Triage Test Research Articles

Evolution of the "Internet Plus Health Care" Mode Enabled by Artificial Intelligence: Development and Application of an Outpatient Triage System.

Although new technologies have increased the efficiency and convenience of medical care, patients still struggle to identify specialized outpatient departments in Chinese tertiary hospitals due to a lack of medical knowledge. The objective of our study was to develop a precise and subdividable outpatient triage system to improve the experiences and convenience of patient care. We collected 395,790 electronic medical records (EMRs) and 500 medical dialogue groups. The EMRs were divided into 3 data sets to design and train the triage model (n=387,876, 98%) and test (n=3957, 1%) and validate (n=3957, 1%) it. The triage system was altered based on the current BERT (Bidirectional Encoder Representations from Transformers) framework and evaluated by recommendation accuracies in Xinhua Hospital using the cancellation rates in 2021 and 2022, from October 29 to December 5. Finally, a prospective observational study containing 306 samples was conducted to compare the system's performance with that of triage nurses, which was evaluated by calculating precision, accuracy, recall of the top 3 recommended departments (recall@3), and time consumption. With 3957 (1%) records each, the testing and validation data sets achieved an accuracy of 0.8945 and 0.8941, respectively. Implemented in Xinhua Hospital, our triage system could accurately recommend 79 subspecialty departments and reduce the number of registration cancellations from 16,037 (3.83%) of the total 418,714 to 15,338 (3.53%) of the total 434200 (P<.05). In comparison to the triage system, the performance of the triage nurses was more accurate (0.9803 vs 0.9153) and precise (0.9213 vs 0.9049) since the system could identify subspecialty departments, whereas triage nurses or even general physicians can only recommend main departments. In addition, our triage system significantly outperformed triage nurses in recall@3 (0.6230 vs 0.5266; P<.001) and time consumption (10.11 vs 14.33 seconds; P<.001). The triage system demonstrates high accuracy in outpatient triage of all departments and excels in subspecialty department recommendations, which could decrease the cancellation rate and time consumption. It also improves the efficiency and convenience of clinical care to fulfill better the usage of medical resources, expand hospital effectiveness, and improve patient satisfaction in Chinese tertiary hospitals.

A comprehensive head-to-head comparison of key plasma phosphorylated tau 217 biomarker tests.

Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarker for reliable detection of Alzheimer's disease (AD) pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET, and cognition as outcomes, and benchmarked them against cerebrospinal fluid (CSF) biomarker tests. Samples from 998 individuals (mean[range] age 68.5[20.0-92.5], 53% female) from the Swedish BioFINDER-2 cohort, including both cognitively unimpaired and cognitively impaired individuals, were analyzed. Plasma p-tau217 was measured with mass spectrometry (MS) assays (the ratio between phosphorylated and non-phosphorylated [%p-tau217WashU] and p-tau217WashU) as well as with immunoassays (p-tau217Lilly, p-tau217Janssen, p-tau217ALZpath). CSF biomarkers included p-tau217Lilly, the FDA-approved p-tau181/Aβ42Elecsys, and p-tau181Elecsys. All plasma p-tau217 tests exhibited a high ability to detect abnormal Aβ-PET (AUC range: 0.91-0.96) and tau-PET (AUC range: 0.94-0.97). Plasma %p-tau217WashU had the highest performance, with significantly higher AUCs than all the immunoassays (Pdiff<0.007). For detecting Aβ-PET status, %p-tau217WashU had an accuracy of 0.93 (immunoassays: 0.83-0.88), sensitivity of 91% (immunoassays: 84-87%), and a specificity of 94% (immunoassays: 85-89%). Among immunoassays, p-tau217Lilly and plasma p-tau217ALZpath had higher AUCs than plasma p-tau217Janssen for Aβ-PET status (Pdiff<0.006), and p-tau217Lilly outperformed plasma p-tau217ALZpath for tau-PET status (Pdiff=0.025). Plasma %p-tau217WashU exhibited stronger associations with all PET load outcomes compared to immunoassays; baseline Aβ-PET load (R2: 0.72; immunoassays: 0.47-0.58; Pdiff<0.001), baseline tau-PET load (R2: 0.51; immunoassays: 0.38-0.45; Pdiff<0.001), longitudinal Aβ-PET load (R2: 0.53; immunoassays: 0.31-0.38; Pdiff<0.001) and longitudinal tau-PET load (R2: 0.50; immunoassays: 0.35-0.43; Pdiff<0.014). Among immunoassays, plasma p-tau217Lilly was more associated with Aβ-PET load than plasma p-tau217Janssen (Pdiff<0.020) and with tau-PET load than both plasma p-tau217Janssen and plasma p-tau217ALZpath (all Pdiff<0.010). Plasma %p-tau217 also correlated more strongly with baseline cognition (Mini-Mental State Examination[MMSE]) than all immunoassays (R2 %p-tau217WashU: 0.33; immunoassays: 0.27-0.30; Pdiff<0.024). The main results were replicated in an external cohort from Washington University in St Louis (n =219). Finally, p-tau217NULISA showed similar performance to other immunoassays in subsets of both cohorts. In summary, both MS- and immunoassay-based p-tau217 tests generally perform well in identifying Aβ-PET, tau-PET, and cognitive abnormalities, but %p-tau217WashU performed significantly better than all the examined immunoassays. Plasma %p-tau217 may be considered as a stand-alone confirmatory test for AD pathology, while some immunoassays might be better suited as triage tests where positive results are confirmed with a second test, which needs to be determined by future reviews incorporating results from multiple cohorts.

