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PloS One 2022We compared diagnostic accuracy of pleural fluid Xpert MTB/RIF (Xpert) and Xpert MTB/RIF Ultra (Ultra) assays for diagnosing tuberculous pleural effusion (TPE), through... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We compared diagnostic accuracy of pleural fluid Xpert MTB/RIF (Xpert) and Xpert MTB/RIF Ultra (Ultra) assays for diagnosing tuberculous pleural effusion (TPE), through systematic review and comparative meta-analysis.
METHODS
We searched PubMed and Embase databases for publications reporting diagnostic accuracy of Xpert or Ultra for TPE. We used bivariate random-effects modeling to summarize diagnostic accuracy information from individual studies using either mycobacterial culture or composite criteria as reference standard. We performed meta-regression through hierarchical summary receiver operating characteristic (HSROC) modeling to evaluate comparative performance of the two tests from studies reporting diagnostic accuracy of both in the same study population.
RESULTS
We retrieved 1097 publications, and included 74 for review. Summary estimates for sensitivity and specificity for Xpert were 0.52 (95% CI 0.43-0.60, I2 82.1%) and 0.99 (95% CI 0.97-0.99, I2 85.1%), respectively, using culture-based reference standard; and 0.21 (95% CI 0.17-0.26, I2 81.5%) and 1.00 (95% CI 0.99-1.00, I2 37.6%), respectively, using composite reference standard. Summary estimates for sensitivity and specificity for Ultra were 0.68 (95% CI 0.55-0.79, I2 80.0%) and 0.97 (95% CI 0.97-0.99, I2 92.1%), respectively, using culture-based reference standard; and 0.47 (95% CI 0.40-0.55, I2 64.1%) and 0.98 (95% CI 0.95-0.99, I2 54.8%), respectively, using composite reference standard. HSROC meta-regression yielded relative diagnostic odds ratio of 1.28 (95% CI 0.65-2.50) and 1.80 (95% CI 0.41-7.84) respectively in favor of Ultra, using culture and composite criteria as reference standard.
CONCLUSION
Ultra provides superior diagnostic accuracy over Xpert for diagnosing TPE, mainly because of its higher sensitivity.
Topics: Antibiotics, Antitubercular; Humans; Mycobacterium tuberculosis; Pleural Effusion; Rifampin; Sensitivity and Specificity; Tuberculosis
PubMed: 35816471
DOI: 10.1371/journal.pone.0268483 -
The International Journal of... May 2017Xpert® MTB/RIF is the most widely used molecular assay for rapid diagnosis of tuberculosis (TB). The number of polymerase chain reaction cycles after which detectable... (Comparative Study)
Comparative Study Meta-Analysis Review
SETTING
Xpert® MTB/RIF is the most widely used molecular assay for rapid diagnosis of tuberculosis (TB). The number of polymerase chain reaction cycles after which detectable product is generated (cycle threshold value, CT) correlates with the bacillary burden.OBJECTIVE To investigate the association between Xpert CT values and smear status through a systematic review and individual-level data meta-analysis.
DESIGN
Studies on the association between CT values and smear status were included in a descriptive systematic review. Authors of studies including smear, culture and Xpert results were asked for individual-level data, and receiver operating characteristic curves were calculated.
RESULTS
Of 918 citations, 10 were included in the descriptive systematic review. Fifteen data sets from studies potentially relevant for individual-level data meta-analysis provided individual-level data (7511 samples from 4447 patients); 1212 patients had positive Xpert results for at least one respiratory sample (1859 samples overall). ROC analysis revealed an area under the curve (AUC) of 0.85 (95%CI 0.82-0.87). Cut-off CT values of 27.7 and 31.8 yielded sensitivities of 85% (95%CI 83-87) and 95% (95%CI 94-96) and specificities of 67% (95%CI 66-77) and 35% (95%CI 30-41) for smear-positive samples.
