Assessment Of Diagnostic Tests Research Articles

Artificial intelligence-based screening for amblyopia and its risk factors: comparison with four classic stereovision tests.

The development of costs-effective and sensitive screening solutions to prevent amblyopia and identify its risk factors (strabismus, refractive problems or mixed) is a significant priority of pediatric ophthalmology. The main objective of our study was to compare the classification performance of various vision screening tests, including classic, stereoacuity-based tests (Lang II, TNO, Stereo Fly, and Frisby), and non-stereoacuity-based, low-density static, dynamic, and noisy anaglyphic random dot stereograms. We determined whether the combination of non-stereoacuity-based tests integrated in the simplest artificial intelligence (AI) model could be an alternative method for vision screening. Our study, conducted in Spain and Hungary, is a non-experimental, cross-sectional diagnostic test assessment focused on pediatric eye conditions. Using convenience sampling, we enrolled 423 children aged 3.6-14 years, diagnosed with amblyopia, strabismus, or refractive errors, and compared them to age-matched emmetropic controls. Comprehensive pediatric ophthalmologic examinations ascertained diagnoses. Participants used filter glasses for stereovision tests and red-green goggles for an AI-based test over their prescribed glasses. Sensitivity, specificity, and the area under the ROC curve (AUC) were our metrics, with sensitivity being the primary endpoint. AUCs were analyzed using DeLong's method, and binary classifications (pathologic vs. normal) were evaluated using McNemar's matched pair and Fisher's nonparametric tests. Four non-overlapping groups were studied: (1) amblyopia (n = 46), (2) amblyogenic (n = 55), (3) non-amblyogenic (n = 128), and (4) emmetropic (n = 194), and a fifth group that was a combination of the amblyopia and amblyogenic groups. Based on AUCs, the AI combination of non-stereoacuity-based tests showed significantly better performance 0.908, 95% CI: (0.829-0.958) for detecting amblyopia and its risk factors than most classical tests: Lang II: 0.704, (0.648-0.755), Stereo Fly: 0.780, (0.714-0.837), Frisby: 0.754 (0.688-0.812), p < 0.02, n = 91, DeLong's method). At the optimum ROC point, McNemar's test indicated significantly higher sensitivity in accord with AUCs. Moreover, the AI solution had significantly higher sensitivity than TNO (p = 0.046, N = 134, Fisher's test), as well, while the specificity did not differ. The combination of multiple tests utilizing anaglyphic random dot stereograms with varying parameters (density, noise, dynamism) in AI leads to the most advanced and sensitive screening test for identifying amblyopia and amblyogenic conditions compared to all the other tests studied.

644. "Impact of heat inactivation and freeze-thaw cycles on detection of influenza A and influenza B antigens and RNA when assessing novel multiplex diagnostic assays"

Abstract Background Advances in diagnostics since the emergence of COVID-19 has resulted in easy availability of rapid antigen tests (RAT). Building on this, multiplex tests for simultaneous detection of Flu A, Flu B, and SARS-CoV-2 are being evaluated as part of NIH’s Rapid Acceleration of Diagnostics (RADx) program. Critically important for assay development and assessment are viral panels prepared under validated conditions to evaluate new tests. These panels may contain live virus or may be inactivated to promote biosafety. They also may undergo freeze-thaw cycles during storage and transport. We characterized the effect of heat inactivation (HI) on detection of Flu A and B using two RATs, and the effect of freeze-thaw cycles on a point-of-care (PoC) molecular assay already on the market. Methods Panels were prepared by serially diluting Flu A or B strains obtained from BEI Resources. Both live and HI panels were prepared. HI was achieved in-house (60°C, 30 minutes). Panels with and without HI were used to assess two RATs by performing triplicate tests and determining limit of detection (LOD) as the lowest TCID50 at which 3 of 3 replicates were positive. Additionally, a molecular-based PoC assay was evaluated by recording cycle threshold (Ct) values before and after freeze-thaw of specimens. All assays were performed according to the manufacturer’s instructions. Results Both RATs detected Flu A with similar sensitivity (2-fold increase in LOD) before and after heat inactivation (Figure 1), whereas Flu B was not detected by either RAT after heat inactivation. These results were consistent across both RATs and two strains of each virus. Live Flu A and B were stable and consistently detected up to four freeze-thaw cycles in the molecular assay with minor attrition of Ct values (Figure 2). Results of LOD characterization for two independent RATs with influenza A and B with and without heat inactivation. Correlation of Flu A and Flu B Ct values for fresh samples versus after four cycles of freeze thaw measured using a PoC molecular assay. Conclusion Pre-treatment and storage of testing material plays a crucial role in the assessment of diagnostic tests used for Flu A and B detection. Loss of reactivity in Flu B antigen tests after inactivation suggests that heating may denature a critical epitope recognized by immunoassays. Selection of live versus HI samples and degradational effects of freeze thaw cycles must be considered by laboratorians and engineers creating or validating diagnostic tests. Disclosures All Authors: No reported disclosures

