Comparison of multiplex arrays: AllergyChip and Alex2. IgE detection for inhalant allergens.

Imaging Methods for Differentiating Pediatric Papilledema from Pseudopapilledema: A Report by the American Academy of Ophthalmology

INTRODUCTION: Small Intestinal Bacterial Overgrowth (SIBO) is associated with abnormally high bacterial counts in the small intestine. SIBO is under-diagnosed and there are significant limitations with currently available testing methods. METHODS: Two research databases (Google Scholar and Web of Science) were used to find relevant published literature using keywords including glucose breath test accuracy, endoscopy aspirate culture and small intestine bacterial overgrowth. Eleven studies with data on patients tested with both a glucose breath test and endoscopy aspirate culture were found. Fixed-effects and random-effects models were fit to the eleven studies’ data using the Metafor (Meta-Analysis Package for R). The mean positive and negative percent agreement across studies is estimated as the weighted average of each study’s percent agreement, where the weights are the inverse of the standard errors, squared, plus the variance of the random study effects. RESULTS: The homogeneity of effects across studies was tested with a Chi-square test and homogeneity of effects was rejected for both positive and negative percent agreement (c2 = 91.5 and 107.5, respectively, df = 10, P-value < 0.0001) (Table 1). The mean percent agreement across studies was estimated with both the fixed-effects and the random-effects models (Table 2). Figure 1 presents each study’s estimate of the positive and negative percent agreement, respectively, and their associated 95% confidence intervals, as well as the overall estimate and its 95% confidence interval. CONCLUSION: Heterogeneity was found in the study designs and the implementation of breath tests such as the differences in dose of the substrate (50g or 75-100g) and the duration of the breath test (120∼240min). Meanwhile, the endoscopy aspirate culture is also not completely standardized, as the amount of liquid collected, the site of collection and the technical details of the microbiological tests may differ. This heterogeneity in practice of the two tests certainly contributes to the heterogeneity in positive and negative percentage agreement observed between the two tests. The random effects models’ estimates of 54% positive agreement and 76% negative agreement indicate moderate to poor agreement between the breath test and endoscopy aspirate culture. Given these limitations, there is an unmet need for novel tools to evaluate patients suspected of SIBO.

Evaluation of the rapid antigen test Panbio COVID-19 in saliva and nasal swabs in a population-based point-of-care study

To compare the performance of vaginitis diagnosis based on clinical assessment to molecular detection of organisms associated with bacterial vaginosis, vulvovaginal candidiasis, and Trichomonas vaginalis using a vaginal panel assay. This cross-sectional diagnostic accuracy study included 489 enrolled participants from five collection sites where those with vaginitis symptoms had a vaginal assay swab collected during their visit and a clinical diagnosis made. The swab was later sent to a separate testing site to perform the vaginal panel assay. Outcome measures include positive, negative, and overall percent agreement (and accompanying 95% CIs) of clinical assessment with the vaginal panel assay. P<.05 was used to distinguish significant differences in paired proportions between the vaginal panel assay and clinical diagnosis, using the McNemar test. Inter-rater agreement between the two diagnostic approaches was determined using Cohen's kappa coefficient. Clinical diagnosis had a positive percent agreement with the vaginal panel assay of 57.9% (95% CI 51.5-64.2%), 53.5% (95% CI 44.5-62.4%), and 28.0% (95% CI 12.1-49.4%) for bacterial vaginosis, vulvovaginal candidiasis, and T vaginalis, respectively. Negative percent agreement for clinical diagnosis was 80.2% (95% CI 74.3-85.2%), 77.0% (95% CI 72.1-81.4%), and 99.8% (95% CI 98.7-99.9%), respectively. Sixty-five percent (67/103), 44% (26/59), and 56% (10/18) of patients identified as having bacterial vaginosis, vulvovaginal candidiasis, and T vaginalis by assay, respectively, were not treated for vaginitis based on a negative clinical diagnosis. Compared with the assay, clinical diagnosis had false-positive rates of 19.8%, 23.0%, and 0.2% for bacterial vaginosis, vulvovaginal candidiasis, and T vaginalis, respectively. Significant differences in paired proportions were observed between the vaginal panel assay and clinical diagnosis for detection of bacterial vaginosis and T vaginalis. The vaginal panel assay could improve the diagnostic accuracy for vaginitis and facilitate appropriate and timely treatment. Becton, Dickinson and Company.

