Target product profiles: leprosy diagnostics.

The World Health Organization (WHO) aims to reduce new leprosy cases by 70% by 2030, necessitating advancements in leprosy diagnostics. Here we discuss the development of two WHO's target product profiles for such diagnostics. These profiles define criteria for product use, design, performance, configuration and distribution, with a focus on accessibility and affordability. The first target product profile outlines requirements for tests to confirm diagnosis of leprosy in individuals with clinical signs and symptoms, to guide multidrug treatment initiation. The second target product profile outlines requirements for tests to detect Mycobacterium leprae or M. lepromatosis infection among asymptomatic contacts of leprosy patients, aiding prophylactic interventions and prevention. Statistical modelling was used to assess sensitivity and specificity requirements for these diagnostic tests. The paper highlights challenges in achieving high specificity, given the varying endemicity of M. leprae, and identifying target analytes with robust performance across leprosy phenotypes. We conclude that diagnostics with appropriate product design and performance characteristics are crucial for early detection and preventive intervention, advocating for the transition from leprosy management to prevention.

L'Organisation mondiale de la Santé (OMS) vise à réduire le nombre de nouveaux cas de lèpre de 70% d'ici 2030, ce qui nécessite un meilleur diagnostic de la maladie. Dans le présent document, nous évoquons le développement de deux profils de produit cible établis par l'OMS à cette fin. Ces profils définissent des critères en matière d'utilisation, de conception, de performances, de configuration et de distribution du produit, en accordant une attention particulière à l'accessibilité et à l'abordabilité. Le premier profil de produit cible décrit les exigences pour les tests servant à confirmer le diagnostic de la lèpre chez les individus qui présentent des signes cliniques et des symptômes, afin d'orienter l'instauration d'un traitement à base de plusieurs médicaments. Le second profil de produit cible décrit les exigences pour les tests servant à détecter une infection à Mycobacterium leprae ou M. lepromatosis parmi les contacts asymptomatiques de patients lépreux, ce qui contribue à l'adoption de mesures prophylactiques et à la prévention. Nous avons eu recours à une modélisation statistique pour évaluer les exigences de sensibilité et de spécificité de ces tests diagnostiques. Cet article met en évidence les obstacles à l'atteinte d'un niveau élevé de spécificité en raison de l'endémicité variable de M. leprae, et à l'identification d'analytes cibles offrant de bons résultats chez les phénotypes lépreux. Nous concluons qu'un diagnostic reposant sur des caractéristiques de performance et de conception appropriées est essentiel pour détecter rapidement la maladie et intervenir en amont, et nous plaidons pour une prévention plutôt qu'une gestion de la lèpre.

La Organización Mundial de la Salud (OMS) pretende reducir los nuevos casos de lepra en un 70% para 2030, lo que requiere avances en el diagnóstico de la lepra. Aquí se analiza el desarrollo de dos perfiles de productos objetivo de la OMS para este tipo de diagnósticos. Estos perfiles definen los criterios de uso, diseño, rendimiento, configuración y distribución de los productos, centrándose en su accesibilidad y asequibilidad. El primer perfil de producto objetivo describe los requisitos de las pruebas para confirmar el diagnóstico de la lepra en personas con signos y síntomas clínicos, con el fin de orientar el inicio del tratamiento con múltiples fármacos. El segundo perfil de producto objetivo describe los requisitos de las pruebas para detectar la infección por Mycobacterium leprae o M. lepromatosis entre los contactos asintomáticos de los pacientes con lepra, para facilitar las intervenciones profilácticas y la prevención. Se utilizaron modelos estadísticos para evaluar los requisitos de sensibilidad y especificidad de estas pruebas diagnósticas. El artículo destaca las dificultades para lograr una alta especificidad, dada la diferente endemicidad de M. leprae, y para identificar analitos diana con un rendimiento sólido en todos los fenotipos de lepra. Concluimos que los diagnósticos con un diseño de producto y unas características de rendimiento adecuados son fundamentales para la detección precoz y la intervención preventiva, lo que favorece la transición del manejo de la lepra a la prevención.

SMaRT-PCR: sampling using masks and RT-PCR, a non-invasive diagnostic tool for paediatric pulmonary TB.

