True Negative Test Research Articles

Comparative Analysis of the Clarus Aspergillus Galactomannan Enzyme Immunoassay Prototype for the Diagnosis of Invasive Pulmonary Aspergillosis in Bronchoalveolar Lavage Fluid

BackgroundGalactomannan (GM) testing using Platelia Aspergillus enzyme immunoassay (Platelia AGM) from bronchoalveolar lavage fluid (BALF) aids in early diagnosis of invasive pulmonary aspergillosis (IPA). Globally, only a minority of laboratories have the capability to perform on-site GM testing, necessitating accessible and affordable alternatives. Hence, we conducted a comparative evaluation of the new clarus Aspergillus GM enzyme immunoassay prototype (clarus AGM prototype) with Platelia AGM using BALF samples.MethodsThis is a single-center, prospective, cross-sectional study, where Platelia AGM testing was routinely performed followed by clarus AGM prototype testing in those with true positive or true negative AGM test results according to the 2020 EORTC/MSG and the 2024 FUNDICU consensus definitions. Descriptive statistics, ROC curve analysis, and Spearman’s correlation analysis were used to evaluate analytical performance of the clarus AGM prototype assay.ResultsThis study enrolled 259 adult patients, of which 53 (20%) were classified as probable IPA, while 206 did not fulfill IPA-criteria. Spearman's correlation analysis revealed a strong correlation between the two assays (rho = 0.727, p < 0.001). The clarus AGM prototype had a sensitivity of 96% (51/53) and a specificity of 74% (153/206) for differentiating probable versus no IPA when using the manufacturer recommended cut-off. ROC curve analysis showed an AUC of 0.936 (95% CI 0.901–0.971) for the clarus AGM prototype, while the Platelia AGM yielded an AUC of 0.918 (95% CI 0.876–0.959).ConclusionsClarus AGM prototype demonstrated a strong correlation and promising test performance, comparable to Platelia AGM, rendering it a viable alternative in patients at risk of IPA.

Efficiency assessment of a two-stage diagnostic strategy combining CT angiography and fractional flow reserve derived from coronary CT angiography for the detection of myocardial ischemia: a simulation study

BackgroundThe importance of a diagnostic strategy combining coronary computed tomography angiography (CCTA) with fractional flow reserve derived from CCTA (FFRCT) for detecting myocardial ischemia is increasing. However, sensitivity and specificity alone may be insufficient to understand the efficiency characteristics of a diagnostic strategy combining CCTA and FFRCT (DSCCF). Our study aimed to evaluate the overall efficiency of DSCCF in detecting myocardial ischemia and compare it with other diagnostic strategies to determine whether evaluation by DSCCF is currently appropriate.ResultsThis simulation study included 1000 patients with stable chest pain and suspected myocardial ischemia. Using a decision tree analysis, assuming a diagnostic strategy of adding FFRCT to CCTA-positive patients, we calculated the following efficiency parameters of DSCCF: (1) true positive (TP), false positive (FP), net false negative (FN), and net true negative (TN) test results; (2) net sensitivity; (3) net specificity; (4) positive predictive value; (5) negative predictive value; (6) post-test probability; (7) diagnostic accuracy; (8) diagnostic odds ratio; and (9) number needed to diagnose. We also calculated the efficiency parameters of other diagnostic strategies and compared them with those of DSCCF. In the basic setting, regarding efficiency parameters (1), the number of TPs, FPs, net FNs, and net TNs were 254, 69, 46, and 631, respectively. Efficiency parameters (2)–(9) were 0.85 (95% confidence interval [CI], 0.80–0.89), 0.90 (95% CI 0.88–0.92), 0.79 (95% CI 0.74–0.83), 0.93 (95% CI 0.91–0.95), 0.07 (95% CI 0.05–0.09), 0.89 (95% CI 0.86–0.90), 50.50 (95% CI 33.83–75.37), and 1.34 (95% CI 1.24–1.48), respectively. Compared with other diagnostic strategies, DSCCF had good efficiency parameters. Moreover, the sensitivity analysis did not reveal any evidence to contradict the findings in the basic setting.ConclusionsThis study demonstrated the diagnostic ability characteristics of DSCCF by assessing various efficiency parameters. Compared with other diagnostic strategies, DSCCF had good efficiency. In terms of efficiency, evaluation using DSCCF for detecting myocardial ischemia appears to be appropriate.

