Diagnostic Test Accuracy Research Articles

Predicting Lost to Follow-Up Status Using an Adolescent HIV Psychosocial Attrition Risk Assessment Tool: Results From a Mixed Methods Prospective Cohort Study in Uganda.

Low retention in care for adolescents living with HIV (ALHIV) has been a key driver of suboptimal viral load suppression rates in Uganda. The objective of this study was to develop a psychosocial risk assessment tool and evaluate its ability to predict the risk of attrition of ALHIV between the ages 15 and 19 years. The study was conducted in 20 facilities in Central and Western Uganda from August 2021 through July 2022. A mixed methods prospective cohort study was conducted in two phases. In the first phase, the Adolescent Psychosocial Attrition Risk Assessment tool was developed and revised using feedback from focus group discussions and interviews. In the second phase, the ability of the Adolescent Psychosocial Attrition Risk Assessment tool to predict attrition among ALHIV was evaluated using diagnostic accuracy tests. A total of 597 adolescents between the ages 15 and 19 years were enrolled, of which 6% were lost to follow-up at the end of the study period. A 20-question tool was developed, with 12 questions being responded to affirmatively by >50% of all participants. Using a cut-off score of 6 or more affirmative answers translated to an area under the curve of 0.58 (95% CI: 0.49 to 0.66), sensitivity of 55% (95% CI: 36% to 72%), and specificity of 61% (95% CI: 56% to 65%). Although the Adolescent Psychosocial Attrition Risk Assessment tool was not effective at predicting lost to follow-up status among ALHIV, the tool was useful for identifying psychosocial issues experienced by ALHIV and may be appropriate to administer during routine care visits to guide action.

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.

Diagnostic accuracy, feasibility and acceptability of stool-based testing for childhood tuberculosis.

Childhood tuberculosis (TB) diagnosis remains challenging, partly because children cannot provide sputum. This study evaluated the diagnostic accuracy of the Simple One-Step (SOS) stool method with Xpert MTB/RIF Ultra (Xpert-Ultra) for childhood TB compared to culture and Xpert-Ultra on a respiratory sample (RS) and clinical diagnosis. It also assessed the feasibility and acceptability of stool testing according to laboratory staff, and caregivers' sample preference. We enrolled children (≤10 years) with presumptive pulmonary tuberculosis in Ethiopia. RS was tested using Xpert-Ultra and culture; stool samples were tested using the SOS stool method with Xpert-Ultra. Laboratory staff and caregivers' opinions were assessed using standardised questionnaires. Of the 898 children enrolled, 792, 832 and 794 were included for assessing the diagnostic accuracy of SOS stool with Xpert-Ultra against culture, RS Xpert-Ultra and clinical diagnosis, respectively, yielding sensitivity estimates for SOS stool with Xpert-Ultra of 69.1% (95% confidence interval (CI) 56.0-79.7%), 76.8% (95% CI 64.2-85.9%) and 59.0% (95% CI 47.9-69.2%), respectively. The specificity was ≥98.8% for all comparisons. The rate of non-determinate test results was 2.8% after one repeat test. According to laboratory staff, stool collection was feasible and acceptable and the SOS stool method was easy to perform. Most caregivers (75%) preferred stool for TB diagnosis over RS. This study shows that SOS stool Xpert-Ultra testing offers a good alternative to RS testing for TB in children who cannot spontaneously produce a sputum sample and would otherwise need to undergo invasive procedures to obtain RS for diagnosis.

Cost-Effectiveness of Lecanemab for Individuals With Early-Stage Alzheimer Disease.

Little is known regarding the cost-effectiveness of lecanemab (Leqembi), a monoclonal antibody approved by the US Food and Drug Administration in January 2023 for the treatment of mild cognitive impairment (MCI) or mild dementia due to Alzheimer disease (AD). This study aims to quantify the cost-effectiveness of lecanemab and how it varies based on the accuracy of AD testing and individuals' APOE ε4 status. Seven alternative test-treat-target strategies defined by combinations of testing approaches (PET, CSF, or plasma assay), treatment choices (standard of care [SoC] alone or lecanemab in addition to SoC), and targeting strategies (targeting APOE ε4 noncarriers or heterozygous patients or not) were compared. A hybrid decision tree-Markov cohort model was constructed with 5 states: (1) MCI (Clinical Dementia Rating-Sum of Boxes [CDR-SB] 0-4.5); (2) mild dementia (CDR-SB 4.6-9.5); (3) moderate dementia (CDR-SB 9.6-16); (4) severe dementia (CDR-SB >16); and (5) death. Effectiveness was measured by quality-adjusted life years and costs from third-party and societal perspectives were estimated in 2022 US dollars over a lifetime horizon. Among the 7 test-treat-target strategies, SoC alone was the optimal strategy from a cost-effectiveness perspective. Neither targeted lecanemab treatment nor treatment unrestricted by APOE ε4 genotype was cost-effective vs SoC alone, regardless of the test used to diagnose patients with early-stage AD. However, CSF assay followed by targeted treatment would become cost-effective if lecanemab is priced below $5,100 per year. These results were robust to the accuracy of diagnostic testing and rates of lecanemab discontinuation and adverse events. Neither targeted lecanemab treatment nor treatment unrestricted by APOE ε4 genotype is cost-effective vs SoC alone for patients with MCI or mild dementia due to AD. Lecanemab would be cost-effective in some settings if priced below $5,100 per year.

