The potential clinical benefits of medicines optimisation through comprehensive geriatric assessment, carried out by secondary care geriatricians, in a general practice care setting in North Staffordshire, UK: a feasibility study.

Objectives: To evaluate the feasibility and potential clinical benefits of medicines optimisation through comprehensive geriatric assessment (CGA) of frail patients with multiple conditions, by secondary care geriatricians in a general practice care setting.

Methods: Seven general practitioner (GP) practices in one region of Stoke-on-Trent volunteered to take part. GPs selected patients (n=186) who were local permanent residents, at least 65 years old and on eight or more medications per day.

Idiopathic pulmonary fibrosis: immunohistochemical analysis provides fresh insights into lung tissue remodelling with implications for novel prognostic markers.

Aim: This study explored the cellular and biological interrelationships involved in Idiopathic Pulmonary Fibrosis (IPF) lung tissue remodelling using immunohistochemical analysis.

Methods And Results: IPF and control lung tissues were examined for localisation of Epithelial Mesenchymal Transition (EMT), proliferation and growth factor markers assessing their relationship to key histological aberrations. E-cadherin was expressed in IPF and control (Alveolar type II) ATII cells (>75%).

Simvastatin inhibits growth factor expression and modulates profibrogenic markers in lung fibroblasts.

Simvastatin is best known for its antilipidemic action and use in cardiovascular disease due to its inhibition of 3-hydroxy-3-methylglutaryl CoenzymeA (HMG CoA) reductase, a key enzyme in the cholesterol synthesis pathway. Inhibition of biological precursors in this pathway also enables pleiotrophic immunomodulatory and anti-inflammatory capabilities, including modulation of growth factor expression. Connective tissue growth factor (CTGF) and persistent myofibroblast formation are major determinants of the aggressive fibrotic disease, idiopathic pulmonary fibrosis (IPF).

Connective tissue growth factor expression and induction by transforming growth factor-beta is abrogated by simvastatin via a Rho signaling mechanism.

Connective tissue growth factor (CTGF), a potent profibrotic mediator, acts downstream and in concert with transforming growth factor (TGF)-beta to drive fibrogenesis. Significant upregulation of CTGF has been reported in fibrogenic diseases, including idiopathic pulmonary fibrosis (IPF), and is partly responsible for associated excessive fibroblast proliferation and extracellular matrix deposition, but no effective therapy exists for averting such fibrogeneic events. Simvastatin has reported putative antifibrotic actions in renal fibroblasts; this study explores such actions on human IPF-derived and normal lung fibroblasts and examines associated driving mechanisms.