Health technology assessment of diagnostic tests: a state of the art review of methods guidance from international organizations.

To identify which international health technology assessment (HTA) agencies are undertaking evaluations of medical tests, summarize commonalities and differences in methodological approach, and highlight examples of good practice. A methodological review incorporating: systematic identification of HTA guidance documents mentioning evaluation of tests; identification of key contributing organizations and abstraction of approaches to all essential HTA steps; summary of similarities and differences between organizations; and identification of important emergent themes which define the current state of the art and frontiers where further development is needed. Seven key organizations were identified from 216 screened. The main themes were: elucidation of claims of test benefits; attitude to direct and indirect evidence of clinical effectiveness (including evidence linkage); searching; quality assessment; and health economic evaluation. With the exception of dealing with test accuracy data, approaches were largely based on general approaches to HTA with few test-specific modifications. Elucidation of test claims and attitude to direct and indirect evidence are where we identified the biggest dissimilarities in approach. There is consensus on some aspects of HTA of tests, such as dealing with test accuracy, and examples of good practice which HTA organizations new to test evaluation can emulate. The focus on test accuracy contrasts with universal acknowledgment that it is not a sufficient evidence base for test evaluation. There are frontiers where methodological development is urgently required, notably integrating direct and indirect evidence and standardizing approaches to evidence linkage.

Developing diagnostic test assessment to measure creative thinking skills of Biology preservice teacher students

The research aims to develop a diagnostic test assessment to measure the creative thinking skills of biology preservice teacher students. This research and development used Thiagarajan's 4D (Define, Design, Develop, and Dissemination) model. The diagnostic test assessment was developed in the form of an essay test with five numbers of scoring rubrics. This research was conducted at the Biology Education Study Program, University of Sintuwu Maroso. The results of the expert validation of the assessment instrument are high, and the reliability value is high. The results of the test found that all questions were valid and reliable. The student's creative thinking skills obtained an average value of fluency of 75.01% in the high category, flexibility thinking skills of 64.13% in the medium category, originality thinking skills of 69.56% in the medium category, elaboration skills of 75.01% in the high category and evaluation skills of 75.07% in the high category. All students' creative thinking skills are in the moderate category with a score of 71.74%, and the follow-up to the diagnostic results is that the lecturer can provide remedial on several learning indicators that have not been achieved.

Performance assessment of a new indirect rapid diagnostic test for plague detection in humans and other mammalian hosts

Plague is a flea-borne zoonosis that affects a wide range of mammals and still causes outbreaks in human populations yearly across several countries. While crucial for proper treatment, early diagnosis is still a major challenge in low- and middle-income countries due to poor access to laboratory infrastructure in rural areas. To tackle this issue, we developed and evaluated a new Fraction 1 capsular antigen (F1)-based rapid diagnostic test (RDT) as an alternative method for plague serological diagnosis and surveillance in humans and other mammals. In this study, 187 serum samples from humans, dogs, rodents and rabbits were retrospectively assessed using the plague RDT method. To calculate its performance, results were compared to those obtained by traditional hemagglutination (HA) and ELISA, which are well-established methods in the plague routine serodiagnosis. Remarkably, the results from RDT were in full agreement with those from the ELISA and HA assays, resulting in 100% (CI 95% = 95.5–100%) of sensitivity and 100% (CI 95% = 96.6–100%) of specificity. Accordingly, the Cohen's Kappa test coefficient was 1.0 (almost perfect agreement). Moreover, the RDT showed no cross-reaction when tested with sera from individuals positive to other pathogens, such as Y. pseudotuberculosis, Yersinia enterocolitica, Anaplasma platys, Ehrlichia canis and Leishmania infantum. Although preliminary, this study brings consistent proof-of-concept results with high performance of the Plague RDT when compared to HA and ELISA. Although further human and animal population-based studies will be necessary to validate these findings, the data presented here show that the plague RDT is highly sensitive and specific, polyvalent to several mammal species and simple to use in field surveillance or point-of-care situations with instant results.

