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Institution

University of Tennessee Health Science Center

EducationMemphis, Tennessee, United States
About: University of Tennessee Health Science Center is a education organization based out in Memphis, Tennessee, United States. It is known for research contribution in the topics: Population & Transplantation. The organization has 15716 authors who have published 26884 publications receiving 1176697 citations.


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Journal ArticleDOI
TL;DR: These ligands represent the first members of a novel class of androgens with potential therapeutic applications in male fertility and hormone replacement therapy and demonstrate that nonsteroidal ligands can be structurally modified to produce agonist activity.

219 citations

Journal ArticleDOI
TL;DR: Analysis of data from the Women's Health Initiative estrogen trial shows that CEE reduced fracture risk, but data do not support overall benefit over risk, even in women at highest risk for fracture.
Abstract: Further analyses from the Women's Health Initiative estrogen trial shows that CEE reduced fracture risk. The fracture reduction at the hip did not differ appreciably among risk strata. These data do not support overall benefit over risk, even in women at highest risk for fracture. Introduction: The Women's Health Initiative provided evidence that conjugated equine estrogen (CEE) can significantly reduce fracture risk in postmenopausal women. Additional analysis of the effects of CEE on BMD and fracture are presented. Materials and Methods: Postmenopausal women 50–79 years of age with hysterectomy were randomized to CEE 0.625 mg daily (n = 5310) or placebo (n = 5429) and followed for an average 7.1 years. Fracture incidence was assessed by semiannual questionnaire and verified by adjudication of radiology reports. BMD was measured in a subset of women (N = 938) at baseline and years 1, 3, and 6. A global index was used to examine whether the balance of risks and benefits differed by baseline fracture risk. Results: CEE reduced the risk of hip (hazard ratio [HR], 0.65; 95% CI, 0.45–0.94), clinical vertebral (HR, 0.64; 95% CI, 0.44–0.93), wrist/lower arm (HR, 0.58; 95% CI, 0.47–0.72), and total fracture (HR, 0.71; 95% CI, 0.64–0.80). This effect did not differ among strata according to age, oophorectomy status, past hormone use, race/ethnicity, fall frequency, physical activity, or fracture history. Total fracture reduction was less in women at the lowest predicted fracture risk in both absolute and relative terms (HR, 0.86; 95% CI, 0.68–1.08). CEE also provided modest but consistent positive effects on BMD. The HRs of the global index for CEE were relatively balanced across tertiles of summary fracture risk (lowest risk: HR, 0.81; 95% CI, 0.62–1.05; mid risk: HR, 1.09; 95% CI, 0.92–1.30; highest risk: HR, 1.04; 95% CI, 0.88–1.23; interaction, p = 0.42). Conclusions: CEE reduces the risk of fracture and increases BMD in hysterectomized postmenopausal women. Even among the women with the highest risk for fractures, when considering the effects of estrogen on other important health outcomes, a summary of the burden of monitored effects does not indicate a significant net benefit.

218 citations

Journal ArticleDOI
TL;DR: Recommendations for EVD management are developed based on a thorough literature review using the Grading of Recommendations Assessment, Development, and Evaluation system, with emphasis placed not only on the quality of the evidence, but also on the balance of benefits versus risks, patient values and preferences, and resource considerations.
Abstract: External ventricular drains (EVDs) are commonly placed to monitor intracranial pressure and manage acute hydrocephalus in patients with a variety of intracranial pathologies. The indications for EVD insertion and their efficacy in the management of these various conditions have been previously addressed in guidelines published by the Brain Trauma Foundation, American Heart Association and combined committees of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. While it is well recognized that placement of an EVD may be a lifesaving intervention, the benefits can be offset by procedural and catheter-related complications, such as hemorrhage along the catheter tract, catheter malposition, and CSF infection. Despite their widespread use, there are a lack of high-quality data regarding the best methods for placement and management of EVDs to minimize these risks. Existing recommendations are frequently based on observational data from a single center and may be biased to the authors’ view. To address the need for a comprehensive set of evidence-based guidelines for EVD management, the Neurocritical Care Society organized a committee of experts in the fields of neurosurgery, neurology, neuroinfectious disease, critical care, pharmacotherapy, and nursing. The Committee generated clinical questions relevant to EVD placement and management. They developed recommendations based on a thorough literature review using the Grading of Recommendations Assessment, Development, and Evaluation system, with emphasis placed not only on the quality of the evidence, but also on the balance of benefits versus risks, patient values and preferences, and resource considerations.

