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Shields, Alexandra

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Shields

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Alexandra

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Shields, Alexandra
Author's Publications: search.filters.isAuthorOfPublication.68e0040f-fc4e-45ce-8293-708c4cf9a994

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    Epigenetic Pathways in Human Disease: The Impact of DNA Methylation on Stress-Related Pathogenesis and Current Challenges in Biomarker Development
    (Elsevier, 2017) Argentieri, M. Austin; Nagarajan, Sairaman; Seddighzadeh, Bobak; Baccarelli, Andrea A.; Shields, Alexandra
    HPA axis genes implicated in glucocorticoid regulation play an important role in regulating the physiological impact of social and environmental stress, and have become a focal point for investigating the role of glucocorticoid regulation in the etiology of disease. We conducted a systematic review to critically assess the full range of clinical associations that have been reported in relation to DNA methylation of CRH, CRH-R1/2, CRH-BP, AVP, POMC, ACTH, ACTH-R, NR3C1, FKBP5, and HSD11β1/2 genes in adults. A total of 32 studies were identified. There is prospective evidence for an association between HSD11β2 methylation and hypertension, and functional evidence of an association between NR3C1 methylation and both small cell lung cancer (SCLC) and breast cancer. Strong associations have been reported between FKBP5 and NR3C1 methylation and PTSD, and biologically-plausible associations have been reported between FKBP5 methylation and Alzheimer's Disease. Mixed associations between NR3C1 methylation and mental health outcomes have been reported according to different social and environmental exposures, and according to varying gene regions investigated. We conclude by highlighting key challenges and future research directions that will need to be addressed in order to develop both clinically meaningful prognostic biomarkers and an evidence base that can inform public policy practice.
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    Mortality Rate in Veterans with Multiple Chronic Conditions
    (Springer Verlag, 2007) Lee, Todd A.; Shields, Alexandra; Vogeli, Christine; Gibson, Teresa B.; Woong-Sohn, Min; Marder, William D.; Blumenthal, David; Weiss, Kevin B.
    Background: Among patients with multiple chronic conditions, there is increasing appreciation of the complex interrelatedness of diseases. Previous studies have focused on the prevalence and economic burden associated with multiple chronic conditions, much less is known about the mortality rate associated with specific combinations of multiple diseases. Objective: Measure the mortality rate in combinations of 11 chronic conditions. Design: Cohort study of veteran health care users. Participants Veterans between 55 and 64 years that used Veterans Health Administration health care services between October 1999 and September 2000. Measurements: Patients were identified as having one or more of the following: COPD, diabetes, hypertension, rheumatoid arthritis, osteoarthritis, asthma, depression, ischemic heart disease, dementia, stroke, and cancer. Mutually exclusive combinations of disease based on these conditions were created, and 5-year mortality rates were determined. Results: There were 741,847 persons included. The number in each group by a count of conditions was: none = 217,944 (29.34%); 1 = 221,111 (29.8%); 2 = 175,228 (23.6%); 3 = 86,447 (11.7%); and 4+ = 41,117 (5.5%). The 5-year mortality rate by the number of conditions was: none = 4.1%; 1 = 6.0%; 2 = 7.8%; 3 = 11.2%; 4+ = 16.7%. Among combinations with the same number of conditions, there was significant variability in mortality rates. Conclusions: Patients with multiple chronic conditions have higher mortality rates. Because there was significant variation in mortality across clusters with the same number of conditions, when studying patients with multiple coexisting illnesses, it is important to understand not only that several conditions may be present but that specific conditions can differentially impact the risk of mortality.
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    Multiple Chronic Conditions: Prevalence, Health Consequences, and Implications for Quality, Care Management, and Costs
    (Springer-Verlag, 2007) Vogeli, Christine; Shields, Alexandra; Lee, Todd A.; Gibson, Teresa B.; Marder, William D.; Weiss, Kevin B.; Blumenthal, David
    Persons with multiple chronic conditions are a large and growing segment of the US population. However, little is known about how chronic conditions cluster, and the ramifications of having specific combinations of chronic conditions. Clinical guidelines and disease management programs focus on single conditions, and clinical research often excludes persons with multiple chronic conditions. Understanding how conditions in combination impact the burden of disease and the costs and quality of care received is critical to improving care for the 1 in 5 Americans with multiple chronic conditions. This Medline review of publications examining somatic chronic conditions co-occurring with 1 or more additional specific chronic illness between January 2000 and March 2007 summarizes the state of our understanding of the prevalence and health challenges of multiple chronic conditions and the implications for quality, care management, and costs.