Background
Tuberculosis (TB) is the world’s leading infectious cause of death. Extrapulmonary TB accounts for 15% of TB cases, but the proportion is increasing, and over half a million people were ...newly diagnosed with rifampicin‐resistant TB in 2016. Xpert® MTB/RIF (Xpert) is a World Health Organization (WHO)‐recommended, rapid, automated, nucleic acid amplification assay that is used widely for simultaneous detection of Mycobacterium tuberculosis complex and rifampicin resistance in sputum specimens. This Cochrane Review assessed the accuracy of Xpert in extrapulmonary specimens.
Objectives
To determine the diagnostic accuracy of Xpert a) for extrapulmonary TB by site of disease in people presumed to have extrapulmonary TB; and b) for rifampicin resistance in people presumed to have extrapulmonary TB.
Search methods
We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature (LILACS), Scopus, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number (ISRCTN) Registry, and ProQuest up to 7 August 2017 without language restriction.
Selection criteria
We included diagnostic accuracy studies of Xpert in people presumed to have extrapulmonary TB. We included TB meningitis and pleural, lymph node, bone or joint, genitourinary, peritoneal, pericardial, and disseminated TB. We used culture as the reference standard. For pleural TB, we also included a composite reference standard, which defined a positive result as the presence of granulomatous inflammation or a positive culture result. For rifampicin resistance, we used culture‐based drug susceptibility testing or MTBDRplus as the reference standard.
Data collection and analysis
Two review authors independently extracted data, assessed risk of bias and applicability using the QUADAS‐2 tool. We determined pooled predicted sensitivity and specificity for TB, grouped by type of extrapulmonary specimen, and for rifampicin resistance. For TB detection, we used a bivariate random‐effects model. Recognizing that use of culture may lead to misclassification of cases of extrapulmonary TB as ‘not TB' owing to the paucibacillary nature of the disease, we adjusted accuracy estimates by applying a latent class meta‐analysis model. For rifampicin resistance detection, we performed univariate meta‐analyses for sensitivity and specificity separately to include studies in which no rifampicin resistance was detected. We used theoretical populations with an assumed prevalence to provide illustrative numbers of patients with false positive and false negative results.
Main results
We included 66 unique studies that evaluated 16,213 specimens for detection of extrapulmonary TB and rifampicin resistance. We identified only one study that evaluated the newest test version, Xpert MTB/RIF Ultra (Ultra), for TB meningitis. Fifty studies (76%) took place in low‐ or middle‐income countries. Risk of bias was low for patient selection, index test, and flow and timing domains and was high or unclear for the reference standard domain (most of these studies decontaminated sterile specimens before culture inoculation). Regarding applicability, in the patient selection domain, we scored high or unclear concern for most studies because either patients were evaluated exclusively as inpatients at tertiary care centres, or we were not sure about the clinical settings.
Pooled Xpert sensitivity (defined by culture) varied across different types of specimens (31% in pleural tissue to 97% in bone or joint fluid); Xpert sensitivity was > 80% in urine and bone or joint fluid and tissue. Pooled Xpert specificity (defined by culture) varied less than sensitivity (82% in bone or joint tissue to 99% in pleural fluid and urine). Xpert specificity was ≥ 98% in cerebrospinal fluid, pleural fluid, urine, and peritoneal fluid.
Xpert testing in cerebrospinal fluid
Xpert pooled sensitivity and specificity (95% credible interval (CrI)) against culture were 71.1% (60.9% to 80.4%) and 98.0% (97.0% to 98.8%), respectively (29 studies, 3774 specimens; moderate‐certainty evidence).
For a population of 1000 people where 100 have TB meningitis on culture, 89 would be Xpert‐positive: of these, 18 (20%) would not have TB (false‐positives); and 911 would be Xpert‐negative: of these, 29 (3%) would have TB (false‐negatives).
For TB meningitis, ultra sensitivity and specificity against culture (95% confidence interval (CI)) were 90% (55% to 100%) and 90% (83% to 95%), respectively (one study, 129 participants).
Xpert testing in pleural fluid
Xpert pooled sensitivity and specificity (95% CrI) against culture were 50.9% (39.7% to 62.8%) and 99.2% (98.2% to 99.7%), respectively (27 studies, 4006 specimens; low‐certainty evidence).
For a population of 1000 people where 150 have pleural TB on culture, 83 would be Xpert‐positive: of these, seven (8%) would not have TB (false‐positives); and 917 would be Xpert‐negative: of these, 74 (8%) would have TB (false‐negatives).
Xpert testing in urine
Xpert pooled sensitivity and specificity (95% CrI) against culture were 82.7% (69.6% to 91.1%) and 98.7% (94.8% to 99.7%), respectively (13 studies, 1199 specimens; moderate‐certainty evidence).