Trial Number and Sample Size Do Not Affect the Accuracy of the I2-Point Estimate for Testing Selection Bias Risk in Meta-Analyses.

Aim This study aims to establish the test sensitivity and specificity of the I2-point estimate for testing selection bias in meta-analyses under the condition of large versus small trial sample size and large versus small trial number in meta-analyses and to test the null hypotheses that the differences are not statistically significant. Material and methods Simulation trials were generated in MS Excel (Microsoft Corp., Redmond, WA), each consisting of a sequence of subject ID (accession) numbers representing trial subjects, a random sequence of allocation to group A or B, and a random sequence of a simulated baseline variable ("age") per subject, ranging from 50 to 55. These simulation trials were included infive types of meta-analyses with large/small numbers of trials, as well as trials with large and small sample sizes. Half of the meta-analyses were artificially biased. All meta-analyses were tested using the I2-point estimate. The numbers of true positive (TP), false positive (FP), false negative (FN), and true negative (TN) test results were established. From these, the test sensitivity and specificity were computed for each of the meta-analysis types and compared. Results All non-biased meta-analyses yielded true negative, and all biased meta-analyses yielded true positive test results, regardless of trial number and trial sample size. No false positive or false negative test results were observed. Accordingly, test sensitivities and specificities of 100% for all meta-analysis types were established, and thus, both null hypotheses failed to be rejected. Conclusion The results suggest that trial number and sample size in a baseline variable meta-analysis do not affect the test accuracy of the I2-point estimate.

Clinical and economic outcomes of adding [18F]FES PET/CT in estrogen receptor status identification in metastatic and recurrent breast cancer in the US.

Correct identification of estrogen receptor (ER) status in breast cancer (BC) is crucial to optimize treatment; however, standard of care, involving biopsy and immunohistochemistry (IHC), and other diagnostic tools such as 2-deoxy-2-[18F]fluoro-D-glucose or 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), can yield inconclusive results. 16α-[18F]fluoro-17β-fluoroestradiol ([18F]FES) can be a powerful tool, providing high diagnostic accuracy of ER-positive disease. The aim of this study was to estimate the budget impact and cost-effectiveness of adding [18F]FES PET/CT to biopsy/IHC in the determination of ER-positive status in metastatic (mBC) and recurrent breast cancer (rBC) in the United States (US). An Excel-based decision tree, combined with a Markov model, was developed to estimate the economic consequences of adding [18F]FES PET/CT to biopsy/IHC for determining ER-positive status in mBC and rBC over 5 years. Scenario A, where the determination of ER-positive status is carried out solely through biopsy/IHC, was compared to scenario B, where [18F]FES PET/CT is used in addition to biopsy/IHC. The proportion of true positive and true negative test results increased by 0.2 to 8.0 percent points in scenario B compared to scenario A, while re-biopsies were reduced by 94% to 100%. Scenario B resulted in cost savings up to 142 million dollars. Adding [18F]FES PET/CT to biopsy/IHC may increase the diagnostic accuracy of the ER status, especially when a tumor sample cannot be obtained, or the risk of a biopsy-related complication is high. Therefore, adding [18F]FES PET/CT to biopsy/IHC would have a positive impact on US clinical and economic outcomes.

The Triglycerides and Glucose Index: A Cost-Effectiveness Analysis Compared With the Homeostatic Model Assessment for Insulin Resistance

