Statistical significance versus clinical relevance in cardiovascular medicine

Evidence-based medicine is the foundation of everyday clinical practices and large clinical trials investigating the effects of various interventions on morbidity and survival and generally provide the most robust evidence. Cardiovascular medicine is considered one of the most evidence-based disciplines of medicine. However, there are a number of limitations to the general applicability of clinical trial results in cardiovascular medicine. Although generally useful to the clinician, clinical trials have often been suboptimally designed from 1 or several points of view. As a consequence of flaws in the design and the execution of the trials, statistical significance is quite often not equal to clinical relevance. This article outlines some of the shortcomings of designing and carrying out clinical trials, as well as inadequacies concerning the publication, interpretation, and implementation of the trial results. Evidence-based medicine is obviously not always as solid as one might think.     

Ethanol modifies zebrafish responses to abrupt changes in light intensity

Zebrafish exhibit a preference for dark areas and this behavior has been used to characterize anxiety. Their responses to light may also be modified by ethanol. Using high-speed video recordings, we demonstrated that untreated animals were relatively more active immediately after a bright-dim transition compared to animals exposed to low dose ethanol (2%). Additionally, ethanol-treated larvae were more prone to initiating behavioral responses following abrupt changes of light intensity. In conclusion, the larval zebrafish is an excellent model for investigating locomotory kinetics as well as drugs with anxiolytic properties. High-speed video recordings of behavioral responses in this species are indeed very promising for high-throughput screening.     

A Multi-Level Examination of Stakeholder Perspectives of Implementation of Evidence-Based Practices in a Large Urban Publicly-Funded Mental Health System

Our goal was to identify barriers and facilitators to the implementation of evidence-based practices from the perspectives of multiple stakeholders in a large publicly funded mental health system. We completed 56 interviews with three stakeholder groups: treatment developers (n = 7), agency administrators (n = 33), and system leadership (n = 16). The three stakeholder groups converged on the importance of inner (e.g., agency competing resources and demands, therapist educational background) and outer context (e.g., funding) factors as barriers to implementation. Potential threats to implementation and sustainability included the fiscal landscape of community mental health clinics and an evolving workforce. Intervention characteristics were rarely endorsed as barriers. Inner context, outer context, and intervention characteristics were all seen as important facilitators. All stakeholders endorsed the importance of coordinated collaboration across stakeholder groups within the system to successfully implement evidence-based practices.     

Improved Long-Term Survival after Major Resection for Hepatocellular Carcinoma: A Multicenter Analysis Based on a New Definition of Major Hepatectomy

Background

Advances in the surgical management of hepatocellular carcinoma (HCC) have expanded the indications for curative hepatectomy, including more extensive liver resections. The purpose of this study was to examine long-term survival trends for patients treated with major hepatectomy for HCC.

Patients and Methods

Clinicopathologic data for 1,115 patients with HCC who underwent hepatectomy between 1981 and 2008 at five hepatobiliary centers in France, China, and the USA were assessed. In addition to other performance metrics, outcomes were evaluated using resection of ≥4 liver segments as a novel definition of major hepatectomy.

Results

Major hepatectomy was performed in 539 patients. In the major hepatectomy group, median tumor size was 10 cm (range: 1–27 cm) and 22 % of the patients had bilateral lesions. The TNM Stage distribution included 29 % Stage I, 31 % Stage II, 38 % Stage III, and 2 % Stage IV. The postoperative histologic examination indicated that chronic liver disease was present in 35 % of the patients and tumor microvascular invasion was identified in 60 % of the patients. The 90-day postoperative mortality rate was 4 %. After a median follow-up time of 63 months, the 5-year overall survival rate was 40 %. Patients treated with right hepatectomy (n?=?332) and those requiring extended hepatectomy (n?=?207) had similar 90-day postoperative mortality rates (4 % and 4 %, respectively, p?=?0.976) and 5-year overall survival rates (42 % and 36 %, respectively, p?=?0.523). Postoperative mortality and overall survival rates after major hepatectomy were similar among the participating countries (p?>?0.1) and improved over time with 5-year survival rates of 30 %, 40 %, and 51 % for the years 1981–1989, 1990–1999, and the most recent era of 2000–2008, respectively (p?=?0.004). In multivariate analysis, factors that were significantly associated with worse survivals included AFP level >1,000 ng/mL, tumor size >5 cm, presence of major vascular invasion, presence of extrahepatic metastases, positive surgical margins, and earlier time period in which the major hepatectomy was performed.

Conclusions

This multinational, long-term HCC survival analysis indicates that expansion of surgical indications to include major hepatectomy is justified by the significant improvement in outcomes over the past three decades observed in both the East and the West.