Constructivist Grounded Theory to Establish the Relationship Between Technical Error and Adverse Patient Outcome: Modeling Technical Error and Adverse Outcomes.

BACKGROUND: Preventable intraoperative errors have the potential to lead to adverse events. Our objective was to build a conceptual model of the relationship between minute technical errors performed by the surgeon and adverse patient outcomes. MATERIALS AND METHODS: We used constructivist grounded theory methodology to build a model for the avoidance of technical errors. We used the Observational Clinical Human Reliability Assessment system, which categorizes granular, technical intraoperative errors, as our conceptual framework. We iteratively interviewed surgeons from multiple adult and pediatric surgical specialties, refined our semi-structured interview, and developed a conceptual model. Our model remained stable after interviewing 11 surgeons, and we reviewed it with earlier interviewed surgeons. RESULTS: Our conceptual model helps us understand how technical errors can be associated with adverse outcomes and is applicable to a broad range of surgical steps. Each technical error is defined by a unique improper technical motion that without a compensatory response, it may lead to 1 or more discreet adverse outcomes. Our model includes 5 primary defenses against an adverse outcome, including perfect technique, recognizing imperfect technique, adequately correcting imperfect technique, recognizing an adverse event, and adequately compensating for an adverse event. It includes multiple examples of compensating for a technical error, resulting in a near miss. DISCUSSION: Our conceptual model suggests that adverse patient outcomes can be related to minute technical deviations in surgical technique and provides a basis to study these preventable errors. Our model can also be used to develop intraoperative strategies to prevent these technical surgical errors.

Evaluation of anti-HIF and anti-angiogenic properties of honokiol for the treatment of ocular neovascular diseases.

Pathological activation of the hypoxia-inducible-factor (HIF) pathway leading to expression of pro-angiogenic genes, such as vascular endothelial growth factor (VEGF), is the fundamental cause of neovascularization in ocular ischemic diseases and cancers. We have shown that pure honokiol inhibits the HIF pathway and hypoxia-mediated expression of pro-angiogenic genes in a number of cancer and retinal pigment epithelial (RPE) cell lines. The crude extracts, containing honokiol, from Magnolia plants have been used for thousands of years in the traditional oriental medicine for a number of health benefits. We have recently demonstrated that daily intraperitoneal injection of honokiol starting at postnatal day (P) 12 in an oxygen induced retinopathy mouse model significantly reduced retinal neovascularization at P17. Here, we evaluate the mechanism of HIF inhibition by honokiol in RPE cells. Using chromatin immunoprecipitation experiments, we demonstrate that honokiol inhibits binding of HIF to hypoxia-response elements present on VEGF promoter. We further show using a number of in vitro angiogenesis assays that, in addition to anti-HIF effect, honokiol manifests potent anti-angiogenic effect on human retinal micro vascular endothelial cells. Our results suggest that honokiol possesses potent anti-HIF and anti-angiogenic properties. These properties of honokiol make it an ideal therapeutic agent for the treatment of ocular neovascular diseases and solid tumors.