Diagnostic Test Accuracy Meta-analysis Research Articles

MRI and SPECT/CT demonstrate, with low certainty of evidence, the highest diagnostic accuracy for aseptic knee arthroplasty loosening: A systematic comparative diagnostic test review and meta-analysis.

The purpose of this study was to evaluate and compare the diagnostic accuracy of modalities used to aid the diagnosis of aseptic knee arthroplasty loosening. A comparative diagnostic test accuracy systematic review and meta-analysis was conducted following the Cochrane and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed, EMBASEand Cochrane databases were searched for original articles evaluating diagnostic modalities up to March 2024. Included studies compared the modality (index test) to the intraoperative finding as reference test. The QUADAS-C (Quality Assessment of Diagnostic Accuracy Studies-Comparative)tool was used to assess the quality of the included studies. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach was used to evaluate the certainty of evidence. Level of evidence was evaluated using the Oxford Levels of Evidence tool. The primary outcome wasthe summary of diagnostic accuracy metrics for each modality as demonstrated by a summary receiver-operating characteristic (SROC) curve. The search yielded 467 articles. Of these, 14 articles were included. These 14 articles evaluated a total of five different diagnostic modalities: bone scintigraphy (three studies, 146 cases), 18-fluorodeoxyglucose positron emission tomography(two studies, 50 cases), single-photon emission computed tomography combined with computed tomography (SPECT/CT) (seven studies, 371 cases), radionuclide arthrogram (three studies, 196 cases)and magnetic resonance imaging (MRI) (one study, 116 cases). Nine studies exhibited a high risk of bias in patient selection, and all studies showed a high risk of bias related to the reference test. The majority of the included studies were classified as Level III evidence, leading to an overall low level of certainty in the evidence. The most accurate tests, as demonstrated by the SROC analysis, were MRI and SPECT/CT, with sensitivities ranging from 0.00 to 1.00 and 0.33 to 1.00 and specificities between 0.31-1.00 and 0.00-1.00, respectively. This review and meta-analysis evaluated available diagnostic modalities to aid the diagnosis of knee arthroplasty loosening and based on a low certainty of evidence suggests that MRI and SPECT/CT are currently the most accurate modalities available to aid the diagnosis of aseptic loosening of knee arthroplasty components. Level III.

A systematic review and meta-analysis of diagnostic test accuracy of chest ultrasound in diagnosing pediatric pulmonary tuberculosis.

Despite medical advancement, pediatric pulmonary tuberculosis (PTB) still has high morbidity and mortality, due to challenging detection in clinical practice. Ultrasound has been touted as the next best diagnostic tool but currently, this claim is unfounded. Therefore, this study aims to systematically review the diagnostic parameters of chest ultrasound in diagnosing pediatric PTB. The literature search started and ended on December 23, 2023. We searched MEDLINE, Cochrane Library, Pubmed, Science Direct, and Google Scholar. Our research question could be formulated as "In pediatric patients who present with signs and symptoms of PTB such as fever, cough, and poor weight gain, how accurate is chest ultrasound in ruling in and ruling out pediatric PTB when the diagnosis is compared to culture, PCR or CXR?" This systematic review adhered to the PRISMA-DTA guidelines while the meta-analysis was conducted with STATA program using the "midas" and "metandi" commands. There are five studies included with 137 positive PTB children. The combined sensitivity is 84% (95% confidence interval [CI]: 76-89), specificity of 38% (95% CI: 24-54), and summary receiver operating curve yields an area under the curve of 0.83 (95% CI: 0.80-0.86). The I2 value is 24% (95% CI: 0-100) with a p-value of 0.13. The combined negative predictive value is 0.68 (95% CI: 0.58-0.79), and the positive predictive value is 0.57 (95% CI: 0.51-0.63). The positive likelihood ratio is 1 with a 6% increase from the baseline while the negative likelihood ratio is 0.43 with a 12% decrease from the baseline. Chest ultrasound is sensitive but currently could neither exclude nor confirm pediatric PTB.

Prognostic nutritional index as a predictive marker for acute kidney injury in adult critical illness population: a systematic review and diagnostic test accuracy meta-analysis

BackgroundThe prognostic nutritional index (PNI), integrating nutrition and inflammation markers, has been increasingly recognized as a prognostic predictor in diverse patient cohorts. Recently, its effectiveness as a predictive marker for acute kidney injury (AKI) in various clinical settings has gained attention. This study aims to assess the predictive accuracy of the PNI for AKI in critically ill populations through systematic review and meta-analysis.MethodsA systematic review was conducted using the databases MEDLINE, EMBASE, PubMed, and China National Knowledge Infrastructure up to August 2023. The included trials reported the PNI assessment in adult population with critical illness and its predictive capacity for AKI. Data on study characteristics, subgroup covariates, and diagnostic performance of PNI, including sensitivity, specificity, and event rates, were extracted. A diagnostic test accuracy meta-analysis was performed. Subgroup analyses and meta-regression were utilized to investigate the sources of heterogeneity. The GRADE framework evaluated the confidence in the meta-analysis’s evidence.ResultsThe analysis encompassed 16 studies with 17 separate cohorts, totaling 21,239 patients. The pooled sensitivity and specificity of PNI for AKI prediction were 0.67 (95% CI 0.58–0.74) and 0.74 (95% CI 0.67–0.80), respectively. The pooled positive likelihood ratio was 2.49 (95% CI 1.99–3.11; low certainty), and the negative likelihood ratio was 0.46 (95% CI 0.37–0.56; low certainty). The pooled diagnostic odds ratio was 5.54 (95% CI 3.80–8.07), with an area under curve of summary receiver operating characteristics of 0.76. Subgroup analysis showed that PNI’s sensitivity was higher in medical populations than in surgical populations (0.72 vs. 0.55; p < 0.05) and in studies excluding patients with chronic kidney disease (CKD) than in those including them (0.75 vs. 0.56; p < 0.01). Overall, diagnostic performance was superior in the non-chronic kidney disease group.ConclusionOur study demonstrated that PNI has practical accuracy for predicting the development of AKI in critically ill populations, with superior diagnostic performance observed in medical and non-CKD populations. However, the diagnostic efficacy of the PNI has significant heterogeneity with different cutoff value, indicating the need for further research.

