Prospective evaluation of mannan and anti-mannan antibodies for diagnosis of invasive Candida infections in patients with neutropenic fever

The diagnostic performance and usefulness of the Platelia antigen and antibody test (Bio-Rad) was investigated in a prospective study of haematological patients at risk for invasive Candida infections. Among 100 patients, 86 were eligible, of whom invasive candidiasis (IC) occurred in 12 (14 %), according to the criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group. These included candidaemia due to Candida albicans (one patient) or Candida tropicalis (four patients), and hepatosplenic candidiasis (seven patients). The comparator group of 74 patients included 50 with febrile neutropenia alone and 24 with mould infections. A strategy was developed to determine diagnostic cut-offs from receiver operating characteristic curves with maximal sensitivity and, given this sensitivity, maximal specificity, both being greater than 0. In this patient population, these values were 0.25 ng ml−1 for mannan (M) and 2.6 arbitrary units ml−1 for anti-mannan (AM), which are lower than those recommended by the manufacturer. All patients developed at least one positive diagnostic M or AM result during the 10 days of persistent febrile neutropenia (PFN). The optimal overall performance was found when two consecutive positive tests for both M and AM were used [sensitivity, specificity, positive predictive value and negative predictive value (NPV) (95 % confidence intervals) of 0.73 (0.39–0.94), 0.80 (0.69–0.89), 0.36 (0.17–0.59) and 0.95 (0.86–0.99), respectively]. There was a positive correlation of M with β-d-glucan (r=0.28, P=0.01). The first positive M test was found up to a mean±sd of 8.8±8.5 (range 2–23) days prior to a clinical/mycological diagnosis of IC. Day-to-day variation in quantitative M levels was high. High-level AM responses were delayed until leucopenia resolved. The low specificities of the test performance may have been due to some of the comparator patients having subclinical Candida infections as evidenced by the high incidence of colonization among them (60 % had a colonization index of ≥0.5). The high NPVs suggest that the tests may be particularly useful in excluding IC. It is feasible to explore the use of serial measurements of M and AM as part of a broader diagnostic strategy for selecting PFN patients to receive antifungal drug therapy.

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Association Between 45° Flexion Anteroposterior Elbow Radiographs and Diagnostic Accuracy of Capitellum Osteochondritis Dissecans

The American Journal of Sports Medicine ◽

10.1177/03635465211027178 ◽

2021 ◽

pp. 036354652110271

Author(s):

Michael G. Saper ◽

Viviana Bompadre ◽

Gregory A. Schmale ◽

Sarah Menashe ◽

Monique Burton ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Osteochondritis Dissecans ◽

Predictive Value ◽

Interobserver Reliability ◽

Intraobserver Reliability ◽

Control Group ◽

Level Of Evidence ◽

Level Of Confidence ◽

High Level ◽

Sensitivity Specificity

Background: An anteroposterior (AP) radiograph of the elbow in 45° of flexion has been suggested to increase the diagnostic accuracy of capitellum osteochondritis dissecans (OCD). Purpose: To assess the diagnostic performance, inter- and intraobserver reliability, and confidence level for identifying capitellum OCD using plain radiographs (AP, lateral, and 45° flexion AP). Study Design: Cohort study (Diagnosis); Level of evidence, 3. Methods: This was a retrospective study of pediatric and adolescent patients with capitellum OCD and a control group. Six independent clinicians who were blinded to the official radiologists’ reports reviewed images on 2 separate occasions, 1 week apart. A 5-point Likert scale was used to assess the clinicians’ level of confidence. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated for individual and combinations of radiographic views. Inter- and intraobserver reliability was determined using Cohen kappa (κ) coefficients. Results: A total of 28 elbows (mean age, 12.5 ± 2 years) were included. There were no differences in age ( P = .18), sex ( P = .62), or laterality ( P > .999) between groups. There were marked variations in the diagnostic accuracy between views: sensitivity (AP, 85.1; lateral, 73.2; 45° flexion AP, 91.7), specificity (AP, 89.3; lateral, 91.7; 45° flexion AP, 91.1), PPV (AP, 88.8; lateral, 89.8; 45° flexion AP, 91.1), NPV (AP, 85.7; lateral, 77.4; 45° flexion AP, 91.6), and accuracy (AP, 87.2; lateral, 82.4; 45° flexion AP, 91.4). Standard radiographs (AP and lateral views) failed to diagnose capitellum OCD in 4.8% of cases. The sensitivity of the 3 combined views was 100%. Confidence intervals in the clinicians’ diagnostic assessments were similar for each view (AP, 4.0; lateral, 4.0; and 45° flexion AP, 4.1). Interobserver reliability was substantial for AP and lateral views (κ = 0.65 and κ = 0.60, respectively) but highest for the 45° flexion AP radiographs (κ = 0.72). Intraobserver reliability for the 45° flexion AP view was moderate to almost perfect (κ = 0.45 to 0.93). Conclusion: The 45° flexion AP view can detect capitellum OCD with excellent accuracy, a high level of confidence, and substantial interobserver agreement. When added to standard AP and lateral radiographs, the 45° flexion AP view aids in the identification of capitellum OCD.

