frailty and osteoporosis. However, there remains insufficient evidence that TRT is associated with increased risk of mortality, prostate cancer, prostatic hyperplasia, venous thromboembolism, and cardiovascular diseases. We are conducting a nationwide cohort study of senior male patients with hypogonadism to establish risk and benefit profiles of testosterone replacement therapy. D. Risks of neurodegenerative disorders associated with the use of alpha-blocking agents prescribed for benign prostatic hyperplasia Benign prostatic hyperplasia (BPH) is a disease that causes lower urinary tract symptoms, and urology guidelines recommend alpha-blockers as the primary treatment of BPH. However, previous studies reported increased risk of neurodegenerative disorders such as Parkinson's disease (PD) associated with the widely prescribed alpha-blocker, tamsulosin. Currently, there are 5 alpha-blockers available: tamsulosin, terazosin, alfuzosin, doxazosin, and silodosin. Recent data suggest a beneficial effect of 3 alpha-blockers (terazosin, alfuzosin, doxazosin) on PD pathogenesis and a null effect of tamsulosin. We are conducting a nationwide cohort study of senior male patients with BPH to estimate risks of 5 alpha blockers on mortality, PD, and Alzheimer's disease. E. Developing a method to combine machine learning methodology with time-to-event data analysis. Several new methods for survival analysis have been proposed by extending the Cox proportional hazard model with neural networks. They were compared to classical Cox regression analysis and were found to be highly competitive, yielding the best performance in terms of Brier score and binomial log-likelihood. Though classical Cox regression analysis yields instantaneous hazards based on covariates that change over time during the follow-up period, none of the newly proposed methods do not incorporate the effects of time-varying covariates. We are updating a currently available Python package combining the Cox model with neural networks, a.k.a PyCOX, to incorporate time-varying covariates and comparing it with a conventional Cox regression with time-varying covariates in terms of hazard ratios and prediction metrics such as Concordance Index, Integrated Brier Score, and Integrated Binomial Log-Likelihood using real-world Medicare data. F. GLP-1 RAs and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Older Patients with Diabetes. As the use of GLP-1 RAs expands for treating diabetes and obesity, understanding their safety profile is critical. Anecdotal reports have highlighted a serious potential risk: NAION, a sudden and irreversible form of vision loss. Our large-scale observational study will provide crucial data by comparing the incidence of NAION among older Medicare enrollees with type 2 diabetes who are prescribed GLP-1 RAs versus other second-line antidiabetic medications. This research will also help clarify potential differences in risk among specific GLP-1 drugs. G. Hospitalization for Bleeding Associated with Apixaban versus Rivaroxaban in Medicare Beneficiaries. Randomized controlled trials, the gold standard for clinical evidence, often have limitations in representing the real-world patient population. While direct oral anticoagulants (DOACs) like apixaban and rivaroxaban are widely used among older adults–especially Medicare beneficiaries–for preventing thromboembolic events such as stroke in atrial fibrillation, comparative real-world data on bleeding risks–which can result in hospitalization–are limited. This retrospective cohort study leverages extensive Medicare claims data to provide a robust comparison of bleeding-related hospitalization rates in older adults prescribed either apixaban or rivaroxaban, adding crucial evidence to the comparative safety profile of these widely used DOACs. H. Second-generation Herpes Zoster Vaccination and Subsequent Health Outcomes in the Elderly Population. Despite the significant burden of herpes zoster (shingles) and its potential health complications in the elderly, research on the effects of vaccination on broader health outcomes is limited. Although the second-generation recombinant vaccine, Shingrix, offers high efficacy (97% overall) against herpes zoster and its complications in immunocompetent adults over 50, a low vaccination rate (22.0%) among the elderly means many remain unprotected. To address this public health issue, this retrospective observational study aims to examine the association between Shingrix vaccination and subsequent health outcomes in this population, specifically focusing on all-cause mortality, composite cardiovascular disease, and dementia.