Diagnostic performance of different imaging modalities for splenic malignancies: A comparative meta-analysis

Background and objectivesThe spleen hosts both benign and malignant lesions. Despite multiple imaging modalities, the distinction between these lesions poses a diagnostic challenge, marked by varying diagnostic accuracy levels across methods. In this study, we aimed to evaluate and compare the diagnostic performance of various imaging techniques for detecting malignant splenic lesions. MethodsFollowing PRISMA guidelines, we searched PubMed, Scopus, and Web of Sciences databases for studies evaluating imaging techniques in detecting malignant splenic lesions. Data extraction included diagnostic accuracy metrics, and methodological quality was assessed using QUADAS-2. Diagnostic Test Accuracy meta-analyses were conducted using R (version: 4.2.1). Subgroup analyses and meta-regression were performed to compare different modalities and clinical settings. ResultsOur study included 28 studies (pooled sample size: 2358), primarily using retrospective designs with histopathology as the reference standard. PET scan demonstrated the highest diagnostic accuracy (AUC: 92 %), demonstrating a sensitivity of 93 % (95 % CI: 80.4 % - 97.7 %) and a specificity of 82.8 % (95 % CI: 71.1 % - 90.4 %). Contrast-enhanced ultrasound (CEUS), Contrast-enhanced CT scan, and contrast-enhanced MRI also showed impressive performance with AUCs of 91.4 %, 90.9 %, and 85.3 %, respectively. Differences among these modalities were not statistically significant, but they outperformed non-contrast-enhanced methods. PET and CEUS exhibited higher specificity for lymphoma cases compared to studies including other malignancies. Conclusion and clinical implicationsOverall, PET emerges as the best modality for splenic malignancies, and CEUS and CE-MRI show promise as potential alternatives, notably due to their reduced radiation exposure. Further research is essential for precise malignancy differentiation.

Ultrasound-based radiomics for the differential diagnosis of breast masses: A systematic review and meta-analysis.

Ultrasound-based radiomics has demonstrated excellent diagnostic performance in differentiating benign and malignant breast masses. Given a few clinical studies on their diagnostic role, we conducted a meta-analysis of the potential effects of ultrasound-based radiomics for the differential diagnosis of breast masses, aiming to provide evidence-based medical basis for clinical research. We searched Embase, Web of Science, Cochrane Library, and PubMed databases from inception through to February 2023. The methodological quality assessment of the included studies was performed according to Quality Assessment of Diagnostic Accuracy Studies checklist. A diagnostic test accuracy systematic review and meta-analysis was performed in accordance with PRISMA guidelines. Sensitivity, specificity, and area under curve delineating benign and malignant lesions were recorded. We also used sensitivity analysis and subgroup analysis to explore potential sources of heterogeneity. Deeks' funnel plots was used to examine the publication bias. A total of 11 studies were included in this meta-analysis. For the diagnosis of malignant breast masses worldwide, the overall mean rates of sensitivity and specificity of ultrasound-based radiomics were 0.90 (95% confidence interval [CI], 0.83-0.95) and 0.89 (95% CI, 0.82-0.94), respectively. The summary diagnostic odds ratio was 76 (95% CI, 26-219), and the area under the curve for the summary receiver operating characteristic curve was 0.95 (95% CI, 0.93-0.97). Ultrasound-based radiomics has the potential to improve diagnostic accuracy to discriminate between benign and malignant breast masses, and could reduce unnecessary biopsies.

Atrial Fibrillation Screening During Routine Automated Office, Home, and Ambulatory Blood Pressure Measurement: A Diagnostic Test Accuracy Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) is often asymptomatic and undiagnosed. As AF and hypertension often coexist, opportunistic AF detection during routine automated blood pressure (BP) measurement appears to be an attractive screening method. A systematic literature search was conducted to identify studies assessing the diagnostic test accuracy of office, home, or 24-hour ambulatory BP measuring devices with AF detection algorithms versus reference electrocardiography. Analyses were performed per participant (AF status based on several BP readings; most office/home devices) or per reading (AF status based on individual readings; all ambulatory devices). A meta-analysis stratified by device type (office/home/ambulatory) was conducted to calculate pooled measures of diagnostic accuracy. Sensitivity/meta-regression analyses were also performed. Among 3096 records initially retrieved, 23 diagnostic test accuracy studies were included. Data derived from 11 093 individuals (weighted age 69 years, males 56%, hypertensives 79%, diabetics 24%, and AF prevalence 17%) indicated a pooled sensitivity 0.97 (95% CI, 0.92-0.99), specificity 0.93 (95% CI, 0.90-0.95), and accuracy 0.93 (95% CI, 0.89-0.95), with generally consistent results using office, home, or ambulatory BP devices (slightly lower specificity with the latter). The positive and negative predictive values were 0.70 (95% CI, 0.60-0.80) and 0.99 (95% CI, 0.98-1.00), respectively. Sensitivity analyses indicated lower specificity in studies implementing reading versus participant analyses. Most studies presented a low risk of bias and minor applicability concerns. There is considerable and consistent evidence suggesting high diagnostic accuracy of AF detection algorithms implemented in automated BP monitors during routine BP measurements in and out of the office. AF diagnosis requires verification (electrocardiography) before treatment is administered.

