Clinical trials in head injury

Secondary brain damage, following severe head injury is considered to be a major cause for bad outcome. Impressive reductions of the extent of brain damage in experimental studies have raised high expectations for cerebral neuroprotective treatment, in the clinic. Therefore multiple compounds were and are being evaluated in trials. In this review we discuss the pathomechanisms of traumatic brain damage, based upon their clinical importance. The role of hypothermia, mannitol, barbiturates, steroids, free radical scavengers, arachidonic acid inhibitors, calcium channel blockers, N-methyl-D-aspartate (NMDA) antagonists, and potassium channel blockers, will be discussed. The importance of a uniform strategic approach for evaluation of potentially interesting new compounds in clinical trials, to ameliorate outcome in patients with severe head injury, is proposed. To achieve this goal, two nonprofit organizations were founded: the European Brain Injury Consortium (EBIC) and the American Brain Injury Consortium (ABIC). Their aim lies in conducting better clinical trials, which incorporate lessons learned from previous trials, such that the succession of negative, or incomplete studies, as performed in previous years, will cease.

Correlation between serum total globulins and gamma globulins and their use to diagnose failure of passive transfer in foals.

Various assays have been used as an aid to diagnose failure of passive transfer (FPT) of immunoglobulins in neonatal foals, but often lack sensitivity as screening tests, or are time consuming to perform and impractical as confirmatory tests. The aim of the present study was to evaluate whether measurement of serum total globulins (TG; i.e. total protein minus albumin) can be used to estimate the electrophoretic gamma globulin (EGG) fraction in hospitalised neonatal foals with suspected FPT. Sample data from 56 foals were evaluated retrospectively. The coefficient of rank correlation was 0.84. The area under the curve of ROC analysis was 0.887, 0.922 and 0.930 for EGG concentrations <2 g/L, < 4 g/L and <8 g/L, respectively. Cut-offs for TG achieved ≥90% sensitivity for detecting EGG <2 g/L, < 4 g/L and <8 g/L, with negative predictive values of >97% and >94%, using prevalence of 15% and 30%, respectively. These results suggest that measurement of TG can be used as a guide to predicting EGG, provided that appropriate cut-off values are selected, and this technique could be a useful initial screening test for FPT in foals.

Balancing Control and Coaching in CSO Governance : A Paradox Perspective on Board Behavior

How can governance of civil society organizations be conceptualized more adequately by accounting for the dual and simultaneous requirements of controlling and coaching in board behavior? Empirically, we seem to agree that effective governance of a civil society organization is crucial to its sustained viability. Conceptually, however, we observe a lack of consensus on how to best conceptualize CSO governance. By critically juxtaposing two major theoretical lenses to conceptualize governance, namely agency and stewardship theory, we identify a number of challenges conceptualizing board-management relations that deserve our attention. While agency theory privileges controlling behavior, stewardship theory emphasizes the coaching behavior of boards. The purpose of this paper is to offer a concept of governance that is informed by a paradox perspective advancing a subtler, more adequate conceptualization of board governance that accounts for the often conflicting demands on CSO governance. Drawing on a longitudinal interpretive case study, we exemplify our propositions empirically. The paper concludes with discussing the implications of our argument for CSO governance research and practice.