CONCLUSION
Xpert CT values and smear status were strongly associated. However, diagnostic accuracy at set cut-off CT values of 27.7 or 31.8 would not replace smear microscopy. How CT values compare with smear microscopy in predicting infectiousness remains to be seen.
Topics: Humans; Microscopy; Polymerase Chain Reaction; Sensitivity and Specificity; Sputum; Tuberculosis
PubMed: 28399963
DOI: 10.5588/ijtld.16.0702 -
PloS One 2016Tuberculosis is an important risk factor for chronic respiratory disease in resource poor settings. The persistence of abnormal spirometry and symptoms after treatment... (Review)
Review
BACKGROUND
Tuberculosis is an important risk factor for chronic respiratory disease in resource poor settings. The persistence of abnormal spirometry and symptoms after treatment are well described, but the structural abnormalities underlying these changes remain poorly defined, limiting our ability to phenotype post-TB lung disease in to meaningful categories for clinical management, prognostication, and ongoing research. The relationship between post-TB lung damage and patient-centred outcomes including functional impairment, respiratory symptoms, and health related quality of life also remains unclear.
METHODS
We performed a systematic literature review to determine the prevalence and pattern of imaging-defined lung pathology in adults after medical treatment for pleural, miliary, or pulmonary TB disease. Data were collected on study characteristics, and the modality, timing, and findings of thoracic imaging. The proportion of studies relating imaging findings to spirometry results and patient morbidity was recorded. Study quality was assessed using a modified Newcastle-Ottowa score. (Prospero Registration number CRD42015027958).
RESULTS
We identified 37 eligible studies. The principle features seen on CXR were cavitation (8.3-83.7%), bronchiectasis (4.3-11.2%), and fibrosis (25.0-70.4%), but prevalence was highly variable. CT imaging identified a wider range of residual abnormalities than CXR, including nodules (25.0-55.8%), consolidation (3.7-19.2%), and emphysema (15.0-45.0%). The prevalence of cavitation was generally lower (7.4-34.6%) and bronchiectasis higher (35.0-86.0%) on CT vs. CXR imaging. A paucity of prospective data, and data from HIV-infected adults and sub-Saharan Africa (sSA) was noted. Few studies related structural damage to physiological impairment, respiratory symptoms, or patient morbidity.
CONCLUSIONS
Post-TB structural lung pathology is common. Prospective data are required to determine the evolution of this lung damage and its associated morbidity over time. Further data are required from HIV-infected groups and those living in sSA.
Topics: Humans; Image Processing, Computer-Assisted; Pattern Recognition, Automated; Prevalence; Tomography, X-Ray Computed; Tuberculosis, Pulmonary; United Kingdom
PubMed: 27518438
DOI: 10.1371/journal.pone.0161176 -
BMJ Open Oct 2023Very few studies and limited information are available regarding the mechanism of fibrosis in tuberculosis (TB). This study aimed to identify, describe and synthesise... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Very few studies and limited information are available regarding the mechanism of fibrosis in tuberculosis (TB). This study aimed to identify, describe and synthesise potential biomarkers of the development of tissue fibrosis induced by TB through a systematic method and meta-analysis.
METHODS
A literature search was performed using keywords according to the topic from electronic databases (ScienceDirect and PubMed) and other methods (websites, organisations and citations). Studies that matched predetermined eligibility criteria were included. The quality assessment tool used was the Quality Assessment of Diagnostic Accuracy Score 2, and the data obtained were processed using Review Manager V.5.3.
RESULTS
Of the 305 studies, 7 met the eligibility criteria with a total sample of 365. The results of the meta-analysis showed that the post-TB group of patients with pulmonary parenchymal fibrosis had a higher transforming growth factor (TGF)-β level (6.09) than the control group (1.82), with a 4.27 (95% CI: 0.92 to 7.61) mean difference. Moreover, patients with residual pleural thickening post-TB had a higher mean of TGF-β (0.61) than the control group (0.56), with a 0.05 (95% CI: 0.04 to 0.06) mean difference. Besides TGF-β, our qualitative synthesis also found that matrix metalloproteinase-1 might have a role in forming and developing pulmonary tissue fibrosis, thus, could be used as a predictor marker in the formation of fibrotic lesions in patients with TB. In addition, several other biomarkers were assessed in the included studies, such as tumour necrosis factor-α, interleukin (IL)-4, IL-8, IL-10, plasminogen activator inhibitor-1 and platelet-derived growth factor. However, this study is not intended to examine these biomarkers.