Key challenges in paediatric TB diagnosis are invasive sampling and poor sensitivity of standard methods. This study demonstrates the diagnostic potential of non-invasive sampling of bioaerosols from children using SMaRT-PCR, comprising mask sampling combined with reverse transcriptase-polymerase chain reaction (RT-PCR) for TB.Exhaled bioaerosols were captured on modified N-95 masks in a 10-min talk-cough-breathe process from 51 children (30 with TB confirmed using standard sampling methods and 21 without TB) aged 2-15 years. All mask samples were tested using in-house RT-PCR for 16s and rpoB RNA transcripts. Additional mask samples from children with TB were tested using Xpert® MTB/RIF (n = 3) and Xpert® MTB/RIF Ultra (n = 27).SMaRT-PCR sensitivity for detecting TB among treatment-naïve children was 96% if 16s or rpoB was present, and 75% if both genes were present, comparable to standard methods (71%) in the same cohort. Specificity was better for both genes, at 95%, than 85% for a single gene detection. Mask sampling with Xpert MTB/RIF or Ultra had a sensitivity of only 13%.This is the first study to provide evidence for testing bioaerosols as a promising alternative for detecting paediatric TB. Sampling is non-invasive and simple, with the potential for point-of-care applications. This pilot study also suggests that RNA transcript-based detection may improve TB diagnostic sensitivity in children; however, further investigation is required to establish its adaptability in clinical settings..

Validity and reliability of the Turkish version of the Informant Assessment of Geriatric Delirium Scale.

Background and purpose:

Delirium is a common complication developing in el­der­ly patients. Therefore, it is important to diagnose delirium earlier. Family caregivers play an active role in early diagnosis of de­lirium and build a bridge between health pro­fessionals and patients. The purpose of this research was to achieve the validity and reliability of the Turkish version of the Informant Assessment of Geriatric Delirium Scale (I-AGeD).

This is a methodological study. The sample comprised 125 caregivers ac­cepting to participate in the study and offering care to older patients with hip fracture aged ≥60 years. Data were gathered preoperatively and on postoperative days 0, 1 and 2. After achieving the linguistic and content validity of the scale, the known-groups comparison was used to achieve its construct validity. The ROC curve analysis was made to determine the sensitivity and specificity of the scale. Item-total correlations, item analysis based on the difference between the upper 27% and lower 27%, Kuder–Richardson 20 (KR-20) coefficient and parallel forms reliability with the NEECHAM Confusion Scale were adapted to assess discriminant indices of the items in the I-AGeD.

The item-total correlation coeffi­cients of the scale ranged from 0.54 to 0.89 and KR-20 coefficient ranged from 0.09 to 0.91 depending on the measurement times. According to the ROC curve analysis, the sensitivity and specificity of the scale were ≥ 91% and ≥ 96% respectively. The parallel forms reliability analysis showed a highly significant, strong negative relation at each measurement between the I-AGeD and the NEECHAM Confusion Scale. 

The I-AGeD is valid and reliable to diagnose delirium in older Turkish patients in perioperative processes.

Functional testing is a complementary tool for the diagnosis of vaginitis.

OBJECTIVE: Vaginal microbiota evaluation is a methodology widely used in China to diagnose various vaginal inflammatory diseases. Although vaginal microbiota evaluation has many advantages, it is time-consuming and requires highly skilled and experienced operators. Here, we investigated a six-index functional test that analyzed pH, hydrogen peroxide (H2O2), leukocyte esterase (LEU), sialidase (SNA), ß-glucuronidase (GUS), and acetylglucossidase (NAG), and determined its diagnostic value by comparing it with morphological tests of vaginal microbiota. MATERIALS AND METHODS: The research was conducted using data extracted from the Laboratory Information System of Women and Children's Hospital. A total of 4902 subjects, ranging in age from 35.4 ± 9.7 years, were analyzed. During the consultation, a minimum of two vaginal swab specimens per patient were collected for both functional and morphological testing. Fisher's exact was used to analyze data using SPSS. RESULTS: Of the 4,902 patients, 2,454 were considered to have normal Lactobacillus morphotypes and 3,334 were considered to have normal dominant microbiota. The sensitivity and specificity of H2O2-indicating Lactobacillus morphotypes were 91.3% and 25.28%, respectively, while those of pH-indicating Lactobacillus morphotypes were 88.09% and 59.52%, respectively. The sensitivity and specificity of H2O2-indicating dominant microbiota were 91.3% and 25.3%, respectively, while those of pH-indicating dominant microbiota were 86.27% and 64.45%, respectively. The sensitivity and specificity of NAG for vulvovaginal candidiasis were 40.64% and 84.8%, respectively. For aerobic vaginitis, GUS sensitivity was low at 0.52%, while its specificity was high at 99.93%; the LEU sensitivity and specificity values were 94.73% and 27.49%, respectively. Finally, SNA sensitivity and specificity for bacterial vaginosis were 80.72% and 96.78%, respectively. CONCLUSION: Functional tests (pH, SNA, H2O2, LEU) showed satisfactory sensitivity for the detection of vaginal inflammatory diseases. However, these tests lacked specificity, making it difficult to accurately identify specific pathologies. By contrast, NAG and GUS showed excellent specificity in identifying vaginal inflammatory diseases, but their sensitivity was limited. Therefore, functional tests alone are not sufficient to diagnose various vaginal inflammatory diseases. When functional and morphological tests are inconsistent, morphological tests are currently considered the preferred reference method.

