Diagnostic Test Accuracy Meta-analysis Research Articles

Loop-mediated isothermal amplification (LAMP) test for diagnosis of uncomplicated malaria in endemic areas: a meta-analysis of diagnostic test accuracy

BackgroundThe global malaria decline has stalled and only a few countries are pushing towards pre-elimination. The aim of the malaria elimination phase is interruption of local transmission of a specified malaria parasite in a defined geographical area. New and improved screening tools and strategies are required for detection and management of very low-density parasitaemia in the field. The objective of this study was to synthesize evidence on the diagnostic accuracy of loop-mediated isothermal amplification (LAMP) test for the detection of malaria parasites among people living in endemic areas.MethodsThis study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy (PRISMA-DTA) guideline. Relevant studies in the health-related electronic databases were searched. According to the criteria set for this study, eligible studies were identified. The quality of included studies was evaluated with the use of a quality assessment checklist. A summary performance estimates such as pooled sensitivity and specificity were stratified by type of LAMP. Bivariate model for data analyses was applied. Summary receiver operating characteristics plots were created to display the results of individual studies in a receiver operating characteristics space. Meta-regression analysis was performed to investigate the sources of heterogeneity among individual studies.ResultsTwenty-seven studies across 17 endemic countries were identified. The vast majority of studies were with unclear risk of bias in the selection of index test. Overall, the pooled test performances were high for Pan LAMP (sensitivity: 0.95, 95% CI 0.91 to 0.97; specificity: 0.98, 95% CI 0.95 to 0.99), Plasmodium falciparum (Pf) LAMP (sensitivity: 0.96, 95% CI 0.94 to 0.98; specificity: 0.99, 95% CI 0.96 to 1.00) or for Plasmodium vivax (Pv) LAMP from 6 studies (sensitivity: 0.98, 95% CI 0.92 to 0.99; specificity: 0.99, 95% CI 0.72 to 1.00). The area under the curve for Pan LAMP (0.99, 95% CI 0.98–1.00), Pf LAMP (0.99, 95% CI 0.97–0.99) and Pv LAMP was (1.00, 95% CI 0.98–1.00) indicated that the diagnostic performance of these tests were within the excellent accuracy range. Meta-regression analysis showed that sample size had the greatest impact on test performance, among other factors.ConclusionsThe current findings suggest that LAMP-based assays are appropriate for detecting low-level malaria parasite infections in the field and would become valuable tools for malaria control and elimination programmes. Future well-designed larger sample studies on LAMP assessment in passive and active malaria surveillances that use PCR as the reference standard and provide sufficient data to construct 2 × 2 diagnostic table are needed.

Point-of-care tests for urinary tract infections: protocol for a systematic review and meta-analysis of diagnostic test accuracy.

IntroductionUrinary tract infections (UTIs) are the second most common type of infection worldwide, accounting for a large number of primary care consultations and antibiotic prescribing. Current diagnosis is based on an empirical approach, relying on symptoms and occasional use of urine dipsticks. The diagnostic reference standard is still urine culture, although it is not routinely recommended for uncomplicated UTIs in the community, due to time to diagnosis (48 hours). Faster point-of-care tests have been developed, but their diagnostic accuracy has not been compared. Our objective is to systematically review and meta-analyse the diagnostic accuracy of currently available point-of-care tests for UTIs.Methods and analysisStudies evaluating the diagnostic accuracy of point-of-care tests for UTIs will be included. PubMed, Web of Science, Embase and Cochrane Database of Systematic Reviews were searched from inception to 1 June 2019. Data extraction and risk-of-bias assessment will be assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Meta-analysis will be performed depending on data availability and heterogeneity.Ethics and disseminationThis is a systematic review protocol and therefore formal ethical approval is not required, as no primary, identifiable, personal data will be collected. Patients or the public were not involved in the design of our research. However, the findings from this review will be shared with key stakeholders, including patient groups, clinicians and guideline developers, and will also be presented and national and international conferences.PROSPERO registration numberCRD42018112019.

