Diagnostic test accuracy of glutamate dehydrogenase for Clostridium difficile: Systematic review and meta-analysis.
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ABSTRACT:
SUBMITTER: Arimoto J
PROVIDER: S-EPMC4945925 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Computer analysis showed that the gene encoding the latex test-reactive protein of Clostridium difficile exhibited high levels of homology with glutamate dehydrogenases from various sources. Further analysis demonstrated that the recombinant protein possessed glutamate dehydrogenase activity. Our results show that the protein that reacts in commercial latex tests for C. difficile is a glutamate dehydrogenase.
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Project description:Clostridium difficile is the principal cause of antibiotic-associated diarrhea. Major metabolic requirements for colonization and expansion of C. difficile after microbiota disturbance have not been fully determined. In this study, we show that glutamate utilization is important for C. difficile to establish itself in the animal gut. When the gluD gene, which codes for glutamate dehydrogenase (GDH), was disrupted, the mutant C. difficile was unable to colonize and cause disease in a hamster model. Further, from the complementation experiment it appears that extracellular GDH may be playing a role in promoting C. difficile colonization and disease progression. Quantification of free amino acids in the hamster gut during C. difficile infection showed that glutamate is among preferred amino acids utilized by C. difficile during its expansion. This study provides evidence of the importance of glutamate metabolism for C. difficile pathogenesis.
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Project description:Muscle ultrasound is an emerging tool for diagnosing sarcopenia. This review aims to summarize the current knowledge on the diagnostic test accuracy of ultrasound for the diagnosis of sarcopenia. We collected data from Ovid Medline, Embase and the Cochrane Central Register of Controlled Trials. Diagnostic test accuracy studies using muscle ultrasound to detect sarcopenia were included. Bivariate random-effects models based on sensitivity and specificity pairs were used to calculate the pooled estimates of sensitivity, specificity and the area under the curves (AUCs) of summary receiver operating characteristic (SROC), if possible. We screened 7332 publications and included 17 studies with 2143 participants (mean age range: 52.6-82.8 years). All included studies had a high risk of bias. The study populations, reference standards and ultrasound measurement methods varied across the studies. Lower extremity muscles were commonly studied, whereas muscle thickness (MT) was the most widely measured parameter, followed by the cross-sectional area (CSA). The MTs of the gastrocnemius, rectus femoris, tibialis anterior, soleus, rectus abdominis and geniohyoid muscles showed a moderate diagnostic accuracy for sarcopenia (SROC-AUC 0.83, 8 studies; SROC-AUC 0.78, 5 studies; AUC 0.82, 1 study; AUC 0.76-0.78, 2 studies; AUC 0.76, 1 study; and AUC 0.79, 1 study, respectively), whereas the MTs of vastus intermedius, quadriceps femoris and transversus abdominis muscles showed a low diagnostic accuracy (AUC 0.67-0.71, 3 studies; SROC-AUC 0.64, 4 studies; and AUC 0.68, 1 study, respectively). The CSA of rectus femoris, biceps brachii muscles and gastrocnemius fascicle length also showed a moderate diagnostic accuracy (AUC 0.70-0.90, 3 studies; 0.81, 1 study; and 0.78-0.80, 1 study, respectively), whereas the echo intensity (EI) of rectus femoris, vastus intermedius, quadriceps femoris and biceps brachii muscles showed a low diagnostic accuracy (AUC 0.52-0.67, 2 studies; 0.48-0.50, 1 study; 0.43-0.49, 1 study; and 0.69, 1 study, respectively). The combination of CSA and EI of biceps brachii or rectus femoris muscles was better than either CSA or EI alone for diagnosing sarcopenia. Muscle ultrasound shows a low-to-moderate diagnostic test accuracy for sarcopenia diagnosis depending on different ultrasound parameters, measured muscles, reference standards and study populations. The combination of muscle quality indicators (e.g., EI) and muscle quantity indicators (e.g., MT) might provide better diagnostic test accuracy.
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Project description:There is an urgent need for rapid and accurate microbiological diagnostic assay for detection of Clostridium difficile infection (CDI). We assessed the diagnostic accuracy of the Xpert Clostridium difficile assay (Xpert CD) for the diagnosis of CDI.We searched PubMed, EMBASE, and Cochrane Library databases to identify studies according to predetermined criteria. STATA 13.0 software was used to analyze the tests for sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curves (AUC). QUADAS-2 was used to assess the quality of included studies with RevMan 5.2. Heterogeneity in accuracy measures was tested with Spearman correlation coefficient and Chi-square.A total of 22 studies were included in the meta-analysis. The pooled sensitivity (95% confidence intervals [CI]) was 0.97 (0.95-0.99) and specificity was 0.95 (0.94-0.96). The AUC was 0.99 (0.97-0.99). Significant heterogeneity was observed when we pooled most of the accuracy measures of selected studies.The Xpert CD assay is a useful diagnostic tool with high sensitivity and specificity in diagnosing toxigenic CDI, and this method has excellent usability due to its rapidity and simplicity.