Evaluation of a 3-item screening tool to identify men with benign prostatic enlargement/obstruction in a primary care cohort.

Benign prostatic hyperplasia (BPH), a progressive condition and common cause of lower urinary tract symptoms (LUTS), is underdiagnosed in primary care, impacting patient outcomes. Here, we evaluate the utility of a BPH screening tool in general practice, to identify men confirmed to have BPH after urologist assessment of diagnostic test results. A 3-item questionnaire was developed to discriminate between LUTS due to BPH versus other conditions and was translated and validated cross-culturally. Its utility was assessed in a cohort study (FDC116114/NCT02757963) conducted in 47 centers across France, Germany, Italy, Russia, and Spain. The study enrolled men ≥50 years of age presenting to general practice clinics with a score of ≥3 on the BPH screening tool or ≥8 on the International Prostate Symptom Score (IPSS). In total, 561 men completed the study. The primary endpoint was the proportion of patients with a urologist-confirmed BPH diagnosis among those with a positive result on the BPH screening tool (score ≥3) and serum prostate specific antigen (PSA) ≥2 ng/mL. The primary endpoint was fulfilled; 88.3% (95% CI: 84.9, 91.2) of patients had urologist-confirmed BPH diagnoses among those with positive results on the BPH screening tool and serum PSA≥2 ng/mL, similar to the proportion seen with IPSS≥8 and serum PSA≥2 ng/mL (87.7%; 95% CI: 84.6, 90.4). The BPH screening tool, in conjunction with serum PSA, demonstrated adequate predictive value by allowing general practitioners to quickly screen men presenting with different medical conditions but identified as having urological symptoms.

Methodological and conceptual challenges in rare and severe event forecast verification

Abstract. There are distinctive methodological and conceptual challenges in rare and severe event (RSE) forecast verification, that is, in the assessment of the quality of forecasts of rare but severe natural hazards such as avalanches, landslides or tornadoes. While some of these challenges have been discussed since the inception of the discipline in the 1880s, there is no consensus about how to assess RSE forecasts. This article offers a comprehensive and critical overview of the many different measures used to capture the quality of categorical, binary RSE forecasts – forecasts of occurrence and non-occurrence – and argues that of skill scores in the literature there is only one adequate for RSE forecasting. We do so by first focusing on the relationship between accuracy and skill and showing why skill is more important than accuracy in the case of RSE forecast verification. We then motivate three adequacy constraints for a measure of skill in RSE forecasting. We argue that of skill scores in the literature only the Peirce skill score meets all three constraints. We then outline how our theoretical investigation has important practical implications for avalanche forecasting, basing our discussion on a study in avalanche forecast verification using the nearest-neighbour method (Heierli et al., 2004). Lastly, we raise what we call the “scope challenge”; this affects all forms of RSE forecasting and highlights how and why working with the right measure of skill is important not only for local binary RSE forecasts but also for the assessment of different diagnostic tests widely used in avalanche risk management and related operations, including the design of methods to assess the quality of regional multi-categorical avalanche forecasts.

Diagnostic and prognostic test assessment in emergency medicine: likelihood and diagnostic odds ratios

Emergency physicians use diagnostic and prognostic tests on a daily basis to assess for life-threatening illness and to inform clinical decisions. Current and new tests must be scientifically evaluated for...

Assessment of Rapid Diagnostic Tests for Typhoid Diagnosis and Assessment of Febrile Illness Outbreaks in Fiji.