Assessment of dental pulp response to carries via MR T2mapping and histological analysis.

OBJECTIVES: The aim of our study was to assess the correlation between T2 relaxation times and their variability with the histopathological results of the same teeth in relation to caries progression. MATERIALS AND METHODS: 52 extracted permanent premolars were included in the study. Prior to extractions, patients underwent magnetic resonance imaging (MRI) scanning and teeth were evaluated using ICDAS classification. Pulps of extracted teeth were histologically analysed. RESULTS: MRI T2 relaxation times (ms) were 111,9 ± 11.2 for ICDAS 0, 132.3 ± 18.5* for ICDAS 1, 124.6 ± 14.8 for ICDAS 2 and 112. 6 ± 18.2 for ICDAS 3 group (p = 0,013). A positive correlation was observed between MRI T2 relaxation times and macrophage and T lymphocyte density in healthy teeth. There was a positive correlation between vascular density and T2 relaxation times of dental pulp in teeth with ICDAS score 1. A negative correlation was found between T2 relaxation times and macrophage density. There was a positive correlation between T2 relaxation time variability and macrophage and T lymphocyte density in teeth with ICDAS score 2. In teeth with ICDAS score 3, a positive correlation between T2 relaxation times and T2 relaxation time variability and lymphocyte B density was found. CONCLUSION: The results of our study confirm the applicability of MRI in evaluation of the true condition of the pulp tissue. CLINICAL RELEVANCE: With the high correlation to histological validation, MRI method serves as a promising imaging implement in the field of general dentistry and endodontics.

Diagnostic values of contrast-enhanced MRI and contrast-enhanced CT for evaluating the response of hepatocellular carcinoma after transarterial chemoembolisation: a meta-analysis.

OBJECTIVES: To assess and compare the diagnostic value of contrast-enhanced MRI (CEMRI) and contrast-enhanced CT (CECT) for evaluating the response of hepatocellular carcinoma (HCC) after transarterial chemoembolisation (TACE). DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, the Cochrane Library, CNKI and Wanfang databases were systematically searched from inception to 1 August 2023. ELIGIBILITY CRITERIA: Studies with any outcome that demonstrates the diagnostic performance of CEMRI and CECT for HCC after TACE were included. DATA EXTRACTION AND SYNTHESIS: Two authors independently extracted the data and assessed the quality of included studies. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2. The diagnostic performance of CEMRI and CECT for the response of HCC was investigated by collecting true and false positives, true and false negatives, or transformed-derived data from each study to calculate specificity and sensitivity. Other outcomes are the positive likelihood ratio/negative likelihood ratio (NLR), the area under the receiver operating characteristic curve (AUC) for diagnostic tests and the diagnostic OR (DOR). Findings were summarised and synthesised qualitatively according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: This study included 5843 HCC patients diagnosed with CEMRI or CECT and treated with TACE from 36 studies. The mean proportion of men in the total sample was 76.3%. The pool sensitivity, specificity and AUC of CEMRI in diagnosing HCC after TACE were 0.92 (95% CI: 0.86 to 0.96), 0.94 (95% CI: 0.86 to 0.98) and 0.98 (95% CI: 0.96 to 0.99). The pool sensitivity, specificity and AUC of CECT in diagnosing HCC after TACE were 0.74 (95% CI: 0.68 to 0.80), 0.98 (95% CI: 0.93 to 1.00) and 0.90 (95% CI: 0.88 to 0.93). CONCLUSIONS: In conclusion, this study found that both CEMRI and CECT had relatively high predictive power for assessing the response of HCC after TACE. Furthermore, the diagnostic value of CEMRI may be superior to CECT in terms of sensitivity, AUC, DOR and NLR.

Evaluation of sensitivity and specificity of Kato-Katz and circulating cathodic antigen in terms of Schistosoma japonicum using latent class analysis.

