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Systematic assessment of decision-analytic models evaluating diagnostic tests for acute myocardial infarction based on cardiac troponin assays. Veličković Vladica M,Rochau Ursula,Conrads-Frank Annette,Kee Frank,Blankenberg Stefan,Siebert Uwe Expert review of pharmacoeconomics & outcomes research INTRODUCTION:Despite the emphasis on the clinical importance of cardiac troponin assays (cTn), there are insufficient cost-effectiveness comparisons of various troponin test protocols for the diagnosis of myocardial infarction (MI). Therefore, the purpose of the review was to identify and systematically assess published economic evaluations using decision-analytic models for diagnostic testing strategies based on cTn and to make recommendations for the development of future models. AREAS COVERED:MEDLINE, Science Direct, Cochrane Database, CRD Database, and gray literature were screened for full economic evaluation studies with relevant clinical outcomes over a defined time horizon addressing a population with suspected MI and comparison of different diagnostic test strategies. Standardized forms for data extraction and evidence tables were used for the summary of study design, methodological framework and data sources. Studies were assessed for quality using the CHEERS and the BMJ checklists. EXPERT COMMENTARY:Although there are 11 identified studies and several well-designed models, there remains a need for decision-analytic models including differential diagnosis for acute MI, different health facility configurations, clinician preferences, and behavioral components, and in the top of the subgroup analyses additional important personalized medicine aspects. 10.1080/14737167.2018.1512857
Routine use of Staphylococcus aureus rapid diagnostic test in patients with suspected ventilator-associated pneumonia. Leone Marc,Malavieille François,Papazian Laurent,Meyssignac Bertrand,Cassir Nadim,Textoris Julien,Antonini François,La Scola Bernard,Martin Claude,Allaouchiche Bernard,Hraiech Sami, Critical care (London, England) INTRODUCTION:In patients with ventilator-associated pneumonia (VAP), administration of an appropriate empirical antimicrobial treatment is associated with improved outcomes, leading to the prescription of broad-spectrum antibiotics, including a drug active against methicillin resistant Staphylococcus aureus (MRSA). In order to avoid the overuse of antibiotics, the present study aimed to evaluate the technical characteristics of a rapid diagnostic test (Cepheid Xpert assay) in patients with suspected VAP. METHODS:From June 2011 to June 2012, in patients with suspected VAP, a sample from the bronchialalveolar lavage (BAL) or miniBAL was tested in a point-of-care laboratory for a rapid diagnostic test of methicillin susceptible Staphylococcus aureus (MSSA) and MRSA. Then, the result was compared to the quantitative culture with a threshold at 10⁴ colony-forming units per milliliter for bronchoalveolar lavage and 10³ colony-forming units per milliliter for minibronchoalveolar lavage. The study was performed in three intensive care units at two institutions. RESULTS:Four hundred, twenty-two samples from 328 patients were analyzed. The culture of 6 (1.1%) and 28 (6.5%) samples were positive for MRSA and MSSA. The test was not interpretable in 41 (9.3%) patients. The negative predictive values of the rapid detection test were 99.7% (98.1 to 99.9%) and 99.8% (98.7 to 99.9%) for MSSA and MRSA, respectively. CONCLUSION:The rapid diagnostic test is reliable in excluding the presence of MSSA and MRSA in the samples of patients with suspected VAP. Its utility should be regarded depending on the prevalence of MRSA. 10.1186/cc12849
Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological review of health technology assessments. Shinkins Bethany,Yang Yaling,Abel Lucy,Fanshawe Thomas R BMC medical research methodology BACKGROUND:Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. METHODS:We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. RESULTS:The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. CONCLUSIONS:The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests. 10.1186/s12874-017-0331-7
Rapid diagnostic tests for infectious diseases in the emergency department. Bouzid D,Zanella M-C,Kerneis S,Visseaux B,May L,Schrenzel J,Cattoir V Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases BACKGROUND:Rapid diagnostic tests (RDTs) for infectious diseases, with a turnaround time of less than 2 hours, are promising tools that could improve patient care, antimicrobial stewardship and infection prevention in the emergency department (ED) setting. Numerous RDTs have been developed, although not necessarily for the ED environment. Their successful implementation in the ED relies on their performance and impact on patient management. OBJECTIVES:The aim of this narrative review was to provide an overview of currently available RDTs for infectious diseases in the ED. SOURCES:PubMed was searched through August 2019 for available studies on RDTs for infectious diseases. Inclusion criteria included: commercial tests approved by the US Food and Drug Administration (FDA) or Conformité Européenne (CE) in vitro diagnostic devices with data on clinical samples, ability to run on fully automated systems and result delivery within 2 hours. CONTENT:A nonexhaustive list of representative commercially available FDA- or CE-approved assays was categorized by clinical syndrome: pharyngitis and upper respiratory tract infection, lower respiratory tract infection, gastrointestinal infection, meningitis and encephalitis, fever in returning travellers and sexually transmitted infection, including HIV. The performance of tests was described on the basis of clinical validation studies. Further, their impact on clinical outcomes and anti-infective use was discussed with a focus on ED-based studies. IMPLICATIONS:Clinicians should be familiar with the distinctive features of each RDT and individual performance characteristics for each target. Their integration into ED work flow should be preplanned considering local constraints of given settings. Additional clinical studies are needed to further evaluate their clinical effectiveness and cost-effectiveness. 10.1016/j.cmi.2020.02.024