The Accuracy of Dried Blood Spots Compared to Plasma or Serum Retinol for the Diagnosis of Vitamin A Deficiency: A DTA Systematic Review and Meta-Analysis

Abstract Objectives Dried blood spots (DBS) do not require a cold chain, making them easier to store and transport compared to serum or plasma samples in resource-limited settings. Our objective was to determine the accuracy of DBS compared to serum or plasma retinol for assessing vitamin A status in individuals and populations. Methods A systematic review of diagnostic test accuracy (DTA) was performed using standard Cochrane Methods for Screening and Diagnostic Tests. All human studies were included if they determined retinol in DBS (index test) and compared results to retinol determined in either plasma or serum samples (reference standard). Index and reference methods could use either capillary or venous blood with retinol quantified by HPLC. We used the WHO threshold of 0.70 μmol/L to define low retinol concentrations. Meta-analysis determined summary estimates of sensitivity and specificity using the bivariate model, which models logit transformed sensitivities and specificities as a bivariate normal distribution including a parameter for the negative correlation between sensitivity and specificity. Rstudio (Version 1.1.456, RStudio, Inc. Boston, MA) was used for analysis. Results Our search (conducted April 10, 2019) identified 9021 records, and 285 studies were assessed in full-text for inclusion; 6 publications reported 8 studies comprising 397 participants, 50 of which had low serum retinol by the reference method. The use of DBS to determine a low retinol level had summary estimates (95% CIs) for sensitivity of 86.7% (71.4 to 94.5) and specificity of 99.5% (89.7 to 100.0). Conclusions Use of DBS to determine low retinol has been shown to have good sensitivity and high specificity compared to serum or plasma. Use of DBS can reduce the need for centrifugation and cold chain for storage and transport. The mixed use of capillary and venous blood in both index and reference methods merits further investigation for the determination of retinol in DBS. Funding Sources None declared.

PSMA-targeted Radiotracers versus 18F Fluciclovine for the Detection of Prostate Cancer Biochemical Recurrence after Definitive Therapy: A Systematic Review and Meta-Analysis

Background National guidelines endorse fluorine 18 (18F) fluciclovine PET/CT for the detection of prostate cancer (PCa) in men with biochemically recurrent PCa. The comparative performance between fluciclovine and gallium 68 or 18F prostate-specific membrane antigen (PSMA) PET/CT, a newer examination, is unclear. Purpose To compare the detection of biochemical recurrence using fluciclovine versus PSMA-targeted radiotracers in patients with a prostate-specific antigen (PSA) level less than 2 ng/mL. Materials and Methods With use of the Preferred Reporting Items for a Systematic Review and Meta-Analysis of Diagnostic Test Accuracy, or PRISMA-DTA, guidelines, a systematic review of PubMed and EMBASE databases between 2012 and 2019 was performed. Studies of fluciclovine PET/CT or PSMA PET/CT in biochemical recurrence were identified. PSA levels, clinical data, and reference standards were obtained when available. A random-effects model was applied to pooled estimates and 95% confidence intervals (CIs) around the prevalence of a positive examination, stratified according to PSA tier. Results Quantitative analysis included 482 patients (median age, 67 years; interquartile range, 67-67 years) in six fluciclovine studies and 3217 patients (median age, 68 years; interquartile range, 67-70 years) in 38 PSMA studies. Pooled detection rates for PSMA and fluciclovine were 45% (95% CI: 38%, 52%) and 37% (95% CI: 25%, 49%), respectively, for a PSA level less than 0.5 ng/mL (P = .46); 59% (95% CI: 52%, 66%) and 48% (95% CI: 34%, 61%) for a PSA level of 0.5-0.9 ng/mL (P = .19); and 80% (95% CI: 75%, 85%) and 62% (95% CI: 54%, 70%) for a PSA level of 1.0-1.9 ng/mL (P = .01). A reference standard was positive in 703 of 735 patients (96%) in the PSMA cohort and 247of 256 (97%) in the fluciclovine cohort. Conclusion Patient-level detection rates for biochemically recurrent prostate cancer were greater for prostate-specific membrane antigen-targeted radiotracers than fluciclovine for prostate specific antigen levels of 1.0-1.9 ng/mL. © RSNA, 2020 Online supplemental material is available for this article.