CONCLUSIONS
There were differences in the results of TGF-β levels in patients with fibrotic lesions compared with controls. TGF-β might be a biomarker of fibrotic tissue formation or increased pulmonary tissue fibrosis in post-TB patients. However, further studies are needed on a larger scale.
Topics: Humans; Transforming Growth Factor beta; Tuberculosis; Fibrosis; Pulmonary Fibrosis; Biomarkers; Matrix Metalloproteinases; Transforming Growth Factors
PubMed: 37827747
DOI: 10.1136/bmjopen-2022-070377 -
BMC Infectious Diseases Dec 2014Although the evidence base regarding the use of the Xpert MTB/RIF assay for diagnosis of pulmonary tuberculosis (TB) when testing respiratory samples is well... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although the evidence base regarding the use of the Xpert MTB/RIF assay for diagnosis of pulmonary tuberculosis (TB) when testing respiratory samples is well established, the evidence base for its diagnostic accuracy for extrapulmonary and sputum-scarce pulmonary TB when testing non-respiratory samples is less clearly defined.
METHODS
A systematic literature search of 7 electronic databases (Medline, EMBASE, ISI Web of Science, BIOSIS, Global Health Database, Scopus and Cochrane Database) was conducted to identify studies of the diagnostic accuracy of the Xpert assay when testing non-respiratory samples compared with a culture-based reference standard. Data were extracted and study quality was assessed using the QUADAS-2 tool. Sensitivities and specificities were calculated on a per-sample basis, stratified by sample type and smear microscopy status and summarised using forest plots. Pooled estimates were calculated for groups with sufficient data.
RESULTS
Twenty-seven studies with a total of 6,026 non-respiratory samples were included. Among the 23 studies comparing Xpert and culture done on the same samples, sensitivity was very heterogeneous with a median sensitivity of 0.83 (IQR, 0.68-0.94) whereas specificities were typically very high (median, 0.98; IQR, 0.89-1.00). The pooled summary estimates of sensitivity when testing smear-positive and smear-negative samples were 0.95 (95% CI 0.91-1.00) and 0.69 (95% CI 0.60-0.80), respectively. Pooled summary estimates of sensitivity varied substantially between sample types: lymph node tissue, 0.96 (95% CI, 0.72-0.99); tissue samples of all types, 0.88 (95% CI, 0.76-0.94); pleural fluid, 0.34 (95% CI, 0.24-0.44); gastric aspirates for diagnosis of sputum-scarce pulmonary TB, 0.78 (IQR, 0.68 - 0.85). Median sensitivities when testing cerebrospinal fluid and non-pleural serous fluid samples were 0.85 (IQR, 0.75-1.00) and 0.67 (IQR, 0.00-1.00), respectively.
CONCLUSION
Xpert detects with high specificity the vast majority of EPTB cases with smear-positive non-respiratory samples and approximately two-thirds of those with smear-negative samples. Xpert is a useful rule-in diagnostic test for EPTB, especially when testing cerebrospinal fluid and tissue samples. In addition, it has a high sensitivity for detecting pulmonary TB when using gastric aspirate samples. These findings support recent WHO guidelines regarding the use of Xpert for TB diagnosis from non-respiratory samples.