Schistosoma japonicum is endemic in the Philippines. The Kato-Katz (KK) method was used to diagnose S. japonicum. This is impractical, particularly when the sample size is limited. Knowledge on point-of-care circulating cathodic antigen (CCA) test performance for S. japonicum is limited. Determining the sensitivity and specificity of new diagnostics is difficult when the gold standard test is less effective or absent. Latent class analysis (LCA) can address some limitations. A total of 484 children and 572 adults from the Philippines were screened for S. japonicum. We performed Bayesian LCA to estimate the infection prevalence, sensitivity and specificity of each test by stratifying them into two age groups. Observed prevalence assessed by KK was 50.2% and 31.8%, and by CCA was 89.9% and 66.8%, respectively. Using Bayesian LCA, among children, the sensitivity and specificity of CCA were 94.8% (88.7-99.4) and 21.5% (10.5-36.1) while those of KK were 66.0% (54.2-83.3) and 78.1% (61.1-91.3). Among adults, the sensitivity and specificity of CCA were 86.4% (76.6-96.9) and 62.8% (49.1-81.1) while those of KK were 43.6% (35.1-53.9) and 85.5% (75.8-94.6). Overall, CCA was more sensitive than KK, regardless of the age group at diagnosis, as KK was more specific. KK and CCA have different diagnostic performance, which should inform their use in the planning and implementation of S. japonicum control programs.

Methods of determining optimal cut-point of diagnostic biomarkers with application of clinical data in ROC analysis: an update review.

INTRODUCTION: An important application of ROC analysis is the determination of the optimal cut-point for biomarkers in diagnostic studies. This comprehensive review provides a framework of cut-point election for biomarkers in diagnostic medicine. METHODS: Several methods were proposed for the selection of optional cut-points. The validity and precision of the proposed methods were discussed and the clinical application of the methods was illustrated with a practical example of clinical diagnostic data of C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and malondialdehyde (MDA) for prediction of inflammatory bowel disease (IBD) patients using the NCSS software. RESULTS: Our results in the clinical data suggested that for CRP and MDA, the calculated cut-points of the Youden index, Euclidean index, Product and Union index methods were consistent in predicting IBD patients, while for ESR, only the Euclidean and Product methods yielded similar estimates. However, the diagnostic odds ratio (DOR) method provided more extreme values for the optimal cut-point for all biomarkers analyzed. CONCLUSION: Overall, the four methods including the Youden index, Euclidean index, Product, and IU can produce quite similar optimal cut-points for binormal pairs with the same variance. The cut-point determined with the Youden index may not agree with the other three methods in the case of skewed distributions while DOR does not produce valid informative cut-points. Therefore, more extensive Monte Carlo simulation studies are needed to investigate the conditions of test result distributions that may lead to inconsistent findings in clinical diagnostics.

Diagnostic accuracy of tests for tuberculous pericarditis: A network meta-analysis.

Tuberculous pericarditis (TBP) is a relatively uncommon but potentially fatal extrapulmonary manifestation of tuberculosis. Despite its severity, there is no universally accepted gold standard diagnostic test for TBP currently. The objective of this study is to compare the diagnostic accuracy of the most commonly used tests in terms of specificity, sensitivity, negative predictive value (NPV), and positive predictive value (PPV), and provide a summary of their diagnostic accuracies. A comprehensive literature review was performed using Scopus, MEDLINE, and Cochrane central register of controlled trials, encompassing studies published from start to April 2022. Studies that compared Interferon Gamma Release Assay (IGRA), Xpert MTB/RIF, Adenosine Deaminase levels (ADA), and Smear Microscopy (SM) were included in the analysis. Bayesian random-effects model was used for statistical analysis and mean and standard deviation (SD) with 95% confidence intervals were calculated using the absolute risk (AR) and odds ratio (OR). Rank probability and heterogeneity were determined using risk difference and Cochran Q test, respectively. Sensitivity and specificity were evaluated using true negative, true positive, false positive, and false negative rates. Area under the receiver operating characteristic (AUROC) was calculated for mean and standard error. A total of seven studies comprising 16 arms and 618 patients were included in the analysis. IGRA exhibited the highest mean (SD) sensitivity of 0.934 (0.049), with a high rank probability of 87.5% for being the best diagnostic test, and the AUROC was found to be 94.8 (0.36). On the other hand, SM demonstrated the highest mean (SD) specificity of 0.999 (0.011), with a rank probability of 99.5%, but a leave-one-out analysis excluding SM studies revealed that Xpert MTB/RIF ranked highest for specificity, with a mean (SD) of 0.962 (0.064). The diagnostic tests compared in our study exhibited similar high NPV, while ADA was found to have the lowest PPV among the evaluated methods. Further research, including comparative studies, should be conducted using a standardized cutoff value for both ADA levels and IGRA to mitigate the risk of threshold effect and minimize bias and heterogeneity in data analysis.