A dataset of Solicited Cough Sound for Tuberculosis Triage Testing

Cough is a common and commonly ignored symptom of lung disease. Cough is often perceived as difficult to quantify, frequently self-limiting, and non-specific. However, cough has a central role in the clinical detection of many lung diseases including tuberculosis (TB), which remains the leading infectious disease killer worldwide. TB screening currently relies on self-reported cough which fails to meet the World Health Organization (WHO) accuracy targets for a TB triage test. Artificial intelligence (AI) models based on cough sound have been developed for several respiratory conditions, with limited work being done in TB. To support the development of an accurate, point-of-care cough-based triage tool for TB, we have compiled a large multi-country database of cough sounds from individuals being evaluated for TB. The dataset includes more than 700,000 cough sounds from 2,143 individuals with detailed demographic, clinical and microbiologic diagnostic information. We aim to empower researchers in the development of cough sound analysis models to improve TB diagnosis, where innovative approaches are critically needed to end this long-standing pandemic.

FibroScan-AST score for diagnosing fibrotic MASH: A systematic review and meta-analysis of diagnostic test accuracy studies.

Following the approval of the first agent for the management of metabolic dysfunction-associated steatohepatitis (MASH), identification of patients with fibrotic MASH (MASH with NAS≥4 and fibrosis stage≥2) is crucial. We assessed the performance of FibroScan-aspartate aminotransferase (AST) score (FAST) for ruling in/out fibrotic MASH. We searched Medline, Cochrane Library, Web of Science, Scopus, and gray literature sources up to January 11, 2024. Studies were eligible if they assessed the accuracy of FAST score for the detection of fibrotic MASH using biopsy as the reference standard at previously reported thresholds (FAST≥0.67 for ruling-in and ≤0.35 for ruling-out fibrotic MASH). We calculated pooled sensitivity and specificity estimates for FAST thresholds alongside 95% confidence intervals following bivariate random- effects models. We assessed the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We included 16 studies with 8838 participants. A FAST score≥0.67 yielded a pooled specificity of 0.87 (0.82-0.90) while a FAST score≤0.35 yielded a summary sensitivity of 0.88 (0.83-0.91). At a prevalence of 30%, the positive predictive value for ruling-in fibrotic MASH was 60% while the negative predictive value for ruling-out the target condition was 91%. AST levels, cirrhosis prevalence, and number of pathologists reviewing biopsies were sources of heterogeneity among studies. The certainty of evidence was low to very low. FAST score can be used as a triage test for ruling out fibrotic MASH. Nevertheless, its low positive predictive value necessitates sequential testing for ruling-in fibrotic MASH.