The aim of this study was to estimate adherence to urate-lowering therapy (ULT), predominately allopurinol, from Australia's Pharmaceutical Benefits Scheme (PBS) claims database in association with (1) patient-reported doses and (2) World Health Organization's (WHO) defined daily doses (DDD), namely, allopurinol (400 mg/day) or febuxostat (80 mg/day). Proportion of days covered (PDC) was calculated in 108 Gout App (Gout APP) trial participants with at least two recorded ULT dispensings in an approximately 12-month period before provision of intervention or control apps. Adherence was defined as PDC ≥80%. We measured the correlation between the two methods of calculating PDC using a Wilcoxon signed rank test. Agreement between ULT-taking status (self-reports) and ULT-dispensed status (PBS records) was tested with Cohen's kappa (κ), and positive and negative percent agreement. Allopurinol was prescribed in 93.5% of participants taking ULT. Their self-reported mean daily dose (SD) was 291 (167) mg/day. Mean PDC (SD) for allopurinol was 83% (21%) calculated using self-reported dose, and 63% (24%) using WHO's DDD. Sixty-three percent of allopurinol users were identified as adherent (PDC ≥80%) using self-reported dose. There was good agreement between self-reported ULT use and PBS dispensing claims (κ = 0.708, P < .001; positive percent agreement = 90%, negative percent agreement = 82%). Participant-reported allopurinol daily doses, in addition to PBS dispensing claims, may enhance confidence in estimating PDC and adherence compared to using DDD. This approach improves adherence estimations from pharmaceutical claims datasets for medications where daily doses vary between individuals or where there is a wide therapeutic dose range.

Several point-of-care (POC) molecular tests have received emergency use authorization (EUA) from the Food and Drug Administration (FDA) for the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The test performance characteristics of the Accula (Mesa Biotech) SARS-CoV-2 POC test need to be evaluated to inform its optimal use. The aim of this study was to assess the test performance of the Accula SARS-CoV-2 test. The performance of the Accula test was assessed by comparing results of 100 nasopharyngeal swab samples previously characterized by the Stanford Health Care EUA laboratory-developed test (SHC-LDT), targeting the envelope (E) gene. Assay concordance was assessed by overall percent agreement, positive percent agreement (PPA), negative percent agreement (NPA), and Cohen's kappa coefficient. Overall percent agreement between the assays was 84.0% (95% confidence interval [CI], 75.3 to 90.6%), PPA was 68.0% (95% CI, 53.3 to 80.5%), and the kappa coefficient was 0.68 (95% CI, 0.54 to 0.82). Sixteen specimens detected by the SHC-LDT were not detected by the Accula test and showed low viral load burden, with a median cycle threshold value of 37.7. NPA was 100% (95% CI, 94.2 to 100%). Compared to the SHC-LDT, the Accula SARS-CoV-2 test showed excellent negative agreement. However, positive agreement was low for samples with low viral load. The false-negative rate of the Accula POC test calls for a more thorough evaluation of POC test performance characteristics in clinical settings and for confirmatory testing in individuals with moderate to high pretest probability of SARS-CoV-2 who test negative on Accula.

BackgroundRapid and accurate diagnosis of chronic obstructive pulmonary disease (COPD) is problematic in acute care settings, particularly in the presence of infective comorbidities.ObjectiveThe aim of this study was to develop a rapid smartphone-based algorithm for the detection of COPD in the presence or absence of acute respiratory infection and evaluate diagnostic accuracy on an independent validation set.MethodsParticipants aged 40 to 75 years with or without symptoms of respiratory disease who had no chronic respiratory condition apart from COPD, chronic bronchitis, or emphysema were recruited into the study. The algorithm analyzed 5 cough sounds and 4 patient-reported clinical symptoms, providing a diagnosis in less than 1 minute. Clinical diagnoses were determined by a specialist physician using all available case notes, including spirometry where available.ResultsThe algorithm demonstrated high positive percent agreement (PPA) and negative percent agreement (NPA) with clinical diagnosis for COPD in the total cohort (N=252; PPA=93.8%, NPA=77.0%, area under the curve [AUC]=0.95), in participants with pneumonia or infective exacerbations of COPD (n=117; PPA=86.7%, NPA=80.5%, AUC=0.93), and in participants without an infective comorbidity (n=135; PPA=100.0%, NPA=74.0%, AUC=0.97). In those who had their COPD confirmed by spirometry (n=229), PPA was 100.0% and NPA was 77.0%, with an AUC of 0.97.ConclusionsThe algorithm demonstrated high agreement with clinical diagnosis and rapidly detected COPD in participants presenting with or without other infective lung illnesses. The algorithm can be installed on a smartphone to provide bedside diagnosis of COPD in acute care settings, inform treatment regimens, and identify those at increased risk of mortality due to seasonal or other respiratory ailments.Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12618001521213; http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375939