Psychometric properties of measures of substance use: a systematic review and meta-analysis of reliability, validity and diagnostic test accuracy

BackgroundSynthesis of psychometric properties of substance use measures to identify patterns of use and substance use disorders remains limited. To address this gap, we sought to systematically evaluate the psychometric properties of measures to detect substance use and misuse.MethodsWe conducted a systematic review and meta-analysis of literature on measures of substance classes associated with HIV risk (heroin, methamphetamine, cocaine, ecstasy, alcohol) that were published in English before June 2016 that reported at least one of the following psychometric outcomes of interest: internal consistency (alpha), test-retest/inter-rater reliability (kappa), sensitivity, specificity, positive predictive value, and negative predictive value. We used meta-analytic techniques to generate pooled summary estimates for these outcomes using random effects and hierarchical logistic regression models.ResultsFindings across 387 paper revealed that overall, 65% of pooled estimates for alpha were in the range of fair-to-excellent; 44% of estimates for kappa were in the range of fair-to-excellent. In addition, 69, 97, 37 and 96% of pooled estimates for sensitivity, specificity, positive predictive value, and negative predictive value, respectively, were in the range of moderate-to-excellent.ConclusionWe conclude that many substance use measures had pooled summary estimates that were at the fair/moderate-to-excellent range across different psychometric outcomes. Most scales were conducted in English, within the United States, highlighting the need to test and validate these measures in more diverse settings. Additionally, the majority of studies had high risk of bias, indicating a need for more studies with higher methodological quality.

Diagnostic accuracy of cardiac MRI, FDG-PET, and myocardial biopsy for the diagnosis of cardiac sarcoidosis: a protocol for a systematic review and meta-analysis

BackgroundCS constitutes a rare but potentially underdiagnosed and fatal disease. Its diagnosis remains difficult owing to the infrequent and indistinguishable symptoms and the lack of formal diagnostic criteria dependent upon the diagnostic techniques used. Early diagnosis and treatment, however, may help to counter its poor prognosis.We aim to characterize and compare the diagnostic accuracy of cardiac MRI, FDG-PET and myocardial biopsy for the diagnosis of cardiac sarcoidosis and to advance and compare methods for complex diagnostic test accuracy reviews and meta-analysis.MethodsFollowing a systematic review on DTA studies on the aforementioned topic, a four-part approach to meta-analysis will be used: (1) direct comparison of index tests with clinical reference standard, (2) indirect comparison of index tests with clinical reference standard, (3) addition of an alternative test to that indirect comparison (4) and Bayesian meta-analysis using results of part 3 as informative prior for comparisons analogous to part 1 and 2.DiscussionThe most widely recognized diagnostic algorithm for cardiac sarcoidosis is considered out of date, as it precedes the introduction of imaging techniques in diagnostic pathways. These novel imaging techniques, like CMR and FDG-PET scan, have emerged as promising diagnostic tools which may fill the current diagnostic gap. Thus, a systematic review and evaluation of CS diagnosis are much needed. Such an attempt is anticipated to alter the current diagnostic guidelines for CS by shedding more light on the role of sophisticated imaging techniques on prompt CS therapy and follow-up.Trial registrationPROSPERO, CRD42019047126

A hierarchical bivariate meta-analysis of diagnostic test accuracy to provide direct comparisons of immunoassays vs. indirect immunofluorescence for initial screening of connective tissue diseases.

To compare indirect immunofluorescence (IIF) for antinuclear antibodies (ANA) against immunoassays (IAs) as an initial screening test for connective tissue diseases (CTDs). A systematic literature review identified cross-sectional or case-control studies reporting test accuracy data for IIF and enzyme-linked immunosorbent assays (ELISA), fluorescence enzyme immunoassay (FEIA), chemiluminescent immunoassay (CLIA) or multiplex immunoassay (MIA). The meta-analysis used hierarchical, bivariate, mixed-effect models with random-effects by test. Direct comparisons of IIF with ELISA showed that both tests had good sensitivity (five studies, 2321 patients: ELISA: 90.3% [95% confidence interval (CI): 80.5%, 95.5%] vs. IIF at a cut-off of 1:80: 86.8% [95% CI: 81.8%, 90.6%]; p = 0.4) but low specificity, with considerable variance across assays (ELISA: 56.9% [95% CI: 40.9%, 71.5%] vs. IIF 1:80: 68.0% [95% CI: 39.5%, 87.4%]; p = 0.5). FEIA sensitivity was lower than IIF sensitivity (1:80: p = 0.005; 1:160: p = 0.051); however, FEIA specificity was higher (seven studies, n = 12,311, FEIA 93.6% [95% CI: 89.9%, 96.0%] vs. IIF 1:80 72.4% [95% CI: 62.2%, 80.7%]; p < 0.001; seven studies, n = 3251, FEIA 93.5% [95% CI: 91.1%, 95.3%] vs. IIF 1:160 81.1% [95% CI: 73.4%, 86.9%]; p < 0.0001). CLIA sensitivity was similar to IIF (1:80) with higher specificity (four studies, n = 1981: sensitivity 85.9% [95% CI: 64.7%, 95.3%]; p = 0.86; specificity 86.1% [95% CI: 78.3%, 91.4%]). More data are needed to make firm inferences for CLIA vs. IIF given the wide prediction region. There were too few studies for the meta-analysis of MIA vs. IIF (MIA sensitivity range 73.7%-86%; specificity 53%-91%). FEIA and CLIA have good specificity compared to IIF. A positive FEIA or CLIA test is useful to support the diagnosis of a CTD. A negative IIF test is useful to exclude a CTD.