Diagnostic Accuracy of Blind Bronchial Sample Testing by BioFire Pneumonia plus Panel in Pediatric Intensive Care Unit Patients and Its Impact in Early Adaptation of Antimicrobial Therapy: A Prospective Observational Study.

Community-acquired and nosocomial lower-respiratory-tract infections in critically ill pediatric patients require early appropriate antibiotic therapy to optimize outcomes. Using blind bronchial samples, we assessed the diagnostic performance of the rapid-multiplex polymerase chain reaction (PCR) assay BioFire Pneumonia plus Panel vs. reference standard culturing with antimicrobial susceptibility testing. For this prospective observational study in a single pediatric intensive care unit, we included consecutive patients younger than 18 years admitted for suspected community-, hospital- or ventilator-associated pneumonia in 2021-2022. Sensitivity, specificity, positive predictive value and negative predictive value of the multiplex PCR assay were determined. The kappa coefficient was computed to assess agreement, and univariate analyses were done to identify factors associated with discrepancies between the 2 diagnostic methods. Of the 36 included patients (median age, 1.4 years; interquartile range, 0.2-9.2), 41.7%, 27.8%, and 30.5% had community-, hospital- and ventilator-associated pneumonia, respectively. The overall κ was 0.74, indicating good agreement. Overall, the sensitivity of the multiplex PCR assay was 92% (95% CI: 77%-98%) and specificity 95% (95% CI: 92%-97%), with variations across microorganisms. The median time from sample collection to antimicrobial susceptibility test results was 3.9 (2.5-15) hours with the multiplex PCR assay and 60.5 (47.6-72.2) hours with the reference technique. The BioFire Pneumonia plus Panel used to test blind bronchial samples had satisfactory diagnostic performance in critically ill pediatric patients. The rapid results provided by this test may improve the appropriateness of antimicrobial therapy and help minimize the use of antibiotics.

Diagnostic Accuracy of Antigen-Based Rapid Test during the Fourth Wave of COVID-19 in Edo State, Nigeria

Background: Since the use of rapid test kits for diagnosis of COVID-19, diagnostic accuracy has been of concern, particularly in resource- limited settings. This study assessed diagnostic accuracy of Abbot Panbio antigen-based rapid diagnostic test (RDT) for COVID-19 using polymerase chain reaction (PCR) as the gold standard in Edo State, Nigeria.
 Methodology: We conducted a descriptive cross-sectional study during the 4th wave of the pandemic in Edo State from January 5 – February 4th, 2022. Nasopharyngeal and oropharyngeal swabs were collected from 240 consenting participants at 10 sample collection sites. The index test (RDT) and gold standard test (real-time reverse transcription PCR) were performed simultaneously. Sensitivity, specificity, predictive values, and ROC analysis were conducted on the RDT compared to RT-PCR using SPSS version 26.0 software. 
 Results: Thirty-six (15.0%) participants tested positive on RDT and 34 (14.2%) tested positive on PCR. RDT had a sensitivity of 73.5% (95% CI: 66.0–81.0) and specificity of 94.7% (95% CI: 91.6-97.8) with a positive predictive value of 69.4% (95% CI: 55.8-80.7), and negative predictive value of 95.6% (95% CI: 91.8-98.0). The area under the curve (AUC) of the ROC for the RDT against PCR was 84.1% (75.1% - 93.1%).
 Conclusion: The diagnostic accuracy of the Panbio rapid antigen test for SARSCoV-2 was below WHO standards. However, they remain useful tools for continued surveillance of the disease. Rigorous evaluations combining the results of rapid antigen tests with other clinical information would prove useful for prompt diagnosis and surveillance of COVID-19 in Nigeria.

Diagnosing adult and pediatric extrapulmonary tuberculosis by MPT64 antigen detection with immunohistochemistry and immunocytochemistry using reproduced polyclonal antibodies.