Machine learning-based medical imaging diagnosis in patients with temporomandibular disorders: a diagnostic test accuracy systematic review and meta-analysis.

Temporomandibular disorders (TMDs) are the second most common musculoskeletal condition which are challenging tasks for most clinicians. Recent research used machine learning (ML) algorithms to diagnose TMDs intelligently. This study aimed to systematically evaluate the quality of these studies and assess the diagnostic accuracy of existing models. Twelve databases (Europe PMC, Embase, etc.) and two registers were searched for published and unpublished studies using ML algorithms on medical images. Two reviewers extracted the characteristics of studies and assessed the methodological quality using the QUADAS-2 tool independently. A total of 28 studies (29 reports) were included: one was at unclear risk of bias and the others were at high risk. Thus the certainty of evidence was quite low. These studies used many types of algorithms including 8 machine learning models (logistic regression, support vector machine, random forest, etc.) and 15 deep learning models (Resnet152, Yolo v5, Inception V3, etc.). The diagnostic accuracy of a few models was relatively satisfactory. The pooled sensitivity and specificity were 0.745 (0.660-0.814) and 0.770 (0.700-0.828) in random forest, 0.765 (0.686-0.829) and 0.766 (0.688-0.830) in XGBoost, and 0.781 (0.704-0.843) and 0.781 (0.704-0.843) in LightGBM. Most studies had high risks of bias in Patient Selection and Index Test. Some algorithms are relatively satisfactory and might be promising in intelligent diagnosis. Overall, more high-quality studies and more types of algorithms should be conducted in the future. We evaluated the diagnostic accuracy of the existing models and provided clinicians with much advice about the selection of algorithms. This study stated the promising orientation of future research, and we believe it will promote the intelligent diagnosis of TMDs.

Accuracy of Intraoperative Neuromonitoring in the Diagnosis of Intraoperative Neurological Decline in the Setting of Spinal Surgery-A Systematic Review and Meta-Analysis.

Systematic review and meta-analysis. In an effort to prevent intraoperative neurological injury during spine surgery, the use of intraoperative neurophysiological monitoring (IONM) has increased significantly in recent years. Using IONM, spinal cord function can be evaluated intraoperatively by recording signals from specific nerve roots, motor tracts, and sensory tracts. We performed a systematic review and meta-analysis of diagnostic test accuracy (DTA) studies to evaluate the efficacy of IONM among patients undergoing spine surgery for any indication. The current systematic review and meta-analysis was performed using the Preferred Reporting Items for a Systematic Review and Meta-analysis statement for Diagnostic Test Accuracy Studies (PRISMA-DTA) and was registered on PROSPERO. A comprehensive search was performed using MEDLINE, EMBASE and SCOPUS for all studies assessing the diagnostic accuracy of neuromonitoring, including somatosensory evoked potential (SSEP), motor evoked potential (MEP) and electromyography (EMG), either on their own or in combination (multimodal). Studies were included if they reported raw numbers for True Positives (TP), False Negatives (FN), False Positives (FP) and True Negative (TN) either in a 2 × 2 contingency table or in text, and if they used postoperative neurologic exam as a reference standard. Pooled sensitivity and specificity were calculated to evaluate the overall efficacy of each modality type using a bivariate model adapted by Reitsma et al, for all spine surgeries and for individual disease groups and regions of spine. The risk of bias (ROB) of included studies was assessed using the quality assessment tool for diagnostic accuracy studies (QUADAS-2). A total of 163 studies were included; 52 of these studies with 16,310 patients reported data for SSEP, 68 studies with 71,144 patients reported data for MEP, 16 studies with 7888 patients reported data for EMG and 69 studies with 17,968 patients reported data for multimodal monitoring. The overall sensitivity, specificity, DOR and AUC for SSEP were 71.4% (95% CI 54.8-83.7), 97.1% (95% CI 95.3-98.3), 41.9 (95% CI 24.1-73.1) and .899, respectively; for MEP, these were 90.2% (95% CI 86.2-93.1), 96% (95% CI 94.3-97.2), 103.25 (95% CI 69.98-152.34) and .927; for EMG, these were 48.3% (95% CI 31.4-65.6), 92.9% (95% CI 84.4-96.9), 11.2 (95% CI 4.84-25.97) and .773; for multimodal, these were found to be 83.5% (95% CI 81-85.7), 93.8% (95% CI 90.6-95.9), 60 (95% CI 35.6-101.3) and .895, respectively. Using the QUADAS-2 ROB analysis, of the 52 studies reporting on SSEP, 13 (25%) were high-risk, 10 (19.2%) had some concerns and 29 (55.8%) were low-risk; for MEP, 8 (11.7%) were high-risk, 21 had some concerns and 39 (57.3%) were low-risk; for EMG, 4 (25%) were high-risk, 3 (18.75%) had some concerns and 9 (56.25%) were low-risk; for multimodal, 14 (20.3%) were high-risk, 13 (18.8%) had some concerns and 42 (60.7%) were low-risk. These results indicate that all neuromonitoring modalities have diagnostic utility in successfully detecting impending or incident intraoperative neurologic injuries among patients undergoing spine surgery for any condition, although it is clear that the accuracy of each modality differs.PROSPERO Registration Number: CRD42023384158.