Delta Neutrophil Index for the Prediction of Prognosis in Acute Gastrointestinal Diseases; Diagnostic Test Accuracy Meta-Analysis.

Delta neutrophil index (DNI) is a novel diagnostic and prognostic biomarker of various infectious or inflammatory conditions. However, data on optimal measurement time are scarce, and no studies have evaluated the potential role of the DNI as a prognostic biomarker of gastrointestinal diseases with diagnostic test accuracy meta-analysis. Core databases were searched. The inclusion criteria were as follows: patients who have gastrointestinal diseases and DNI measurements presenting diagnostic indices for predicting the prognosis, including severity, surgical outcomes, and mortality from gastrointestinal diseases. We identified twelve studies for the systematic review and ten studies for the quantitative analysis. Pooled area under the curve, sensitivity, specificity, and diagnostic odds ratio of DNI at the initial admission date were 0.82 (95% confidence interval: 0.78–0.85), 0.75 (0.52–0.89), 0.76 (0.63–0.86), and 10 (3–35), respectively. Meta-regression showed no reasons for heterogeneity and publication bias was not detected. Fagan’s nomogram indicated that the posterior probability of ‘poor prognosis’ was 76% if the test was positive, and ‘no poor prognosis’ was 25% if the test was negative. The DNI can be considered as a reliable initial measurement biomarker for predicting prognosis in patients with gastrointestinal diseases,

Diagnostic Performance of Pre-Treatment 18f-Fluoro-Deoxy-Glucose Positron Emission Tomography With or Without Computed Tomography in Patients with Primary Central Nervous System Lymphoma: Updated Systematic Review and Diagnostic Test Accuracy Meta-Analyses

Background: There is low-quality evidence regarding the value of pre-treatment 18F-flouro-deoxyglucose positron emission tomography (FDG-PET) with or without computed tomography (CT) in the diagnostic evaluation of primary central nervous system lymphoma (PCNSL). This review aimed to assess diagnostic performance of FDG-PET(CT) in PCNSL. Methods: Eligible studies reporting diagnostic accuracy of pre-treatment FDG-PET(CT) in immunocompetent adults with PCNSL were identified through systematic literature review of Medline via PubMed from 1990 till 2019 using validated search strategy. Data on diagnostic performance from individual studies was summarized in a 2 X 2 table on per-patient level classifying them as truepositives, true-negatives, false-positives, and false-negatives using histo-pathological diagnosis as reference standard and pooled together using DerSimonian Laird method (random-effects model) to calculate weighted-mean pooled sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic odds ratio (DOR) with 95% confidence intervals (95%CI). Quality of primary studies including risk of bias was assessed using QUality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Findings: A total of 603 studies were identified of which 29 primary studies involving 967 patients were included. Weighted-mean (95%CI) pooled sensitivity, specificity, PPV, NPV, and DOR of pretreatment FDG-PET(CT) for diagnosis of PCNSL was 87% (83-90%), 85% (81-88%), 84% (81-88%), 87% (84-90%) and 29.78 (18.34-48.35) respectively. Included studies were generally associated with low to unclear risk of bias and low concerns regarding applicability. Interpretation: This is the largest dataset using modern meta-analytic methods including rigorous quality assessment demonstrating acceptably high diagnostic accuracy of pre-treatment FDG-PET(CT) in immunocompetent patients with PCNSL. Funding Statement: No funding was involved in this study. Declaration of Interests: None of the authors have any conflicts of interest to declare.