Ultrasound Performed by Emergency Physicians for Deep Vein Thrombosis: A Systematic Review.

Introduction: Point-of-care ultrasound (POCUS) performed by emergency physicians (EP) has emerged as an effective alternative to radiology department ultrasounds for the diagnosis of lower extremity deep vein thrombosis (DVT). Systematic reviews suggested good sensitivity and specificity overall for EP-performed POCUS for DVT diagnosis, yet high levels of heterogeneity were reported. Methods: In this systematic review and meta-analysis, we aimed to provide the most up-to-date estimates of the accuracy of EP-performed POCUS for diagnosis of DVT and to explore potential correlations with test performance. We performed systematic searches in MEDLINE and Embase for original, primary data articles from January 2012-June 2021 comparing the efficacy of POCUS performed by EPs to the local standard. Quality Assessment of Diagnostic Accuracy Studies-2 for individual articles are reported. We obtained summary measures of sensitivity, specificity, and their corresponding 95% confidence intervals (CI) using bivariate mixed-effects regression models. We performed meta-regression, subgroup, and sensitivity analyses as planned in the protocol CRD42021268799 submitted to PROSPERO. Results: Fifteen publications fit the inclusion criteria, totaling 2,511 examinations. Pooled sensitivity and specificity were 90% (95% CI 82%-95%) and 95% (CI 91%-97%), respectively. Subgroup analyses by EP experience found significantly better accuracy for exams performed by EP specialists (93%, CI 88%-97%) vs trainees (77%, CI 60%-94%). Specificity for EP specialists (97%, CI 94%-99%) was higher than for trainees (87%, CI 76%-99%, P = 0.01). Three-point compression ultrasound (CUS) was more sensitive than two-point CUS but was only statistically significant when limited to EP specialists (92% vs 88%, P = 0.07, and 95% vs 88%, P = 0.02, respectively). Conclusion: Point-of-care ultrasound performed by emergency physicians is sensitive and specific for the diagnosis of suspected DVT when performed by trained attending EPs. Three-point compression ultrasound examination may be more sensitive than two-point CUS.

The correlation between ultrasonographic findings and clinical symptoms of pelvic endometriosis.

OBJECTIVE: Considering the importance of endometriosis and its relatively high prevalence among women, this study sought to investigate clinical and Transrectal and transvaginal ultrasounds (TVS) findings of disease. METHODS: This descriptive-analytical study was performed based on medical records of 155 women with endometriosis admitted to Rasool-e Akram Hospital in Tehran for a TVS. All the sonography data and patients' information were collected into checklists and analyzed in SPSS-25 software (IBM). RESULTS: The mean age of participants was 32.4 ± 6.1 years, ranging from 18 to 50 years. Endometrioma was prevalent in 129 patients (84.8%). Size of endometrioma (diameter) was more than 3 cm in 79.9% of patients, and 3 cm or fewer in 20.1% of cases. Bladder, intestinal, vaginal, and rectosigmoid involvements with endometriosis implants were observed in 4 (2.6%), 54 (35.5), 3 (0.2%), and 51 (33.5) of patients, respectively. A total of 64.5% of patients were diagnosed with incomplete stenosis of the Douglas pouch and 35.5% had complete stenosis. Deep infiltrating endometriosis (DIE) was less than 1 cm in 20.7%, 1 to 3 cm in 42.3%, and over 3 cm in 37% of patients. The most common manifestations of endometriosis Obliteration of the Douglas pouch, endometrioma, and DIE. In addition, imaging modalities have shown promising results, indicating the necessity to use transvaginal ultrasound as the first line of diagnosis in patients with clinically suspected endometriosis.

Clinical application of metagenomic next-generation sequencing for the diagnosis of suspected infection in adults: A cross-sectional study.