ABSTRACT.Typhoid is an endemic in Fiji with increases observed since the early 2000s and frequent outbreaks reported. We assessed the diagnostic accuracy of currently available typhoid rapid diagnostic tests (RDTs) (TUBEX, Typhidot Rapid, and Test-It assay) to establish their performance against blood culture in Fiji and to examine their suitability for rapid typhoid outbreak identification. The performance of RDTs was assessed in the public health reference laboratory in Suva, Fiji, according to the manufacturers’ instructions. A simulation was used to examine the potential use of RDTs for attribution of a febrile illness outbreak to typhoid. For the diagnostic evaluation, 179 patients were included; 49 had blood culture–confirmed typhoid, 76 had fever as a result of non-typhoid etiologies, and 54 were age-matched community controls. The median (interquartile range) age was 29 (20–46) years. Of the participants, 92 (51.4%) were male and 131 (73.2%) were indigenous Fijians. The sensitivities of the tests were 77.6% for TUBEX, 75.5% for Typhidot Rapid, and 57.1% for Test-It assay. The Test-It assay had the highest specificity of 93.4%, followed by Typhidot Rapid 85.5% and TUBEX 60.5%. Typhidot Rapid had the best performance in the simulation for attribution of a febrile illness outbreak to typhoid. Typhoid RDTs performed suboptimally for individual patient diagnosis due to low sensitivity and variable specificity. We demonstrate that RDTs could be useful in the field for rapid attribution of febrile illness outbreaks to typhoid. Typhidot Rapid had the best combination of sensitivity, specificity, positive and negative predictive values, cost, and ease of use for this purpose.

Comparative assessment of immunochromatography and ELISA diagnostic tests for HBsAg detection in PCR-confirmed HBV infection

Introduction and aimsViral hepatitis, which appears most frequently at birth or during childhood, is a disease whose transmission routes include tears, bile, sexual fluids, sweat, milk, urine, feces, and saliva. The aim of the present study was to analyze the specificity of the immunochromatographic and ELISA diagnostic tests for hepatitis B surface antigen and compare them with PCR testing. Materials and methodsThe study sample was made up of 140 men and 60 women referred to the Urmia Medical University hospital to undergo PCR testing for HBV diagnosis. The ELISA test was performed using the Pioneer Medicine Company kit (Tehran, Iran). ResultsThe results of the HBs-Ag rapid test and the ELISA test were compared with the PCR test. The HBs-Ag rapid test had 97% sensitivity and 91% specificity, whereas the ELISA test had 78% sensitivity and 76% specificity. Discussion and conclusionAccording to our results, the immunochromatographic test was accurate for diagnosing HBs-Ag in blood and the ELISA test had acceptable sensitivity and specificity, compared with PCR testing.

The Trifecta of Diagnostic Stewardship, Antimicrobial Stewardship, and Value Assessment of New Diagnostic Tests

The Trifecta of Diagnostic Stewardship, Antimicrobial Stewardship, and Value Assessment of New Diagnostic Tests

Studies for the Evaluation of Diagnostic Tests–Part 28 of a Series on Evaluation of Scientific Publications.

The accurate diagnosis of a disease is a prerequisite for its appropriate treatment. How well a medical test is able to correctly identify or rule out a target disease can be assessed by diagnostic accuracy studies. The main statistical parameters that are derived from diagnostic accuracy studies, and their proper interpretation, will be presented here in the light of publications retrieved by a selective literature search, supplemented by the authors' own experience. Aspects of study planning and the analysis of complex studies on diagnostic tests will also be discussed. In the usual case, the findings of a diagnostic accuracy study are presented in a 2 × 2 contingency table containing the number of true-positive, true-negative, false-positive, and true-positive test results. This information allows the calculation of various statistical parameters, of which the most important are the two pairs sensitivity/ specificity and positive/negative predictive value. All of these parameters are quotients, with the number of true positive (resp. true negative) test results in the numerator; the denominator is, in the first pair, the total number of ill (resp. healthy) patients, and in the second pair, the total number of patients with a positive (resp. negative) test. The predictive values are the parameters of greatest interest to phy - sicians and patients, but their main disadvantage is that they can easily be misinterpreted. We will also present the receiver operating characteristic (ROC) curve and the area under the curve (AUC) as additional important measures for the assessment of diagnostic tests. Further topics are discussed in the supplementary materials. The statistical parameters used to assess diagnostic tests are primarily based on 2 × 2 contingency tables. These parameters must be interpreted with care in order to draw correct conclusions for use in medical practice.

Cytokine Imprint in Preeclampsia.

