Key Components of the Safe Surgical Ward: International Delphi Consensus Study to Identify Factors for Quality Assessment and Service Improvement.

OBJECTIVE: The aim of this study was to prioritize key factors contributing to safety on the surgical ward BACKGROUND:: There is a variation in the quality and safety of postoperative care between institutions. These variations may be attributed to a combination of process-related issues and structural factors. The aim of this study is to reach a consensus, by means of Delphi methodology, on the most influential of these components that may determine safety in this environment. METHODS: The Delphi questionnaire was delivered via an online questionnaire platform. The panel were blinded. An international panel of safety experts, both clinical and nonclinical, and safety advocates participated. Individuals were selected according to their expertise and extent of involvement in patient safety research, regulation, or patient advocacy. RESULTS: Experts in patient safety from the UK, Europe, North America, and Australia participated. The panel identified the response to a deteriorating patient and the care of outlier patients as error-prone processes. Prioritized structural factors included organizational and environmental considerations such as use of temporary staff, out-of-hours reduction in services, ward cleanliness, and features of layout. The latter includes dedicated areas for medication preparation and adequate space around the patient for care delivery. Potential quality markers for safe care that achieved the highest consensus include leadership, visibility between patients and nurses, and nursing team skill mix and staffing levels. CONCLUSION: International consensus was achieved for a number of factors across process-related and structural themes that may influence safety in the postoperative environment. These should be championed and prioritized for future improvements in patient safety at the ward-level.

Direct transcriptional regulation of Bim by FoxO3a mediates STI571-induced apoptosis in Bcr-Abl-expressing cells.

In this study, we have used the human BV173 and the mouse BaF3/Bcr-Abl-expressing cell lines as model systems to investigate the molecular mechanisms whereby STI571 and FoxO3a regulate Bim expression and apoptosis. FoxO3a lies downstream of Bcr-Abl signalling and is constitutively phosphorylated in the Bcr-Abl-positive BV173 and BaF3/Bcr-Abl cells. Inhibition of Bcr-Abl kinase by STI571 results in FoxO3a activation, induction of Bim expression and apoptosis. Using reporter gene assays, we demonstrate that STI571 and FoxO3a activate Bim transcription through a FoxO-binding site (FHRE) located within the promoter. This was verified by DNA pull-down and chromatin immunoprecipitation analyses. We find that conditional activation of FoxO3a leads to induction of Bim expression and apoptosis. Conversely, silencing of FoxO3a in Bcr-Abl-expressing cells abolishes STI571-mediated Bim induction and apoptosis. Together, the results presented clearly confirm FoxO3a as a key regulator of apoptosis induced by STI571, and show that Bim is a direct transcriptional target of FoxO3a that mediates the STI571-induced apoptosis. Thus, STI571 induces an accumulation of FoxO3a activity which in turn binds directly to an FHRE in the promoter to activate Bim expression and apoptosis.