Diagnosing extrapulmonary tuberculosis (EPTB) is challenging. Immunohistochemistry or immunocytochemistry has been used to diagnose tuberculosis (TB) by detection of MPT64 antigen from various extrapulmonary specimens and has shown good diagnostic performance in our previous studies. The test can distinguish between disease caused by Mycobacterium tuberculosis (Mtb) complex and nontuberculous mycobacteria and can be applied on formalin-fixed paraffin-embedded tissue. As the antibodies previously used were in limited supply, a new batch of polyclonal antibodies was developed for scale-up and evaluated for the first time in this study. Our aim was to assess the diagnostic accuracy of the MPT64 test with reproduced antibodies in the high burden settings of Pakistan and India. Patients were enrolled prospectively. Samples from suspected sites of infection were collected and subjected to histopathologic and/or cytologic evaluation, routine TB diagnostics, GeneXpert MTB/RIF (Xpert), and the MPT64 antigen detection test. Patients were followed until the end of treatment. Based on a composite reference standard (CRS), 556 patients were categorized as TB cases and 175 as non-TB cases. The MPT64 test performed well on biopsies with a sensitivity and specificity of 94% and 75%, respectively, against a CRS. For cytology samples, the sensitivity was low (36%), whereas the specificity was 81%. Overall, the MPT64 test showed higher sensitivity (73%) than Xpert (38%) and Mtb culture (33%). The test performed equally well in adults and children. We found an additive diagnostic value of the MPT64 test in conjunction with histology and molecular tests, increasing the yield for EPTB. In conclusion, immunochemical staining with MPT64 antibodies improves the diagnosis of EPTB in high burden settings and could be a valuable addition to routine diagnostics.

Diagnostic accuracy of cartridge-based nucleic acid amplification test and resistance pattern in new and previously treated tuberculosis cases: A prospective observational study

Background: Diagnostic methods, particularly sputum microscopy, are the standard method for diagnosing tuberculosis (TB) in many settings. The emergence of cartridge-based nucleic acid amplification test (CBNAAT) as a newer diagnostic tool for TB has shown promising results. CBNAAT is a rapid molecular test that detects the genetic material of Mycobacterium tuberculosis (MTB), the bacterium causing TB, in sputum samples. It offers higher sensitivity and faster results compared to sputum microscopy. Aim: The study aimed to 1) compare the diagnostic accuracy of CBNAAT in detecting smear-positive and smear-negative pulmonary TB cases, and 2) compare rifampicin resistance prevalence between newly diagnosed and previously treated pulmonary TB patients. Methodology: A hospital-based prospective study was conducted in the Respiratory Medicine Department of Guru Gobind Singh Government Hospital, Jamnagar, on PTB patients from August 2019 to December 2020. Data were collected through a self-structured questionnaire that included detailed clinical history, radiological, biochemical, and microbiological investigations. Descriptive statistical analyses were performed to present data as percentages and frequencies. Diagnostic accuracy analysis was conducted. A P-value <0.05 was considered significant. Results: Out of 150 cases, 104 (69.3 %) were male, while 46 (30.7%) were female. Sixty-one percent of new and 86% of previously treated cases were male, whereas 39% of new and 14% of previously treated cases were female. The sensitivity of sputum smear microscopy is 77.33% in cases of PTB, whereas sputum CBNAAT detected 94% of cases of PTB. The sensitivity of CBNAAT for MTB detection in smear microscopy–positive samples was 93.97%, whereas the sensitivity in smear microscopy–negative samples was 94.12%. Regarding rifampicin resistance, the prevalence was lower in newly diagnosed (3/100) compared to previously treated patients with rifampicin-resistant PTB (3/50). Conclusion: These findings suggest that CBNAAT can be a valuable tool for the detection of TB, particularly in cases where sputum smear microscopy results are negative. However, further research is needed to validate these results and evaluate the clinical implications of using CBNAAT in routine TB diagnostics.

Comparative diagnostic accuracy of transcranial Doppler and contrast-enhanced transthoracic echocardiography for the diagnosis of patent foramen ovale and atrial septal defect.

