1,626 research outputs found

    Traumatic brain injury-associated epigenetic changes and the risk for neurodegenerative diseases

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    Epidemiological studies have shown that traumatic brain injury (TBI) increases the risk for developing neurodegenerative diseases (NDs). However, molecular mechanisms that underlie this risk are largely unidentified. TBI triggers widespread epigenetic modifications. Similarly, NDs such as Alzheimer’s or Parkinson’s are associated with numerous epigenetic changes. Although epigenetic changes can persist after TBI, it is unresolved if these modifications increase the risk of later ND development and/or dementia. We briefly review TBI-related epigenetic changes, and point out putative feedback loops that might contribute to long-term persistence of some modifications. We then focus on evidence suggesting persistent TBI-associated epigenetic changes may contribute to pathological processes (e.g., neuroinflammation) which may facilitate the development of specific NDs – Alzheimer’s disease, Parkinson’s disease, or chronic traumatic encephalopathy. Finally, we discuss possible directions for TBI therapies that may help prevent or delay development of NDs

    Cost-effectiveness of rosuvastatin in comparison with generic atorvastatin and simvastatin in a Swedish population at high risk of cardiovascular events

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    Background: To assess the long-term cost-effectiveness of rosuvastatin therapy compared with generic simvastatin and generic atorvastatin in reducing the incidence of cardiovascular events and mortality in a Swedish population with Framingham risk ≥20%. Methods: A probabilistic Monte Carlo simulation model based on data from JUPITER (the Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) was used to estimate the long-term cost-effectiveness of rosuvastatin 20 mg daily versus simvastatin or atorvastatin 40 mg for the prevention of cardiovascular death and morbidity. The three-stage model included cardiovascular event prevention simulating the 4 years of JUPITER, initial prevention beyond the trial, and subsequent cardiovascular event prevention. A Swedish health care payer perspective (direct costs only) was modeled for a lifetime horizon, with 2008/2009 as the costing period. Univariate and probabilistic sensitivity analyses were performed. Results: The incremental cost per quality-adjusted life-year (QALY) gained with rosuvastatin 20 mg over simvastatin or atorvastatin 40 mg ranged from SEK88,113 (rosuvastatin 20 mg versus simvastatin 40 mg; Framingham risk ≥30%; net avoidance of 34 events/1000 patients) to SEK497,542 (versus atorvastatin 40 mg: Framingham risk ≥20%; net avoidance of 11 events/1000 patients) over a lifetime horizon. Probabilistic sensitivity analyses indicated that at a willingness-to-pay threshold of SEK500,000/QALY, rosuvastatin 20 mg would be cost-effective for approximately 75%–85% of simulations relative to atorvastatin or simvastatin 40 mg. Sensitivity analyses indicated the findings to be robust. Conclusion: Rosuvastatin 20 mg is cost-effective over a lifetime horizon compared with generic simvastatin or atorvastatin 40 mg in patients at high cardiovascular risk in Sweden
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