A Clinical Practice Guideline for Prevention, Diagnosis and Management of Intraoperative Spinal Cord Injury: Recommendations for Use of Intraoperative Neuromonitoring and for the Use of Preoperative and Intraoperative Protocols for Patients Undergoing Spine Surgery.

Development of a clinical practice guideline following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) process. The objectives of this study were to develop guidelines that outline the utility of intraoperative neuromonitoring (IONM) to detect intraoperative spinal cord injury (ISCI) among patients undergoing spine surgery, to define a subset of patients undergoing spine surgery at higher risk for ISCI and to develop protocols to prevent, diagnose, and manage ISCI. All systematic reviews were performed according to PRISMA standards and registered on PROSPERO. A multidisciplinary, international Guidelines Development Group (GDG) reviewed and discussed the evidence using GRADE protocols. Consensus was defined by 80% agreement among GDG members. A systematic review and diagnostic test accuracy (DTA) meta-analysis was performed to synthesize pooled evidence on the diagnostic accuracy of IONM to detect ISCI among patients undergoing spinal surgery. The IONM modalities evaluated included somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), electromyography (EMG), and multimodal neuromonitoring. Utilizing this knowledge and their clinical experience, the multidisciplinary GDG created recommendations for the use of IONM to identify ISCI in patients undergoing spine surgery. The evidence related to existing care pathways to manage ISCI was summarized and based on this a novel AO Spine-PRAXIS care pathway was created. Our recommendations are as follows: (1) We recommend that intraoperative neurophysiological monitoring be employed for high risk patients undergoing spine surgery, and (2) We suggest that patients at "high risk" for ISCI during spine surgery be proactively identified, that after identification of such patients, multi-disciplinary team discussions be undertaken to manage patients, and that an intraoperative protocol including the use of IONM be implemented. A care pathway for the prevention, diagnosis, and management of ISCI has been developed by the GDG. We anticipate that these guidelines will promote the use of IONM to detect and manage ISCI, and promote the use of preoperative and intraoperative checklists by surgeons and other team members for high risk patients undergoing spine surgery. We welcome teams to implement and evaluate the care pathway created by our GDG.

Heterogeneity in Systematic Reviews of Medical Imaging Diagnostic Test Accuracy Studies

Systematic reviews of medical imaging diagnostic test accuracy (DTA) studies are affected by between-study heterogeneity due to a range of factors. Failure to appropriately assess the extent and causes of heterogeneity compromises the interpretability of systematic review findings. To assess how heterogeneity has been examined in medical imaging DTA studies. The PubMed database was searched for systematic reviews of medical imaging DTA studies that performed a meta-analysis. The search was limited to the 40 journals with highest impact factor in the radiology, nuclear medicine, and medical imaging category in the InCites Journal Citation Reports of 2021 to reach a sample size of 200 to 300 included studies. Descriptive analysis was performed to characterize the imaging modality, target condition, type of meta-analysis model used, strategies for evaluating heterogeneity, and sources of heterogeneity identified. Multivariable logistic regression was performed to assess whether any factors were associated with at least 1 source of heterogeneity being identified in the included meta-analyses. Methodological quality evaluation was not performed. Data analysis occurred from October to December 2022. A total of 242 meta-analyses involving a median (range) of 987 (119-441 510) patients across a diverse range of disease categories and imaging modalities were included. The extent of heterogeneity was adequately described (ie, whether it was absent, low, moderate, or high) in 220 studies (91%) and was most commonly assessed using the I2 statistic (185 studies [76%]) and forest plots (181 studies [75%]). Heterogeneity was rated as moderate to high in 191 studies (79%). Of all included meta-analyses, 122 (50%) performed subgroup analysis and 87 (36%) performed meta-regression. Of the 242 studies assessed, 189 (78%) included 10 or more primary studies. Of these 189 studies, 60 (32%) did not perform meta-regression or subgroup analysis. Reasons for being unable to investigate sources of heterogeneity included inadequate reporting of primary study characteristics and a low number of included primary studies. Use of meta-regression was associated with identification of at least 1 source of variability (odds ratio, 1.90; 95% CI, 1.11-3.23; P = .02). In this systematic review of assessment of heterogeneity in medical imaging DTA meta-analyses, most meta-analyses were impacted by a moderate to high level of heterogeneity, presenting interpretive challenges. These findings suggest that, despite the development and availability of more rigorous statistical models, heterogeneity appeared to be incomplete, inconsistently evaluated, or methodologically questionable in many cases, which lessened the interpretability of the analyses performed; comprehensive heterogeneity assessment should be addressed at the author level by improving personal familiarity with appropriate statistical methodology for assessing heterogeneity and involving biostatisticians and epidemiologists in study design, as well as at the editorial level, by mandating adherence to methodologic standards in primary DTA studies and DTA meta-analyses.