Comparing visual inspection with acetic acid, with and without Lugol’s Iodine for triage of HPV self-sample positive women in Ethiopia: a randomized controlled trial

BackgroundMost women who are high-risk human papilloma virus (hrHPV) positive in a cervical cancer screening test will spontaneously heal from their infection. Visual inspection with acetic acid (VIA) is recommended...

Cost-effectiveness analysis of alternative screening strategies for the detection of cervical cancer among women in rural areas of Western Kenya.

While the incidence of cervical cancer has dropped in high-income countries due to organized cytology-based screening programs, it remains the leading cause of cancer death among women in Eastern Africa. Therefore, the World Health Organization (WHO) now urges providers to transition from widely prevalent but low-performance visual inspection with acetic acid (VIA) screening to primary human papillomavirus (HPV) DNA testing. Due to high HPV prevalence, effective triage tests are needed to identify those lesions likely to progress and so avoid over-treatment. To identify the optimal cost-effective strategy, we compared the VIA screen-and-treat approach to primary HPV DNA testing with p16/Ki67 dual-stain cytology or VIA as triage. We used a Markov model to calculate the budget impact of each strategy with incremental quality-adjusted life years and incremental cost-effectiveness ratios (ICER) as the main outcome. Deterministic cost-effectiveness analyses show that the screen-and-treat approach is highly cost-effective (ICER 2469 Int$), while screen, triage, and treat with dual staining is the most effective with favorable ICER than triage with VIA (ICER 9943 Int$ compared with 13,177 Int$). One-way sensitivity analyses show that the results are most sensitive to discounting, VIA performance, and test prices. In the probabilistic sensitivity analyses, the triage option using dual stain is the optimal choice above a willingness to pay threshold of 7115 Int$ being cost-effective as per WHO standards. The result of our analysis favors the use of dual staining over VIA as triage in HPV-positive women and portends future opportunities and necessary research to improve the coverage and acceptability of cervical cancer screening programs.

Performance of visual inspection, partial genotyping, and their combination for the triage of women living with HIV who are screen positive for human papillomavirus: Results from the AIMA-CC ANRS 12375 multicentric screening study.

The WHO recommends the use of human papillomavirus (HPV) testing for primary cervical cancer (CC) screening because of its high sensitivity. However, triage is desirable to correctly identify HPV+ women who have high-grade lesions (CIN2+) and require treatment. The ANRS-12375 study was conducted in Côte d'Ivoire, Burkina Faso and Cambodia to assess the performance, feasibility and benefits of different triage options for detecting CIN2+ lesions: partial (HPV16 and HPV16/18/45) and extended genotyping, visual inspection (VIA) alone and VIA combined with partial genotyping. VIA was performed by gynecologists. The sensitivity, specificity, and diagnostic likelihood ratio (DLR) of each triage option for detecting CIN2+ lesions with histology as a reference standard were calculated. Of the 2253 women living with HIV (WLHIV) included, 932 (41%) were HPV+. A CIN2+ lesion was identified in 105 (13%) of the 777 participants with histopathology results. The sensitivity of VIA as a triage test for CIN2+ patients was 89%, while that for extended genotyping was 89%, that for HPV16/18/45 partial genotyping was 51%, and that for HPV16 partial genotyping was 36%. The specificities for these tests were 45%, 29%, 72%., and 85%, respectively. Combining VIA and/or partial genotyping positivity slightly increased the sensitivity (94%) at the cost of lower specificity (28%). There was significant intersite heterogeneity (p = .04). Among the three triage tests with a sensitivity ≥85%, the VIA had the highest specificity and positive likelihood ratio (p < .001). VIA and extended genotyping, whether independent or combined, are good triage options with high sensitivity for identifying WLHIV needing treatment for CIN2+.

Diagnostic application of the ColonFlag AI tool in combination with faecal immunochemical test in patients on an urgent lower gastrointestinal cancer pathway

ObjectiveColorectal cancer (CRC) is the fourth most common cancer in the UK. Patients with symptoms suggestive of CRC should be referred for urgent investigation. However, gastrointestinal symptoms are often non-specific...

Review of triage strategies for atypical squamous cells of undetermined significance among young women.