Metagenomic next-generation sequencing (mNGS) has become an available method for pathogen detection. The clinical application of mNGS requires further evaluation. We conducted a cross-sectional study of 104 patients with suspected infection between May 2019 and May 2021. The risk factors associated with infection were analyzed using univariate logistic analysis. The diagnostic performance of pathogens was compared between mNGS and conventional microbiological tests. About 104 patients were assigned into 3 groups: infected group (n = 69), noninfected group (n = 20), and unknown group (n = 15). With the composite reference standard (combined results of all microbiological tests, radiological testing results, and a summary of the hospital stay of the patient) as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value of mNGS was 84.9%, 50.0%, 88.6%, and 42.1%, respectively. Compared with conventional microbiological tests, mNGS could detect more pathogens and had obvious advantages in Mycobacterium tuberculosis, Aspergillus, and virus detection. Moreover, mNGS had distinct benefits in detecting mixed infections. Bacteria-fungi-virus mixed infections were the most common in patients with severe pneumonia. mNGS had a higher sensitivity than conventional microbiological tests, especially for M. tuberculosis, Aspergillus, viruses, and mixed infections. We suggest that mNGS should be used more frequently in the early diagnosis of pathogens in critically ill patients in the future.

Psychometric Evaluation of a Tablet-Based Tool to Detect Mild Cognitive Impairment in Older Adults: Mixed Methods Study.

BACKGROUND: With the rapid aging of the global population, the prevalence of mild cognitive impairment (MCI) and dementia is anticipated to surge worldwide. MCI serves as an intermediary stage between normal aging and dementia, necessitating more sensitive and effective screening tools for early identification and intervention. The BrainFx SCREEN is a novel digital tool designed to assess cognitive impairment. This study evaluated its efficacy as a screening tool for MCI in primary care settings, particularly in the context of an aging population and the growing integration of digital health solutions. OBJECTIVE: The primary objective was to assess the validity, reliability, and applicability of the BrainFx SCREEN (hereafter, the SCREEN) for MCI screening in a primary care context. We conducted an exploratory study comparing the SCREEN with an established screening tool, the Quick Mild Cognitive Impairment (Qmci) screen. METHODS: A concurrent mixed methods, prospective study using a quasi-experimental design was conducted with 147 participants from 5 primary care Family Health Teams (FHTs; characterized by multidisciplinary practice and capitated funding) across southwestern Ontario, Canada. Participants included health care practitioners, patients, and FHT administrative executives. Individuals aged ≥55 years with no history of MCI or diagnosis of dementia rostered in a participating FHT were eligible to participate. Participants were screened using both the SCREEN and Qmci. The study also incorporated the Geriatric Anxiety Scale-10 to assess general anxiety levels at each cognitive screening. The SCREEN's scoring was compared against that of the Qmci and the clinical judgment of health care professionals. Statistical analyses included sensitivity, specificity, internal consistency, and test-retest reliability assessments. RESULTS: The study found that the SCREEN's longer administration time and complex scoring algorithm, which is proprietary and unavailable for independent analysis, presented challenges. Its internal consistency, indicated by a Cronbach α of 0.63, was below the acceptable threshold. The test-retest reliability also showed limitations, with moderate intraclass correlation coefficient (0.54) and inadequate κ (0.15) values. Sensitivity and specificity were consistent (63.25% and 74.07%, respectively) between cross-tabulation and discrepant analysis. In addition, the study faced limitations due to its demographic skew (96/147, 65.3% female, well-educated participants), the absence of a comprehensive gold standard for MCI diagnosis, and financial constraints limiting the inclusion of confirmatory neuropsychological testing. CONCLUSIONS: The SCREEN, in its current form, does not meet the necessary criteria for an optimal MCI screening tool in primary care settings, primarily due to its longer administration time and lower reliability. As the number of digital health technologies increases and evolves, further testing and refinement of tools such as the SCREEN are essential to ensure their efficacy and reliability in real-world clinical settings. This study advocates for continued research in this rapidly advancing field to better serve the aging population. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/25520.

Magnetic resonance imaging for jawbone assessment: a systematic review.

PURPOSE: To evaluate the accuracy of magnetic resonance imaging (MRI) for jawbone assessment compared to reference-standard measurements in the literature. MATERIALS AND METHODS: An electronic database search was conducted in PubMed, EMBASE, Scopus, Web of Science, and the Cochrane Library in June 2022, and updated in August 2023. Studies evaluating the accuracy of MRI for jawbone assessment compared with reference-standard measurements (histology, physical measurements, or computed tomography) were included. The outcome measures included bone histomorphometry and linear measurements. The risk of bias was assessed by the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2). The review was registered in the PROSPERO database (CRD42022342697). RESULTS: From 63 studies selected for full-text analysis, nine manuscripts were considered eligible for this review. The studies included assessments of 54 participants, 35 cadavers, and one phantom. A linear measurement error ranging from 0.03 to 3.11 mm was shown. The accuracy of bone histomorphometry varies among studies. Limitations of the evidence included heterogeneity of MRI protocols and the methodology of the included studies. CONCLUSION: Few studies have suggested the feasibility of MRI for jawbone assessment, as MRI provides comparable results to those of standard reference tests. However, further advancements and optimizations are needed to increase the applicability, validate the efficacy, and establish clinical utility of these methods.