COVID-19: a meta-analysis of diagnostic test accuracy of commercial assays registered in Brazil

The accuracy of commercially available tests for COVID-19 in Brazil remains unclear. We aimed to perform a meta-analysis to describe the accuracy of available tests to detect COVID-19 in Brazil. We searched at the Brazilian Health Regulatory Agency (ANVISA) online platform to describe the pooled sensitivity (Se), specificity (Sp), diagnostic odds ratio (DOR) and summary receiver operating characteristic curves (SROC) for detection of IgM/IgG antibodies and for tests using naso/oropharyngeal swabs in the random-effects models. We identified 16 tests registered, mostly rapid-tests. Pooled diagnostic accuracy measures [95%CI] were: (i) for IgM antibodies Se=82% [76–87]; Sp=97% [96–98]; DOR=168 [92–305] and SROC=0.98 [0.96–0.99]; (ii) for IgG antibodies Se=97% [90–99]; Sp=98% [97–99]; DOR=1994 [385–10334] and SROC=0.99 [0.98–1.00]; and (iii) for detection of SARS-CoV-2 by antigen or molecular assays in naso/oropharyngeal swabs Se=97% [85–99]; Sp=99% [77–100]; DOR=2649 [30–233056] and SROC=0.99 [0.98–1.00]. These tests can be helpful for emergency testing during the COVID-19 pandemic in Brazil. However, it is important to highlight the high rate of false negative results from tests which detect SARS-CoV-2 IgM antibodies in the initial course of the disease and the scarce evidence-based validation results published in Brazil. Future studies addressing the diagnostic performance of tests for COVID-19 in the Brazilian population are urgently needed.

Serological assays for the diagnosis of Strongyloides stercoralis infection: a systematic review and meta-analysis of diagnostic test accuracy.

The standard method for the diagnosis of Strongyloides stercoralis, stool examinations, is inconvenient and, therefore, serological methods have been proposed. This study aimed to evaluate the accuracy of serological assays for the diagnosis of strongyloidiasis using a systematic review and meta-analysis model. Four electronic databases were reviewed. We used a random effects model and 95% CIs to determine the overall sensitivity, specificity and diagnostic odds ratio (DOR). Heterogeneity was intended with Cochran Q χ2 test and I2 statistic. The accuracy of serological assays resulted in a sensitivity of 71.7% (95% CI: 56.07 to 83.4%), a specificity of 89.9% (95% CI: 80.8 to 94.9%) and a DOR of 22.5 (95% CI: 10.8 to 46.9). The forest plot showed high heterogeneity regarding sensitivity (I2=90.4%, 95% CI: 87.4 to 93.3%; Q=228.1, p=0.000) and specificity (I2=98.9%, 95% CI: 98.8 to 99.1%; Q=2066.4, p=0.000). Fagan's nomogram showed that the probability of someone having the infection and with a positive test result was 49%. Deeks' funnel plots showed no evidence of potential publication bias for the studies (p=0.26). The current review suggests that serological techniques have acceptable sensitivity and specificity and therefore can be recommended for the screening of S. stercoralis infection.

Skew-normal random-effects model for meta-analysis of diagnostic test accuracy (DTA) studies.

Hierarchical models are recommended for meta-analyzing diagnostic test accuracy (DTA) studies. The bivariate random-effects model is currently widely used to synthesize a pair of test sensitivity and specificity using logit transformation across studies. This model assumes a bivariate normal distribution for the random-effects. However, this assumption is restrictive and can be violated. When the assumption fails, inferences could be misleading. In this paper, we extended the current bivariate random-effects model by assuming a flexible bivariate skew-normal distribution for the random-effects in order to robustly model logit sensitivities and logit specificities. The marginal distribution of the proposed model is analytically derived so that parameter estimation can be performed using standard likelihood methods. The method of weighted-average is adopted to estimate the overall logit-transformed sensitivity and specificity. An extensive simulation study is carried out to investigate the performance of the proposed model compared to other standard models. Overall, the proposed model performs better in terms of confidence interval width of the average logit-transformed sensitivity and specificity compared to the standard bivariate linear mixed model and bivariate generalized linear mixed model. Simulations have also shown that the proposed model performed better than the well-established bivariate linear mixed model in terms of bias and comparable with regards to the root mean squared error (RMSE) of the between-study (co)variances. The proposed method is also illustrated using a published meta-analysisdata.