In the present study we reviewed the existing literature regarding management approaches for ASC-US and highlight their pros and cons. The ASC-US entity emerged from Bethesda classification 2001. We conducted this review using search words ASC-US triage, ASC-US management in young women, triage tests for ASC-US, and ASC-US outcome from the English literature. We included different cervical cancer policies (American, European and for WHO) and research articles published on ASC-US in young women from the year 2001. We searched in Google Scholar, PubMed, MEDLINE (NCBI) library, Embase (Elsevier), Wiley online library as well as Cochrane library. We defined young women as aged 30 years and below. We identified 52 articles which focused on management approaches of ASC-US, seven articles focused on young women aged <30 years. Five of these articles combined ASC-US with low-grade squamous intraepithelial lesions (ASC-US/LSIL) while only two addressed ASC-US as a standalone entity. The limited number of articles restricts the evidence base supporting the adoption of triage strategies. There is yet, no consensus in the literature regarding the management of ASC-US, more so in young women below the age of 30 years. Researchers, however, agree on a few aspects, which include the necessity for applying a conservative strategy for managing ASC-US in young women, avoiding direct referral for colposcopy at the initial detection of ASC-US, and avoiding the use of human papillomavirus (HPV) testing on young women (unless living with HIV). Newer techniques such as HPV E6/E7 messenger RNA (mRNA), and dual staining p16/ki-67, may serve as better triage to identify cases of HPV persistence and integration which may subsequently lead to preinvasive or invasive lesions.

Compliance Rate With Triage Test and Treatment for Participants Screening Positive in Cervical Cancer Screening Programs: A Systematic Review and Meta-analysis.

To assess the rates of adherence to triage testing after positive screening results and referral to treatment for precancerous lesions in global cervical cancer screening programs. We searched three electronic databases (Medline, EMBASE, and Web of Science) for articles published in the English language from January 1, 2018, to December 31, 2023. We included studies reporting the compliance rate of triage testing and precancer treatment in cervical cancer screening programs. ClinicalTrials.gov was reviewed, and no more studies were identified. The combined search strategies identified 1,673 titles, of which 858 titles and abstracts were screened and 113 full-text articles were assessed for eligibility. A total of 33 studies met the inclusion criteria and were included in the meta-analysis. Thirty-three studies were included in the systematic review and meta-analysis. The average compliance rate for women screening positive was 77.1% for triage testing and 69.4% for referral to treatment. Compliance varied by country income level, screening guideline approach, and target population. The current compliance rate was lower than the 90% target set by the World Health Organization's global strategy to eliminate cervical cancer. Inadequate follow-up of participants screening positive revealed a gap between the screening program and clinical care.

Exhaled breath analysis: A promising triage test for tuberculosis in young children

The diagnosis of paediatric pulmonary tuberculosis is difficult, especially in young infants who cannot expectorate sputum spontaneously. Breath testing has shown promise in diagnosing respiratory tract infections, but data on paediatric tuberculosis are limited.We performed a prospective cross-sectional study in Kenya in children younger than five years with symptoms of tuberculosis. We analysed exhaled breath with a hand-held battery-powered nose device. For data analysis, machine learning was applied using samples classified as positive (microbiologically confirmed) or negative (unlikely tuberculosis) to assess diagnostic accuracy.Breath analysis was performed in 118 children. The area under the curve of the optimal model was 0.73. At a sensitivity of 86 % (CI 62–96 %), this resulted in a specificity of 42 % (95 % CI 30–55 %).Exhaled breath analysis shows promise as a triage test for TB in young children, although the WHO target product characteristics were not met.

Early economic evaluation of magnetic resonance imaging for prostate cancer detection in primary care.