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Project description:BackgroundThe global COVID-19 pandemic has led to extensive development in many fields, including the diagnosis of COVID-19 infection by mass spectrometry. The aim of this systematic review and meta-analysis was to assess the accuracy of mass spectrometry diagnostic tests developed so far, across a wide range of biological matrices, and additionally to assess risks of bias and applicability in studies published to date.Method23 retrospective observational cohort studies were included in the systematic review using the PRISMA-DTA framework, with a total of 2858 COVID-19 positive participants and 2544 controls. Risks of bias and applicability were assessed via a QUADAS-2 questionnaire. A meta-analysis was also performed focusing on sensitivity, specificity, diagnostic accuracy and Youden's Index, in addition to assessing heterogeneity.FindingsSensitivity averaged 0.87 in the studies reviewed herein (interquartile range 0.81-0.96) and specificity 0.88 (interquartile range 0.82-0.98), with an area under the receiver operating characteristic summary curve of 0.93. By subgroup, the best diagnostic results were achieved by viral proteomic analyses of nasopharyngeal swabs and metabolomic analyses of plasma and serum. The performance of other sampling matrices (breath, sebum, saliva) was less good, indicating that these protocols are currently insufficiently mature for clinical application.ConclusionsThis systematic review and meta-analysis demonstrates the potential for mass spectrometry and 'omics in achieving accurate test results for COVID-19 diagnosis, but also highlights the need for further work to optimize and harmonize practice across laboratories before these methods can be translated to clinical applications.
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Project description:To perform a meta-analysis to compare the diagnostic test accuracy (DTA) of deep learning (DL) in detecting coronavirus disease 2019 (COVID-19), and to investigate how network architecture and type of datasets affect DL performance. We searched PubMed, Web of Science and Inspec from January 1, 2020, to December 3, 2020, for retrospective and prospective studies on deep learning detection with at least reported sensitivity and specificity. Pooled DTA was obtained using random-effect models. Sub-group analysis between studies was also carried out for data source and network architectures. The pooled sensitivity and specificity were 91% (95% confidence interval [CI]: 88%, 93%; I2 = 69%) and 92% (95% CI: 88%, 94%; I2 = 88%), respectively for 19 studies. The pooled AUC and diagnostic odds ratio (DOR) were 0.95 (95% CI: 0.88, 0.92) and 112.5 (95% CI: 57.7, 219.3; I2 = 90%) respectively. The overall accuracy, recall, F1-score, LR+ and LR- are 89.5%, 89.5%, 89.7%, 23.13 and 0.13. Sub-group analysis shows that the sensitivity and DOR significantly vary with the type of network architectures and sources of data with low heterogeneity are (I2 = 0%) and (I2 = 18%) for ResNet architecture and single-source datasets, respectively. The diagnosis of COVID-19 via deep learning has achieved incredible performance, and the source of datasets, as well as network architectures, strongly affect DL performance.
| S-EPMC8445811 | biostudies-literature
Project description:Introduction: Xpert MTB/RIF is a rapid diagnostic instrument for pulmonary tuberculosis (TB). However, studies reported varied accuracy of Xpert MTB/RIF in detecting Mycobacterium tuberculosis in pericardial effusion. Methods: We performed a systematic review of literature in PubMed, published up to February 1, 2020, according to PRISMA guidelines. We screened cross-sectional studies, observational cohort studies, and randomized control trials that evaluated the accuracy of Xpert MTB/RIF in diagnosing TB pericarditis. Papers with noninterpretable results of sensitivity and specificity, non-English articles, and unpublished studies were excluded. The primary outcomes were the sensitivity and specificity of Xpert MTB/RIF. We conducted a quality assessment using QUADAS-2 to evaluate the quality of the studies. A bivariate model pooled the overall sensitivity, specificity, positive likelihood ratios (PLRs), and negative likelihood ratios (NLRs) of included studies. Results: In total, 581 subjects from nine studies were analyzed in this meta-analysis. Our pooled analysis showed that the overall sensitivity, specificity, PLRs and NLRs of included studies were 0.676 (95% CI: 0.580-0.759), 0.994 (95% CI: 0.919-1.000), 110.11 (95% CI: 7.65-1584.57) and 0.326 (95% CI: 0.246-0.433), respectively. Conclusions: Xpert MTB/RIF had a robust specificity but unsatisfactory sensitivity in diagnosing TB pericarditis. These findings indicated that although positive Xpert MTB/RIF test results might be valuable in swiftly distinguishing the diagnosis of TB pericarditis, negative test results might not be able to rule out TB pericarditis. Registration: PROSPERO CRD42020167480 28/04/2020.