Utility of the methylated SEPT9 test for the early detection of colorectal cancer: a systematic review and meta-analysis of diagnostic test accuracy

BackgroundCirculating tumour DNA from colorectal cancer (CRC) is a biomarker for early detection of the disease and therefore potentially useful for screening. One such biomarker is the methylated SEPT9 (mSEPT9)...

MRI vs. CT for the Detection of Liver Metastases in Patients With Pancreatic Carcinoma: A Comparative Diagnostic Test Accuracy Systematic Review and Meta-Analysis.

The detection of liver metastases is important for pancreatic cancer curative treatment eligibility. The data suggest that magnetic resonance imaging (MRI) is more sensitive than computed tomography (CT) for the diagnosis of pancreatic cancer liver metastases. However, MRI is not currently recommended in multiple published guidelines. To perform a comparative diagnostic test accuracy systematic review and meta-analysis comparing CT and MRI for pancreatic cancer liver metastases detection. Systematic review and meta-analysis. MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and multiple radiology society meeting archives were searched until November 2018. Comparative design studies reporting on liver CT and MRI accuracy for detection of pancreatic cancer liver metastases in the same cohort were included. 1.5T or 3.0T. Demographic, methodologic, and diagnostic test accuracy data were extracted. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. Accuracy metrics were obtained using bivariate random-effects meta-analysis. The impact of different covariates on accuracy estimates was assessed using a meta-regression model. Covariates included modality, study design, tumor characteristics, risk of bias, and imaging protocols. Fourteen studies including 987 patients with pancreatic cancer (205 with liver metastases) were included. Sensitivity for CT and MRI was 45% (confidence intervals [95% CI] 21-71%) and 83% (95% CI 74-88%), respectively. Specificity for CT and MRI was 94% (95% CI 84-98%) and 96% (95% CI 93-97%), respectively. The greater observed sensitivity of MRI was preserved in the meta-regression model (P = 0.01), while no difference in specificity was detected (P = 0.16). CT sensitivity was highest for triphasic and quadriphasic examinations compared to single phase or biphasic protocols (P = 0.03). Most studies were at high risk of bias. MRI is more sensitive than CT for pancreatic cancer liver metastases detection, accounting for confounding variables. Consideration of this finding in clinical practice guidelines is recommended. 3 TECHNICAL EFFICACY STAGE: 3.

Digital breast tomosynthesis for breast cancer detection: a diagnostic test accuracy systematic review and meta-analysis.

No consensus exists on digital breast tomosynthesis (DBT) utilization for breast cancer detection. We performed a diagnostic test accuracy systematic review and meta-analysis comparing DBT, combined DBT and digital mammography (DM), and DM alone for breast cancer detection in average-risk women. MEDLINE and EMBASE were searched until September 2018. Comparative design studies reporting on the diagnostic accuracy of DBT and/or DM for breast cancer detection were included. Demographic, methodologic, and diagnostic accuracy data were extracted. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. Accuracy metrics were pooled using bivariate random-effects meta-analysis. The impact of multiple covariates was assessed using meta-regression. CRD 42018111287. Thirty-eight studies reporting on 488,099 patients (13,923 with breast cancer) were included. Eleven studies were at low risk of bias. DBT alone, combined DBT and DM, and DM alone demonstrated sensitivities of 88% (95% confidence interval [CI] 83-92), 88% (CI 83-92), and 79% (CI 75-82), as well as specificities of 84% (CI 76-89), 81% (CI 73-88), and 79% (CI 71-85), respectively. The greater sensitivities of DBT alone and combined DBT and DM compared to DM alone were preserved in the combined meta-regression models accounting for other covariates (p = 0.003-0.006). No significant difference in diagnostic accuracy between DBT alone and combined DBT and DM was identified (p = 0.175-0.581). DBT is more sensitive than DM, while the addition of DM to DBT provides no additional diagnostic benefit. Consideration of these findings in breast cancer imaging guidelines is recommended. • Digital breast tomosynthesis with or without additional digital mammography is more sensitive in detecting breast cancer than digital mammography alone in women at average risk for breast cancer. • The addition of digital mammography to digital breast tomosynthesis provides no additional diagnostic benefit in detecting breast cancer compared to digital breast tomosynthesis alone. • The specificity of digital breast tomosynthesis with or without additional digital mammography is no different than digital mammography alone in the detection of breast cancer.