To explore the potential impacts of incorporating prebiopsy magnetic resonance imaging into primary care as a triage test within the prostate cancer diagnostic pathway. Decision analytic modelling with decision trees was utilised for this early economic evaluation. A conceptual model was developed reflecting the common primary care routes to diagnosis for prostate cancer: opportunistic, asymptomatic prostate-specific antigen (PSA) screening or symptomatic presentation. The use of multiparametric MRI (mpMRI) or biparametric MRI (bpMRI) as a primary care triage test following an elevated PSA result was evaluated. A health system perspective was adopted with a time horizon of 12 months. Health effects were expressed in terms of utilities drawn from the literature. The primary outcome was prostate cancer diagnosis. Evidence used to inform the model was drawn from published primary studies, systematic reviews, and secondary analyses of primary and secondary care datasets. Base case analysis showed that the PSA pathway was dominated by both mpMRI- and bpMRI-based pathways for patients undergoing opportunistic screening and symptomatic assessment. bpMRI pathways had greater improvement in cost and utility than mpMRI pathways in both clinical scenarios. Significantly more MRI scans would be performed using the modelled approach (66 626 scans vs. 37 456 scans per 100 000 patients per annum), with fewer subsequent urgent suspected cancer referrals for both mpMRI (38% reduction for screening and symptomatic patients) and bpMRI (72% reduction for screening; 71% for symptomatic) pathways, and a small increase in number of missed cancer diagnoses. Deterministic sensitivity analyses, varying each parameter to its upper and lower 95% confidence intervals, showed no significant change in the dominance of the MRI-based prostate cancer diagnostic pathways. Using prostate MRI as a second-level triage test for suspected prostate cancer in primary care could reduce health service costs without a detrimental effect on patient utility.

Diagnostic accuracy of an exhaled breath test for TB in hospitalized patients with cough or risk.

<sec><title>INTRODUCTION</title>Closing the TB diagnostic gap is an urgent priority, for which non-sputum-based tests are needed. We evaluated the diagnostic accuracy of Aeonose, an exhaled breath test (EBT), as a TB triage test.</sec><sec><title>METHODS</title>Patients with cough or TB risk factors admitted to a tertiary hospital in Lima, Peru, were prospectively enrolled and underwent EBT. We evaluated EBT sensitivity and specificity for diagnosing pulmonary TB using culture and Xpert as primary and secondary reference standards and conducted stratified analyses based on risk factors.</sec><sec><title>RESULTS</title>EBT sensitivity was 85% (95% CI 72.9-93.4), and specificity was 51% (95% CI 46.0-56.6) in the training cohort (n = 417). EBT sensitivity was 70% (95% CI 47.1-86.8), and specificity was 54% (95% CI 44.8-63.6) in the validation cohort (n = 139) using the culture reference standard, with higher sensitivity (78%) when using the Xpert reference standard (n = 156). Sensitivity (60%) and specificity (48%) were lower when patients with prior TB were included. In a subset of participants randomly selected for interviews, 94% (15/16) preferred EBT to sputum-based testing.</sec><sec><title>CONCLUSIONS</title>EBT had moderate sensitivity and low specificity as a TB triage test in this hospitalised cohort with cough or risk factors. Diagnostic accuracy was lower in people with prior TB.</sec>.

Evaluation of C-Reactive Protein and Computer-Aided Analysis of Chest X-rays as Tuberculosis Triage Tests at Health Facilities in Lesotho and South Africa.

To improve tuberculosis case-finding, rapid, non-sputum triage tests need to be developed according to the World Health Organization target product profile (TPP) (>90% sensitivity, >70% specificity). We prospectively evaluated and compared artificial intelligence-based, computer-aided detection software, CAD4TBv7, and C-reactive protein assay (CRP) as triage tests at health facilities in Lesotho and South Africa. Adults (≥18 years) presenting with ≥1 of the 4 cardinal tuberculosis symptoms were consecutively recruited between February 2021 and April 2022. After informed consent, each participant underwent a digital chest X-ray for CAD4TBv7 and a CRP test. Participants provided 1 sputum sample for Xpert MTB/RIF Ultra and Xpert MTB/RIF and 1 for liquid culture. Additionally, an expert radiologist read the chest X-rays via teleradiology. For primary analysis, a composite microbiological reference standard (ie, positive culture or Xpert Ultra) was used. We enrolled 1392 participants, 48% were people with HIV and 24% had previously tuberculosis. The receiver operating characteristic curve for CAD4TBv7 and CRP showed an area under the curve of .87 (95% CI: .84-.91) and .80 (95% CI: .76-.84), respectively. At thresholds corresponding to 90% sensitivity, specificity was 68.2% (95% CI: 65.4-71.0%) and 38.2% (95% CI: 35.3-41.1%) for CAD4TBv7 and CRP, respectively. CAD4TBv7 detected tuberculosis as well as an expert radiologist. CAD4TBv7 almost met the TPP criteria for tuberculosis triage. CAD4TBv7 is accurate as a triage test for patients with tuberculosis symptoms from areas with a high tuberculosis and HIV burden. The role of CRP in tuberculosis triage requires further research. Clinicaltrials.gov identifier: NCT04666311.