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Anti-Toxoplasma IgG assays: What performances for what purpose? A systematic review

Parasite ◽

10.1051/parasite/2021035 ◽

2021 ◽

Vol 28 ◽

pp. 39

Author(s):

Florence Robert-Gangneux ◽

Hélène Guegan

Keyword(s):

Systematic Review ◽

Predictive Value ◽

Opportunistic Infections ◽

Evaluation Studies ◽

Reference Method ◽

Western Blot Assay ◽

Patients At Risk ◽

The Mean ◽

Sensitivity Specificity ◽

Rule Out

Chronic infection with Toxoplasma gondii is attested by the detection of specific anti-Toxoplasma IgG. A wide panel of serologic methods is currently marketed, and the most suitable method should be chosen according to the laboratory resources and the screened population. This systematic review of evaluation studies aimed at establishing an overview of the performances, i.e. sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of marketed anti-Toxoplasma IgG assays, and discussing their technical characteristics to guide further choice for routine diagnostic use. According to PRISMA guidelines, the search performed in PubMed and Web of Science databases recovered 826 studies, of which 17 were ultimately included. Twenty commercial anti-Toxoplasma IgG assays were evaluated, in comparison with an accepted reference method. Most of them were enzyme-immunoassays (EIAs, n = 12), followed by agglutination tests (n = 4), immunochromatographic tests (n = 3), and a Western-Blot assay (WB, n = 1). The mean sensitivity of IgG assays ranged from 89.7% to 100% for standard titers and from 13.4% to 99.2% for low IgG titers. A few studies pointed out the ability of some methods, especially WB to detect IgG early after primary infection. The specificity of IgG assays was generally high, ranging from 91.3% to 100%; and higher than 99% for most EIA assays. The PPV was not a discriminant indicator among methods, whereas significant disparities (87.5%–100%) were reported among NPVs, a key-parameter assessing the ability to definitively rule out a Toxoplasma infection in patients at-risk for opportunistic infections.

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Validation of rapid antibody (IgG-IgM) test kit for SARS COV-2 infection in Qatar

Journal of Public Health Research ◽

10.4081/jphr.2021.2421 ◽

2021 ◽

Author(s):

Jesha Mundodan ◽

Samina Hasnain ◽

Hayat Khogali ◽

Soha Shawqi Al Bayat ◽

Dina Ali ◽

...

Keyword(s):