Endoscopic ultrasound versus computed tomography in determining the resectability of pancreatic cancer: A diagnostic test accuracy meta-analysis.

Background/Aim:Endoscopic ultrasound (EUS) and contrast-enhanced computed tomography (CT) with pancreas protocol are used in assessing the resectability of neoplastic pancreatic lesions. Here, we performed a diagnostic test accuracy (DTA) meta-analysis, comparing the diagnostic accuracy of EUS and CT in evaluating the resectability of pancreatic cancer using surgical assessment as the reference standard.Patients and Methods:A comprehensive electronic search was conducted up to March 2020. Studies comparing EUS and CT in assessing the resectability of pancreatic cancer using surgical assessment as reference standard were included. QUADAS-2 tool was used to assess the quality of the included studies. After data extraction, an analysis was done using DerSimonian Laird method (random-effects model) to estimate the overall diagnostic odds ratio (DOR) and determine the best-fitting receiver operating characteristics (ROC) curve.Results:Two studies, with 77 subjects combined, were included in the analysis. Overall, the risk of bias was moderate. EUS and CT were comparable in determining the resectability of pancreatic cancer with AUC = 75% (95% confidence interval (CI) 66%- 84%) for EUS as compared to 78% (95% CI 69%- 87%) for CT (P > 0.05). Pooled sensitivity and specificity was 87% (95% CI 70%- 96%) and 63% (95% CI 48%- 77%), respectively for EUS and 87% (95% CI 70%- 96%) and 70% (95% CI 55%- 83%), respectively for CT. DOR was 11.51 (95% CI 3.55- 36.81) for EUS as compared to 15.91 (95% CI 4.83- 51.62) for CT (P > 0.05).Conclusions:Both EUS and CT provide reasonable sensitivity and specificity to detect the resectability of pancreatic cancer.

Influence diagnostics and outlier detection for meta-analysis of diagnostic test accuracy.

Meta-analyses of diagnostic test accuracy (DTA) studies have been gaining prominence in research in clinical epidemiology and health technology development. In these DTA meta-analyses, some studies may have markedly different characteristics from the others and potentially be inappropriate to include. The inclusion of these "outlying" studies might lead to biases, yielding misleading results. In addition, there might be influential studies that have notable impacts on the results. In this article, we propose Bayesian methods for detecting outlying studies and their influence diagnostics in DTA meta-analyses. Synthetic influence measures based on the bivariate hierarchical Bayesian random effects models are developed because the overall influences of individual studies should be simultaneously assessed by the two outcome variables and their correlation information. We propose four synthetic measures for influence analyses: (a) relative distance, (b) standardized residual, (c) Bayesian p-value, and (d) influence statistic on the area under the summary receiver operating characteristic curve. We also show that conventional univariate Bayesian influential measures can be applied to the bivariate random effects models, which can be used as marginal influential measures. Most of these methods can be similarly applied to the frequentist framework. We illustrate the effectiveness of the proposed methods by applying them to a DTA meta-analysis of ultrasound in screening for vesicoureteral reflux among children with urinary tract infections.

Imaging Modalities for Diagnosis of Deep Pelvic Endometriosis: Comparison between Trans-Vaginal Sonography, Rectal Endoscopy Sonography and Magnetic Resonance Imaging. A Head-to-Head Meta-Analysis.

Objectives: A meta-analysis, with a head-to-head approach, was carried out to compare the three most common techniques for a deep pelvic endometriosis (DPE) diagnosis. We focused on: transvaginal-sonography (TVS), magnetic-resonance imaging (MRI), and rectal-endoscopy-sonography (RES). Methods: Electronic databases were searched from their inception until December 2018. All prospective and well-defined retrospective studies carried out in tertiary referral centers were considered. This review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Synthesizing Evidence from Diagnostic Accuracy Tests (SEDATE) guidelines. We considered only papers in which at least two imaging modalities were compared in the same set of patients (head-to-head approach). Meta-analysis of diagnostic test accuracy (DTA) was performed separately for each location of interest. Bivariate or univariate approach has been applied when appropriate. We analyze the DTA of TVS vs. MRI, TVS vs. RES, and MRI vs. RES. Results: Our meta-analysis (17 studies included) showed high-to-moderate DTA of TVS for all endometriosis locations (apart from recto-vaginal septum (RVS)) that were not statistically different from MRI and RES for those localized in the posterior compartment. RES results were more accurate than MRI for RS lesions but less accurate than TVS for other pelvic locations, except for RVS. Conclusions: All approaches provide good accuracy with specific strong points. Ultrasonography demonstrated a diagnostic accuracy not inferior to MRI and RES; therefore, it must be considered the primary approach for DPE diagnosis. MRI has to be considered as a valuable approach in settings where highly skilled sonographers are not available. Keypoints: (1) We confirmed the non-inferiority of TVS compared to MRI and RES for the diagnosis of specific pelvic anatomic location of endometriosis lesions. (2) Ultrasonography could be considered the primary approach for DPE diagnosis (less invasive than RES and less expensive than MRI). (3) MRI has to be considered as a valuable approach in settings where skilled sonographers are not available.