218 citations

Journal ArticleDOI
TL;DR: Estrogen plus progestin results among women who initiated use soon after menopause were similar for venous thromboembolism, stroke, and hip fracture but also included evidence of longer-term elevations in breast cancer, total cancer, and the global index.
Abstract: The Women's Health Initiative (WHI) randomized controlled trials—trials of the use of 0.625 mg/day of conjugated equine estrogens (CEE) among 10,739 posthysterectomy women and CEE plus 2.5 mg/day of medroxyprogesterone acetate (MPA) among 16,608 women with an intact uterus—were designed to examine the effects of hormone therapy on coronary heart disease (CHD) risk and overall health benefits versus risks. The trial design projected a major reduction in CHD risk, based on observational studies, for both regimens. Recruitment into both trials took place during 1993–1998. The CEE/MPA trial was stopped early in 2002 (1–8), after an average of 5.6 years of follow-up, on the basis of an elevation in breast cancer incidence in conjunction with an unfavorable global index—defined as time to incident CHD, stroke, pulmonary embolism, breast cancer, colorectal cancer, endometrial cancer, or hip fracture or to death from other causes. As a result, the potential use of this regimen for primary disease prevention was much reduced, and interest began to focus on the safety and efficacy of relatively short-term hormone therapy among recently postmenopausal women. This focus intensified after the CEE trial was also stopped early in 2004 (9–15), after an average of 7.1 years of follow-up, on the basis of an elevation in stroke in conjunction with a limited likelihood of demonstrating a CHD benefit. The global index in the CEE trial, defined as above but without endometrial cancer, differed little between randomization groups, reflecting a balance of health benefits and risks (9). Among women who were assigned to active hormone therapy and reported no prior hormone therapy, only 10% in the CEE trial and 17% in the CEE/MPA trial were within 5 years of menopause at randomization. As such, effects of hormone therapy could not be estimated with precision for these important subsets. An additional sizeable group of women had used hormones prior to WHI enrollment and had either stopped hormone use or chosen to undergo a 3-month washout period prior to randomization. Approximately 84% of these women first initiated hormone therapy within 5 years following menopause in both the CEE and CEE/MPA trials. These women contribute information on health effects among women who initiate hormone therapy soon after menopause, particularly concerning benefits and risks some years after first use of hormone therapy. The WHI observational study, carried out among 93,676 postmenopausal women in the same age range (50–79 years) at enrollment in 1993–1998, is available as an additional source of information on the health effects of these regimens. Women in the observational study were drawn from the same populations as the clinical trial women, and many elements of the protocol were common to the 2 WHI components. These included much baseline questionnaire and interview data, as well as the clinical outcomes ascertained and most aspects of the outcome ascertainment methods (16). Results from joint analyses of clinical trial and observational study data have been reported for cardiovascular disease in relation to CEE/MPA (17) and CEE (18); hazard ratio estimates were in agreement between the clinical trials and the observational study for CHD and venous thromboembolism after allowing for confounding and time since hormone therapy initiation, though there was lesser agreement for stroke. Allowance for duration of hormone therapy use is essential in such analyses, since hormone therapy users in the observational study had often been on the regimen reported at enrollment for several preceding years, and hazard ratios declined with increasing duration of use for both CHD and venous thromboembolism. Similar analyses have been conducted for invasive breast cancer (19, 20). Hazard ratios were higher in the observational study than in the clinical trials for both CEE and CEE/MPA, even after consideration of confounding and duration of use. This residual discrepancy could be explained, however, by higher breast cancer hazard ratios among women who first used hormone therapy soon after menopause, as compared with those who initiated hormone therapy following a lengthy “gap” time. These analyses, suggesting comparatively unfavorable breast cancer effects among recently postmenopausal women, contrast with corresponding results for CHD (21) and coronary calcification (22) that may suggest more favorable effects among younger, recently postmenopausal women. A “postmenopausal estrogen timing hypothesis,” suggesting that estrogens have favorable effects on CHD in recently postmenopausal women but null or harmful effects among older women, has been debated recently (23, 24), with WHI data being central to both sides of the argument. Of course, evaluation of a broader timing hypothesis involving a range of health effects is needed for decision-making concerning use of hormone therapy and is a major focus of this paper. We analyzed the effects of CEE and CEE/MPA (particularly longer-term effects), when initiated soon after menopause, on a range of clinical outcomes, including the global index described above, as well as total invasive cancer incidence and total mortality. The analyses used both WHI clinical trial data and combined WHI clinical trial and observational study data.

217 citations

Journal ArticleDOI
TL;DR: Data support the concept that the inhibition of chain initiation at the β-ketoacyl-ACP synthase III step contributes to the attenuation of fatty acid biosynthesis by acyl-ACP.

217 citations


Authors

Showing all 15827 results

NameH-indexPapersCitations
George P. Chrousos1691612120752
Steven N. Blair165879132929
Bruce L. Miller1631153115975
Ralph A. DeFronzo160759132993
Frank J. Gonzalez160114496971
Robert G. Webster15884390776
Anne B. Newman15090299255
Ching-Hon Pui14580572146
Barton F. Haynes14491179014
Yoshihiro Kawaoka13988375087
Seth M. Steinberg13793680148
Richard J. Johnson13788072201
Kristine Yaffe13679472250
Leslie L. Robison13185464373
Gerardo Heiss12862369393
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
202338
2022194
20211,699
20201,503
20191,401
20181,292