Predictive Value ◽

Local Population ◽

Rapid Test ◽

Antibody Test ◽

Molecular Testing ◽

Rt Pcr ◽

Test Kit ◽

Asymptomatic Individuals ◽

Sensitivity Specificity ◽

Rapid Antibody

Background: In response to the growing coronavirus disease 2019 (COVID-19) pandemic and the shortage of laboratory based molecular testing capacity and reagents, multiple diagnostic test manufacturers have developed rapid and easy to use devices to facilitate testing outside laboratory settings. These kits are either based on detection of proteins from SARS-CoV-2 virus or detection of antigen or human antibodies generated in response to the infection. However, it is important to understand their performance characteristics and they must be validated in the local population setting.Design and Methods: The objective is to assess the validity of the rapid test for IgG and IgM immunoglobulins compared to the current gold standard reverse transcription polymerase chain reaction (RT-PCR) test. A total of 16951 asymptomatic individuals were tested by the Ministry of Public Health track-and-trace team using both rapid immunodiagnostic test and RT-PCR as part of screening across various random settings with potential risk of community interaction prior to gradual lifting of restrictions in Qatar. Rapid test was considered to be posiive if both IgG and IgM are positive, while only IgG/IgM positive was considered as rapid test negative. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated.Results: The sensitivity of rapid test kit was found to be 0.9%, whereas the specificity was found to be 97.8%. the PPV was found to be 0.3% whereas the NPV was found to be 99.4%.Conclusion: Based on the outcome and results of the study, it appears that the sensitivity and PPV of the rapid antibody test are low. As such, this test is not recommended for use to assist in taking clinic-based decisions or decisions related to quarantine/isolation.

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Early Radiologic Diagnosis of Pulmonary Infection in Febrile Neutropenic Patients: A Comparison of Serial Chest Radiography and Single CT Chest

Radiology Research and Practice ◽

10.1155/2021/8691363 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Wanaporn Burivong ◽

Thanatorn Sricharoen ◽

Apichart Thachang ◽

Sunsiree Soodchuen ◽

Panitpong Maroongroge ◽

...

Keyword(s):

Febrile Neutropenia ◽

Positive Predictive Value ◽

Absolute Neutrophil Count ◽

Predictive Value ◽

Pulmonary Infection ◽

False Positive Rate ◽

Radiologic Diagnosis ◽

Chest Film ◽

Positive Rate ◽

Sensitivity Specificity

Objective. The purpose of this study is to compare the early radiologic diagnosis of pulmonary infection between serial chest radiography (chest film) and single chest computed tomography (CT chest) in the first seven days of febrile neutropenia. Methods. This study included 78 patients with hematologic malignancies who developed 107 episodes of febrile neutropenia from January 2012 to October 2017 and had a chest film performed within the first seven days. Demographic and radiographic data were retrospectively reviewed. Three radiologists independently and blindly evaluated chest films and CT chests. The sensitivity, specificity, and correlation of chest film with absolute neutrophil count were carried out. Results. A total of 222 chest films were performed during this period and found thirty-nine episodes (36.4%) of radiographic active pulmonary infection. The diagnosis of clinical positive for pulmonary infection is 44.8% (48/107). Sensitivity, specificity, positive predictive value, and negative predictive value of serial chest film in the early radiologic diagnosis of pulmonary infection are 50%, 74%, 61%, and 64%, respectively. The false-positive rate was 14%, and the false-negative rate was 22%. For single CT chest examinations, twenty-six studies were assessed, and 42.3% was indicative of radiographic active pulmonary infection. Sensitivity, specificity, positive predictive value, and negative predictive value of CT chest in the early radiologic diagnosis of pulmonary infection are 91%, 40%, 53%, and 86%, respectively. The false-positive rate was 60%. The absolute neutrophil count was not useful for predicting radiographic active pulmonary infection. Conclusion. Serial chest film for early radiologic diagnosis of pulmonary infection within the first seven days of febrile neutropenia has lower sensitivity with higher specificity as compared to a single CT chest. Conversely, CT chest may not only have a higher sensitivity in determining early pulmonary infection but also has a higher rate of false-positives.