The hallmark of preeclampsia (PE) is a shift toward persistent inflammatory response, accompanied by endothelial dysfunction. The driving forces in PE are proinflammatory cytokine and growth factors, in parallel with reduced functionality of anti-inflammatory effectors, like regulatory T cells are observed. Unfortunately, no conclusive mechanism underlying preeclampsia has been identified. For this reason, research on preeclampsia is needed to provide a state of the art understanding of the pathophysiology, identification of new diagnostics tools and the development of targeted therapies. The 68 patients were divided into three groups: gestational hypertension (GH) group (n = 19) and PE group (n = 28) and a control group (n = 21). We have tested a set of 53 cytokines, chemokines and growth factors in preeclampsia and gestational hypertension, and then compared them with normal pregnancies. Using a diagnostic test assessment characteristic parameters (IL-22, MDC/CCL22, IL-2/IL-4 ratio) have been identified and cut-off values have been proposed to diagnose preeclampsia. All parameters had high negative or positive predictive values, above 80%. In conclusion, we have proposed a potential set of immune parameters to diagnose preeclampsia.

Coronavirus disease (COVID-19) pandemic: an overview of systematic reviews

BackgroundNavigating the rapidly growing body of scientific literature on the SARS-CoV-2 pandemic is challenging, and ongoing critical appraisal of this output is essential. We aimed to summarize and critically appraise systematic reviews of coronavirus disease (COVID-19) in humans that were available at the beginning of the pandemic.MethodsNine databases (Medline, EMBASE, Cochrane Library, CINAHL, Web of Sciences, PDQ-Evidence, WHO’s Global Research, LILACS, and Epistemonikos) were searched from December 1, 2019, to March 24, 2020. Systematic reviews analyzing primary studies of COVID-19 were included. Two authors independently undertook screening, selection, extraction (data on clinical symptoms, prevalence, pharmacological and non-pharmacological interventions, diagnostic test assessment, laboratory, and radiological findings), and quality assessment (AMSTAR 2). A meta-analysis was performed of the prevalence of clinical outcomes.ResultsEighteen systematic reviews were included; one was empty (did not identify any relevant study). Using AMSTAR 2, confidence in the results of all 18 reviews was rated as “critically low”. Identified symptoms of COVID-19 were (range values of point estimates): fever (82–95%), cough with or without sputum (58–72%), dyspnea (26–59%), myalgia or muscle fatigue (29–51%), sore throat (10–13%), headache (8–12%) and gastrointestinal complaints (5–9%). Severe symptoms were more common in men. Elevated C-reactive protein and lactate dehydrogenase, and slightly elevated aspartate and alanine aminotransferase, were commonly described. Thrombocytopenia and elevated levels of procalcitonin and cardiac troponin I were associated with severe disease. A frequent finding on chest imaging was uni- or bilateral multilobar ground-glass opacity. A single review investigated the impact of medication (chloroquine) but found no verifiable clinical data. All-cause mortality ranged from 0.3 to 13.9%.ConclusionsIn this overview of systematic reviews, we analyzed evidence from the first 18 systematic reviews that were published after the emergence of COVID-19. However, confidence in the results of all reviews was “critically low”. Thus, systematic reviews that were published early on in the pandemic were of questionable usefulness. Even during public health emergencies, studies and systematic reviews should adhere to established methodological standards.

Introduction to diagnostic test accuracy studies.

Diagnostic accuracy studies are fundamental for the assessment of diagnostic tests. Researchers need to understand the implications of their chosen design, opting for comparative designs where possible. Researchers should analyse test accuracy studies using the appropriate methods, acknowledging the uncertainty of results and avoiding overstating conclusions and ignoring the clinical situation which should inform the trade-off between sensitivity and specificity. Test accuracy studies should be reported with transparency using the STAndards for the Reporting of Diagnostic accuracy studies (STARD) checklist.