Loop-mediated isothermal amplification (LAMP) is a molecular diagnostic method known for its rapid processing and operational simplicity due to its isothermal amplification process. While LAMP has demonstrated comparable diagnostic accuracy to PCR in certain applications, its performance may vary depending on assay design and implementation. This study aimed to evaluate the diagnostic performance of the MmaxSure™ assay (MmaxSure™; Mmonitor, Daegu, South Korea) in detecting SARS-CoV-2, comparing it with the STANDARD™ M nCoV Real-Time Detection Kit (STANDARD; SD BioSensor, Suwon, South Korea) using nasopharyngeal and oropharyngeal swab specimens. A total of 333 specimens were included in the analysis, consisting of 113 positive and 220 negative nasopharyngeal and oropharyngeal swab samples. All specimens were tested using the MmaxSure™ assay, and the results were compared to those obtained using the STANDARD™ M nCoV Real-Time Detection Kit. The diagnostic performance of the MmaxSure™ assay was evaluated in terms of positive percent agreement (PPA), negative percent agreement (NPA), and Cohen's kappa index for inter-assay agreement. Sensitivity, specificity, and limit of detection (LOD) for SARS-CoV-2 variants were also determined. The MmaxSure™ assay demonstrated a 100% PPA and a 100% NPA with the STANDARD™ M nCoV Real-Time Detection Kit. The Cohen's kappa index was 1.0, indicating perfect agreement between the two diagnostic methods. The MmaxSure™ assay exhibited a high sensitivity, detecting SARS-CoV-2 variants at a LOD of 2 - 4 copies/µL, without cross-reactivity with other pathogens. The MmaxSure™ Fast SARS-CoV-2 Detection Kit, based on LAMP technology, exhibited a high level of diagnostic accuracy in detecting SARS-CoV-2. Its rapid turnaround time and minimal equipment requirements suggest its potential suitability for point-of-care applications. However, further prospective studies with a broader range of clinical specimens and real-world validation are needed to confirm its diagnostic utility across diverse settings.

Accuracy of T2 magnetic resonance assays as point-of-care methods in the intensive care unit

There are limited data on the role of multigene tests and their correlation with immunohistochemistry (IHC), especially on core biopsy. MammaTyper is a quantitative conformite Europeeanne (CE) marked, National Institute for Health and Care excellence (NICE) approved, in in vitro diagnostic quantitative real-time polymerase chain reaction (RT-qPCR) test for assessment of mRNA expression of four biomarkers (ESR1, PGR, ERBB2, MKI67). We evaluated the concordance of MammaTyper with oestrogen receptor (ER), progesterone receptor(PR), HER2, and Ki67 by IHC on 133 core needle biopsies of breast cancer. HER2 was positive if IHC 3+ or 2+ and fluorescence in situ hybridization (FISH)-amplified. Global and hotspot Ki67 expression was analysed using a cutoff of ≥20% assessed manually and by digital image analysis. Agreements were expressed as overall percent agreement (OPA), positive percent agreement (PPA), negative percent agreement (NPA), and Cohen's kappa. RT-qPCR results of ESR1 were highly concordant with IHC with OPA of 94.7% using 1% cutoff and 91.7% when the low ER-positive category was included. The PPA and NPA between RT-qPCR and IHC for PR was 91.5% and 88.0%, respectively, when using the 1% cutoff. For ERBB2/HER2, the OPA was 95% and the PPA was 84.6%. 40 of 72 HER2 IHC score 0 tumours were classified as ERBB2 low. Best concordance between MKI67 by MammaTyper and Ki67 IHC was achieved using hotspot digital image analysis (OPA: 87.2%, PPA: 90.6%, NPA: 80%). RT-qPCR-based assessment of the mRNA expression of ESR1, PGR, ERBB2, and MKI67 showed high concordance with IHC, suggesting that the MammaTyper test on core needle biopsies represents a reliable, efficient, and reproducible alternative for breast cancer classification and refining HER2 low categorisation.