Variation of a test's sensitivity and specificity with disease prevalence. Leeflang Mariska M G,Rutjes Anne W S,Reitsma Johannes B,Hooft Lotty,Bossuyt Patrick M M CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne BACKGROUND:Anecdotal evidence suggests that the sensitivity and specificity of a diagnostic test may vary with disease prevalence. Our objective was to investigate the associations between disease prevalence and test sensitivity and specificity using studies of diagnostic accuracy. METHODS:We used data from 23 meta-analyses, each of which included 10-39 studies (416 total). The median prevalence per review ranged from 1% to 77%. We evaluated the effects of prevalence on sensitivity and specificity using a bivariate random-effects model for each meta-analysis, with prevalence as a covariate. We estimated the overall effect of prevalence by pooling the effects using the inverse variance method. RESULTS:Within a given review, a change in prevalence from the lowest to highest value resulted in a corresponding change in sensitivity or specificity from 0 to 40 percentage points. This effect was statistically significant (p < 0.05) for either sensitivity or specificity in 8 meta-analyses (35%). Overall, specificity tended to be lower with higher disease prevalence; there was no such systematic effect for sensitivity. INTERPRETATION:The sensitivity and specificity of a test often vary with disease prevalence; this effect is likely to be the result of mechanisms, such as patient spectrum, that affect prevalence, sensitivity and specificity. Because it may be difficult to identify such mechanisms, clinicians should use prevalence as a guide when selecting studies that most closely match their situation. 10.1503/cmaj.121286
Rapid diagnostic tests for group A streptococcal pharyngitis: a meta-analysis. Lean Wei Ling,Arnup Sarah,Danchin Margie,Steer Andrew C Pediatrics BACKGROUND AND OBJECTIVE:Effective management of group A streptococcal (GAS) pharyngitis is hindered by impracticality of the gold standard diagnostic test: throat culture. Rapid antigen diagnostic tests (RADTs) are a promising alternative, although concerns about their sensitivity and specificity, and variation between test methodologies, have limited their clinical use. The objective of this study was to perform a systematic review with meta-analysis of the diagnostic accuracy of RADTs for GAS pharyngitis. METHODS:Medline and Embase from 1996 to 2013 were used as data sources. Of 159 identified studies, 48 studies of diagnostic accuracy of GAS RADTs using throat culture on blood agar as a reference standard were selected. Bivariate random-effects regression was used to estimate sensitivity and specificity with 95% confidence intervals (CIs). Additional meta-analyses were performed for pediatric data. RESULTS:A total of 60 pairs of sensitivity and specificity from 48 studies were included. Overall summary estimates for sensitivity and specificity of RADTs were 0.86 (95% CI 0.83 to 0.88) and 0.96 (95% CI 0.94 to 0.97), respectively, and estimates for pediatric data were similar. Molecular-based RADTs had the best diagnostic accuracy. Considerable variability exists in methodology between studies. There were insufficient studies to allow meta-regression/subgroup analysis within each test type. CONCLUSIONS:RADTs can be used for accurate diagnosis of GAS pharyngitis to streamline management of sore throat in primary care. RADTs may not require culture backup for negative tests in most low-incidence rheumatic fever settings. Newer molecular tests have the highest sensitivity, but are not true point-of-care tests. 10.1542/peds.2014-1094
Optimum binary cut-off threshold of a diagnostic test: comparison of different methods using Monte Carlo technique. Reibnegger Gilbert,Schrabmair Walter BMC medical informatics and decision making BACKGROUND:Using Monte Carlo simulations, we compare different methods (maximizing Youden index, maximizing mutual information, and logistic regression) for their ability to determine optimum binary cut-off thresholds for a ratio-scaled diagnostic test variable. Special attention is given to the stability and precision of the results in dependence on the distributional characteristics as well as the pre-test probabilities of the diagnostic categories in the test population. METHODS:Fictitious data sets of a ratio-scaled diagnostic test with different distributional characteristics are generated for 50, 100 and 200 fictitious "individuals" with systematic variation of pre-test probabilities of two diagnostic categories. For each data set, optimum binary cut-off limits are determined employing different methods. Based on these optimum cut-off thresholds, sensitivities and specificities are calculated for the respective data sets. Mean values and SD of these variables are computed for 1000 repetitions each. RESULTS:Optimizations of cut-off limits using Youden index and logistic regression-derived likelihood ratio functions with correct adaption for pre-test probabilities both yield reasonably stable results, being nearly independent from pre-test probabilities actually used. Maximizing mutual information yields cut-off levels decreasing with increasing pre-test probability of disease. The most precise results (in terms of the smallest SD) are usually seen for the likelihood ratio method. With this parametric method, however, cut-off values show a significant positive bias and, hence, specificities are usually slightly higher, and sensitivities are consequently slightly lower than with the two non-parametric methods. CONCLUSIONS:In terms of stability and bias, Youden index is best suited for determining optimal cut-off limits of a diagnostic variable. The results of Youden method and likelihood ratio method are surprisingly insensitive against distributional differences as well as pre-test probabilities of the two diagnostic categories. As an additional bonus of the parametric procedure, transfer of the likelihood ratio functions, obtained from logistic regression analysis, to other diagnostic scenarios with different pre-test probabilities is straightforward. 10.1186/s12911-014-0099-1