Recognition of right-to-left shunt is crucial in the work-up of patients with suspected patent foramen ovale (PFO) or atrial septal defect (ASD). While transesophageal echocardiography (TEE) remains the gold standard diagnostic tool for the anatomic assessment of PFO/ASD, transcranial Doppler (TCD) and contrast-enhanced transthoracic echocardiogram (CE-TTE) hold the promise of providing minimally invasive yet accurate clinical details. Their comparative accuracy remains however debated. We conducted a retrospective observational study leveraging our extensive institutional experience with systematic TCD and CE-TTE in patients with suspected PFO/ASD. Several measures of diagnostic test accuracy were computed, with point estimates and 95% confidence intervals, when applicable. A total of 1358 patients were included, with age 48±14 years and 772 (58%) women. Tests were performed for diagnostic purposes in 797 (58.6%) and during follow-up in 740 (54.5%). A PFO was eventually diagnosed in 1038 (77.9%) patients, and an ASD in 60 (4.5%). Agreement between TCD and CE-TTE occurred in 1309 (85.2%) cases, with TCD yielding worse findings than CE-TTE in 91 (5.9%) patients, and vice versa in 137 (8.9%), yielding a Cohen kappa of 78.6% (95% CI: 76.3-81.1%) and a highly significant P value at McNemar test (P<0.001). After dichotomization, and using TCD as benchmark, CE-TTE yielded sensitivity 96.9%, specificity 95.1%, area under the curve 92.1%, and P=0.249. Similar findings were obtained when focusing only on diagnostic tests or follow-up ones (Cohen kappa respectively 74.0% [70.2-77.1%], P<0.001 and 80.3% [76.4-84.3%], P<0.001). Notably, Valsalva was necessary to disclose the presence of shunt during TCD in 487 (31.7%) patients and during CE-TTE in 482 (31.4%) cases. Finally, performance of TCD and CE-TTE in a subset of patients eventually undergoing TTE was quite similar. The diagnostic accuracy of CE-TTE appears favorable, and this imaging test may identify patients who may be missed if only TCD is used to screen patients with suspected PFO/ASD. Accordingly, CE-TTE is recommended as an adjunct diagnostic modality for all patients with a high pre-test probability of PFO/ASD and right-to-left shunt.

IJCM_129A: Is intelligent Breast Exam (iBE) a sensitive and specific test compared with mammography in the early detection of breast cancer and patient triage in adults? A Diagnostic review and Meta-analysis

Background: Breast cancer represents the most common cause of cancer death among women globally. Early cancer detection in low-income countries is difficult because of the relatively expensive mammographic screening. Intelligent Breast Exam [iBE] is a portable device that is available at low cost and provides electronic documentation for additional diagnostic workup. Objectives: This study aims to investigate the diagnostic accuracy of i breast device in the early detection of breast cancer and patient triage in adults. Secondary objectives: 1) To review the usability of i Breast device as a triage test for breast pathologies in primary care setting. 2) To review the feasibility, ease and cost-effectiveness of i Breast device Methodology: A systematic literature search of the MEDLINE, Embase and Cochrane Library databases will be performed to identify the studies reporting the accuracy of i breast device for the detection of breast cancer from January 2010 to December 2023. The search strategy will be carried out by using key words and MeSH (Medical Subject Headings) terms. The reference test will be mammogram. The search will be in accordance with the PRISMA-DTA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy studies) guidelines. Two reviewer authors will independently screen the results. The full-text articles will be reviewed when studies meet the inclusion criteria or in any uncertainty. Non-consensus will be resolved by a third reviewer. The quality of the studies will be examined using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. The review will be registered with PROSPERO (Prospective Register of Systematic Reviews). The estimates of sensitivity, specificity and area under the curve will be attempted using the bivariate model for the diagnostic meta-analysis.

Development of clinical screening tool for exocrine pancreatic insufficiency in patients with definite chronic pancreatitis

Background/ObjectivesNo simple, accurate diagnostic tests exist for exocrine pancreatic insufficiency (EPI), and EPI remains underdiagnosed in chronic pancreatitis (CP). We sought to develop a digital screening tool to assist clinicians to predict EPI in patients with definite CP. MethodsThis was a retrospective case-control study of patients with definite CP with/without EPI. Overall, 49 candidate predictor variables were utilized to train a Classification and Regression Tree (CART) model to rank all predictors and select a parsimonious set of predictors for EPI status. Five-fold cross-validation was used to assess generalizability, and the full CART model was compared with 4 additional predictive models. EPI misclassification rate (mRate) served as primary endpoint metric. Results274 patients with definite CP from 6 pancreatitis centers across the United States were included, of which 58 % had EPI based on predetermined criteria. The optimal CART decision tree included 10 variables. The mRate without/with 5-fold cross-validation of the CART was 0.153 (training error) and 0.314 (prediction error), and the area under the receiver operating characteristic curve was 0.889 and 0.682, respectively. Sensitivity and specificity without/with 5-fold cross-validation was 0.888/0.789 and 0.794/0.535, respectively. A trained second CART without pancreas imaging variables (n = 6), yielded 8 variables. Training error/prediction error was 0.190/0.351; sensitivity was 0.869/0.650, and specificity was 0.728/0.649, each without/with 5-fold cross-validation. ConclusionWe developed two CART models that were integrated into one digital screening tool to assess for EPI in patients with definite CP and with two to six input variables needed for predicting EPI status.