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Project description:Melanoma has the highest mortality rate among skin cancers, and early-diagnosis is essential to maximize survival rate. The current procedure for melanoma diagnosis is based on dermoscopy, i.e., a qualitative visual inspection of lesions with intrinsic limited diagnostic reliability and reproducibility. Other non-invasive diagnostic techniques may represent valuable solutions to retrieve additional objective information of a lesion. This review aims to compare the diagnostic performance of non-invasive techniques, alternative to dermoscopy, for melanoma detection in clinical settings. A systematic review of the available literature was performed using PubMed, Scopus and Google scholar databases (2010-September 2020). All human, in-vivo, non-invasive studies using techniques, alternative to dermoscopy, for melanoma diagnosis were included with no restriction on the recruited population. The reference standard was histology but dermoscopy was accepted only in case of benign lesions. Attributes of the analyzed studies were compared, and the quality was evaluated using CASP Checklist. For studies in which the investigated technique was implemented as a diagnostic tool (DTA studies), the QUADAS-2 tool was applied. For DTA studies that implemented a melanoma vs. other skin lesions classification task, a meta-analysis was performed reporting the SROC curves. Sixty-two references were included in the review, of which thirty-eight were analyzed using QUADAS-2. Study designs were: clinical trials (13), retrospective studies (10), prospective studies (8), pilot studies (10), multitiered study (1); the remain studies were proof of concept or had undefined study type. Studies were divided in categories based on the physical principle employed by each diagnostic technique. Twenty-nine out of thirty-eight DTA studies were included in the meta-analysis. Heterogeneity of studies' types, testing strategy, and diagnostic task limited the systematic comparison of the techniques. Based on the SROC curves, spectroscopy achieved the best performance in terms of sensitivity (93%, 95% CI 92.8-93.2%) and specificity (85.2%, 95%CI 84.9-85.5%), even though there was high concern regarding robustness of metrics. Reflectance-confocal-microscopy, instead, demonstrated higher robustness and a good diagnostic performance (sensitivity 88.2%, 80.3-93.1%; specificity 65.2%, 55-74.2%). Best practice recommendations were proposed to reduce bias in future DTA studies. Particular attention should be dedicated to widen the use of alternative techniques to conventional dermoscopy.
| S-EPMC8103840 | biostudies-literature
Project description:The Verigene Clostridium difficile Nucleic Acid Test (Verigene CDF Test) (Nanosphere, Northbrook, IL, USA) is a new multiplex qualitative polymerase chain reaction (PCR) test used to detect C. difficile toxin genes in fecal specimens. To evaluate the performance of the new method, we tested 69 fecal samples from patients with suspected C. difficile infection using the Verigene CDF test, an enzyme immunoassay (EIA) and PCR following anaerobic fecal culture. The sensitivity, specificity, and accuracy of the Verigene CDF test were 96.7% (29/30), 97.4% (38/39), and 97.1% (67/69) respectively, using PCR following fecal culture as a reference method. We also analyzed the potential clinical impact of the Verigene CDF test using chart reviews of the 69 patients with suspected C. difficile infection and found that 11 of the 69 patients were incorrectly diagnosed, and the Verigene CDF test would have led to them receiving more appropriate management including practice of treatment and contact precaution, although, of the 69 patients, there are two whose samples were incorrectly identified with the Verigene CDF test. The Verigene CDF test will have a positive impact on patient care.
| S-EPMC4149505 | biostudies-other
Project description:BackgroundWilms tumour (WT) is caused by aberrant embryonic kidney development and associated with dysregulated expression of short, non-protein-coding RNAs termed microRNAs (miRNAs). At present, there is no reliable circulating biomarker of WT, and this remains an urgent unmet clinical need. Such biomarkers may assist diagnosis, subtyping/prognostication, and disease-monitoring. Here, we established the list of dysregulated circulating miRNAs in WT from the existing published literature.MethodsRegardless of publication date, PubMed, Scopus, Web-of-Science, and Wiley online library databases were searched for English/French studies on WT circulating miRNAs. The PRISMA-compliant search was registered in PROSPERO. The QUADAS tool measured retained article quality. The meta-analysis assessed the sensitivity and specificity of miRNAs for WT diagnosis.ResultsQualitative analysis included 280 samples (172 WT patients; 108 healthy controls) from five of 450 published articles. The study uncovered 301 dysregulated miRNAs (144 up-regulated, 143 down-regulated, 14 conflicting). The pooled sensitivity, specificity, and AUC of the 49 significantly dysregulated microRNAs from two studies was 0.67 [0.62; 0.73], 0.95 [0.92; 0.96] and 0.77 [0.73; 0.81] respectively, indicating a stronger diagnostic potential for WT.ConclusionsCirculating miRNAs show promise for WT diagnosis and prognosis. More research is needed to confirm these findings and determine associations with tumour stage/subtype.Prospero registration numberCRD42022301597.
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