Clinical utilization of multiple antibodies of for serodiagnosis evaluation of tuberculosis: a retrospective observational cohort study. Annals of medicine OBJECTIVES:We aimed to investigate clinical uncertainties by characterizing the accuracy and utility of commercially available antibodies of in the diagnostic assessment of suspected tuberculosis in high-burden countries. METHODS:We conducted a retrospective, descriptive, cohort study among participants aged ≥ 18 years with suspected tuberculosis in Nanning, Guangxi, and China. Participants were tested for infection using commercially available antibodies against . Specificity, sensitivity, negative and positive predictive values, and negative and positive likelihood ratios of the tests were determined. Sputum specimens and bronchoalveolar lavage fluid were sent for mycobacterial culture, Xpert MTB/RIF assay, and cell-free M. tuberculosis DNA or RNA assay. Blood samples were used for IGRAs, T-cell counts (CD3 + CD4+ and CD3 + CD8+), and antibodies to tuberculosis test. RESULTS:Of the 1857 participants enrolled in this study, 1772 were included in the analyses, among which, 1311 were diagnosed with active tuberculosis. The specificity of antibody against 16kD for active tuberculosis was 92.7% (95% confidence interval [CI]: 89.3-95.4) with a positive likelihood ratio for active tuberculosis cases of 3.1 (95% CI: 2.1-4.7), which was higher than that of antibody to Rv1636 (90.5% [95% CI: 86.6-93.5]), antibody to 38kD (89.5% [95% CI: 85.5-92.7]), antibody against CFP-10 (82.6% [95% CI: 77.9-86.7]), and antibody against LAM (79.3% [95% CI: 74.3-83.7]). Sensitivity ranged from 15.8% (95% CI: 13.9-17.9) for antibody against Rv1636 to 32.9% (95% CI: 30.4-35.6) for antibody to LAM. CONCLUSIONS:Commercially available antibodies against to do not have sufficient sensitivity for the diagnostic evaluation of active tuberculosis. However, antibody against Rv1636 and 16kD may have sufficiently high specificities, high positive likelihood ratios, and correspondingly high positive predictive values to facilitate the rule-in of active tuberculosis. 10.1080/07853890.2023.2238186
Impact of Point-of-Care Rapid Diagnostic Tests on Antibiotic Prescription Among Patients Aged <18 Years in Primary Healthcare Settings in 2 Peri-Urban Districts in Ghana: Randomized Controlled Trial Results. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America BACKGROUND:Inappropriate antibiotic prescriptions are a known driver of antimicrobial resistance in settings with limited diagnostic capacity. This study aimed to assess the impact of diagnostic algorithms incorporating rapid diagnostic tests on clinical outcomes and antibiotic prescriptions compared with standard-of-care practices, of acute febrile illness cases at outpatient clinics in Shai-Osudoku and Prampram districts in Ghana. METHODS:This was an open-label, centrally randomized controlled trial in 4 health facilities. Participants aged 6 months to <18 years of both sexes with acute febrile illness were randomized to receive a package of interventions to guide antibiotic prescriptions or standard care. Clinical outcomes were assessed on day 7. RESULTS:In total, 1512 patients were randomized to either the intervention (n = 761) or control (n = 751) group. Majority were children aged <5 years (1154 of 1512, 76.3%) and male (809 of 1512, 53.5%). There was 11% relative risk reduction of antibiotic prescription in intervention group (RR, 0.89; 95% CI, .79 to 1.01); 14% in children aged <5 years (RR, 0.86; 95% CI, .75 to .98), 15% in nonmalaria patients (RR, 0.85; 95% CI, .75 to .96), and 16% in patients with respiratory symptoms (RR, 0.84; 95% CI, .73 to .96). Almost all participants had favorable outcomes (759 of 761, 99.7% vs 747 of 751, 99.4%). CONCLUSIONS:In low- and middle-income countries, the combination of point-of-care diagnostics, diagnostic algorithms, and communication training can be used at the primary healthcare level to reduce antibiotic prescriptions among children with acute febrile illness, patients with nonmalarial fevers, and respiratory symptoms. CLINICAL TRIALS REGISTRATION:NCT04081051. 10.1093/cid/ciad328
Diagnosis and features of hospital-acquired pneumonia: a retrospective cohort study. Russell C D,Koch O,Laurenson I F,O'Shea D T,Sutherland R,Mackintosh C L The Journal of hospital infection BACKGROUND:Hospital-acquired pneumonia (HAP) is defined as radiologically confirmed pneumonia occurring ≥48h after hospitalization, in non-intubated patients. Empirical treatment regimens use broad-spectrum antimicrobials. AIM:To evaluate the accuracy of the diagnosis of HAP and to describe the demographic and microbiological features of patients with HAP. METHODS:Medical and surgical inpatients receiving intravenous antimicrobials for a clinical diagnosis of HAP at a UK tertiary care hospital between April 2013 and 2014 were identified. Demographic and clinical details were recorded. FINDINGS:A total of 166 adult patients with a clinical diagnosis of HAP were identified. Broad-spectrum antimicrobials were prescribed, primarily piperacillin-tazobactam (57.2%) and co-amoxiclav (12.5%). Sputum from 24.7% of patients was obtained for culture. Sixty-five percent of