Comparison of Xpert MTB RIF (G4) With Xpert MTB (Ultra) in Diagnosis of Mycobacterium Tuberculosis in Clinical Samples

Abstract Background: Tuberculosis (TB) continues to be a major cause of morbidity and mortality worldwide. The main strategy to fight the pandemic is the development of rapid, accurate diagnostic tests, which helps to reduce the time for initiation of therapy. In 2010, WHO recommended the use of Xpert Mycobacterium tuberculosis/rifampicin (MTB/RIF) (G4), which is a cartridge-based semi-automated nucleic acid amplification test (NAAT) as a primary test with an aim to improve the detection of MTB. Later on, to improve the diagnostic efficacy, the new and improved cartridges called Xpert Ultra were introduced in 2017. Materials and Methods: One thousand and sixty-nine clinical samples were utilized for the study for microscopy, culture, and NAATs (Xpert MTB/RIF G4 and Ultra). The samples were randomly allocated. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated while assuming trace results as positive and negative in two separate scenarios. Results: The sensitivity of Xpert MTB/RIF Ultra cartridge was higher (100%) than Xpert MTB/RIF G4 cartridge (95.23%) and the specificity of Ultra cartridge was lower (71.79%) when compared to G4 cartridge (91.63%). However, the specificity of Xpert Ultra cartridge improved by reclassifying the “trace” interpretation as negative (89.1%). The NPV was 100% and 99.09% for Xpert Ultra cartridge and the Xpert G4 cartridge, respectively, and did not change by reclassifying the “trace” interpretation as negative. In contrast, the PPV varied greatly between the two tests, 26.66% for Xpert Ultra cartridge and 66.66% for Xpert G4 cartridge. The PPV of Xpert Ultra cartridge was improved to 48.48% by including “trace” samples in the negative pool. Conclusion: Xpert Ultra and G4 shows good performance as a first line diagnostic test. Caution should be exercised when interpreting ‘trace’ results in a country like India without parallel confirmatory tests like microscopy and culture. Data is limited on this newly incorporated value assigned in the automated report. Conducting further studies on results interpreted as ‘trace’ will help in improving the guidelines and as well as utilisation of such tests.

Investigation of the Clinical Diagnostic Significance of the T-Cell Test for Tuberculosis combined with Erythrocyte Sedimentation Test in Pulmonary Tuberculosis

Objective: To investigate the clinical diagnostic significance of peripheral blood T-cell test (T-spot test) for tuberculosis (TB) infection combined with erythrocyte sedimentation rate (ESR) in pulmonary TB. Methods: 41 patients with a clinical diagnosis of TB during hospitalization from January 2020 to April 2023 in our hospital were selected as the experimental group, and 45 patients without TB (bronchopneumonia patients) were selected as the control group. The diagnostic specificity, sensitivity, and accuracy of the T-spot TB test, ESR test, and the combined test of the two were calculated respectively. Results: The sensitivity, specificity, and accuracy of the T-spot TB test combined with ESR for the diagnosis of TB in the experimental group were significantly higher than the individual results of the T-spot TB test and ESR test alone (P &lt; 0.05). Conclusion: The T-spot TB test combined with the ESR test for TB diagnosis has greater clinical value than carrying out the tests individually.

Accuracy of molecular diagnostic assays for detection of Mycobacterium bovis: A systematic review and meta-analysis

Bovine tuberculosis (bovine TB) is a chronic wasting disease of cattle caused primarily by Mycobacterium bovis. Controlling bovine TB requires highly sensitive, specific, quick, and reliable diagnostic methods. This systematic review and meta-analysis evaluated molecular diagnostic tests for M. bovis detection to inform the selection of the most viable assay. On a per-test basis, loop-mediated isothermal amplification (LAMP) showed the highest overall sensitivity of 99.0% [95% CI: 86.2%-99.9%] and specificity of 99.8% [95% CI: 96.2%-100.00%]. Quantitative real-time polymerase chain reaction (qPCR) outperformed conventional PCR and nested PCR (nPCR) with a diagnostic specificity of 96.6% [95% CI: 88.9%-99.0%], while the diagnostic sensitivity of 70.8% [95% CI: 58.6–80.5%] was comparable to that of nPCR at 71.4% [95% CI: 60.7–80.2%]. Test sensitivity was higher with the input of milk samples (90.9% [95% CI: 56.0%-98.7%]), while specificity improved with tests based on major M. bovis antigens (97.8% [95% CI: 92.3%-99.4%]), the IS6110 insertion sequence (95.4% [95% CI: 87.6%-98.4%]), and the RD4 gene (90.7% [95% CI: 52.2%-98.9%]). The design of the currently available molecular diagnostic assays, while mostly based on nonspecific gene targets, prevents them from being accurate enough to diagnose M. bovis infections in cattle, despite their promise. Future assay development should focus on the RD4 region since it is the only target identified by genome sequence data as being distinctive for detecting M. bovis. The availability of a sufficiently accurate diagnostic test combined with the routine screening of milk samples can decrease the risk of zoonotic transmissions of M. bovis.