Systematic review and meta-analysis of diagnostic test accuracy of ST-segment elevation for acute coronary occlusion

ObjectiveTo evaluate the diagnostic sensitivity and specificity of ST-segment elevation on a 12‑lead ECG in detecting ACO across any coronary artery, challenging the current STEMI-NSTEMI paradigm. MethodsStudies from MEDLINE and Scopus (2012−2023) comparing ECG findings with coronary angiograms were systematically reviewed and analyzed following PRISMA-DTA guidelines. QUADAS-2 assessed the risk of bias. Study selectionStudies included focused on AMI patients and provided data enabling the construction of contingency tables for sensitivity and specificity calculation, excluding those with non-ACS conditions, outdated STEMI criteria, or a specific focus on bundle branch blocks or other complex diagnoses. Data were extracted systematically and pooled test accuracy estimates were computed using MetaDTA software, employing bivariate analyses for within- and between-study variation. The primary outcomes measured were the sensitivity and specificity of ST-segment elevation in detecting ACO. ResultsThree studies with 23,704 participants were included. The pooled sensitivity of ST-segment elevation for detecting ACO was 43.6% (95% CI: 34.7%–52.9%), indicating that over half of ACO cases may not exhibit ST-segment elevation. The specificity was 96.5% (95% CI: 91.2%–98.7%). Additional analysis using the OMI-NOMI strategy showed improved sensitivity (78.1%, 95% CI: 62.7%–88.3%) while maintaining similar specificity (94.4%, 95% CI: 88.6%–97.3%). ConclusionThe findings reveal a significant diagnostic gap in the current STEMI-NSTEMI paradigm, with over half of ACO cases potentially lacking ST-segment elevation. The OMI-NOMI strategy could offer an improved diagnostic approach. The high heterogeneity and limited number of studies necessitate cautious interpretation and further research in diverse settings.

Urea breath test for Helicobacter pylori infection in adult dyspeptic patients: A meta-analysis of diagnostic test accuracy.

Helicobacter pylori (H. pylori) infection has been well-established as a significant risk factor for several gastrointestinal disorders. The urea breath test (UBT) has emerged as a leading non-invasive method for detecting H. pylori. Despite numerous studies confirming its substantial accuracy, the reliability of UBT results is often compromised by inherent limitations. These findings underscore the need for a rigorous statistical synthesis to clarify and reconcile the diagnostic accuracy of the UBT for the diagnosis of H. pylori infection. To determine and compare the diagnostic accuracy of 13C-UBT and 14C-UBT for H. pylori infection in adult patients with dyspepsia. We conducted an independent search of the PubMed/MEDLINE, EMBASE, and Cochrane Central databases until April 2022. Our search included diagnostic accuracy studies that evaluated at least one of the index tests (13C-UBT or 14C-UBT) against a reference standard. We used the QUADAS-2 tool to assess the methodological quality of the studies. We utilized the bivariate random-effects model to calculate sensitivity, specificity, positive and negative test likelihood ratios (LR+ and LR-), as well as the diagnostic odds ratio (DOR), and their 95% confidence intervals. We conducted subgroup analyses based on urea dosing, time after urea administration, and assessment technique. To investigate a possible threshold effect, we conducted Spearman correlation analysis, and we generated summary receiver operating characteristic (SROC) curves to assess heterogeneity. Finally, we visually inspected a funnel plot and used Egger's test to evaluate publication bias. The titles and abstracts of 4621 studies were screened; 79 articles were retrieved and selected for full-text reading. Finally, 60 studies were included in the diagnostic test accuracy meta-analysis. Our analysis demonstrates superior diagnostic accuracy of 13C-UBT over 14C-UBT, indicated by higher sensitivity (96.60% vs 96.15%), specificity (96.93% vs 89.84%), likelihood ratios (LR+ 22.00 vs 10.10; LR- 0.05 vs 0.06), and area under the curve (AUC; 0.979 vs 0.968). Notably, 13C-UBT's DOR (586.47) significantly outperforms 14C-UBT (DOR 226.50), making it the preferred diagnostic tool for dyspeptic individuals with H. pylori infection. Correlation analysis revealed no threshold effect (13C-UBT: r = 0.48; 14C-UBT: r = -0.01), and SROC curves showed consistent accuracy. Both 13C-UBT and 14C-UBT showed high AUC values (13C-UBT 0.979; 14C-UBT 0.968) near 1.00, reinforcing their excellent accuracy and endorsing both as reliable diagnostic tools in clinical practice. In summary, our study has demonstrated that 13C-UBT has been found to outperform the 14C-UBT, making it the preferred diagnostic approach. Additionally, our results emphasize the significance of carefully considering urea dosage, assessment timing, and measurement techniques for both tests to enhance diagnostic precision. Nevertheless, it is crucial for researchers and clinicians to evaluate the strengths and limitations of our findings before implementing them in practice.

Risk of Endometrial Cancer in Asymptomatic Postmenopausal Women in Relation to Ultrasonographic Endometrial Thickness: Systematic Review and Diagnostic Test Accuracy Meta-analysis

(Abstracted from Am J Obstet Gynecol 2023;228:22–35.e2) Endometrial carcinoma (EC) can be suspected in cases of postmenopausal bleeding (PMB) with a thickened endometrium on transvaginal ultrasonography (TVS) examination. Typical guidelines recommend further investigation of PMB when the endometrial lining is greater than 4–5 mm, indicating an elevated risk of EC.