patients had radiological evidence of new/progressive infiltrate at the time of HAP treatment, therefore meeting HAP diagnostic criteria (2005 American Thoracic Society/Infectious Diseases Society of America guidelines). Radiologically confirmed HAP was associated with higher levels of inflammatory markers and sputum culture positivity. Previous surgery and/or endotracheal intubation were associated with radiologically confirmed HAP. A bacterial pathogen was identified from 17/35 sputum samples from radiologically confirmed HAP patients. These were Gram-negative bacilli (N = 11) or Staphylococcus aureus (N = 6). Gram-negative bacteria tended to be resistant to co-amoxiclav, but susceptible to ciprofloxacin, piperacillin-tazobactam and meropenem. Five of the six S. aureus isolates were meticillin susceptible and all were susceptible to doxycycline. CONCLUSION:In ward-level hospital practice 'HAP' is an over-used diagnosis that may be inaccurate in 35% of cases when objective radiological criteria are applied. Radiologically confirmed HAP represents a distinct clinical and microbiological phenotype. Potential risk factors were identified that could represent targets for preventive interventions. 10.1016/j.jhin.2015.11.013
PET-CT has low specificity for mediastinal staging of non-small-cell lung cancer in an endemic area for tuberculosis: a diagnostic test study (LACOG 0114). Werutsky Gustavo,Hochhegger Bruno,Lopes de Figueiredo Pinto José Antônio,Martínez-Mesa Jeovany,Zanini Mara Lise,Berdichevski Eduardo Herz,Vilas Eduardo,da Silva Vinícius Duval,Tsukazan Maria Teresa Ruiz,Vieira Arthur,Fritscher Leandro Genehr,Hartmann Louise,Alba Marcos,Sartori Guilherme,Matushita Cristina,Bortolotto Vanessa,do Amaral Rayssa Ruszkowski,Junior Luís Carlos Anflor,Zaffaroni Facundo,Barrios Carlos H,Debiasi Márcio,Frietscher Carlos Cezar BMC cancer BACKGROUND:The present study aims to assess the performance of 18F-FDG PET-CT on mediastinal staging of non-small cell lung cancer (NSCLC) in a location with endemic granulomatous infectious disease. METHODS:Diagnostic test study including patients aged 18 years or older with operable stage I-III NSCLC and indication for a mediastinal lymph node biopsy. All patients underwent a 18F-FDG PET-scan before invasive mediastinal staging, either through mediastinoscopy or thoracotomy, which was considered the gold-standard. Surgeons and pathologists were blinded for scan results. Primary endpoint was to evaluate sensitivity, specificity and positive and negative predictive values of PET-CT with images acquired in the 1st hour of the exam protocol, using predefined cutoffs of maximal SUV, on per-patient basis. RESULTS:Overall, 85 patients with operable NSCLC underwent PET-CT scan followed by invasive mediastinal staging. Mean age was 65 years, 49 patients were male and 68 were white. One patient presented with active tuberculosis and none had HIV infection. Using any SUV_max > 0 as qualitative criteria for positivity, sensitivity and specificity were 0.87 and 0.45, respectively. Nevertheless, even when the highest SUV cut-off was used (SUV_max ≥5), specificity remained low (0.79), with an estimated positive predictive value of 54%. CONCLUSIONS:Our findings are in line with the most recent publications and guidelines, which recommend that PET-CT must not be solely used as a tool to mediastinal staging, even in a region with high burden of tuberculosis. TRIAL REGISTRATION:The LACOG 0114 study was registered at ClinicalTrials.gov , before study initiation, under identifier NCT02664792. 10.1186/s12885-018-5233-5
Ferritin levels in children with juvenile idiopathic arthritis of systemic onset and children with other causes of fever of unknown origin: A multicenter study of diagnostic tests Eraso Ruth,Benítez Claudia Patricia,Jaramillo Sergio,Acosta-Reyes Jorge,Aristizábal Beatriz Helena,Quevedo Augusto Biomedica : revista del Instituto Nacional de Salud Introduction: There are no sensitive or specific tests available to diagnose systemic juvenile idiopathic arthritis (sJIA).Objective: To assess the utility as diagnostic tests of total ferritin (TF) levels greater than 5 times the normal value (TF>5N) and the decreased percentage (less than or equal to 20% of TF) of glycosylated ferritin (GF≤20%) for the diagnosis of sJIA in patients with fever of unknown origin evaluated by pediatric rheumatology.Materials and methods: We conducted an observational, cross-sectional study of diagnostic tests in children under 16 years of age hospitalized between 2010 and 2014. The reference diagnostic standard was the fulfillment of the classification criteria or confirmed diagnosis at follow-up. We determined the measures of utility of the tests.Results: We included 40 patients with fever of unknown origin, 11 with sJIA, and 29 with other diagnoses. The median TF was higher in sAIJ (3992 ng/ml) versus other causes of fever of unknown origin (155 ng/ml) (p=0.0027), as well as TF>5N (90.91% versus 51.72%) (p=0.023). The percentage of GF≤20% was higher in patients with other causes of fever of unknown origin (96.5%) compared to sJIA (81.8%) (p=0.178). TF>5N had a sensitivity of 91%, specificity of 48%, positive likelihood ratio (LR) of 1.76, and negative LR of 0.19 demonstrating greater utility for the diagnosis of sJIA than the combination of FT> 5N with GFR <20%, with a sensitivity of 81.8%, specificity of 48.3%, positive LR of 1.58, and negative LR of 0.38.Conclusion: In patients with FUO evaluated by pediatric rheumatology, TF> 5N proved useful as a screening test for the diagnosis of sJIA. 10.7705/biomedica.5849