Relationship between Mathematics Diagnostic Test and Mathematics Final Assessment Among Pre-University Students Based on Gender

Diagnostic testing is considered as an important device that can be used by educators to identify students' strong and weak points in Mathematics subjects as it is often used as a preliminary evaluation of basic Mathematics skills of students. Educators must be able to detect the students' mathematical capacity earlier before delivering new content to them. This article purposes are to identify the achievement of pre-university students in Mathematics diagnostic test and Mathematics final assessment based on their gender, the differences between the gender of the students with their achievement in Mathematics diagnostic test, and the correlation between the students' Mathematics diagnostic test and their achievement in pre-university Mathematics final assessment. The findings demonstrated that students of both genders, who accomplished good results in their Mathematics diagnostic test, did similarly good in their final assessment. Also, students who carried out badly in their Mathematics diagnostic test did poorly in their final assessment. From this diagnostic result, it facilitates the educator to provide the students with the best teaching method and material required.

Diagnostic test assessment. Validation study of an alternative system to detect microsatellite instability in colorectal carcinoma.

SummaryThe American Society for Clinical Pathology (ASCP), College of American Pathologists (CAP), Association for Molecular Pathology (AMP), and the American Society of Clinical Oncology (ASCO) have been recently strongly recommended the evaluation of mismatch repair status (MMS) as molecular biomarkers in colorectal cancer for a better prognostic stratification of patients. This recommendation is emphasized by the recent evidence of Microsatellite Instability (MSI) as a predictive marker for chemotherapy and immunotherapy.In this scenario, the validation of molecular biomarker testing methods seems to be essential to design the most appropriate tailored therapy and the most suitable care strategy, respectively.In this study, we validated an alternative method based on capillary electrophoresis system label-free PCR (Qiaxcel system) to evaluate the MSI Bethesda Panel. We also parallel the results with a standard approach.Our data showed total concordance with the standard approach, with a highly time-efficient and easy procedure combined with high sensitivity for MSI detection.Alternative capillary electrophoresis based on label-free PCR such as the Qiaxel system is a very sensitive and specific method to detect MSI for the management of patients with colorectal cancer. This procedure is adequate and suitable in diagnostic routine for the evaluation of microsatellite repeats compared to standard procedures.

Assessment of a rapid diagnostic test to exclude bacteraemia and effect on clinical decision-making for antimicrobial therapy

Unnecessary antimicrobial treatment promotes the emergence of resistance. Early confirmation that a blood culture is negative could shorten antibiotic courses. The Cognitor Minus test, performed on blood culture samples after 12 hours incubation has a negative predictive value (NPV) of 99.5%. The aim of this study was to determine if earlier confirmation of negative blood culture result would shorten antibiotic treatment. Paired blood cultures were taken in the Critical Care Unit at a teaching hospital. The Cognitor Minus test was performed on one set >12 hours incubation but results kept blind. Clinicians were asked after 24 and 48 hours whether a result excluding bacteraemia or fungaemia would affect decisions to continue or stop antimicrobial treatment. Over 6 months, 125 patients were enrolled. The median time from start of incubation to Cognitor Minus test was 27.1 hours. When compared to 5 day blood culture results from both the control and test samples, Cognitor Minus gave NPVs of 99% and 100% respectively. Test results would have reduced antibiotic treatment in 14% (17/119) of patients at 24 and 48 hours (24% at either time) compared with routine blood culture. The availability of rapid tests to exclude bacteraemia may be of benefit in antimicrobial stewardship.

Comparative assessment of commercial enzyme-linked immunosorbent assay & rapid diagnostic tests used for dengue diagnosis in India.