Infrared Spectroscopy of Synovial Fluid Shows Accuracy as an Early Biomarker in an Equine Model of Traumatic Osteoarthritis.

Osteoarthritis is a leading cause of lameness and joint disease in horses. A simple, economical, and accurate diagnostic test is required for routine screening for OA. This study aimed to evaluate infrared (IR)-based synovial fluid biomarker profiling to detect early changes associated with a traumatically induced model of equine carpal osteoarthritis (OA). Unilateral carpal OA was induced arthroscopically in 9 of 17 healthy thoroughbred fillies; the remainder served as Sham-operated controls. The median age of both groups was 2 years. Synovial fluid (SF) was obtained before surgical induction of OA (Day 0) and weekly until Day 63. IR absorbance spectra were acquired from dried SF films. Following spectral pre-processing, predictive models using random forests were used to differentiate OA, Sham, and Control samples. The accuracy for distinguishing between OA and any other joint group was 80%. The classification accuracy by sampling day was 87%. For paired classification tasks, the accuracies by joint were 75% for OA vs. OA Control and 70% for OA vs. Sham. The accuracy for separating horses by group (OA vs. Sham) was 68%. In conclusion, SF IR spectroscopy accurately discriminates traumatically induced OA joints from controls.

Diagnostic Accuracy of the Passive Straight Leg Raise Test in Detecting Compression of the Lower Lumbar Nerve Roots

Background: Lumbar nerve root compression is a pathological condition that occurs commonly in the low back pain population. Passive straight leg raise (SLR) is a clinical test widely used to confirm this pathological condition. Yet, its diagnostic accuracy needs further investigation. Objective: To assess the sensitivity and specificity of the passive SLR test in detecting compression of the lower lumbar nerve roots using magnetic resonance imaging as a reference standard. Design: This study is a prospective diagnostic-accuracy study. Methods: One hundred-and-twelve participants (82 males and 30 females) met the inclusion criteria and joined the study. Participants were recruited through direct communication and poster announcement and allocated into positive and negative MRI groups. A standardized passive SLR test was applied to all participants; then 2 X 2 cross-tabulation statistics were conducted to determine the sensitivity and specificity. Results: The passive SLR test was considered positive in 62 (56.36%) participants while it was negative in 50 (45.45%) participants. Sensitivity, specificity, positive and negative likelihood ratios were found to be 77.1%., 81.0%, 6.75, and 0.47 respectively. The diagnostic accuracy was found to be 80.95%. ROC curve revealed positive fair sensitivity and specificity of the test with the area under the curve equal to 0.775. Conclusion: The passive SLR test is a useful tool for the diagnosis of lower lumbar nerve root compression.

Triage tools for detecting cervical spine injury in paediatric trauma patients.