Validation and reliability of the rapid diagnostic test 'SD Bioeasy Dengue Duo' for dengue diagnosis in Brazil: a phase III study. Prado Paulo Sousa,Almeida Júnior José Teófilo Duarte,Abreu Lanna Takada de,Silva Cristina Gabriel,Souza Larissa da Costa,Gomes Marizoneide Cavalcante,Mendes Lucinda Malheiros Teixeira,Santos Eliane Maria Dos,Romero Gustavo Adolfo Sierra Memorias do Instituto Oswaldo Cruz BACKGROUND:The diagnosis of dengue is complex. Until recently, only specialised laboratories were able to confirm dengue infection. However, this has changed with the newly available immunochromatographic rapid tests. Early diagnosis is of great interest, and point-of-care rapid tests have been increasingly used in Brazil. Most of those tests have not undergone validation in the Brazilian population. In this context, we decided to evaluate a rapid test introduced in the Federal District (FD). OBJECTIVES:To estimate the accuracy and reliability of the SD Bioeasy Dengue Duo rapid test and its components to detect dengue infections in a consecutive sample of symptomatic residents in the FD, Brazil. METHODS:In total, 1353 venous blood samples were collected between 2013 and 2014. Two hundred and six positive samples (cases) and 246 negative samples (non cases) were required for sensitivity and specificity estimation, respectively; for agreement evaluation, we used 401 samples. The reference standard used was a composite of MAC-ELISA, virus isolation and real-time polymerase chain reaction (RT-qPCR). The evaluation was conducted prospectively under field conditions in the public health units of the FD. FINDINGS:The results for the overall accuracy of the rapid test (NS1/IgM combined) showed 76% sensitivity and 98% specificity. The sensitivity for the NS1 component (67%) was better than that for the IgM component (35%). The positive likelihood ratio was 46, and the negative likelihood ratio was 0.24. The reliability of the test (NS1/IgM combined) demonstrated crude agreement of 98% (Kappa index 0.94). MAIN CONCLUSIONS:The present phase III, large-scale validation study demonstrates that the rapid test SD Bioeasy Dengue Duo has moderate sensitivity (NS1/IgM combined) and high specificity. Therefore, the test is useful in confirming the diagnosis of dengue, but not enough to rule out the diagnosis. Our results also suggest that Dengue virus (DENV) viral load estimated through the RT-qPCR and antibody level measured through the MAC-ELISA could have had a direct influence on the accuracy of the rapid test. 10.1590/0074-02760170433
More Accurate Diagnosis of Vitreoretinal Lymphoma Using a Combination of Diagnostic Test Results: A Prospective Observational Study. Ocular immunology and inflammation PURPOSE:To establish diagnostic criteria for vitreoretinal lymphoma (VRL) using cytology and laboratory tests from vitreous samples: interleukin (IL)-10/IL-6 ratio, immunoglobulin (Ig) H gene rearrangement, and clonal B-cells on flow cytometry. METHODS:Fifty-six patients with and 39 without VRL were included. We assessed the sensitivity and specificity of each test and those of diagnostic criteria based on combinations of these tests. RESULTS:The sensitivity values for malignant cytology, IL-10/IL-6 > 1, IgH gene rearrangement, and flow cytometry were 0.554, 0.821, 0.732, and 0.625 with specificity of 1.000, 1.000, 0.846, and 0.974, respectively. When the diagnostic criteria were set at malignant cytology or at two or more of of four tests (atypical cells, IL-10/IL-6 > 1, IgH gene rearrangement, and flow cytometry), the sensitivity and specificity values for accurate diagnosis were 0.929 and 1.00, respectively. CONCLUSION:Malignant cytology or positive results for two or more of four tests may be adequate for VRL diagnosis. 10.1080/09273948.2021.1873394
A Pragmatic Study to Evaluate the Use of a Rapid Diagnostic Test to Detect Group A Streptococcal Pharyngitis in Children With the Aim of Reducing Antibiotic Use in a UK Emergency Department. Pediatric emergency care OBJECTIVE:Sore throat is a common presentation to the children's emergency department (ED), and many patients are likely prescribed antibiotics unnecessarily. We aimed to reduce antibiotic prescribing for sore throat in our UK ED through use of an established scoring system combined with a rapid diagnostic test (RDT) to detect group A streptococcal (GAS) pharyngitis. METHODS:AB single-subject and diagnostic accuracy studies were used to measure both antibiotic prescribing rates over time and the performance of the McIsaac clinical score combined with RDT to screen for and treat GAS pharyngitis. All children between the age of 6 months and 16 years with symptoms of sore throat were eligible for inclusion. The study adhered to SQUIRE guidelines. RESULTS:During 2014 and 2016, antibiotic prescribing rates for 210 children at baseline (median age, 3 years) and 395 children during the intervention (median age, 2 years) were assessed. The baseline prescribing rate was 79%, whereas rates after intervention were 24% and 27%, respectively. The RDT had an acceptable false-negative rate of 7.9%, poor sensitivity of 64.3%, and a negative predictive value of 92.1% when compared with conventional throat culture. A McIsaac score of 3 or more had good sensitivity (92.11%) but very low specificity (12.62%) for predicting GAS infection. CONCLUSIONS:Despite poor RDT sensitivity and the McIsaac score's poor specificity in children, their use in combination decreased antibiotic prescribing rates in a children's ED setting. 10.1097/PEC.0000000000001560