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Diagnostic Performance of Plasma Gastrin Concentration for the Diagnosis of Type 1 Abomasal Ulcer in Water Buffalo: A Preliminary Case Control Study

10.21203/rs.3.rs-592148/v1 ◽

2021 ◽

Author(s):

Syed Ashaq Hussain ◽

S K Uppal ◽

N K Sood

Keyword(s):

Test Performance ◽

Predictive Value ◽

Histopathological Examination ◽

Clinical Signs ◽

Plasma Gastrin ◽

Roc Curve Analysis ◽

Optimal Value ◽

Sensitivity Specificity ◽

Control Study

Abstract The type 1 abomasal ulcer (AU1) does not have specific clinical signs, and there is a need to identify some early biochemical markers for diagnosis of AU1 in cattle and buffaloes. Plasma gastrin is reported to reflect the gastric mucosa damage but its utility for diagnosis of AU1 in buffaloes has not been evaluated. The objective of this study was to study the test performance of plasma gastrin to distinguish healthy buffaloes and buffaloes with AU1. Twenty-three buffaloes with AU1 and six buffaloes without abomasal ulcer were used. Blood samples were collected from the buffaloes, slaughtered in a buffalo specific slaughter house, for estimation of plasma gastrin. After slaughter abomasa were examined for presence of AU1 and were confirmed by histology. The mean plasma gastrin concentration of ulcer positive buffaloes was significantly (p<0.05) higher than the ulcer negative buffaloes. The ROC curve analysis suggested optimal value of plasma gastrin for diagnosis of AU1 was 106.2 pg/ml. Since the abomasal ulcer negative animals were established to be ulcer negative on histopathological examination we consider the values of gastrin valid for detection of abomasal ulceration in buffaloes. The sensitivity, specificity, positive predictive value and negative predictive value of plasma gastrin to diagnose AU1 in buffalo were 78.3, 100, 100 and 69.9, respectively.

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A Prospective Risk Model for Neutropenic Complications in Patients with Malignant Lymphoma.

Blood ◽

10.1182/blood.v106.11.3328.3328 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3328-3328

Author(s):

Gary H. Lyman ◽

Jeffrey Crawford ◽

Debra Wolff ◽

Eva Culakova ◽

Marek S. Poniewierski ◽

...

Keyword(s):

Febrile Neutropenia ◽

Malignant Lymphoma ◽

Likelihood Ratio ◽

Cancer Chemotherapy ◽

Test Performance ◽

Predictive Value ◽

Risk Model ◽

Chemotherapy Regimen ◽

Performance Characteristics ◽

Increased Risk

Abstract Background: Myelosuppression including severe and febrile neutropenia continues to represent a major cause of dose-limiting toxicity of cancer chemotherapy. Neutropenic complications in cycle 1 have been shown to frequently lead to reduced dose intensity or addition of a myeloid growth factor. A prospective, nationwide study was undertaken to develop and validate risk models for first cycle neutropenic events associated with cancer chemotherapy. Methods: Patients with malignant lymphoma initiating a new chemotherapy regimen have been prospectively registered at 115 randomly selected practice sites. Data on at least one cycle of chemotherapy were available on 357 patients including 56 with Hodgkin’s disease and 301 with non-Hodgkin’s lymphoma. A logistic regression model for first cycle neutropenic events based on pretreatment characteristics was developed and predictive test performance characteristics examined. Results: Severe or febrile neutropenia occurred in 81 (22.7%) of patients in cycle 1. Two-thirds of patients with one or more neutropenic events experienced their initial event in cycle 1. Significant independent pretreatment predictive factors for first cycle neutropenic complications were: history of renal disease (OR=33.15, P=.011) or recent infection (OR=12.41, P=.035), Caucasian (OR=4.13, P=.053), use of an anthracycline-based chemotherapy regimen (OR=6.9, P<.001), baseline absolute neutrophil count (OR=0.95, P<.001) and lymphocyte count (OR=0.95, P<.001), anemia (OR=2.14, P=.043), elevated lactate dehydrogenase (OR=2.0, P=.040) and elevated bilirubin (OR=2.25, P=.051). Model fit was excellent (P<.001), R2= 0.503 and c-statistic = 0.769 [95% CL: .71–.83, P<.0001]. Individual predicted risk of cycle 1 events based on the model ranged from 0 to 96% with mean and median probabilities of 0.23 and 0.21, respectively. Two-thirds of patients were classified as high risk with mean risk scores in high and low risk subjects of 32.0% and 5.6%, respectively. Model test performance characteristics [±95% CL] included: sensitivity: 92% [84–96]; specificity: 40% [34–46]; likelihood ratio positive: 1.53 [1.36–1.73]; likelihood ratio negative: 0.19 [0.09–0.42]; positive predictive value: 32% [26–38]; negative predictive value: 94% [88–97] and diagnostic odds ratio: 7.92 [3.32–18.91]. Discussion: The risk model identified lymphoma patients at increased risk for first cycle neutropenic complications using common clinical parameters. Validation of the model in a separate population of patients is in progress.