Topics: Antibiotics, Antitubercular; Drug Resistance, Bacterial; Exudates and Transudates; Feces; Humans; Mycobacterium tuberculosis; Rifampin; Sensitivity and Specificity; Tuberculosis, Pulmonary
PubMed: 25599808
DOI: 10.1186/s12879-014-0709-7 -
PloS One 2019Pleural fluid adenosine deaminase (ADA) is a useful diagnostic test for tuberculous pleural effusion (TPE), but its exact threshold and accuracy in clinical... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Pleural fluid adenosine deaminase (ADA) is a useful diagnostic test for tuberculous pleural effusion (TPE), but its exact threshold and accuracy in clinical decision-making is unclear. We aimed to assess diagnostic performance of ADA in TPE and to clarify its optimal diagnostic threshold.
METHODS
We searched PubMed, Embase, and Cochrane Library databases for articles indexed up to October 2018. We included English language studies that provided both sensitivity and specificity of ADA in TPE diagnosis. Summary estimates for sensitivity and specificity were obtained through bivariate random effects model, both overall and at prespecified threshold ranges of <36, 40±4, 45-65 and >65 IU/L.
RESULTS
We retrieved 2162 citations, and included 174 publications with 27009 patients. All studies showed high risk of bias. Summary sensitivity, specificity and diagnostic odds ratio estimates were 0.92 (95% CI 0.90-0.93), 0.90 (95% CI 0.88-0.91) and 97.42 (95% CI 74.90-126.72) respectively. 65 studies with ADA threshold of 40±4 IU/L showed summary sensitivity and specificity of 0.93 (95% CI 0.90-0.95) and 0.90 (95% CI 0.87-0.91) respectively. Four studies with ADA threshold >65 IU/L showed summary sensitivity and specificity of 0.86 (95% CI 0.61-0.96) and 0.94 (95% CI 0.80-0.99) respectively.
CONCLUSION
ADA levels in pleural fluid show good diagnostic accuracy in diagnosis of TPE; however, all included studies showed high risk of bias. It was not possible to derive any firm inference on relative clinical utility of different diagnostic thresholds.
Topics: Adenosine Deaminase; Animals; Female; Humans; Male; Pleural Effusion; Tuberculosis, Pleural
PubMed: 30913213
DOI: 10.1371/journal.pone.0213728 -
Tuberculosis (Edinburgh, Scotland) Jul 2022Tuberculous infection of T cell spot test (T-SPOT.TB) and adenosine deaminase (ADA) have a high diagnostic value in pleural effusion for tuberculous pleurisy. However,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tuberculous infection of T cell spot test (T-SPOT.TB) and adenosine deaminase (ADA) have a high diagnostic value in pleural effusion for tuberculous pleurisy. However, there were major differences in existing research in regard to the clinical application of the two trials. Therefore, we conducted a meta-analysis to systematically evaluate the diagnostic value of T-SPOT.TB and ADA.
METHODS
Pubmed, Web of Science and Embase databases were searched to compare diagnosis of tuberculous pleurisy by T-SPOT.TB and ADA. The search period was from inception to August 31, 2021. Statistical analyses were performed using Meta-disc 1.4, Revman 5.4 and Stata 16.0. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were determined. Summary receiver operating characteristic (SROC) curves and the area under the curve (AUC) were used to summarize overall diagnostic performance.
RESULTS
10 qualified original research studies were included, with a total of 2075 patients, of which were 1391 tuberculous pleurisy and 684 non-tuberculous pleurisy. The pooled estimates of diagnostic accuracy of T-SPOT.TB were as follows: sensitivity, 0.88 (95% CI: 0.86-0.90; I = 92.7%); specificity, 0.79 (95% CI: 0.76-0.82; I = 93.7%); PLR, 4.49 (95% CI: 2.29-8.80; I = 94.9%); NLR, 0.15 (95% CI: 0.08-0.30; I = 94.3%), DOR, 35.72 (95% CI: 11.15-114.47; I = 91.5%). The AUC for SROC was 0.9283 (95% CI: 0.8912-0.9654). The pooled estimates of diagnostic accuracy of ADA were as follows: sensitivity, 0.65 (95% CI: 0.62-0.67; I = 98.2%); specificity, 0.90 (95% CI: 0.88-0.92; I = 69.4%); PLR, 6.12 (95% CI: 4.71-7.96; I = 11.9%); NLR, 0.33 (95% CI: 0.12-0.89; I = 99.5%), DOR, 23.18 (95% CI: 12.75-42.14; I = 66.7%). The AUC for SROC was 0.9208 (95% CI: 0.9029-0.9387).
