Background The development of a fast and accurate, non-sputum-based point-of-care triage test for tuberculosis (TB) would have a major impact on combating the TB burden worldwide. A new fingerstick blood test has been developed by Cepheid (the Xpert-MTB-Host Response (HR)-Prototype), which generates a ‘TB score’ based on mRNA expression of 3 genes. Here we describe the first prospective findings of the MTB-HR prototype. Methods Fingerstick blood from adults presenting with symptoms compatible with TB in South Africa, The Gambia, Uganda and Vietnam was analysed using the Cepheid GeneXpert MTB-HR prototype. Accuracy of the Xpert MTB-HR cartridge was determined in relation to GeneXpert Ultra results and a composite microbiological score (GeneXpert Ultra and liquid culture) with patients classified as having TB or other respiratory diseases (ORD). Results When data from all sites (n=75 TB, 120 ORD) were analysed, the TB score discriminated between TB and ORD with an AUC of 0·94 (CI, 0·91-0·97), sensitivity of 87% (CI, 77-93%) and specificity of 94% (88-97%). When sensitivity was set at 90% for a triage test, specificity was 86% (CI, 75-97%). These results were not influenced by HIV status or geographical location. When evaluated against a composite microbiological score (n=80 TB, 111 ORD), the TB score was able to discriminate between TB and ORD with an AUC of 0·88 (CI, 0·83-0·94), 80% sensitivity (CI, 76-85%) and 94% specificity (CI, 91-96%). Conclusions Our interim data indicate the Cepheid MTB-HR cartridge reaches the minimal target product profile for a point of care triage test for TB using fingerstick blood, regardless of geographic area or HIV infection status.
As long ago as 1871 it was reported by Bowditch that changes in heart frequency influences the degree of contractility of isolated myocardial preparations. This was subsequently confirmed by Koch-Weser & Blinks (1963). It has recently been shown that quantitative differences exist between structure-activity relation for chronotropic and inotropic effects of 8-adrenoceptor stimulants and 8-sympatholytics and it was postulated that the cardiac &adrenoceptors could probably be subdivided into two groups (Dreyer & Offermeier, 1975). For quantitative in vitro assessments of apparent affinity values on the inotropic j,-receptors it would be preferable to employ methods which could exclude, as far as possible, factors which may influence the results in one way or another.The purpose of this investigation was to determine whether changes in frequency of contraction would influence the apparent affinities of different j3-sympathomimetic drugs for the inotropic 8-receptors to the same extent. To demonstrate that frequency of contraction does in fact influence the force of contraction, isolated left atrial strips from guinea-pigs were mounted in an organ bath perfused by a modified Locke solution at 37" gassed with 5 % C 0 2 in oxygen. A driving stimulus was applied through a pair of silver electrodes in contact with the left atrial strip. The strips were stimulated at different frequencies by squarewave pulses of 5 ms duration. Stimulus intensity was kept constant at approximately 50 % above threshold. Fig. 1 indicates that an increase in frequency of stimulation leads to an increase in the force of contraction up to a certain limit. Frequencies between 0.5 and 5 stimuli s-l may be regarded as the physiological range.To determine to what extent frequency of contraction influences the apparent affinities of j3-sympathomimetic l ' , f
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