Paediatric cervical spine injury (CSI) after blunt trauma is rare but can have severe consequences. Clinical decision rules (CDRs) have been developed to guide clinical decision-making, minimise unnecessary tests and associated risks, whilst detecting all significant CSIs. Several validated CDRs are used to guide imaging decision-making in adults following blunt trauma and clinical criteria have been proposed as possible paediatric-specific CDRs. Little information is known about their accuracy. To assess and compare the diagnostic accuracy of CDRs or sets of clinical criteria, alone or in comparison with each other, for the evaluation of CSI following blunt trauma in children. For this update, we searched CENTRAL, MEDLINE, Embase, and six other databases from 1 January 2015 to 13 December 2022. As we expanded the index test eligibility for this review update, we searched the excluded studies from the previous version of the review for eligibility. We contacted field experts to identify ongoing studies and studies potentially missed by the search. There were no language restrictions. We included cross-sectional or cohort designs (retrospective and prospective) and randomised controlled trials that compared the diagnostic accuracy of any CDR or clinical criteria compared with a reference standard for the evaluation of paediatric CSI following blunt trauma. We included studies evaluating one CDR or comparing two or more CDRs (directly and indirectly). We considered X-ray, computed tomography (CT) or magnetic resonance imaging (MRI) of the cervical spine, and clinical clearance/follow-up as adequate reference standards. Two review authors independently screened titles and abstracts for relevance, and carried out eligibility, data extraction and quality assessment. A third review author arbitrated. We extracted data on study design, participant characteristics, inclusion/exclusion criteria, index test, target condition, reference standard and data (diagnostic two-by-two tables) and calculated and plotted sensitivity and specificity on forest plots for visual examination of variation in test accuracy. We assessed methodological quality using the Quality Assessment of Diagnostic Accuracy Studies Version 2 tool. We graded the certainty of the evidence using the GRADE approach. We included five studies with 21,379 enrolled participants, published between 2001 and 2021. Prevalence of CSI ranged from 0.5% to 1.85%. Seven CDRs were evaluated. Three studies reported on direct comparisons of CDRs. One study (973 participants) directly compared the accuracy of three index tests with the sensitivities of NEXUS, Canadian C-Spine Rule and the PECARN retrospective criteria being 1.00 (95% confidence interval (CI) 0.48 to 1.00), 1.00 (95% CI 0.48 to 1.00) and 1.00 (95% CI 0.48 to 1.00), respectively. The specificities were 0.56 (95% CI 0.53 to 0.59), 0.52 (95% CI 0.49 to 0.55) and 0.32 (95% CI 0.29 to 0.35), respectively (moderate-certainty evidence). One study (4091 participants) compared the accuracy of the PECARN retrospective criteria with the Leonard de novo model; the sensitivities were 0.91 (95% CI 0.81 to 0.96) and 0.92 (95% CI 0.83 to 0.97), respectively. The specificities were 0.46 (95% CI 0.44 to 0.47) and 0.50 (95% CI 0.49 to 0.52) (moderate- and low-certainty evidence, respectively). One study (270 participants) compared the accuracy of two NICE (National Institute for Health and Care Excellence) head injury guidelines; the sensitivity of the CG56 guideline was 1.00 (95% CI 0.48 to 1.00) compared to 1.00 (95% CI 0.48 to 1.00) with the CG176 guideline. The specificities were 0.46 (95% CI 0.40 to 0.52) and 0.07 (95% CI 0.04 to 0.11), respectively (very low-certainty evidence). Two additional studies were indirect comparison studies. One study (3065 participants) tested the accuracy of the NEXUS criteria; the sensitivity was 1.00 (95% CI 0.88 to 1.00) and specificity was 0.20 (95% CI 0.18 to 0.21) (low-certainty evidence). One retrospective study (12,537 participants) evaluated the PEDSPINE criteria and found a sensitivity of 0.93 (95% CI 0.78 to 0.99) and specificity of 0.70 (95% CI 0.69 to 0.72) (very low-certainty evidence). We did not pool data within the broader CDR categories or investigate heterogeneity due to the small quantity of data and the clinical heterogeneity of studies. Two studies were at high risk of bias. We identified two studies that are awaiting classification pending further information and two ongoing studies. There is insufficient evidence to determine the diagnostic test accuracy of CDRs to detect CSIs in children following blunt trauma, particularly for children under eight years of age. Although most studies had a high sensitivity, this was often achieved at the expense of low specificity and should be interpreted with caution due to a small number of CSIs and wide CIs. Well-designed, large studies are required to evaluate the accuracy of CDRs for the cervical spine clearance in children following blunt trauma, ideally in direct comparison with each other.

Abstract 961: Detection of minimal residual disease in lymph predicts recurrence in HPV-negative head and neck cancer patients