CONCLUSION
Both T-SPOT.TB and ADA had high value in the diagnosis of tuberculous pleurisy. The sensitivity of T-SPOT.TB was higher than ADA, but the specificity of ADA was higher than T-SPOT.TB. On the whole, T-SPOT. TB had similar diagnostic accuracy to ADA.
Topics: Adenosine Deaminase; Humans; Mycobacterium tuberculosis; Pleural Effusion; Pleurisy; Sensitivity and Specificity; T-Lymphocytes; Tuberculosis, Pleural
PubMed: 35777322
DOI: 10.1016/j.tube.2022.102223 -
BMC Infectious Diseases Feb 2024To evaluate the efficacy of urokinase (UK) treatment for tuberculous pleural effusion (TPE). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy of urokinase (UK) treatment for tuberculous pleural effusion (TPE).
METHODS
We searched Chinese biomedical literature database, WanFang data, CNKI, PubMed, EMbase, Web of Science and The Cochrane Library for the randomized controlled trials (RCTs) of urokinase treatment for tuberculous pleurisy from January 2000 to February 2023. Pleural tuberculosis, urokinase and randomized controlled trial were used as keywords. The eligible studies were meta-analyzed by using Revman 5.4.1: risk of bias was assessed, mean difference (MD) and 95% CI were used for continuous variables, pooled studies were conducted using random-effects or fixed-effects models, forest plots were drawn to analyze efficacy, and funnel plots were drawn to discuss publication bias.
RESULTS
Twenty-nine RCTs were included. The meta-analyzed results showed that, on the basis of routine anti-tuberculosis, comparison between the treatment group treated with urokinase and the control group treated with antituberculosis alone, the time of pleural effusion absorption [MD-5.82, 95%CI (- 7.77, - 3.87); P<0.00001] and the residual pleural thickness [MD-1.31, 95%CI (- 1.70, - 0.91); P<0.00001], pleural effusion drainage volume [MD 822.81, 95%CI (666.46,977.96); P<0.00001], FVC%pred [MD 7.95, 95%CI (4.51,11.40); P<0.00001], FEV1%pred [MD 12.67, 95%CI (10.09,15.24); P<0.00001] were significantly different.
CONCLUSION
The clinical effect of urokinase is better than that of antituberculous therapy alone: it can increase total pleural effusion, decrease residual pleural thickness, improve the pulmonary function, and shorten the time of pleural effusion absorption.
Topics: Humans; Tuberculosis, Pleural; Urokinase-Type Plasminogen Activator; Pleural Effusion; Exudates and Transudates; Drainage
PubMed: 38402168
DOI: 10.1186/s12879-024-08975-0 -
Scientific Reports Feb 2022To clarify the predominance of Th1 or Th2 immune responses in malignant and tuberculous pleural effusion (MPE and TPE, respectively), we performed a meta-analysis of...
To clarify the predominance of Th1 or Th2 immune responses in malignant and tuberculous pleural effusion (MPE and TPE, respectively), we performed a meta-analysis of previously published results of the levels of Th1/Th2 cytokines associated with these two types of pleural effusion to evaluate the use of Th1/Th2 cytokine profiles in distinguishing TPE from MPE. We searched the PubMed and EMBASE databases for studies indexed from 2000 to March 2021. We included studies that (a) diagnosed TPE and MPE based on culture or pleural tissue biopsy and that (b) compared levels of Th1/Th2 cytokines between TPE and MPE. Pooled data based on a random-effects model or fixed-effects model and standardized mean differences (SMDs) across studies were used to compare TPE and MPE. We also performed Egger's test to assess publication bias. Of 917 identified studies, a total of 42 studies were selected for the meta-analysis. Compared with MPE subjects, TPE subjects had a significantly higher level of TNF-α [2.22, (1.60-2.84)], an elevated level of IFN-γ [3.30, (2.57-4.40)] in pleural effusion, a situation where the Th1 immune response dominated. Conversely, the levels of interleukin-4 (IL-4) and IL-10 (Th2 cytokines) were higher in the MPE subjects than in the TPE subjects, showing statistically nonsignificant tiny effects [-0.15, (-0.94 to 0.63) and -0.04, (-0.21 to 0.12), respectively]. We confirmed that TPE, a situation in which the Th1 cytokines are predominant. The slight preponderance of Th2 cytokines in MPE, which is not convincing enough to prove.