HPV Extended Genotyping to Triage Abnormal Cervical Cancer Screens-Balancing the Harms and Benefits of an Additional Triage Test before Direct Colposcopy Referral.

The Netherlands' cervical cancer screening program transitioned to primary human papillomavirus (HPV) screening in 2017. After the introduction of HPV-based screening, the country saw increases in colposcopy referral rates and detections of low-grade lesions. In July 2022, genotyping was introduced, and those with borderline or mild dyskaryotic (BMD) cytologic abnormalities were only referred to colposcopy if positive for HPV type 16 or 18, and repeat screening otherwise. In this article, various strategies using extended genotyping (HPV16/18/31/33/45/52/58) as a triage test after an abnormal screen were explored using data from HPV-positive participants with normal or BMD cytology in the Population-Based Screening Study Amsterdam (POBASCAM) trial. The authors assessed positive and negative predictive values and colposcopy referral rates for each strategy using extended genotyping to triage women to either direct referral to colposcopy or repeat screening. Direct referral did not meet positive and negative predictive value thresholds for efficiency for any strategies. However, the authors note that direct referral may nonetheless be useful among those with BMD due to minimal increases in colposcopy referrals and concerns of loss to follow-up at repeat screening. These findings demonstrate the potential utility of extended genotyping as a triage test in primary HPV screening programs. The results should be considered alongside the fact that referral to repeat screening may result in loss of engagement of women who need treatment to prevent invasive cancer. See related article by Kroon et al., p. 1037.

Evaluation of Host Gene Methylation as a Triage Test for HPV-Positive Women-A Cohort Study.

This study was designed to evaluate the performance of a host gene methylation marker panel (ASTN1, DLX1, ITGA4, RXFP3, SOX17, and ZNF671) in the triage of human papillomavirus (HPV)-positive women, its possible impact in a cervical cancer screening program, and the possible influence of the variation of the rate of HPV16/18 in its performance. Cohort study in which consecutive women referred for colposcopy in an organized cervical cancer screening program had repeated HPV testing, colposcopy, and biopsies. The women that remained HPV positive at the time of colposcopy were tested with the panel of DNA methylation markers. The performance of the test was evaluated and compared to standard practice. The study test had a sensitivity and specificity for cervical intraepithelial neoplasia (CIN) 2+ of 60.8% (49.1-71.6%) and 88.4% (83.2-92.5%), respectively. For CIN3+, it was of 78.0% (64.0-88.5%) and 86.0% (80.8-90.2%), respectively.The rate and level of methylation positively correlated with the severity of disease. The use of methylation reduces the referral for colposcopy to 25.5%, while detecting 78.0% of the CIN3+ cases. Referral of all HPV16/18-positive cases and triage of the other high-risk HPV-positive cases with methylation, detects 90.0% of the cases of CIN3+, while reducing the number of referrals to 43.2%.The variation in the rate of HPV16/18 does not relevantly affect the performance of the methylation panel. The studied methylation panel has a high sensitivity and specificity for CIN3+ and reduces the rate of referrals for colposcopy, without relevant variation according to the rate of HPV16/18.

A prospective evaluation of the diagnostic accuracy of the point-of-care VISITECT CD4 Advanced Disease test in seven countries.