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High diagnostic accuracy of automated rapid Strep A test reduces antibiotic prescriptions for children in the United Arab Emirates

BMC Pediatrics ◽

10.1186/s12887-021-02516-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Salama Bin Hendi ◽

Zainab A. Malik ◽

Amar Hassan Khamis ◽

Fadil Y. A. Al-Najjar

Keyword(s):

Diagnostic Accuracy ◽

United Arab Emirates ◽

Predictive Value ◽

High Sensitivity ◽

Signs And Symptoms ◽

Throat Culture ◽

Clinical Criteria ◽

Variable Sensitivity ◽

High Level ◽

Sensitivity Specificity

Abstract Background Diagnosis of Group A Streptococcus (GAS) pharyngitis in children is hindered by variable sensitivity of clinical criteria and rapid Strep A tests (SAT), resulting in reliance on throat cultures as the gold standard for diagnosis. Delays while awaiting culture reports result in unnecessary antibiotic prescriptions among children, contributing to the spread of antimicrobial resistance (AMR). Methods Diagnostic accuracy study of an automated SAT (A-SAT) in children up to 16 years of age presenting to an emergency room with signs and symptoms of pharyngitis between March and June 2019. Paired throat swabs for A-SAT and culture were collected. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for A-SAT were calculated. Results Two hundred and ninety-one children were included in this study. 168 (57.7%) were boys and the mean age was 4.2 years. A-SAT was positive in 94 (32.3%) and throat culture was positive in 90 (30.9%) children. A-SAT and throat culture results showed a high level of consistency in our cohort. Only 6 (2%) children had inconsistent results, demonstrating that the A-SAT has a high sensitivity (98.9%), specificity (97.5%), PPV (94.7%) and NPV (99.5%) for the diagnosis of GAS pharyngitis in children. Only 92 (32%) children were prescribed antibiotics while the vast majority (68%) were not. Conclusions A-SAT is a quick and reliable test with diagnostic accuracy comparable to throat culture. Its widespread clinical use can help limit antibiotic prescriptions to children presenting with pharyngitis, thus limiting the spread of AMR.

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Assessment of Oropharyngeal Specimens for Discontinuation of Transmission-Based COVID-19 Precautions

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa382 ◽

2020 ◽

Vol 7 (9) ◽

Author(s):

Joshua A Barocas ◽

Miriam Komaromy ◽

Deeanna Haidar ◽

Tamar F Barlam ◽

Beverley L Orr ◽

...

Keyword(s):

Negative Predictive Value ◽

Retrospective Review ◽

Test Performance ◽

Predictive Value ◽

Reference Standard ◽

Paired Samples ◽

Oropharyngeal Swab ◽

Sensitivity Specificity

Abstract We compared oropharyngeal swab test performance with nasopharyngeal testing for discontinuation of transmission-based COVID-19 precautions. We performed a retrospective review of confirmed COVID-19-positive patients who received paired nasopharyngeal and oropharyngeal SARS-CoV-2 tests for clearance from isolation from May 4, 2020, to May 26, 2020. Using nasopharyngeal swabs as the reference standard, we calculated the sensitivity, specificity, and negative predictive value of oropharyngeal swabs. We also calculated the kappa between the 2 tests. A total of 189 paired samples were collected from 74 patients. Oropharyngeal swab sensitivity was 38%, specificity was 87%, and negative predictive value was 70%. The kappa was 0.25. Our study suggests that oropharyngeal swabs are inferior to nasopharyngeal swabs for test-based clearance from COVID-19 isolation.

