Clinical management of patients with hip and knee osteoarthritis: patient satisfaction with treatment switch.

Hip and knee osteoarthritis (OA) is a common cause of disability, with great quality of life and economic impact, hence the need for effective treatment. Patient satisfaction with treatment is a measure of therapeutic effectiveness and may be used to assess treatment switch in OA patients. A 3-month multicenter, prospective, epidemiologic, non-interventional study was conducted in patients with hip and/or knee OA to assess therapeutic efficacy in patients requiring treatment switch due to lack of effectiveness and/or tolerability in primary care settings. Therapeutic effectiveness was assessed by patient satisfaction using the osteoARthritis Treatment Satisfaction (ARTS) scale. The 3-month disease change [by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and a pain visual analog scale (VAS)] and its correlation with treatment satisfaction were also assessed, as well as patient gastrointestinal (GI) and cardiovascular (CV) profiles. 5,976 patients were analyzed (mean age 68.8 years, 65.1 % female). 67 and 61.8 % showed high GI and CV risk, respectively. The proportion of patients on acetaminophen treatment during the study decreased from 74.8 % at baseline to 23.9 %, while the proportion on non-steroidal anti-inflammatory drugs (NSAIDs) increased from 59.8 to 85.8 %. At 3 months, the standardized (0-100) overall ARTS score increased from 57.7 to 71.6 (p < 0.0001), while disease severity decreased. There was a significant (p < 0.0001) negative association between the ARTS, and the WOMAC and VAS scores. Treatment switching from acetaminophen to NSAIDs as a consequence of poor effectiveness and/or tolerability resulted in increased patient satisfaction with treatment and lower OA severity.

CDC6 expression is regulated by lineage-specific transcription factor GATA1.

GATA1 is a hematopoietic transcription factor essential for expression of most genes encoding erythro-megakaryocytic proteins, i.e., globins and platelet glycoproteins. A role for GATA1 as a cell proliferation regulator has been proposed, as some of its bona fide targets comprise global regulators, such as c-KIT or c-MYC, or cell cycle factors, i.e., CYCLIN D or p21CIP1. In this study, we describe that GATA1 directly regulates the expression of replication licensing factor CDC6. Using reporter transactivation, electrophoretic mobility shift and chromatin immunoprecipitation assays, we show that GATA1 stimulates CDC6 transcription by binding to a canonical binding site located within a 166bp enhancer region upstream CDC6 promoter. This evolutionary conserved GATA binding site conforms to recently described chromatin occupancy rules, i.e., preferred bases within core WGATAR (TGATAA), 5' and 3' flanking bases (GGTGATAAGG) and distance to the transcription initiation site. We also found adjacent conserved binding sites for ubiquitously expressed transcription factor CP2, needed for GATA activity on CDC6 enhancer. Our results add to the growing evidence for GATA1 acting as a direct transcriptional regulator of the cell cycle machinery, thus linking cell proliferation control and specific gene expression programs during lineage differentiation.