An empirical comparison of statistical methods for multiple cut-off diagnostic test accuracy meta-analysis of the Edinburgh postnatal depression scale (EPDS) depression screening tool using published results vs individual participant data

BackgroundSelective reporting of results from only well-performing cut-offs leads to biased estimates of accuracy in primary studies of questionnaire-based screening tools and in meta-analyses that synthesize results. Individual participant data meta-analysis (IPDMA) of sensitivity and specificity at each cut-off via bivariate random-effects models (BREMs) can overcome this problem. However, IPDMA is laborious and depends on the ability to successfully obtain primary datasets, and BREMs ignore the correlation between cut-offs within primary studies.MethodsWe compared the performance of three recent multiple cut-off models developed by Steinhauser et al., Jones et al., and Hoyer and Kuss, that account for missing cut-offs when meta-analyzing diagnostic accuracy studies with multiple cut-offs, to BREMs fitted at each cut-off. We used data from 22 studies of the accuracy of the Edinburgh Postnatal Depression Scale (EPDS; 4475 participants, 758 major depression cases). We fitted each of the three multiple cut-off models and BREMs to a dataset with results from only published cut-offs from each study (published data) and an IPD dataset with results for all cut-offs (full IPD data). We estimated pooled sensitivity and specificity with 95% confidence intervals (CIs) for each cut-off and the area under the curve.ResultsCompared to the BREMs fitted to the full IPD data, the Steinhauser et al., Jones et al., and Hoyer and Kuss models fitted to the published data produced similar receiver operating characteristic curves; though, the Hoyer and Kuss model had lower area under the curve, mainly due to estimating slightly lower sensitivity at lower cut-offs. When fitting the three multiple cut-off models to the full IPD data, a similar pattern of results was observed. Importantly, all models had similar 95% CIs for sensitivity and specificity, and the CI width increased with cut-off levels for sensitivity and decreased with an increasing cut-off for specificity, even the BREMs which treat each cut-off separately.ConclusionsMultiple cut-off models appear to be the favorable methods when only published data are available. While collecting IPD is expensive and time consuming, IPD can facilitate subgroup analyses that cannot be conducted with published data only.

UTILITY OF PR3-ANCA IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract BACKGROUND/PURPOSE Anti-neutrophil cytoplasmic antibodies (ANCA) directed to proteinase 3 (PR3) represent a highly established marker for patients with ANCA-associated vasculitis (AAV). PR3-ANCA have also demonstrated utility in the management of inflammatory bowel disease (IBD) with certain immunoassays. More specifically, PR3-ANCA discriminated patients with ulcerative colitis (UC) from Crohn`s disease (CrD) patients and were associated with disease severity and activity. Lastly, evidence is mounting that PR3-ANCA helps to stratify patients according to treatment response. Here, we aimed to summarize the current data on the diagnostic utility of PR3-ANCA in IBD. METHODS A structured systematic literature review including three electronic databases (Pubmed, Scopes, and Web Of Science) was conducted on June 6th 2023 to identify studies assessing the diagnostic accuracy of the QUANTA Flash PR3 assay (RUO for IBD) in UC vs. CrD patients. Electronic searches were supplemented by hand searching. A hierarchical, bivariate, mixed-effect meta-analysis was conducted using metandi function in STATA MP v17.0, as per the Cochrane collaboration recommendations for a review of diagnostic test accuracy studies. Study quality was assessed using QUADAS-2 tool which considers the risk of bias and applicability. RESULTS Out of 111 citations retrieved for titles and abstracts screen, a total of 6 studies met the inclusion criteria and reported QUANTA Flash PR3 diagnostic accuracy in UC vs. CrD. Diagnostic test accuracy of individual studies is available in Table 1. The six studies included 667 UC patients and 682 individuals with CrD. Of these, 2 articles (Horn et al. and Laass et al) were case-control studies in children. Sensitivity point estimate for UC was 34.9% [95% confidence interval (CI): 26.2-44.6%]. Specificity point estimate for CrD was 95.9% (95% CI: 92.0-98.0%). This results in a Diagnostic Odds Ratio (DOR) of 12.6 (95% CI: 5.7-27.9%), a positive likelihood ratio of 8.5 (95% CI: 4.2-17.5), and a negative likelihood ratio of 0.68 (95% CI: 0.59-0.78) (Table 2). The risk of bias was low in the index test and reference standard domains. Four studies (67%) showed an unclear risk of bias in the patient selection and flow and timing domains. All studies had low concerns of applicability in all the domains. CONCLUSION In this meta-analysis QUANTA Flash PR3 assay has demonstrated to be able to discriminate between UC from CrD with a sensitivity of 34.9% and a specificity of 95.9%. Due to the limited number of studies published, clinical trials should consider the inclusion of PR3-ANCA as an exploratory biomarker for patient stratification. Table 1 Summary of diagnostic test accuracy of individual studies. Table 2 Meta-analysis of diagnostic test accuracy of QUANTA Flash PR3.

Intraoperative parathyroid hormone monitoring in parathyroidectomy for hyperparathyroidism: a protocol for a network meta-analysis of diagnostic test accuracy.