Abstract Background: Locoregional cancer relapse remains a major cause of failure in head and neck squamous cell carcinoma (HNSCC), particularly for HPV-negative patients whose 2-year locoregional failure rate is up to 50%. There is unmet need for an accurate diagnostic test that predicts risk of recurrence prior to adjuvant therapy selection. We present a novel proximal assay for minimal residual disease (MRD) profiled in lymphatic exudate collected via surgical drains (“lymph”). Methods: Lymph, plasma, and blood were collected from 46 HPV-negative HNSCC patients postoperatively at 24 hours along with resected tumor. Cell-free DNA was extracted from lymph and plasma and sequenced using the TruSeq Oncology 500 panel to a depth of &amp;gt;100 million reads. Somatic mutations were identified by exome sequencing (200x) tumor and blood. Five patients had &amp;lt;2 mutations in tumor and were excluded. Two patients were censored due to lack of clinical data, yielding 18 patients with disease recurrence (REC) and 21 with no evidence of disease (NED) with &amp;gt;1 year of follow-up. Tumor-specific variants were force-called in lymph and plasma using a custom pipeline. Patients were considered MRD positive if the mean variant allele fraction (mVAF) was greater than 0.015% (the estimated limit of detection). The Kaplan-Meier (KM) estimator with log-rank test and Cox proportional-hazards model were used for survival analyses. Logistic regression model was performed with 5-fold cross-validation. Results: KM survival analyses showed lymph accurately predicts recurrence (sensitivity (SN) = 78%, specificity (SP) = 67%; p = 0.003, Hazard ratio (HR) = 4.7), while plasma was not significant (p = 0.92) at this postoperative timepoint. Performance was enhanced for locoregional relapse (SN = 92%, SP = 67%; p = 0.001, HR = 13.9. N=33). We also observed accurate recurrence prediction (SN = 83%, SP = 69%, p = 0.03, HR = 7.7) in the 19 N0 patients (node-negative by pathology). Lymph MRD outperformed individual pathology features (extranodal extension, perineural invasion, lymphovascular invasion, and nodal disease status) for recurrence prediction (HR = 3.4, 0.88, 2.5, 2.4, respectively). A logistic regression model combining lymph MRD with these 4 high-risk pathologic features showed superior performance over lymph alone or pathology alone (SN = 89%, SP = 67%; p = 0.0007, HR = 8.6). Conclusions: ctDNA analysis of lymph from surgical drains represents a novel proximal MRD approach in HPV-negative HNSCC. Postoperative lymph significantly outperforms plasma for prediction of recurrence, particularly in patients with locoregional relapse. Accurate MRD identification in patients with lower risk pathologic features suggests that lymph MRD testing has potential to augment traditional pathology and provide more personalized adjuvant treatment decision-making in patients with HPV-negative HNSCC. Citation Format: Wendy Winckler, Zhuosheng Gu, Damion Whitfield, Noah Earland, Adam Harmon, Megan Long, Peter Harris, Zhongping Xu, Ricardo Ramirez, Sophie Gerndt, Maciej Pacula, Marra S. Francis, Jose P. Zevallos, Aadel A. Chaudhuri. Detection of minimal residual disease in lymph predicts recurrence in HPV-negative head and neck cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 961.

Rapid review: A review of methods and recommendations based on current evidence.

Rapid review (RR) could accelerate the traditional systematic review (SR) process by simplifying or omitting steps using various shortcuts. With the increasing popularity of RR, numerous shortcuts had emerged, but there was no consensus on how to choose the most appropriate ones. This study conducted a literature search in PubMed from inception to December 21, 2023, using terms such as "rapid review" "rapid assessment" "rapid systematic review" and "rapid evaluation". We also scanned the reference lists and performed citation tracking of included impact studies to obtain more included studies. We conducted a narrative synthesis of all RR approaches, shortcuts and studies assessing their effectiveness at each stage of RRs. Based on the current evidence, we provided recommendations on utilizing certain shortcuts in RRs. Ultimately, we identified 185 studies focusing on summarizing RR approaches and shortcuts, or evaluating their impact. There was relatively sufficient evidence to support the use of the following shortcuts in RRs: limiting studies to those published in English-language; conducting abbreviated database searches (e.g., only searching PubMed/MEDLINE, Embase, and CENTRAL); omitting retrieval of grey literature; restricting the search timeframe to the recent 20 years for medical intervention and the recent 15 years for reviewing diagnostic test accuracy; conducting a single screening by an experienced screener. To some extent, the above shortcuts were also applicable to SRs. This study provided a reference for future RR researchers in selecting shortcuts, and it also presented a potential research topic for methodologists.

Endoscopic Ultrasound-Guided Needle-Based Confocal Endomicroscopy as a Diagnostic Imaging Biomarker for Intraductal Papillary Mucinous Neoplasms.

Pancreatic cancer is on track to become the second leading cause of cancer-related deaths by 2030, yet there is a lack of accurate diagnostic tests for early detection. Intraductal papillary mucinous neoplasms (IPMNs) are precursors to pancreatic cancer and are increasingly being detected. Despite the development and refinement of multiple guidelines, diagnosing high-grade dysplasia or cancer in IPMNs using clinical, radiologic, endosonographic, and cyst fluid features still falls short in terms of accuracy, leading to both under- and overtreatment. EUS-guided needle-based confocal laser endomicroscopy (nCLE) is a novel technology that allows real-time optical biopsies of pancreatic cystic lesions. Emerging data has demonstrated that EUS-nCLE can diagnose and risk stratify IPMNs more accurately than conventional diagnostic tools. Implementing EUS-nCLE in clinical practice can potentially improve early diagnosis of pancreatic cancer, reduce unnecessary surgeries of IPMNs with low-grade dysplasia, and advance the field of digital pathomics. In this review, we summarize the current evidence that supports using EUS-nCLE as a diagnostic imaging biomarker for diagnosing IPMNs and for risk stratifying their degree of neoplasia. Moreover, we will present emerging data on the role of adding artificial intelligence (AI) algorithms to nCLE and integrating novel fluid biomarkers into nCLE.