For a population of 1000 people where 70 have genitourinary TB on culture, 70 would be Xpert‐positive: of these, 12 (17%) would not have TB (false‐positives); and 930 would be Xpert‐negative: of these, 12 (1%) would have TB (false‐negatives).
Xpert testing for rifampicin resistance
Xpert pooled sensitivity (20 studies, 148 specimens) and specificity (39 studies, 1088 specimens) were 95.0% (89.7% to 97.9%) and 98.7% (97.8% to 99.4%), respectively (high‐certainty evidence).
For a population of 1000 people where 120 have rifampicin‐resistant TB, 125 would be positive for rifampicin‐resistant TB: of these, 11 (9%) would not have rifampicin resistance (false‐positives); and 875 would be negative for rifampicin‐resistant TB: of these, 6 (1%) would have rifampicin resistance (false‐negatives).
For lymph node TB, the accuracy of culture, the reference standard used, presented a greater concern for bias than in other forms of extrapulmonary TB.
Authors' conclusions
In people presumed to have extrapulmonary TB, Xpert may be helpful in confirming the diagnosis. Xpert sensitivity varies across different extrapulmonary specimens, while for most specimens, specificity is high, the test rarely yielding a positive result for people without TB (defined by culture). Xpert is accurate for detection of rifampicin resistance. For people with presumed TB meningitis, treatment should be based on clinical judgement, and not withheld solely on an Xpert result, as is common practice when culture results are negative.
2 April 2019
Up to date
All studies incorporated from most recent search
Updated review: all eligible published studies found in the last search (7 Aug, 2017) were included
Substandard (including degraded) and falsified (SF) vaccines are a relatively neglected issue with serious global implications for public health. This has been highlighted during the rapid and ...widespread rollout of COVID-19 vaccines. There has been increasing interest in devices to screen for SF non-vaccine medicines including tablets and capsules to empower inspectors and standardise surveillance. However, there has been very limited published research focussed on repurposing or developing new devices for screening for SF vaccines. To our knowledge, rapid diagnostic tests (RDTs) have not been used for this purpose but have important potential for detecting falsified vaccines. We performed a proof-in-principle study to investigate their diagnostic accuracy using a diverse range of RDT-vaccine/falsified vaccine surrogate pairs. In an initial assessment, we demonstrated the utility of four RDTs in detecting seven vaccines. Subsequently, the four RDTs were evaluated by three blinded assessors with seven vaccines and four falsified vaccines surrogates. The results provide preliminary data that RDTs could be used by multiple international organisations, national medicines regulators and vaccine manufacturers/distributors to screen for falsified vaccines in supply chains, aligned with the WHO global ‘Prevent, Detect and Respond’ strategy.
Egg yolk constitutes a relevant alternative source of antibodies. It presents some advantages over mammalian serum immunoglobulins regarding productivity, animal welfare and specificity. The main ...immunoglobulin present in avian blood (IgY) is transmitted to their offspring and accumulates in egg yolks, which enables the non-invasive harvesting of high amounts of antibodies. Moreover, due to structural differences and phylogenetic distance, IgY is more suitable for diagnostic purposes than mammalian antibodies, since it does not react with certain components of the human immune system and displays greater avidity for mammalian conserved proteins. IgY has been extensively used in health researches, as both therapeutic and diagnostic tool. This article aims to review its applications in both human and veterinary health.
•IgY-technology is a new frontier for biological products•IgY Abs is a non-invasive technology obtained from egg yolks of immunized hens.•A wide range of IgY applications has been successfully tested in both human and animal health.•IgY technology constitutes a relevant alternative for the mammalian antibodies production.
The introduction of molecular methods into the diagnostics of central nervous system (CNS) tumours and the subsequent deciphering of their molecular heterogeneity has resulted in a significant impact ...on paediatric neurooncology. Particularly in the field of rare embryonal and sarcomatous CNS tumours, novel tumour types have been delineated and introduced in the recent 5th edition of the WHO classification of CNS tumours. The rarity and novelty of these tumour types result in diagnostic and therapeutic challenges. Apart from distinct histopathological and molecular features, these tumour types exhibit characteristic clinical properties and require different therapeutic approaches for optimal patient management. However, based on the limited availability of clinical data, current therapeutic recommendations have to be based on data from small, predominantly retrospective patient cohorts. Within this article, we provide guidance for diagnostic work-up and clinical management of rare CNS embryonal tumours (‘embryonal tumour with multi-layered rosettes’, ETMR; ‘CNS neuroblastoma, FOXR2-activated’, CNS NB-FOXR2; ‘CNS tumour with BCOR-ITD, CNS BCOR-ITD) and rare CNS sarcomatous tumours (‘primary intracranial sarcoma, DICER1-mutant’, CNS DICER1; ‘CIC-rearranged sarcoma’, CNS CIC). By emphasizing the significant consequences on patient management in paediatric CNS tumours, we want to encourage wide implementation of comprehensive molecular diagnostics and stress the importance for joint international efforts to further collect and study these rare tumour types.