Development and evaluation of Order of Magnitude (OM): a virtual reality-based visual field analyzer for glaucoma detection.

PURPOSE: This study introduces the Order of Magnitude (OM), a cost-effective, indigenous, virtual reality-based visual field analyzer designed for detecting glaucomatous visual field loss. METHODS: The OM test employs a two-step supra-thresholding algorithm utilizing stimuli of 0.43°diameter (equivalent to Goldmann size III) at low and high thresholds. A comparative analysis was conducted against the Humphrey visual field (HVF) test, considered the gold standard in clinical practice. Participants, including those with glaucoma and normal individuals, underwent comprehensive eye examinations alongside the OM and HVF tests between April and October 2019. Diagnostic sensitivity and specificity of the OM test were assessed against clinical diagnoses made by specialists. RESULTS: We studied 157 eyes (74 glaucomatous, 83 control) of 152 participants. Results demonstrated a high level of reliability for both OM and HVF tests, with no significant difference observed (P = 0.19, Chi-square test). The sensitivity and specificity of the OM test were found to be 93% (95% CI 86-100%) and 83% (95% CI 72.4-93%), respectively, while the HVF test showed sensitivity and specificity of 98% (95% CI 93.9-100%) and 83% (95% CI 73.9-92.8%), respectively. CONCLUSION: These findings suggest that the OM test is non-inferior to the reference standard HVF test in identifying glaucomatous visual field loss.

Meta-analysis of machine learning models for the diagnosis of central precocious puberty based on clinical, hormonal (laboratory) and imaging data.

Background: Central precocious puberty (CPP) is a common endocrine disorder in children, and its diagnosis primarily relies on the gonadotropin-releasing hormone (GnRH) stimulation test, which is expensive and time-consuming. With the widespread application of artificial intelligence in medicine, some studies have utilized clinical, hormonal (laboratory) and imaging data-based machine learning (ML) models to identify CPP. However, the results of these studies varied widely and were challenging to directly compare, mainly due to diverse ML methods. Therefore, the diagnostic value of clinical, hormonal (laboratory) and imaging data-based ML models for CPP remains elusive. The aim of this study was to investigate the diagnostic value of ML models based on clinical, hormonal (laboratory) and imaging data for CPP through a meta-analysis of existing studies. Methods: We conducted a comprehensive search for relevant English articles on clinical, hormonal (laboratory) and imaging data-based ML models for diagnosing CPP, covering the period from the database creation date to December 2023. Pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), summary receiver operating characteristic (SROC) curve, and area under the curve (AUC) were calculated to assess the diagnostic value of clinical, hormonal (laboratory) and imaging data-based ML models for diagnosing CPP. The I2 test was employed to evaluate heterogeneity, and the source of heterogeneity was investigated through meta-regression analysis. Publication bias was assessed using the Deeks funnel plot asymmetry test. Results: Six studies met the eligibility criteria. The pooled sensitivity and specificity were 0.82 (95% confidence interval (CI) 0.62-0.93) and 0.85 (95% CI 0.80-0.90), respectively. The LR+ was 6.00, and the LR- was 0.21, indicating that clinical, hormonal (laboratory) and imaging data-based ML models exhibited an excellent ability to confirm or exclude CPP. Additionally, the SROC curve showed that the AUC of the clinical, hormonal (laboratory) and imaging data-based ML models in the diagnosis of CPP was 0.90 (95% CI 0.87-0.92), demonstrating good diagnostic value for CPP. Conclusion: Based on the outcomes of our meta-analysis, clinical and imaging data-based ML models are excellent diagnostic tools with high sensitivity, specificity, and AUC in the diagnosis of CPP. Despite the geographical limitations of the study findings, future research endeavors will strive to address these issues to enhance their applicability and reliability, providing more precise guidance for the differentiation and treatment of CPP.

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.

Blood RNA biomarkers for tuberculosis screening in people living with HIV before antiretroviral therapy initiation: a diagnostic accuracy study.