Topics: Cytokines; Diagnosis, Differential; Humans; Pleural Effusion, Malignant; Th1 Cells; Th2 Cells; Tuberculosis, Pleural
PubMed: 35177742
DOI: 10.1038/s41598-022-06685-8 -
Cureus Mar 2023Multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR TB) is a global concern, with 450,000 new cases and 191,000 deaths in 2021. TB and chronic kidney disease... (Review)
Review
Multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR TB) is a global concern, with 450,000 new cases and 191,000 deaths in 2021. TB and chronic kidney disease (CKD) have been associated since 1974, with suggested explanations such as oxidative stress, malnutrition, dysfunction in vitamin D metabolism, and a compromised cell-mediated immune response. End-stage renal failure patients are more likely to acquire drug resistance due to poor adherence, adverse drug reactions, and inappropriate dose adjustment. We then aim to evaluate the therapeutic outcome of multidrug-resistant TB of the lungs in patients who require hemodialysis in terms of successful treatment (cured and treatment completed) and the associated factors for a favorable outcome. Our secondary goal is to identify unfavorable treatment outcomes (treatment failed, patient died, or patient lost to follow-up) and the underlying associated factors. We conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Guidelines for this systematic review. We included adults (>19 years old) with chronic kidney disease who needed hemodialysis and had microbiologically confirmed multidrug-resistant pulmonary TB, excluding patients who had a renal allograft transplant, were on peritoneal dialysis, had extrapulmonary TB, were children and pregnant patients. We searched PubMed, MEDLINE, PubMed Central, ScienceDirect, Public Library of Science (PLOS), and Google Scholar. Keywords were combined with the Boolean "AND" operator to gather results as well as the medical subject heading (MeSH) search strategy. After screening study articles by reading their titles and abstracts, the following tools were used to assess the risk of bias: the Newcastle-Ottawa scale for observational studies, the Assessment of Multiple Systematic Reviews (AMSTAR) checklist for systematic reviews, and the Joanna Briggs Institute (JBI) assessment tool for case reports. Primary and secondary outcomes were assessed, and a conclusion was made. We gathered 21,570 studies from the databases between 2013 and 2023, with 30,062 total participants. There were eight eligible studies for review. Patients with CKD, particularly those on dialysis, are at increased risk of TB due to a combination of factors that contribute to immunosuppression. TB reactivation is common in chronic renal failure patients. Diagnostic samples such as sputum and pleural fluid had lower sensitivity rates compared to tissue samples, which led to delays in diagnosis and treatment and, most importantly, contributed to drug resistance. All new dialysis patients should undergo interferon-gamma release assay testing. TB-infected patients with severe renal disease (eGFR 30 ml/min) had increased morbidity and mortality; however, the use of directly observed treatment, short-course (DOTS), and renal-dose adjustment of anti-TB medications significantly reduced these risks. Drug-induced hepatitis and cutaneous reactions were common adverse effects of anti-TB medications. A therapeutic drug monitoring guideline is required to reduce these adverse events and even mortality. Additional research is required to assess the safety and efficacy of therapeutic regimens, as well as their outcomes, in this population with multidrug-resistant TB.
PubMed: 37123717
DOI: 10.7759/cureus.36833