Diagnostic criteria to classify severity of internal carotid artery (ICA) stenosis vary across vascular laboratories. Consensus-based criteria, proposed by the Society of Radiologists in Ultrasound ...in 2003 (SRUCC), have been broadly implemented but have not been adequately validated. We conducted a multicentered, retrospective correlative imaging study of duplex ultrasound versus catheter angiography for evaluation of severity of ICA stenosis. Velocity data were abstracted from bilateral duplex studies performed between 1/1/2009 and 12/31/2015 and studies were interpreted using SRUCC. Percentage ICA stenosis was determined using North American Symptomatic Carotid Endarterectomy Trial (NASCET) methodology. Receiver operating characteristic analysis evaluated the performance of SRUCC parameters compared with angiography. Of 448 ICA sides (from 224 patients), 299 ICA sides (from 167 patients) were included. Agreement between duplex ultrasound and angiography was moderate (κ = 0.42), with overestimation of degree of stenosis for both moderate (50–69%) and severe (⩾ 70%) ICA lesions. The primary SRUCC parameter for ⩾ 50% ICA stenosis of peak-systolic velocity (PSV) of ⩾ 125 cm/sec did not meet prespecified thresholds for adequate sensitivity, specificity, and accuracy (sensitivity 97.8%, specificity 64.2%, accuracy 74.5%). Test performance was improved by raising the PSV threshold to ⩾ 180 cm/sec (sensitivity 93.3%, specificity 81.6%, accuracy 85.2%) or by adding the additional parameter of ICA/common carotid artery (CCA) PSV ratio ⩾ 2.0 (sensitivity 94.3%, specificity 84.3%, accuracy 87.4%). For ⩾ 70% ICA stenosis, analysis was limited by a low number of cases with angiographically severe disease. Interpretation of carotid duplex examinations using SRUCC resulted in significant overestimation of severity of ICA stenosis when compared with angiography; raising the PSV threshold for ⩾ 50% ICA stenosis to ⩾ 180 cm/sec as a single parameter or requiring the ICA/CCA PSV ratio ⩾ 2.0 in addition to PSV of ⩾ 125 cm/sec for laboratories using the SRUCC is recommended to improve the accuracy of carotid duplex examinations.
Diffusion‐weighted MRI (DWI) holds potential to improve the detection and biological characterization of breast cancer. DWI is increasingly being incorporated into breast MRI protocols to address ...some of the shortcomings of routine clinical breast MRI. Potential benefits include improved differentiation of benign and malignant breast lesions, assessment and prediction of therapeutic efficacy, and noncontrast detection of breast cancer. The breast presents a unique imaging environment with significant physiologic and inter‐subject variations, as well as specific challenges to achieving reliable high quality diffusion‐weighted MR images. Technical innovations are helping to overcome many of the image quality issues that have limited widespread use of DWI for breast imaging. Advanced modeling approaches to further characterize tissue perfusion, complexity, and glandular organization may expand knowledge and yield improved diagnostic tools.
Level of Evidence: 5
J. Magn. Reson. Imaging 2016 J. Magn. Reson. Imaging 2017;45:337–355.
Objective The utilisation of pH level measurements from gastric contents may indicate the preferred tip position of a nasogastric tube or monitor the efficacy of stress ulcer prophylaxis in ...critically ill patients. We aimed to determine the accuracy of pH strip (pHS) tests and pH liquid (pHL) tests compared with the standard pH meter (pHM). Design Diagnostic accuracy study. Setting Gastric contents from medically critically ill patients. Participants In total, 113 gastric samples were collected from 27 critically ill patients. Outcome measure The level of pH measured by pHM, pHS and pHL. Results The pH values measured by pHM, pHS and pHL were 5.83 (IQR 5.12–6.61), 5.50 (IQR 5.00–6.00) and 5.75 (IQR 5.25–6.25), respectively. The pHS test showed greater accuracy, exhibiting a more positive correlation with the standard pHM measurement than the pHL test, with Y=0.95*X+0.56; rho=0.91, p<0.001, and Y=1.09*X - 0.72; rho=0.75, p<0.001, respectively. However, the pHS test demonstrated less agreement with the pHM than the pHL test, with biases of –0.27 versus 0.18, respectively. Noticeably, a slight variation in pHL from the standard pH values was found when we measured gastric contents with a pH lower than 5. Conclusion Both the pHS and pHL methods were good options for measuring gastric pH in critically ill patients. However, it was advisable to find alternative approaches to the pHL testing method when anticipated gastric acidity levels fall below 5. Trial registration number TCTR20220530004.
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