Prehospital stroke scales as screening tools for early identification of stroke and transient ischemic attack

This is the final version. Available from Wiley via the DOI in this recordBACKGROUND: Rapid and accurate detection of stroke by paramedics or other emergency clinicians at the time of first contact is crucial for timely initiation of appropriate treatment. Several stroke recognition scales have been developed to support the initial triage. However, their accuracy remains uncertain and there is no agreement which of the scales perform better. OBJECTIVES: To systematically identify and review the evidence pertaining to the test accuracy of validated stroke recognition scales, as used in a prehospital or emergency room (ER) setting to screen people suspected of having stroke. SEARCH METHODS: We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid) and the Science Citation Index to 30 January 2018. We handsearched the reference lists of all included studies and other relevant publications and contacted experts in the field to identify additional studies or unpublished data. SELECTION CRITERIA: We included studies evaluating the accuracy of stroke recognition scales used in a prehospital or ER setting to identify stroke and transient Ischemic attack (TIA) in people suspected of stroke. The scales had to be applied to actual people and the results compared to a final diagnosis of stroke or TIA. We excluded studies that applied scales to patient records; enrolled only screen-positive participants and without complete 2 × 2 data. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted a two-stage screening of all publications identified by the searches, extracted data and assessed the methodologic quality of the included studies using a tailored version of QUADAS-2. A third review author acted as an arbiter. We recalculated study-level sensitivity and specificity with 95% confidence intervals (CI), and presented them in forest plots and in the receiver operating characteristics (ROC) space. When a sufficient number of studies reported the accuracy of the test in the same setting (prehospital or ER) and the level of heterogeneity was relatively low, we pooled the results using the bivariate random-effects model. We plotted the results in the summary ROC (SROC) space presenting an estimate point (mean sensitivity and specificity) with 95% CI and prediction regions. Because of the small number of studies, we did not conduct meta-regression to investigate between-study heterogeneity and the relative accuracy of the scales. Instead, we summarized the results in tables and diagrams, and presented our findings narratively. MAIN RESULTS: We selected 23 studies for inclusion (22 journal articles and one conference abstract). We evaluated the following scales: Cincinnati Prehospital Stroke Scale (CPSS; 11 studies), Recognition of Stroke in the Emergency Room (ROSIER; eight studies), Face Arm Speech Time (FAST; five studies), Los Angeles Prehospital Stroke Scale (LAPSS; five studies), Melbourne Ambulance Stroke Scale (MASS; three studies), Ontario Prehospital Stroke Screening Tool (OPSST; one study), Medic Prehospital Assessment for Code Stroke (MedPACS; one study) and PreHospital Ambulance Stroke Test (PreHAST; one study). Nine studies compared the accuracy of two or more scales. We considered 12 studies at high risk of bias and one with applicability concerns in the patient selection domain; 14 at unclear risk of bias and one with applicability concerns in the reference standard domain; and the risk of bias in the flow and timing domain was high in one study and unclear in another 16.We pooled the results from five studies evaluating ROSIER in the ER and five studies evaluating LAPSS in a prehospital setting. The studies included in the meta-analysis of ROSIER were of relatively good methodologic quality and produced a summary sensitivity of 0.88 (95% CI 0.84 to 0.91), with the prediction interval ranging from approximately 0.75 to 0.95. This means that the test will miss on average 12% of people with stroke/TIA which, depending on the circumstances, could range from 5% to 25%. We could not obtain a reliable summary estimate of specificity due to extreme heterogeneity in study-level results. The summary sensitivity of LAPSS was 0.83 (95% CI 0.75 to 0.89) and summary specificity 0.93 (95% CI 0.88 to 0.96). However, we were uncertain in the validity of these results as four of the studies were at high and one at uncertain risk of bias. We did not report summary estimates for the rest of the scales, as the number of studies per test per setting was small, the risk of bias was high or uncertain, the results were highly heterogenous, or a combination of these.Studies comparing two or more scales in the same participants reported that ROSIER and FAST had similar accuracy when used in the ER. In the field, CPSS was more sensitive than MedPACS and LAPSS, but had similar sensitivity to that of MASS; and MASS was more sensitive than LAPSS. In contrast, MASS, ROSIER and MedPACS were more specific than CPSS; and the difference in the specificities of MASS and LAPSS was not statistically significant. AUTHORS' CONCLUSIONS: In the field, CPSS had consistently the highest sensitivity and, therefore, should be preferred to other scales. Further evidence is needed to determine its absolute accuracy and whether alternatives scales, such as MASS and ROSIER, which might have comparable sensitivity but higher specificity, should be used instead, to achieve better overall accuracy. In the ER, ROSIER should be the test of choice, as it was evaluated in more studies than FAST and showed consistently high sensitivity. In a cohort of 100 people of whom 62 have stroke/TIA, the test will miss on average seven people with stroke/TIA (ranging from three to 16). We were unable to obtain an estimate of its summary specificity. Because of the small number of studies per test per setting, high risk of bias, substantial differences in study characteristics and large between-study heterogeneity, these findings should be treated as provisional hypotheses that need further verification in better-designed studies.National Institute for Health Research (NIHR

