I.V. fluid therapy does not result in the extracellular volume distribution expected from Starling's original model of semi-permeable capillaries subject to hydrostatic and oncotic pressure gradients within the extracellular fluid. Fluid therapy to support the circulation relies on applying a physiological paradigm that better explains clinical and research observations. The revised Starling equation based on recent research considers the contributions of the endothelial glycocalyx layer (EGL), the endothelial basement membrane, and the extracellular matrix. The characteristics of capillaries in various tissues are reviewed and some clinical corollaries considered. The oncotic pressure difference across the EGL opposes, but does not reverse, the filtration rate (the 'no absorption' rule) and is an important feature of the revised paradigm and highlights the limitations of attempting to prevent or treat oedema by transfusing colloids. Filtered fluid returns to the circulation as lymph. The EGL excludes larger molecules and occupies a substantial volume of the intravascular space and therefore requires a new interpretation of dilution studies of blood volume and the speculation that protection or restoration of the EGL might be an important therapeutic goal. An explanation for the phenomenon of context sensitivity of fluid volume kinetics is offered, and the proposal that crystalloid resuscitation from low capillary pressures is rational. Any potential advantage of plasma or plasma substitutes over crystalloids for volume expansion only manifests itself at higher capillary pressures.

Within minutes of a traumatic impact, a robust inflammatory response is elicited in the injured brain. The complexity of this post-traumatic squeal involves a cellular component, comprising the activation of resident glial cells, microglia, and astrocytes, and the infiltration of blood leukocytes. The second component regards the secretion immune mediators, which can be divided into the following sub-groups: the archetypal pro-inflammatory cytokines (Interleukin-1, Tumor Necrosis Factor, Interleukin-6), the anti-inflammatory cytokines (IL-4, Interleukin-10, and TGF-beta), and the chemotactic cytokines or chemokines, which specifically drive the accumulation of parenchymal and peripheral immune cells in the injured brain region. Such mechanisms have been demonstrated in animal models, mostly in rodents, as well as in human brain. Whilst the humoral immune response is particularly pronounced in the acute phase following Traumatic brain injury (TBI), the activation of glial cells seems to be a rather prolonged effect lasting for several months. The complex interaction of cytokines and cell types installs a network of events, which subsequently intersect with adjacent pathological cascades including oxidative stress, excitotoxicity, or reparative events including angiogenesis, scarring, and neurogenesis. It is well accepted that neuroinflammation is responsible of beneficial and detrimental effects, contributing to secondary brain damage but also facilitating neurorepair. Although such mediators are clear markers of immune activation, to what extent cytokines can be defined as diagnostic factors reflecting brain injury or as predictors of long term outcome needs to be further substantiated. In clinical studies some groups reported a proportional cytokine production in either the cerebrospinal fluid or intraparenchymal tissue with initial brain damage, mortality, or poor outcome scores. However, the validity of cytokines as biomarkers is not broadly accepted. This review article will discuss the evidence from both clinical and laboratory studies exploring the validity of immune markers as a correlate to classification and outcome following TBI.

Improvement (defined broadly as purposive efforts to secure positive change) has become an increasingly important activity and field of inquiry within healthcare. This article offers an overview of possible methods for the study of improvement interventions. The choice of available designs is wide, but debates continue about how far improvement efforts can be simultaneously practical (aimed at producing change) and scientific (aimed at producing new knowledge), and whether the distinction between the practical and the scientific is a real and useful one. Quality improvement projects tend to be applied and, in some senses, self-evaluating. They are not necessarily directed at generating new knowledge, but reports of such projects if well conducted and cautious in their inferences may be of considerable value. They can be distinguished heuristically from research studies, which are motivated by and set out explicitly to test a hypothesis, or otherwise generate new knowledge, and from formal evaluations of improvement projects. We discuss variants of trial designs, quasi-experimental designs, systematic reviews, programme evaluations, process evaluations, qualitative studies, and economic evaluations. We note that designs that are better suited to the evaluation of clearly defined and static interventions may be adopted without giving sufficient attention to the challenges associated with the dynamic nature of improvement interventions and their interactions with contextual factors. Reconciling pragmatism and research rigour is highly desirable in the study of improvement. Trade-offs need to be made wisely, taking into account the objectives involved and inferences to be made.

The implementation of evidence-based treatments to deliver high-quality care is essential to meet the healthcare demands of aging populations. However, the sustainable application of recommended practice is difficult to achieve and variable outcomes well recognised. The NHS Institute for Innovation and Improvement Sustainability Model (SM) was designed to help healthcare teams recognise determinants of sustainability and take action to embed new practice in routine care. This article describes a formative evaluation of the application of the SM by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Northwest London (CLAHRC NWL).Data from project teams’ responses to the SM and formal reviews was used to assess acceptability of the SM and the extent to which it prompted teams to take action. Projects were classified as ‘engaged,’ ‘partially engaged’ and ‘non-engaged.’ Quarterly survey feedback data was used to explore reasons for variation in engagement. Score patterns were compared against formal review data and a ‘diversity of opinion’ measure was derived to assess response variance over time.Of the 19 teams, six were categorized as ‘engaged,’ six ‘partially engaged,’ and seven as ‘non-engaged.’ Twelve teams found the model acceptable to some extent. Diversity of opinion reduced over time. A minority of teams used the SM consistently to take action to promote sustainability but for the majority SM use was sporadic. Feedback from some team members indicates difficulty in understanding and applying the model and negative views regarding its usefulness.The SM is an important attempt to enable teams to systematically consider determinants of sustainability, provide timely data to assess progress, and prompt action to create conditions for sustained practice. Tools such as these need to be tested in healthcare settings to assess strengths and weaknesses and findings disseminated to aid development. This study indicates the SM provides a potentially useful approach to measuring teams’ views on the likelihood of sustainability and prompting action. Securing engagement of teams with the SM was challenging and redesign of elements may need to be considered. Capacity building and facilitation appears necessary for teams to effectively deploy the SM.