Intraoperative parathyroid hormone (iPTH) monitoring is standard-of-care in the surgical management of hyperparathyroidism. It involves real-time determination of circulating PTH levels to guide parathyroid gland excision. There exists several iPTH monitoring criteria, such as the Miami criteria, and a lack of standardization in the timing of post-parathyroid gland excision samples. We present a protocol of a systematic review and network meta-analysis of diagnostic test accuracy to identify the iPTH criteria and post-gland excision timepoint that best predicts surgical cure in hyperparathyroidism. The database search strategy will be developed in conjunction with a librarian specialist. We will perform a search of Medline (Ovid), EMBASE (Ovid), CINAHL, Cochrane Collaboration, and Web of Science from 1990-present. Studies will be eligible if they include adult patients diagnosed with hyperparathyroidism who undergo parathyroidectomy with iPTH monitoring. We will only include studies that report diagnostic test properties for iPTH criteria and/or post-excision sampling timepoints. All screening, full-text review, data extraction, and critical appraisal will be performed in duplicate. Critical appraisal will be performed using QUADAS-2 instrument. A descriptive analysis will present study and critical appraisal characteristics. We will perform evaluation of between-study heterogeneity using I2 and Cochrane Q and where applicable, we will perform sensitivity analysis. Our network meta-analysis will include Bayesian hierarchical framework with random effects using multiple models. Ethics approval is not required. This proposed systematic review will utilize a novel Bayesian network meta-analysis model to help standardize iPTH monitoring in hyperparathyroidism, thereby optimizing patient outcomes and healthcare expenditures.

Artificial intelligence for X-ray scaphoid fracture detection: a systematic review and diagnostic test accuracy meta-analysis

Abstract Objectives Scaphoid fractures are usually diagnosed using X-rays, a low-sensitivity modality. Artificial intelligence (AI) using Convolutional Neural Networks (CNNs) has been explored for diagnosing scaphoid fractures in X-rays. The aim of this systematic review and meta-analysis is to evaluate the use of AI for detecting scaphoid fractures on X-rays and analyze its accuracy and usefulness. Materials and methods This study followed the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and PRISMA-Diagnostic Test Accuracy. A literature search was conducted in the PubMed database for original articles published until July 2023. The risk of bias and applicability were evaluated using the QUADAS-2 tool. A bivariate diagnostic random-effects meta-analysis was conducted, and the results were analyzed using the Summary Receiver Operating Characteristic (SROC) curve. Results Ten studies met the inclusion criteria and were all retrospective. The AI’s diagnostic performance for detecting scaphoid fractures ranged from AUC 0.77 to 0.96. Seven studies were included in the meta-analysis, with a total of 3373 images. The meta-analysis pooled sensitivity and specificity were 0.80 and 0.89, respectively. The meta-analysis overall AUC was 0.88. The QUADAS-2 tool found high risk of bias and concerns about applicability in 9 out of 10 studies. Conclusions The current results of AI’s diagnostic performance for detecting scaphoid fractures in X-rays show promise. The results show high overall sensitivity and specificity and a high SROC result. Further research is needed to compare AI’s diagnostic performance to human diagnostic performance in a clinical setting. Clinical relevance statement Scaphoid fractures are prone to be missed secondary to assessment with a low sensitivity modality and a high occult fracture rate. AI systems can be beneficial for clinicians and radiologists to facilitate early diagnosis, and avoid missed injuries. Key Points • Scaphoid fractures are common and some can be easily missed in X-rays. • Artificial intelligence (AI) systems demonstrate high diagnostic performance for the diagnosis of scaphoid fractures in X-rays. • AI systems can be beneficial in diagnosing both obvious and occult scaphoid fractures.

Relapse in clinically stable adult patients with schizophrenia or schizoaffective disorder: evidence-based criteria derived by equipercentile linking and diagnostic test accuracy meta-analysis

There is no consensus on defining relapse in schizophrenia, and scale-derived criteria with unclear clinical relevance are widely used. We aimed to develop an evidence-based scale-derived set of criteria to define relapse in patients with schizophrenia or schizoaffective disorder. We searched the Yale University Open Data Access (YODA) for randomised controlled trials (RCTs) in clinically stable adults with schizophrenia or schizoaffective disorder, and obtained individual participant data on Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity (CGI-S), Personal and Social Performance (PSP), and Social and Occupational Functioning Assessment Scale (SOFAS). Our main outcomes were PANSS-derived criteria based on worsening in PANSS total score. We examined their relevance using equipercentile linking with CGI-S and functioning scales, and their test-performance in defining relapse with diagnostic test accuracy meta-analysis against CGI-S worsening (≥1-point increase together with a score ≥4 points) and psychiatric hospitalisation. Based on data from seven RCTs (2354 participants; 1348 men [57·3%] and 1006 women [42·7%], mean age of 39·5 years [SD 12·0, range 17-89]; 303 Asian [12.9%], 255 Black [10.8%], 1665 White [70.7%], and other or unspecified 131 [5.6%]), an increase of 12 points or more in PANSS total (range 30-210 points) corresponded to clinically important deterioration in global severity of illness (≥1 point increase in CGI-S, range 1-7) and functioning (≥10 points decline in PSP or SOFAS, range 1-100). The interpretation of percentage changes varied importantly across different baseline scores. An increase of 12 points or more in PANSS total had good sensitivity and specificity using CGI-S as reference standard (sensitivity 82·1% [95% CI 77·1-86·4], specificity 86·9% [82·9-90·3]), as well as good sensitivity but lower specificity compared to hospitalisation (sensitivity 81·7% [74·1-87·7], specificity 69·2% [60·5-76·9]). Requiring either an increase in PANSS total or in specific items for positive and disorganization symptoms further improved test-performance. Cutoffs for situations where high sensitivity or specificity is needed are presented. An increase of either 12 points or more in the PANSS total score, or worsening of specific positive and disorganisation symptom items could be a reasonable evidence-based definition of relapse in schizophrenia, potentially linking symptoms used to define remission and relapse. Percentage changes should not be used to define relapse because their interpretation depends on baseline scores. German Research Foundation (grant number: 428509362).