ABSTRACTTests to diagnose acute SARS-CoV-2 infection are at the center of controlling the COVID-19 pandemic. Rapid tests benefit from providing quick results but suffer from lower sensitivity, while PCR tests usually take longer to provide more reliable results and can be difficult to scale to meet population needs. We evaluated the diagnostic efficacy of a Molecular Mirror assay (MMA) using nucleic acid extraction and a nucleic acid extraction-free method to determine its ability to identify SARS-CoV-2 in nasal specimens from individuals suspected of having SARS-CoV-2. We compared the MMA using nucleic acid extraction to the emergency use authorization (EUA)-approved TaqPath reverse transcriptase PCR (RT-PCR) assay to determine its performance characteristics. From 412 total specimens (including 115 previous positives and 297 previous negatives), we found that the positive percent agreement (PPA) was 99.1% (confidence interval [CI], 97.4% to 100.0%) and the negative percent agreement (NPA) was 99.3% (95% CI, 98.4% to 100.0%) for SARS-CoV-2 detection. Using the extraction-free method, we analyzed 109 specimens (51 previous positives and 58 previous negatives) and found that the PPA for the more rapid version of the assay was 87.8% (95% CI, 78.5% to 96.9%) and the NPA was 100.0% (95% CI, 100.0%) for virus detection. The extraction method has performance comparable to what is observed in many PCR-based assays. The extraction-free method has lower PPA but has the advantage of being more rapid and having a higher throughput. Our data offer a proof of concept that nuclear magnetic resonance (NMR) detection can be used in SARS-CoV-2 diagnostic testing and may allow for alternative supply chains to increase testing options.IMPORTANCE Accurate diagnostics for SARS-CoV-2 infections have been critical for responding to the COVID-19 pandemic. Both high-sensitivity/specificity PCR-based tests and lower-sensitivity/specificity rapid antigen assays have been the subject of worldwide supply chain limitations as individual facilities and countries have struggled to meet their population testing needs. We evaluated the diagnostic efficacy of a Molecular Mirror assay (MMA), which uses nuclear magnetic resonance to detect the presence of SARS-CoV-2 nucleic acids both with and without full nucleic acid extractions. We found that compared to a U.S. emergency use authorization (EUA) approved assay (TaqPath) that uses reverse transcriptase PCR (RT-PCR), the MMA had high PPA and NPA with full nucleic acid extractions, and acceptable positive percent agreement (PPA) and negative percent agreement (NPA) with an extraction-free protocol. In a landscape marred by supply chain shortages across the world, altered SARS-CoV-2 detection methods such as the MMA can add to testing supplies while providing quality SARS-CoV-2 testing results.

Validation and Characterization of FGFR2 Rearrangements in Cholangiocarcinoma with Comprehensive Genomic Profiling

BackgroundVarious nucleic acid amplification assays for the diagnosis of SARS‐CoV‐2 infection have been developed, and there is a need to assess their test performance relative to one another. The aim of this study was to compare the performance characteristics of the Biosewoom Real‐Q 2019‐nCoV assay targeting the E and RdRP genes to DaAn Gene 2019‐nCoV kit targeting the N gene and ORF1ab in the diagnosis of SARS‐CoV‐2.MethodsWe performed a diagnostic comparison study by testing nasopharyngeal samples for SARS‐CoV‐2 using the two reverse transcription polymerase chain reaction (RT‐PCR) assays. Assay agreement was assessed by overall percent agreement, negative percent agreement, positive percent agreement, and Cohen's kappa coefficient.ResultsA total of 48 nasopharyngeal samples were tested using the two assays. One sample was invalid, and three showed inconclusive results with Real‐Q; hence, 44 were included for the comparative analysis. Overall, percent agreement between the assays was 93.2% (95% CI 81.3%–98.6%), Positive percent agreement (PPA) was 86.4% (95% CI 65.1%–97.1%) and negative percent agreement (NPA) was 100% (95% CI 84.6%–100%). The kappa coefficient was 0.86 (95% CI 0.72–1.01). Three samples (6.8%) were positive with DaAn gene kit and negative with Real‐Q. The fluorescence intensity for Real‐Q reporter dyes was low.ConclusionThe two kits showed high levels of concordance in their detection of SARS‐CoV‐2 despite having different gene targets. The Biosewoom kit can be improved through addressing the fluorescence intensity of the target dyes, and feedback was given to the manufacturer.