CD4 measurement is pivotal in the management of advanced HIV disease. VISITECT® CD4 Advanced Disease (AccuBio Limited, Alva, UK; VISITECT) is an instrument-free, point-of-care, semi-quantitative test allowing visual identification of a CD4 ≤200 cells/µl, or >200 cells/µl from finger-prick or venous blood. As part of a diagnostic accuracy study of FUJIFILM SILVAMP TB LAM (clinicaltrials.gov: NCT04089423), people living with HIV of ≥18 years old were prospectively recruited in seven countries from outpatient departments if a tuberculosis symptom was present, and from inpatient departments. Participants provided venous blood for CD4 measurement using flow cytometry (reference standard) and finger-prick blood for VISITECT (index text), performed at point-of-care. Sensitivity, specificity, and positive and negative predictive values of VISITECT to determine a CD4 ≤200 cells/µl were evaluated. Among 1604 participants, the median flow cytometry CD4 was 367 (IQR 128-626) cells/µl and 521 (32.5%) had a CD4 ≤200 cells/µl. VISITECT sensitivity was 92.7% (483/521, 95% CI 90.1-94.7%) and specificity was 61.4% (665/1083, 95% CI 58.4-64.3%). For participants with a CD4 between 0-100, 101-200, 201-300, 301-500, and >500 cells/µl, VISITECT misclassified 4.5% (95% CI 2.5-7.2%), 12.5 (95% CI 8.0-18.2%), 74.1% (95% CI 67.0-80.5%), 48.0% (95% CI 42.5-53.6%), and 22.6% (95% CI 19.3-26.3%), respectively. VISITECT's sensitivity, but not specificity, met the World Health Organization's minimal sensitivity and specificity threshold of 80% for point-of-care CD4 tests. VISITECT's quality needs to be assessed and its accuracy optimized. VISITECT´s utility as CD4 triage test should be investigated.

Sex-specific blood-derived RNA biomarkers for childhood tuberculosis

Confirmatory diagnosis of childhood tuberculosis (TB) remains a challenge mainly due to its dependence on sputum samples and the paucibacillary nature of the disease. Thus, only ~ 30% of suspected cases in children are diagnosed and the need for minimally invasive, non-sputum-based biomarkers remains unmet. Understanding host molecular changes by measuring blood-based transcriptomic markers has shown promise as a diagnostic tool for TB. However, the implication of sex contributing to disease heterogeneity and therefore diagnosis remains to be understood. Using publicly available gene expression data (GSE39939, GSE39940; n = 370), we report a sex-specific RNA biomarker signature that could improve the diagnosis of TB disease in children. We found four gene biomarker signatures for male (SLAMF8, GBP2, WARS, and FCGR1C) and female pediatric patients (GBP6, CELSR3, ALDH1A1, and GBP4) from Kenya, South Africa, and Malawi. Both signatures achieved a sensitivity of 85% and a specificity of 70%, which approaches the WHO-recommended target product profile for a triage test. Our gene signatures outperform most other gene signatures reported previously for childhood TB diagnosis.

A Comprehensive Head-to-Head Comparison of Key Plasma Phosphorylated Tau 217 Biomarker Tests.