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An investigation of new toxicity test method performance in validation studies: 2. comparison of three measures of toxicity test performance

Human & Experimental Toxicology ◽

10.1191/0960327102ht253oa ◽

2002 ◽

Vol 21 (6) ◽

pp. 313-323 ◽

Cited By ~ 7

Author(s):

L H Bruner ◽

G J Carr ◽

J W Harbell ◽

R D Curren

Keyword(s):

Test Performance ◽

Predictive Value ◽

Validation Studies ◽

Toxicity Test ◽

Prediction Interval ◽

Test Method ◽

Data Sets ◽

Method Performance ◽

Quantitative Measurements ◽

Sensitivity Specificity

An area that requires further research is how best to measure test method performance in validation studies and how to set criteria that should be used to judge the adequacy of this performance. The studies reported here were designed to begin an investigation of these questions. Computer simulations were used to generate data sets similar to those that might be obtained from a large validation study. These data were then analysed using three procedures including determination of the 95% prediction interval (PI), calculation of Pearson's correlation coefficient and calculation of the contingent probability statistics (CPS), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The results of this work suggest that of the three approaches examined, quantitative measurements with calculation of the 95% PI provide the most information to allow discrimination between the performance of several different NTMs. The results also suggest that dividing data sets into positive and negative toxicity classifications followed by the calculation of CPS leads to considerable information loss. This loss of information may be so significant that it is not possible in certain circumstances to distinguish between NTMs that are adequate and those that are not.

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Diagnostic Indexes of a Rapid IgG/IgM Combined Antibody Test for SARS-CoV-2

10.1101/2020.03.26.20044883 ◽

2020 ◽

Cited By ~ 17

Author(s):

Liu Ying ◽

Liu Yue-ping ◽

Diao Bo ◽

Ren Feifei ◽

Wang Yue ◽

...

Keyword(s):

Predictive Value ◽

Antibody Test ◽

Turnaround Time ◽

Ease Of Use ◽

Sample Collection ◽

Rt Pcr ◽

Illness Onset ◽

Test Kit ◽

Combined Test ◽

Sensitivity Specificity

[Abstract]ObjectiveCoronavirus disease 2019 (COVID-19) has become pandemic in the world. The need for IgG-IgM combined antibody test is booming, but data on diagnostic indexes evaluation was inadequate. The aim of this study was to evaluate diagnostic indexes of a rapid IgG-IgM combined antibody test for SARS-CoV-2.MethodsA total of 179 patients were enrolled. Serum were collected for IgG-IgM combined antibody test and corresponding nasal and pharyngeal swab specimens were collected for SARS-CoV-2 RT-PCR. According to SARS-CoV-2 RT-PCR results, patients under study were categorized as PCR positive group in 90 patients and PCR negative group in 89 patients.Results1. Of the 90 PCR positive samples, 77 were tested positive by SARS-CoV-2 IgG-IgM test kit, yielding a sensitivity of 85.6%. Meanwhile, of the 89 PCR negative sample, 8 samples were detected positive, resulting in a specificity of 91%. Positive predictive value, negative predictive value and accuracy of this test kit was 95.1%, 82.7%, and 88.3%, respectively. Kappa efficiency between IgG/IgM test kit and RT-PCR were 0.75. 2. Accuracy in mild/common and severe/critical subgroup were 73.9% and 97.7%, respectively. Accuracy in clinical confirmed, suspected cases and other disease subgroups were 70%, 60%, and 100%, respectively. 3. Patients were further divided into ‘0 - 7’, ‘8 - 15’ and ‘>= 16’ groups according to the time from illness onset to sample collection. Sensitivity, specificity and accuracy in these three groups were 18.8%, 77.8% and 40%; 100%, 50% and 87.5%; 100%, 64.3%, and 93.9, respectively.ConclusionThe sensitivity and specificity of this ease-of-use IgG/IgM combined test kit were adequate, plus short turnaround time, no specific requirements for additional equipment or skilled technicians, all of these collectively contributed to its competence for mass testing. At the current stage, it cannot take the place of SARA-CoV-2 nucleic acid RT-PCR, but can be served as a complementary option for RT-PCR. The combination of RT-PCR and IgG-IgM combined test kit could provide further insight into SARS-CoV-2 infection diagnosis.

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