BACKGROUND: Undiagnosed tuberculosis remains a major threat for people living with HIV. Multiple blood transcriptomic biomarkers have shown promise for tuberculosis diagnosis. We sought to evaluate their diagnostic accuracy and clinical utility for systematic pre-antiretroviral therapy (ART) tuberculosis screening. METHODS: We enrolled consecutive adults (age ≥18 years) referred to start ART at a community health centre in Cape Town, South Africa, irrespective of symptoms. Sputa were obtained (using induction if required) for two liquid cultures. Whole-blood RNA samples underwent transcriptional profiling using a custom Nanostring gene panel. We measured the diagnostic accuracy of seven candidate RNA signatures (one single gene biomarker [BATF2] and six multigene biomarkers) for the reference standard of Mycobacterium tuberculosis culture status, using area under the receiver-operating characteristic curve (AUROC) analysis, and sensitivity and specificity at prespecified thresholds (two standard scores above the mean of healthy controls; Z2). Clinical utility was assessed by calculating net benefit in decision curve analysis. We compared performance with C-reactive protein (CRP; threshold ≥5 mg/L), WHO four-symptom screen (W4SS), and the WHO target product profile for tuberculosis triage tests. FINDINGS: A total of 707 people living with HIV (407 [58%] female and 300 [42%] male) were included, with median CD4 count 306 cells per mm3 (IQR 184-486). Of 676 participants with available sputum culture results, 89 (13%) had culture-confirmed tuberculosis. The seven RNA signatures were moderately to highly correlated (Spearman rank coefficients 0·42-0·93) and discriminated tuberculosis culture positivity with similar AUROCs (0·73-0·80), but none statistically better than CRP (AUROC 0·78, 95% CI 0·72-0·83). Diagnostic accuracy was similar across CD4 count strata, but lower among participants with negative W4SS (AUROCs 0·56-0·65) compared with positive (AUROCs 0·75-0·84). The RNA biomarker with the highest AUROC point estimate was a four-gene signature (Suliman4; AUROC 0·80, 95% CI 0·75-0·86), with sensitivity 83% (95% CI 74-90) and specificity 59% (55-63) at the Z2 threshold. In decision curve analysis, Suliman4 and CRP had similar clinical utility to guide confirmatory tuberculosis testing, but both had higher net benefit than W4SS. In exploratory analyses, an approach combining CRP (≥5 mg/L) and Suliman4 (≥Z2) had sensitivity of 80% (70-87), specificity of 70% (66-74), and higher net benefit than either biomarker alone. INTERPRETATION: RNA biomarkers showed better clinical utility to guide confirmatory tuberculosis testing for people living with HIV before ART initiation than symptom-based screening, but their performance did not exceed that of CRP and fell short of WHO recommended targets. Interferon-independent approaches might be required to improve accuracy of host-response biomarkers to support tuberculosis screening before ART initiation. FUNDING: South African Medical Research Council, European and Developing Countries Clinical Trials Partnership 2, National Institutes of Health National Institute of Allergy and Infectious Diseases, The Wellcome Trust, National Institute for Health and Care Research, Royal College of Physicians London.

Congestive Hepatopathy: Pathophysiology, Workup, and Imaging Findings with Pathologic Correlation.

Liver congestion is increasingly encountered in clinical practice and presents diagnostic pitfalls of which radiologists must be aware. The complex altered hemodynamics associated with liver congestion leads to diffuse parenchymal changes and the development of benign and malignant nodules. Distinguishing commonly encountered benign hypervascular lesions, such as focal nodular hyperplasia (FNH)-like nodules, from hepatocellular carcinoma (HCC) can be challenging due to overlapping imaging features. FNH-like lesions enhance during the hepatic arterial phase and remain isoenhancing relative to the background liver parenchyma but infrequently appear to wash out at delayed phase imaging, similar to what might be seen with HCC. Heterogeneity, presence of an enhancing capsule, washout during the portal venous phase, intermediate signal intensity at T2-weighted imaging, restricted diffusion, and lack of uptake at hepatobiliary phase imaging point toward the diagnosis of HCC, although these features are not sensitive individually. It is important to emphasize that the Liver Imaging Reporting and Data System (LI-RADS) algorithm cannot be applied in congested livers since major LI-RADS features lack specificity in distinguishing HCC from benign hypervascular lesions in this population. Also, the morphologic changes and increased liver stiffness caused by congestion make the imaging diagnosis of cirrhosis difficult. The authors discuss the complex liver macro- and microhemodynamics underlying liver congestion; propose a more inclusive approach to and conceptualization of liver congestion; describe the pathophysiology of liver congestion, hepatocellular injury, and the development of benign and malignant nodules; review the imaging findings and mimics of liver congestion and hypervascular lesions; and present a diagnostic algorithm for approaching hypervascular liver lesions. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.