Plasma phosphorylated-tau 217 (p-tau217) is currently the most promising biomarkers for reliable detection of Alzheimer's disease (AD) pathology. Various p-tau217 assays have been developed, but their relative performance is unclear. We compared key plasma p-tau217 tests using cross-sectional and longitudinal measures of amyloid-β (Aβ)-PET, tau-PET, and cognition as outcomes, and benchmarked them against cerebrospinal fluid (CSF) biomarker tests. Samples from 998 individuals (mean[range] age 68.5[20.0-92.5], 53% female) from the Swedish BioFINDER-2 cohort were analyzed. Plasma p-tau217 was measured with mass spectrometry (MS) assays (the ratio between phosphorylated and non-phosphorylated [%p-tau217WashU]and ptau217WashU) as well as with immunoassays (p-tau217Lilly, p-tau217Janssen, p-tau217ALZpath). CSF biomarkers included p-tau217Lilly, and the FDA-approved p-tau181/Aβ42Elecsys and p-tau181Elecsys. All plasma p-tau217 tests exhibited high ability to detect abnormal Aβ-PET (AUC range: 0.91-0.96) and tau-PET (AUC range: 0.94-0.97). Plasma %p-tau217WashU had the highest performance, with significantly higher AUCs than all the immunoassays (P diff<0.007). For detecting Aβ-PET status, %p-tau217WashU had an accuracy of 0.93 (immunoassays: 0.83-0.88), sensitivity of 91% (immunoassays: 84-87%), and a specificity of 94% (immunoassays: 85-89%). Among immunoassays, p-tau217Lilly and plasma p-tau217ALZpath had higher AUCs than plasma p-tau217Janssen for Aβ-PET status (P diff<0.006), and p-tau217Lilly outperformed plasma p-tau217ALZpath for tau-PET status (P diff=0.025). Plasma %p-tau217WashU exhibited higher associations with all PET load outcomes compared to immunoassays; baseline Aβ-PET load (R2: 0.72; immunoassays: 0.47-0.58; Pdiff<0.001), baseline tau-PET load (R2: 0.51; immunoassays: 0.38-0.45; Pdiff<0.001), longitudinal Aβ-PET load (R2: 0.53; immunoassays: 0.31-0.38; Pdiff<0.001) and longitudinal tau-PET load (R2: 0.50; immunoassays: 0.35-0.43; Pdiff<0.014). Among immunoassays, plasma p-tau217Lilly was more strongly associated with Aβ-PET load than plasma p-tau217Janssen (P diff<0.020) and with tau-PET load than both plasma p-tau217Janssen and plasma p-tau217ALZpath (all P diff<0.010). Plasma %p-tau217 also correlated more strongly with baseline cognition (Mini-Mental State Examination[MMSE]) than all immunoassays (R2 %p-tau217WashU: 0.33; immunoassays: 0.27-0.30; P diff<0.024). The main results were replicated in an external cohort from Washington University in St Louis (n =219). Finally, p-tau217Nulisa showed similar performance to other immunoassays in subsets of both cohorts. In summary, both MS- and immunoassay-based p-tau217 tests generally perform well in identifying Aβ-PET, tau-PET, and cognitive abnormalities, but %p-tau217WashU performed significantly better than all the examined immunoassays. Plasma %p-tau217 may be considered as a stand-alone confirmatory test for AD pathology, while some immunoassays might be better suited as triage tests where positive results are confirmed with a second test.

Blood transcriptomic signatures for symptomatic tuberculosis in an African multicohort study.

Multiple host blood transcriptional signatures have been developed as non-sputum triage tests for tuberculosis (TB). We aimed to compare the diagnostic performance of 20 blood transcriptomic TB signatures for differentiating between symptomatic patients who have TB versus other respiratory diseases (ORD). As part of a nested case-control study, individuals presenting with respiratory symptoms at primary healthcare clinics in Ethiopia, Malawi, Namibia, Uganda, South Africa and The Gambia were enrolled. TB was diagnosed based on clinical, microbiological and radiological findings. Transcriptomic signatures were measured in whole blood using microfluidic real-time quantitative PCR. Diagnostic performance was benchmarked against the World Health Organization Target Product Profile (TPP) for a non-sputum TB triage test. Among 579 participants, 158 had definite, microbiologically confirmed TB, 32 had probable TB, while 389 participants had ORD. Nine signatures differentiated between ORD and TB with equivalent performance (Satproedprai7: area under the curve 0.83 (95% CI 0.79-0.87); Jacobsen3: 0.83 (95% CI 0.79-0.86); Suliman2: 0.82 (95% CI 0.78-0.86); Roe1: 0.82 (95% CI 0.78-0.86); Kaforou22: 0.82 (95% CI 0.78-0.86); Sambarey10: 0.81 (95% CI 0.77-0.85); Duffy9: 0.81 (95% CI 0.76-0.86); Gliddon3: 0.8 (95% CI 0.75-0.85); Suliman4 0.79 (95% CI 0.75-0.84)). Benchmarked against a 90% sensitivity, these signatures achieved specificities between 44% (95% CI 38-49%) and 54% (95% CI 49-59%), not meeting the TPP criteria. Signature scores significantly varied by HIV status and country. In country-specific analyses, several signatures, such as Satproedprai7 and Penn-Nicholson6, met the minimal TPP criteria for a triage test in Ethiopia, Malawi and South Africa. No signatures met the TPP criteria in a pooled analysis of all countries, but several signatures met the minimum criteria for a non-sputum TB triage test in some countries.