Radiomics to Differentiate Malignant and Benign Breast Lesions: A Systematic Review and Diagnostic Test Accuracy Meta-Analysis.

Breast cancer is a prevalent global health concern, necessitating accurate diagnostic tools for effective management. Diagnostic imaging plays a pivotal role in breast cancer diagnosis, staging, treatment planning, and outcome evaluation. Radiomics is an emerging field of study in medical imaging that contains a broad set of computational methods to extract quantitative features from radiographic images. This can be utilized to guide diagnosis, treatment response, and prognosis in clinical settings. A systematic review was performed in concordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. Quality was assessed using the radiomics quality score. Diagnostic sensitivity and specificity of radiomics analysis, with 95% confidence intervals (CIs), were included for meta-analysis. The area under the curve analysis was recorded. An extensive statistical analysis was performed following the Cochrane guidelines. Statistical significance was determined if p-values were less than 0.05. Statistical analyses were conducted using Review Manager (RevMan), Version 5.4.1. A total of 31 manuscripts involving 8,773 patients were included, with 17 contributing to the meta-analysis. The cohort comprised 56.2% malignant breast cancers and 43.8% benign breast lesions. MRI demonstrated a sensitivity of 0.91 (95% CI: 0.89-0.92) and a specificity of 0.84 (95% CI: 0.82-0.86) in differentiating between benign and malignant breast cancers. Mammography-based radiomic features predicted breast cancer subtype with a sensitivity of 0.79 (95% CI: 0.76-0.82) and a specificity of 0.81 (95% CI: 0.79-0.84). Ultrasound-based analysis yielded a sensitivity of 0.92 (95% CI: 0.90-0.94) and a specificity of 0.85 (95% CI: 0.83-0.88). Only one study reported the results of radiomic evaluation from CT, which had a sensitivity of 0.95 (95% CI: 0.88-0.99) and a specificity of 0.56 (95% CI: 0.45-0.67). Across different imaging modalities, radiomics exhibited robust diagnostic accuracy in differentiating benign and malignant breast lesions. The results underscore the potential of radiomic assessment as a minimally invasive alternative or adjunctive diagnostic tool for breast cancer. This is pioneering data that reports on a novel diagnostic approach that is understudied and underreported. However, due to study limitations, the complexity of this technology, and the need for future development, biopsy still remains the current gold standard method of determining breast cancer type.

A multiple cut-off diagnostic meta-analysis to identify the atrial high-rate episodes threshold that better relates to thromboembolic events

Abstract Background Despite the high prevalence of atrial high-rate episodes (AHRE) detected by cardiac implantable electronic devices (CIED), clinical guidelines and consensus documents have failed to agree on a universal AHRE definition. Clear evidence on the best management strategy is lacking. Purpose The present is a diagnostic test accuracy meta-analysis aiming to derive from available literature the optimal AHRE threshold to predict thromboembolic events. Methods PubMed/MEDLINE and EMBASE databases were screened for studies on CIED patients reporting incidence of thromboembolic events referred to at least one AHRE definition. A random-effect diagnostic test accuracy meta-analysis with multiple cut-offs was performed: duration of AHRE was the "diagnostic test" (positive test if the patients experienced an AHRE lasting at least as long as the time cut-off under examination) whose performance in predicting the "disease" (thromboembolic events) was evaluated across multiple cut-offs. Two analyses, according to AHRE definition (longest episode vs. cumulative burden), were performed. Results 23 studies were included in the analyses (Fig. 1 Panel A), encompassing 46,189 patients: 19 considering the longest single AHRE and 4 the AHRE burden, respectively. Median follow-up was 40.75 (IQR 28.25-52.80) months. The analysis on the longest single AHRE indicated 0.07 minutes as the optimal cut-off to differentiate AHRE associated or not to thromboembolic events [sensitivity 65.4% (95% CI 48.8-79.0%), specificity 52.7% (95%CI 46.0-59.4%), area under the summary receiver operating characteristic curve (AUC-SROC): 0.62; Fig. 1 Panel B]. The analysis on AHRE burden indicated, instead, 1.4 minutes as the optimal cut-off [sensitivity 58.2% (95%CI 25.6-85.0%), specificity 57.5% (95% CI 42.0-71.7%), AUC-SROC 0.60; Fig. 1 Panel C]. PPV and NPV for 6 minutes and 24 hours cut-offs were similar in each analysis (Figure 2). Sensitivity analyses exclusively considering studies reporting data on patients without previous AF diagnosis and high-quality studies only yield similar results. Conclusion The present evidence-based approach suggests the presence (or not) of AHRE, rather than a specific duration, relates to an increased thromboembolic risk in CIED patients. A linear relationship between AHRE duration (both in terms of single longest episode than cumulative burden) and thromboembolic events was not observed.