Development of machine learning support for reading whole body diffusion-weighted MRI (WB-MRI) in myeloma for the detection and quantification of the extent of disease before and after treatment (MALIMAR): protocol for a cross-sectional diagnostic test accuracy study. BMJ open INTRODUCTION:Whole-body MRI (WB-MRI) is recommended by the National Institute of Clinical Excellence as the first-line imaging tool for diagnosis of multiple myeloma. Reporting WB-MRI scans requires expertise to interpret and can be challenging for radiologists who need to meet rapid turn-around requirements. Automated computational tools based on machine learning (ML) could assist the radiologist in terms of sensitivity and reading speed and would facilitate improved accuracy, productivity and cost-effectiveness. The MALIMAR study aims to develop and validate a ML algorithm to increase the diagnostic accuracy and reading speed of radiological interpretation of WB-MRI compared with standard methods. METHODS AND ANALYSIS:This phase II/III imaging trial will perform retrospective analysis of previously obtained clinical radiology MRI scans and scans from healthy volunteers obtained prospectively to implement training and validation of an ML algorithm. The study will comprise three project phases using approximately 633 scans to (1) train the ML algorithm to identify active disease, (2) clinically validate the ML algorithm and (3) determine change in disease status following treatment via a quantification of burden of disease in patients with myeloma. Phase 1 will primarily train the ML algorithm to detect active myeloma against an expert assessment ('reference standard'). Phase 2 will use the ML output in the setting of radiology reader study to assess the difference in sensitivity when using ML-assisted reading or human-alone reading. Phase 3 will assess the agreement between experienced readers (with and without ML) and the reference standard in scoring both overall burden of disease before and after treatment, and response. ETHICS AND DISSEMINATION:MALIMAR has ethical approval from South Central-Oxford C Research Ethics Committee (REC Reference: 17/SC/0630). IRAS Project ID: 233501. CPMS Portfolio adoption (CPMS ID: 36766). Participants gave informed consent to participate in the study before taking part. MALIMAR is funded by National Institute for Healthcare Research Efficacy and Mechanism Evaluation funding (NIHR EME Project ID: 16/68/34). Findings will be made available through peer-reviewed publications and conference dissemination. TRIAL REGISTRATION NUMBER:NCT03574454. 10.1136/bmjopen-2022-067140
Clinical examination for hyperlinear palms to determine filaggrin genotype: A diagnostic test accuracy study. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology BACKGROUND:Palmar hyperlinearity is a feature of ichthyosis vulgaris, the monogenic skin disorder caused by FLG loss-of-function mutations. OBJECTIVE:To investigate how well the presence or absence of hyperlinear palms (HLP) detect FLG genotype in children. METHODS:STARD criteria are used to report this diagnostic accuracy study. Phenotype and genotype data (four most prevalent FLG null mutations) were obtained from a total of 3656 children in three studies: the UK CLOTHES trial (children 1-5 years with moderate-severe atopic eczema); UK BEEP trial (2 year olds at high risk of developing atopic eczema); UK-Irish eczema case collection (0-16 year olds with atopic eczema). All participants included in analyses of HLP as the index test and FLG genotype as the reference were of white European ancestry. RESULTS:Thirty-two percent of participants (1159/3656) had FLG null mutation(s) and 37% (1347/3656) had HLP. In 13% (464/3656), HLP was recorded as 'unsure' or not recorded. The sensitivity and specificity of HLP for detecting FLG mutations in each of the studies was: 67% (95% CI 55-78%) and 75% (67-82%) in CLOTHES; 46% (36-55%) and 89% (86-91%) in BEEP; 72% (68-75%) and 60% (57-62%) in the UK-Irish case collection. Positive and negative likelihood ratios were: 2.73 (1.95-3.81) and 0.44 (0.31-0.62) in CLOTHES; 4.02 (2.99-5.40) and 0.61 (0.52-0.73) in BEEP; 1.79 (1.66-1.93) and 0.47 (0.42-0.53) in the UK-Irish collection. DISCUSSION:Trained observers were able to define palmar hyperlinearity in the majority (3191/3656, 87%) of cases. The presence of HLP is not a reliable sign to detect FLG mutations, but the absence of HLP excludes FLG null genotype with a reasonable degree of certainty. 10.1111/cea.14025
Adapting Rapid Diagnostic Tests to Detect Historical Dengue Virus Infections. Frontiers in immunology The only licensed dengue vaccine, Dengvaxia, increases risk of severe dengue when given to individuals without prior dengue virus (DENV) infection but is protective against future disease in those with prior DENV immunity. The World Health Organization has recommended using rapid diagnostic tests (RDT) to determine history of prior DENV infection and suitability for vaccination. Dengue experts recommend that these assays be highly specific (≥98%) to avoid erroneously vaccinating individuals without prior DENV infection, as well as be sensitive enough (≥95%) to detect individuals with a single prior DENV infection. We evaluated one existing and two newly developed anti-flavivirus RDTs using samples collected >6 months post-infection from individuals in non-endemic and DENV and ZIKV endemic areas. We first evaluated the IgG component of the SD BIOLINE Dengue IgG/IgM RDT, which was developed to assist in confirming acute/recent DENV infections (n=93 samples). When evaluated following the manufacturer's instructions, the SD BIOLINE Dengue RDT had 100% specificity for both non-endemic and endemic samples but low sensitivity for detecting DENV seropositivity (0% non-endemic, 41% endemic). Sensitivity increased (53% non-endemic, 98% endemic) when tests were allowed to run beyond manufacturer recommendations (0.5 up to 3 hours), but specificity decreased in endemic samples (36%). When tests were evaluated using a quantitative reader, optimal specificity could be achieved (≥98%) while still retaining sensitivity at earlier timepoints in non-endemic (44-88%) and endemic samples (31-55%). We next evaluated novel dengue and Zika RDTs developed by Excivion to detect prior DENV or ZIKV infections and reduce cross-flavivirus reactivity (n=207 samples). When evaluated visually, the Excivion Dengue RDT had sensitivity and specificity values of 79%, but when evaluated with a quantitative reader, optimal specificity could be achieved (≥98%) while still maintaining moderate sensitivity (48-75%). The Excivion Zika RDT had high specificity (>98%) and sensitivity (>93%) when evaluated quantitatively, suggesting it may be used alongside dengue RDTs to minimize misclassification due to cross-reactivity. Our findings demonstrate the potential of RDTs to be used for dengue pre-vaccination screening to reduce vaccine-induced priming for severe dengue and show how assay design adaptations as well quantitative evaluation can further improve RDTs for this purpose. 10.3389/fimmu.2021.703887