Performance of Indocyanine green for sentinel lymph node mapping and lymph node metastasis in colorectal cancer: a diagnostic test accuracy meta-analysis

Indocyanine green has been widely employed as a secure and easy technique for sentinel lymph node mapping in different types of cancer. Nonetheless, the usage of Indocyanine green has not been fully implemented due to the heterogeneous results found in published studies. Thus, the objective of this meta-analysis is to evaluate the overall performance of Indocyanine green for sentinel lymph node mapping and node metastasis in patients undergoing colorectal cancer surgery. An extensive systematic search was performed to identify relevant studies in English and Spanish with no time limit restrictions. For the meta-analysis, a hierarchical summary receiver operating characteristic curve (HSROCs) was constructed, and quantitative data synthesis was performed using random effects models. Specificity, sensitivity, positive, and negative likelihood ratios were obtained from the corresponding HSROC. Between-study heterogeneity was visually evaluated using Galbraith plot, and publication bias was quantified using Deeks' method. A total of 11 studies were included for analysis. The pooled detection rate for sentinel lymph node mapping was 91% (80-98%). Covariates significantly influencing the pooled detection rate were having colon cancer (estimate: 1.3001; 1.114 to 1.486; p < 0.001) and the usage of a laparoscopic approach (estimate: 1.3495; 1.1029 to 1.5961; p < 0.001). The performance of Indocyanine green for the detection of metastatic lymph nodes yielded an area under the roc curve of 66.5%, sensitivity of 64.3% (51-76%), and specificity of 65% (36-85%). Indocyanine green for the detection of sentinel lymph node mapping demonstrates better accuracy when used in colonic cancer and by a laparoscopic approach. Nevertheless, its overall performance for the detection of lymph node metastasis is poor.

Measuring the impact of screening automation on meta-analyses of diagnostic test accuracy

BackgroundThe large and increasing number of new studies published each year is making literature identification in systematic reviews ever more time-consuming and costly. Technological assistance has been suggested as an alternative to the conventional, manual study identification to mitigate the cost, but previous literature has mainly evaluated methods in terms of recall (search sensitivity) and workload reduction. There is a need to also evaluate whether screening prioritization methods leads to the same results and conclusions as exhaustive manual screening. In this study, we examined the impact of one screening prioritization method based on active learning on sensitivity and specificity estimates in systematic reviews of diagnostic test accuracy.MethodsWe simulated the screening process in 48 Cochrane reviews of diagnostic test accuracy and re-run 400 meta-analyses based on a least 3 studies. We compared screening prioritization (with technological assistance) and screening in randomized order (standard practice without technology assistance). We examined if the screening could have been stopped before identifying all relevant studies while still producing reliable summary estimates. For all meta-analyses, we also examined the relationship between the number of relevant studies and the reliability of the final estimates.ResultsThe main meta-analysis in each systematic review could have been performed after screening an average of 30% of the candidate articles (range 0.07 to 100%). No systematic review would have required screening more than 2308 studies, whereas manual screening would have required screening up to 43,363 studies. Despite an average 70% recall, the estimation error would have been 1.3% on average, compared to an average 2% estimation error expected when replicating summary estimate calculations.ConclusionScreening prioritization coupled with stopping criteria in diagnostic test accuracy reviews can reliably detect when the screening process has identified a sufficient number of studies to perform the main meta-analysis with an accuracy within pre-specified tolerance limits. However, many of the systematic reviews did not identify a sufficient number of studies that the meta-analyses were accurate within a 2% limit even with exhaustive manual screening, i.e., using current practice.