Background & objectives:Dengue diagnosis is routinely carried out by detection of dengue virus (DENV) antigen NS1 and/or anti-DENV IgM antibodies using enzyme-linked immunosorbent assays (ELISAs) and rapid diagnostic tests (RDTs). This study was aimed at evaluation of quality of diagnostic assays currently in use in India for the identification of DENV infection.Methods:During 2016 dengue season (July-November) in Pune, India, comparative assessment of a few immunoassays was undertaken using (i) WHO-approved Panbio-Dengue-Early-(NS1)-ELISA and Panbio-Dengue-IgM-Capture-ELISA as reference tests, and (ii) Bayesian latent class analysis (BLCA) which assumes that no test is perfect. The assays included J.Mitra-Dengue-NS1-Ag-MICROLISA (JME-NS1), J.Mitra-Dengue-IgM-MICROLISA (JME-IgM), and two RDTs, namely, J.Mitra-Dengue-Day- 1-Test (JM-RDT) and SD-BIOLINE-Dengue-Duo (SDB-RDT). Serum samples from patients seeking dengue diagnosis (n=809) were tested using the diagnostic kits. The presence of NS1 and/or IgM was taken as evidence for dengue-positive diagnosis.Results:Panbio-NS1/IgM-ELISAs identified 38.6 per cent patients as dengue positive. With Panbio-ELISA as reference, all the tests were less sensitive for IgM detection, while for NS1, JM-RDT was less sensitive. For combined diagnosis (both markers), sensitivity of all the tests was low (55.7-76.6%). According to BLCA, Panbio-ELISA was 84 per cent sensitive for NS1, 86 per cent specific for IgM and 87 per cent specific for combined diagnosis. Accordingly, performance of the other tests was substantially improved with BLCA; however, sensitivity of both the RDTs for IgM detection remained unacceptable. The NS1 ELISAs and RDTs detected all four DENV serotypes, JME being most efficient. All IgM tests exhibited higher sensitivity in secondary infections.Interpretation & conclusions:These results confirmed superiority of ELISAs, and testing for both NS1 and IgM markers for dengue diagnosis, and emphasized on improvement in sensitivity of RDTs.

Prospective Assessment of Diagnostic Tests for Pediatric Penicillin Allergy: From Clinical History to Challenge Tests

To determine the efficacy of available diagnostic tools in penicillin allergy relative to the results of drug provocation tests (DPTs).The population included 732 children ≤14 years of age presenting to participating allergy departments who reported an adverse drug reaction with benzylpenicillin (penicillin G), phenoxymethyl penicillin (penicillin V), amoxicillin-clavulanic acid, or cloxacillin. Patients with a history of severe skin conditions during the index reaction (IR), presence of skin disease not allowing skin testing, and/or any condition for which epinephrine use was contraindicated were excluded.This was a multicenter study (38 allergists from 23 centers) across Spanish allergy departments (from the Spanish Society of Allergy and Clinical Immunology). After a detailed history, IRs were classified as immediate (symptoms within 1 hour of the first dose) or nonimmediate. Researchers then classified reactions as a “clear-positive” case, “doubtful” case, or a “clear-negative” case to assess accuracy of clinical history alone. Then, every patient underwent a uniform protocol of skin tests (skin prick test and intradermal test), serum-specific immunoglobulin E (IgE) tests, and then, regardless of the results of these tests, DPTs.Of the 732 participants who completed the study, 35 (4.8%) were diagnosed with a penicillin allergy at the end of the tests: 6 (17% of the patients with a penicillin allergy) with immediate reactions and 29 (83%) with nonimmediate reactions. A family history of drug allergy was associated with a higher risk of penicillin allergy (odds ratio: 2.56). Amoxicillin alone or with clavulanic acid was the most frequent trigger. The most frequently reported symptom was an exanthema and was more commonly associated with nonimmediate IR (58.4% vs 30% in immediate IR). Urticaria was next most common, associated more with an immediate IR (55.5% vs 37.6% of nonimmediate IRs). Thirty-one cases (4.2%) were classified as clear positive on the basis of history alone, 518 were classified (70.8%) as clear negative, and 183 (25%) were classified as doubtful. One of the clear-positive cases turned out to be a true penicillin allergy on the basis of DPTs. Twenty-three of the cases initially classified as clear negative and 12 of the doubtful cases turned out to be a true allergy. Only 1 positive skin prick test result was recorded for benzylpenicilloyl polylysine, and none were recorded for the other tests. Few had positive intradermal test results. Overall skin testing had low sensitivity (0% to 20%) and high specificity (97% to 100%) for skin testing. For serum-specific IgE, sensitivity was low (2.9% to 17%), but specificity was high (94.4% to 99.9%).Currently available diagnostic methods (clinical history, skin testing, and serum-specific IgE) performed poorly compared with DPT. DPTs performed in specialized centers should be used as the first diagnostic tool to evaluate children with mild to moderate penicillin IRs when anaphylaxis and severe skin syndromes have been excluded.With the knowledge that most adults labeled as penicillin allergic are not and a push to confirm the diagnosis, the allergist is performing more penicillin allergy evaluations. With regards to a pediatric population, this study shows the need for DPTs to best evaluate children labeled as penicillin allergic, despite the logistic difficulties in performing this diagnostic test.