Effect of Timing by Endometrial Receptivity Testing vs Standard Timing of Frozen Embryo Transfer on Live Birth in Patients Undergoing In Vitro Fertilization: A Randomized Clinical Trial. JAMA Importance:Endometrial receptivity testing is purported to improve live birth following frozen embryo transfer by identifying the optimal embryo transfer time for an individual patient; however, data are conflicting. Objective:To compare live birth from single euploid frozen embryo transfer according to endometrial receptivity testing vs standardized timing. Design, Setting, and Participants:Double-blind, randomized clinical trial at 30 sites within a multicenter private fertility practice in the Eastern US. Enrollment was from May 2018 to September 2020; follow-up concluded in August 2021. Participants underwent in vitro fertilization, preimplantation genetic testing for aneuploidy, endometrial receptivity testing, and frozen embryo transfer. Those with euploid blastocyst(s) and an informative receptivity result were randomized. Exclusion criteria included recurrent pregnancy loss, recurrent implantation failure, surgically aspirated sperm, donor egg(s), and unmitigated anatomic uterine cavity defects. Interventions:The intervention group (n = 381) underwent receptivity-timed frozen embryo transfer, with adjusted duration of progesterone exposure prior to transfer, if indicated by receptivity testing. The control group (n = 386) underwent transfer at standard timing, regardless of receptivity test results. Main Outcomes and Measures:The primary outcome was live birth. There were 3 secondary outcomes, including biochemical pregnancy and clinical pregnancy. Results:Among 767 participants who were randomized (mean age, 35 years), 755 (98%) completed the trial. All randomized participants were analyzed. The primary outcome of live birth occurred in 58.5% of transfers (223 of 381) in the intervention group vs 61.9% of transfers (239 of 386) in the control group (difference, -3.4% [95% CI, -10.3% to 3.5%]; rate ratio [RR], 0.95 [95% CI, 0.79 to 1.13]; P = .38). There were no significant differences in the intervention vs the control group for the prespecified secondary outcomes, including biochemical pregnancy rate (77.2% vs 79.5%, respectively; difference, -2.3% [95% CI, -8.2% to 3.5%]; RR, 0.97 [95% CI, 0.83 to 1.14]; P = .48) and clinical pregnancy rate (68.8% vs 72.8%, respectively; difference, -4.0% [95% CI, -10.4% to 2.4%]; RR, 0.94 [95% CI, 0.80 to 1.12]; P = .25). There were no reported adverse events. Conclusions and Relevance:Among patients for whom in vitro fertilization yielded a euploid blastocyst, the use of receptivity testing to guide the timing of frozen embryo transfer, compared with standard timing for transfer, did not significantly improve the rate of live birth. The findings do not support routine use of receptivity testing to guide the timing of embryo transfer during in vitro fertilization. Trial Registration:ClinicalTrials.gov Identifier: NCT03558399. 10.1001/jama.2022.20438
Clinical Impact of Metagenomic Next-Generation Sequencing of Bronchoalveolar Lavage in the Diagnosis and Management of Pneumonia: A Multicenter Prospective Observational Study. Zhou Hua,Larkin Paige M K,Zhao Dongdong,Ma Qiang,Yao Yake,Wu Xiaohong,Wang Jiaoli,Zhou XiaoHu,Li Yaqing,Wang Gang,Feng Malong,Wu Lei,Chen Jinyin,Zhou Changsheng,Hua Xiaoting,Zhou Jianying,Yang Shangxin,Yu Yunsong The Journal of molecular diagnostics : JMD Rapid and accurate pathogen identification is necessary for appropriate treatment of pneumonia. Here, we describe the use of shotgun metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage for pathogen identification in pneumonia in a large-scale multicenter prospective study with 159 patients enrolled. The results of mNGS were compared with standard methods including culture, staining, and targeted PCR, and the clinical impact of mNGS was evaluated. A positive impact was defined by a definitive diagnosis made using the mNGS results, or change of management because of the mNGS results, leading to a favorable clinical outcome. Overall, mNGS identified more organisms than standard methods (117 versus 72), detected 17 pathogens that consistently were missed in all cases by standard methods, and had an overall positive clinical impact in 40.3% (64 of 159) of cases. mNGS was especially useful in identification of fastidious and atypical organisms causing pneumonia, contributing to detection of definitive pathogens in 45 (28.3%) cases in which standard results were either negative or insufficient. mNGS also helped reassure antibiotic de-escalation in 19 (11.9%) cases. Overall, mNGS led to a change of treatment in 59 (37.1%) cases, including antibiotic de-escalation in 40 (25.2%) cases. This study showed the significant value of mNGS of bronchoalveolar lavage for improving the diagnosis of pneumonia and contributing to better patient care. 10.1016/j.jmoldx.2021.06.007