Affective processes as network hubs

The practical problems of designing and coding a web-based flight simulator for teachers has led to a ‘three-tier plus environment’ model (COVE model) for a software agent’s cognition (C), psychologicsal (O), physical (V) processes and responses to tasks and interpersonal relationships within a learning environment (E). The purpose of this article is to introduce how some of the COVE model layers represent preconscious processing hubs in an AI human-agent’s representation of learning in a serious game, and how an application of the Five Factor Model of psychology in the O layer determines the scope of dimensions for a practical computational model of affective processes. The article illustrates the model with the classroom-learning context of the simSchool application (www.simschool.org); presents details of the COVE model of an agent’s reactions to academic tasks; discusses the theoretical foundations; and outlines the research-based real world impacts from external validation studies as well as new testable hypotheses of simSchool

Increased cholinergic contractions of jejunal smooth muscle caused by a high cholesterol diet are prevented by the 5-HT(4 )agonist – tegaserod

BACKGROUND: Excess cholesterol in bile and in blood is a major risk factor for the respective development of gallbladder disease and atherosclerosis. This lipid in excess negatively impacts the functioning of other smooth muscles, including the intestine. Serotonin is an important mediator of the contractile responses of the small intestine. Drugs targeting the serotonin receptor are used as prokinetic agents to manage intestinal motor disorders, in particular irritable bowel syndrome. Thus, tegaserod, acting on 5-HT(4 )receptor, ideally should obviate detrimental effects of excessive cholesterol on gastrointestinal smooth muscle. In this study we examined the effect of tegaserod on cholesterol-induced changes in the contractile responses of intestinal smooth muscle. METHODS: The effects of a high cholesterol (1%) diet on the in vitro contractile responses of jejunal longitudinal smooth muscle from Richardson ground squirrels to the cholinergic agonist carbachol were examined in the presence or absence of tetrodrodotoxin (TTX). Two groups of animals, fed either low (0.03%) or high cholesterol rat chow diet, were further divided into two subgroups and treated for 28 days with either vehicle or tegaserod. RESULTS: The high cholesterol diet increased, by nearly 2-fold, contractions of the jejunal longitudinal smooth muscle elicited by carbachol. These cholinergic contractions were mediated by muscarinic receptors since they were blocked by scopolamine, a muscarinic receptor antagonist, but not by the nicotinic receptor antagonist, hexamethonium. Tegaserod treatment, which did not affect cholinergic contractions of tissues from low cholesterol fed animals, abrogated the increase caused by the high cholesterol diet. With low cholesterol diet TTX enhanced carbachol-evoked contractions, whereas this action potential blocker did not affect the augmented cholinergic contractions seen with tissues from animals on the high cholesterol diet. Tegaserod-treatment removed the effects of a high cholesterol diet on neuronal muscarinic receptors, as the potentiating effect of TTX on carbachol-elicited contractions was maintained in these animals. CONCLUSION: A high cholesterol diet causes significant changes to cholinergic neurotransmission in the enteric nerves of the jejunum. The mechanisms by which these effects of cholesterol are reversed by tegaserod are unknown, but relate to removal of an inhibitory effect of cholesterol on enteric nerves

Simulation of macroamylasaemia by salivary-type ('S type') hyperamylasaemia

SUMMARY Hyperamylasaemia with low or normal urinary amylase excretion in the face of normal renal function has been noted to be indirect evidence for the existence of macroamylasaemia. A more refined indicator is a low ratio of renal amylase clearance to creatinine clearance. This report describes observations made in three patients, each ofwhom displayed the indirect features suggestive of macroamylasaemia. In none of these patients, however, could a serum macroamylase be demonstrated by chromatography. Ultracentrifugation was also done in one of the patients and likewise failed to disclose a macroamylase in the serum. When the isozyme nature of the serum amylase in each of these patients was examined, there was found to be a marked rise in activity of the salivarytype isoamylase ('S-type amylase').The pancreatic-type isoamylase ('P-type amylase') was normal in one patient and perhaps slightly above normal in the other two. These data indicate that (1) S-type hyperamylasaemia may exhibit the indirect criteria taken to indicate macroamylasaemia and thereby simulate the latter disorder; and (2) unequivocal identification of macroamylasaemia requires the direct demonstration of the presence in the serum of a macromolecular amylase complex. The features originally identified for hyperamylasaemia were the occurrence of hyperamylasaemia with low or normal urinary amylase excretion in the face of normal renal functio