Syphilis infections are high among men who have sex with men (MSM) on HIV pre-exposure prophylaxis (PrEP). Point-of-care (POC) testing may improve diagnosis and treatment. We performed a field evaluation of the Chembio dual path platform (DPP) Syphilis Screen and Confirm treponemal/non-treponemal POC test within an HIV PrEP programme in Hanoi, Vietnam. From December 2023 to July 2024, males aged ≥16 years enrolled in the HIV PrEP programme who reported sex with men in the last year were enrolled. Specimens were tested using the Chembio DPP syphilis screen and confirm test and reference treponemal (Abbott Bioline or Determine) and non-treponemal (rapid plasma reagin (RPR)) tests. Positive per cent agreement (PPA), negative per cent agreement (NPA), positive predictive value (PPV), negative predictive value (NPV) and Cohen's kappa were calculated comparing the DPP versus reference tests. We enrolled 400 participants; median age was 26.4 years (IQR 22.5-30.4); one invalid test was excluded. The prevalence of a reactive treponemal test was 35.3% (141/399). For the DPP treponemal test, PPA was 75.2% (95% CI 67.2% to 82.2%), NPA was 96.9% (95% CI 94% to 98.7%), PPV was 93% (95% CI 86.8% to 96.4%), NPV was 87.7% (95% CI 83.4% to 91%), and Cohen's kappa was 0.75. For the DPP non-treponemal test, PPA was 36.5% (95% CI 23.6% to 51%), NPA was 99.4% (95% CI 97.9% to 99.9%), PPV was 90.5% (95% CI 71.1% to 97.4%), NPV was 91.3% (95% CI 88% to 93.7%), and Cohen's kappa was 0.48 (95% CI 0.33 to 0.61). For RPR titres ≥1:8, PPA and Cohen's kappa increased to 85.7% (95% CI 57.2% to 98.2%) and 0.67 (95% CI 0.47 to 0.81), respectively. Among MSM in an HIV PrEP programme with high syphilis prevalence, the DPP treponemal test performed well. While non-treponemal performance was lower, it was strong for RPR titres ≥1:8, suggesting it could aid in identifying high-titre syphilis infections more likely to be transmissible.

Severe periodontitis affects about 10% of the world population. In addition, associations between periodontitis and systemic diseases exist. Therefore, the diagnosis should be made quickly and at an early stage. Matrix metalloproteinase-8 (MMP-8) is the most prominent collagenase found in inflamed periodontal tissues. Its active form (aMMP-8) is increasingly used as a diagnostic biomarker. Aim of the present study is to evaluate the diagnostic accuracy of a novel aMMP-8 point-of-care (POC) test in comparison to the standard laboratory test to diagnose the disease rapidly and reliably. In a prospective, mono-center, double-blinded, case-control study, participants with healthy gums (n = 35), gingivitis (n = 60) and periodontitis (n = 35) were investigated before and after therapy. Beside clinical variables for plaque and inflammation, aMMP-8 concentrations were determined in oral rinsing specimens by the enzyme-linked immunosorbent assay (ELISA) and by POC. Positive and negative percent agreements with their exact one-sided lower 95% confidence limits were calculated. Of 130 participants, 111 finished the study. Overall, positive percent agreements were 75.8% (57.7-88.9) before treatment and 73.7% (56.9-86.6) after treatment. Negative percent agreements were 92.8% (85.7-97.0) before and 93.3% (85.1-97.8) after treatment. Positive test results (POC and ELISA) ranged from 5.7% to 8.6% in healthy patients, 25.0-29.8% in patients with gingivitis and 40.0-48.1% in patients with periodontitis. Patients who had positive aMMP-8 test results (POC) showed higher scores for plaque and inflammation. The novel POC test to detect aMMP-8 has proved to agree strongly with the standard method, ELISA. The test can be recommended to screen patients at risk for periodontitis in dental offices, at the general practitioner and at specialists for associated diseases.