Uptake of newer methodological developments and the deployment of meta-analysis in diagnostic test research: a systematic review. BMC medical research methodology BACKGROUND:The last decade has seen a number of methodological developments in meta-analysis of diagnostic test studies. However, it is unclear whether such developments have permeated the wider research community and on which applications they are being deployed. The objective was to assess the uptake and deployment of the main methodological developments in the meta-analysis of diagnostic tests, and identify the tests and target disorders most commonly evaluated by meta-analysis. METHODS:Design--systematic review. Data Sources--Medline, EMBASE, CINAHL, Cochrane, PsychInfo, Global health, HMIC, and AMED were searched for studies published before 31st December 2008. Selection criteria--studies were included if they satisfied all of the following: evaluated a diagnostic test; measured test performance; searched two or more databases; stated search terms and inclusion criteria; used a statistical method to summarise performance. Data extraction--included the following data items: year; test; reference standard; target disorder; setting; statistical and quality methods. RESULTS:236 studies were included. Over the last 5 years the number of meta-analyses published has increased, but the uptake of new statistical methods lags behind. Pooling the sensitivity and specificity and using the SROC remain the preferred methods for analysis in 70% of studies, with the bivariate random effects and HSROC model being used in only 22% and 5% of studies respectively. In contrast, between 2006 and 2008 the QUADAS tool was used in 40% of studies. Broadly, radiological imaging was the most frequent category of tests analysed (36%), with cancer (22%) and infection (21%) being the most common categories of target disorder. Nearly 80% of tests analysed were those normally used in specialist settings. CONCLUSION:Although quality assessment in meta-analyses has improved with the introduction of QUADAS, uptake of the newer statistical methods is still lagging behind. Furthermore, the focus of secondary research seems to be in evaluating specialist tests in specialist settings, in contrast to the more routine tests and settings encountered in the majority of clinical practice. 10.1186/1471-2288-11-27
Nephroscreen: a diagnostic test for predicting acute renal failure? Howard Marion A Expert review of molecular diagnostics Acute renal failure is a frequent and often fatal complication of hospitalized patients. While the risk of acute renal failure among select patient groups is well recognized, physicians currently rely on diagnostic tests such as changes of serum creatinine and indirect assessment of the glomerular filtration rate to diagnose acute renal failure. Although these parameters capture the degree of kidney function lost, they are not warning signs of evolving kidney injury. While the clinical emergence of acute renal failure is sudden, the pathologic changes preceding loss of kidney function are not so sudden. Nephroscreen is a fast and easy-to-use urine enzyme-linked immunosorbent assay test designed to quantify specific pathologic events preceding death of renal proximal tubule cells. It detects acute kidney damage days before serum creatinine rises and may open new avenues to defining acute renal failure as well as treating acute renal failure patients earlier and more effectively. 10.1586/14737159.5.5.633
Diagnostic test interpretation and referral delay in patients with interstitial lung disease. Pritchard David,Adegunsoye Ayodeji,Lafond Elyse,Pugashetti Janelle Vu,DiGeronimo Ryan,Boctor Noelle,Sarma Nandini,Pan Isabella,Strek Mary,Kadoch Michael,Chung Jonathan H,Oldham Justin M Respiratory research BACKGROUND:Diagnostic delays are common in patients with interstitial lung disease (ILD). A substantial percentage of patients experience a diagnostic delay in the primary care setting, but the factors underpinning this observation remain unclear. In this multi-center investigation, we assessed ILD reporting on diagnostic test interpretation and its association with subsequent pulmonology referral by a primary care physician (PCP). METHODS:A retrospective cohort analysis of patients referred to the ILD programs at UC-Davis and University of Chicago by a PCP within each institution was performed. Computed tomography (CT) of the chest and abdomen and pulmonary function test (PFT) were reviewed to identify the date ILD features were first present and determine the time from diagnostic test to pulmonology referral. The association between ILD reporting on diagnostic test interpretation and pulmonology referral was assessed, as was the association between years of diagnostic delay and changes in fibrotic features on longitudinal chest CT. RESULTS:One hundred and forty-six patients were included in the final analysis. Prior to pulmonology referral, 66% (n = 97) of patients underwent chest CT, 15% (n = 21) underwent PFT and 15% (n = 21) underwent abdominal CT. ILD features were reported on 84, 62 and 33% of chest CT, PFT and abdominal CT interpretations, respectively. ILD reporting was associated with shorter time to pulmonology referral when undergoing chest CT (1.3 vs 15.1 months, respectively; p = 0.02), but not PFT or abdominal CT. ILD reporting was associated with increased likelihood of pulmonology referral within 6 months of diagnostic test when undergoing chest CT (rate ratio 2.17, 95% CI 1.03-4.56; p = 0.04), but not PFT or abdominal CT. Each year of diagnostic delay was associated with a 1.8% increase in percent fibrosis on chest CT. Patients with documented dyspnea had shorter time to chest CT acquisition and pulmonology referral than patients with documented cough and lung crackles. CONCLUSIONS:Determinants of ILD diagnostic delays in the primary care setting include underreporting of ILD features on diagnostic testing and prolonged time to pulmonology referral even when ILD is reported. Interventions to modulate these factors may reduce ILD diagnostic delays in the primary care setting. 10.1186/s12931-019-1228-2
Circulating Endometrial Cells: A Diagnostic Test for Distinguishing Catamenial From Spontaneous Pneumothorax? Manaker Scott Chest 10.1016/j.chest.2019.10.036