Appraising and applying evidence about a diagnostic test during a performance-based assessment

BACKGROUND: The practice of Evidence-based Medicine requires that clinicians assess the validity of published research and then apply the results to patient care. We wanted to assess whether our soon-to-graduate medical students could appraise and apply research about a diagnostic test within a clinical context and to compare our students with peers trained at other institutions. METHODS: 4(th )year medical students who previously had demonstrated competency at probability revision and just starting first-year Internal Medicine residents were used for this research. Following an encounter with a simulated patient, subjects critically appraised a paper about an applicable diagnostic test and revised the patient's pretest probability given the test result. RESULTS: The medical students and residents demonstrated similar skills at critical appraisal, correctly answering 4.7 and 4.9, respectively, of 6 questions (p = 0.67). Only one out of 28 (3%) medical students and none of the 15 residents were able to correctly complete the probability revision task (p = 1.00). CONCLUSIONS: This study found that most students completing medical school are able to appraise an article about a diagnostic test but few are able to apply the information from the article to a patient. These findings raise questions about the clinical usefulness of the EBM skills possessed by graduating medical students within the area of diagnostic testing

Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences

Efficient processing of information by the central nervous system (CNS) represents an important evolutionary advantage. Thus, homeostatic mechanisms have developed that provide appropriate circumstances for neuronal signaling, including a highly controlled and stable microenvironment. To provide such a milieu for neurons, extracellular fluids of the CNS are separated from the changeable environment of blood at three major interfaces: at the brain capillaries by the blood-brain barrier (BBB), which is localized at the level of the endothelial cells and separates brain interstitial fluid (ISF) from blood; at the epithelial layer of four choroid plexuses, the blood-cerebrospinal fluid (CSF) barrier (BCSFB), which separates CSF from the CP ISF, and at the arachnoid barrier. The two barriers that represent the largest interface between blood and brain extracellular fluids, the BBB and the BCSFB, prevent the free paracellular diffusion of polar molecules by complex morphological features, including tight junctions (TJs) that interconnect the endothelial and epithelial cells, respectively. The first part of this review focuses on the molecular biology of TJs and adherens junctions in the brain capillary endothelial cells and in the CP epithelial cells. However, normal function of the CNS depends on a constant supply of essential molecules, like glucose and amino acids from the blood, exchange of electrolytes between brain extracellular fluids and blood, as well as on efficient removal of metabolic waste products and excess neurotransmitters from the brain ISF. Therefore, a number of specific transport proteins are expressed in brain capillary endothelial cells and CP epithelial cells that provide transport of nutrients and ions into the CNS and removal of waste products and ions from the CSF. The second part of this review concentrates on the molecular biology of various solute carrier (SLC) transport proteins at those two barriers and underlines differences in their expression between the two barriers. Also, many blood-borne molecules and xenobiotics can diffuse into brain ISF and then into neuronal membranes due to their physicochemical properties. Entry of these compounds could be detrimental for neural transmission and signalling. Thus, BBB and BCSFB express transport proteins that actively restrict entry of lipophilic and amphipathic substances from blood and/or remove those molecules from the brain extracellular fluids. The third part of this review concentrates on the molecular biology of ATP-binding cassette (ABC)-transporters and those SLC transporters that are involved in efflux transport of xenobiotics, their expression at the BBB and BCSFB and differences in expression in the two major blood-brain interfaces. In addition, transport and diffusion of ions by the BBB and CP epithelium are involved in the formation of fluid, the ISF and CSF, respectively, so the last part of this review discusses molecular biology of ion transporters/exchangers and ion channels in the brain endothelial and CP epithelial cells