ObjectivesThis study aimed to evaluate the cost-effectiveness of the triglycerides and glucose index (TyG) versus the homeostatic model assessment for insulin resistance index (HOMA-IR) for diagnosing insulin resistance. MethodsA cost-effectiveness analysis using a decision tree based on the false-negative and false-positive tests and the true-positive and true-negative tests of both the TyG and HOMA-IR was conducted. Based on the costs and effectiveness of both tests, the average and incremental cost-effectiveness ratios were calculated. Furthermore, one-way sensitivity analysis was conducted regarding sensitivity of both indexes. Using the Monte Carlo simulation with 10 000 iterations, a probabilistic sensitivity analysis that included sensitivity, specificity, and cost of diagnostic tests was conducted. Finally, using the α and β values obtained from the primary data, the beta distribution was used for estimation of sensitivity and specificity. ResultsThe cost-effectiveness per test was $1.64 versus $4.26 for TyG and HOMA-IR. The effectiveness of true-positive (0.77 vs 0.74) and true-negative (0.17 vs 0.15) tests was higher for the TyG than HOMA-IR. The cost-effectiveness ratio was lower for the TyG than the HOMA-IR, for both the true-positive ($1.64 vs $4.26) and true-negative ($7.33 vs $20.70) tests. Diagnosing IR using the TyG was 61.5% lower than using the HOMA-IR. ConclusionsOur findings indicate that the TyG is a high effectiveness and cost-effective test for diagnosing insulin resistance than the HOMA-IR.

Correcting Diagnostic Test Sensitivity and Specificity for Patient Misclassifications Resulting from Use of an Imperfect Reference Standard.

Investigational diagnostic tests are validated by using a reference standard (RS). If the RS is imperfect (i.e., it has sensitivity [Se] and/or specificity [Sp] < 1), incorrect values for the investigational test’s Se and Sp may result because of patient misclassification by the RS. Formulas were derived to correct a test’s Se and Sp that were determined by using an imperfect RS. The following derived formulas correct for misclassification and give the true numbers of disease-positive [nDP] and disease-negative patients [nDN] from the apparent number of disease-positive and disease-negative patients (anDP and anDN), and the Se and Sp of the RS (SeR, SpR): nDP = (anDP × SpR + anDN × SpR − anDN)/JR; nDN = (anDP × SeR + anDN × SeR − anDP)/JR, where JR is Youden’s Index for the RS (JR = SeR + SpR − 1). The following derived formulas give the correct Se and Sp of an investigational test (SeI and SpI): SeI = (anTPI × SpR − nDP × SeR × SpR + nDP × JR + nDN × SpR2 − nDN × SpR − SpR × anTNI + anTNI)/(nDP × JR); SpI = (anTPI − anTPI × SeR + nDP × SeR2 − nDP × SeR − SeR × nDN × SpR + nDN × JR + SeR × anTNI)/(nDN × JR), where anTPI is the apparent number of true-positive test results, and anTNI is the apparent number of true-negative test results. The derived formulas correct for patient misclassification by an imperfect RS and give the correct values of a diagnostic test’s Se and Sp.

Assessment of the Efficiency of Non-Invasive Diagnostic Imaging Modalities for Detecting Myocardial Ischemia in Patients Suspected of Having Stable Angina

This study aimed to assess and compare the efficiency of non-invasive imaging modalities in detecting myocardial ischemia in patients with suspected stable angina as easy-to-understand indices. Our study included 1000 patients with chest pain and possible stable myocardial ischemia. The modalities to be assessed were cardiac magnetic resonance imaging (CMRI), single-photon emission computed tomography, positron emission computed tomography (PET), stress echocardiography, and fractional flow reserve derived from coronary computed tomography angiography (FFRCT). As a simulation study, we assumed that all five imaging modalities were performed on these patients, and a decision tree analysis was conducted. From the results, the following efficiencies were assessed and compared: (1) number of true positive (TP), false positive (FP), false negative (FN), and true negative (TN) test results; (2) positive predictive value (PPV); (3) negative predictive value (NPV); (4) post-test probability; (5) diagnostic accuracy (DA); and (6) number needed to diagnose (NND). In the basic settings (pre-test probability: 30%), PET generated the highest TP (267) and NPV (95%, 95% confidence interval (CI): 93-96%). In contrast, CMRI produced the highest TN (616), PPV (76%, 95% CI: 71-80%), and DA (88%, 95% CI: 86-90%) and the lowest NND (1.33, 95% CI: 1.24-1.47). Although FFRCT generated the highest TP (267) and lowest FN (33), it generated the highest FP (168). In terms of detecting myocardial ischemia, compared with the other modalities, PET and CMRI were more efficient. The results of our study might be helpful for both patients and medical professionals associated with their examination.

Utilization of a Risk Stratification Tool and Volume-Based Cuff Leak Test to Assess Postextubation Stridor.

Postextubation stridor (PES) is an imminently life-threatening event. Maximizing patient safety requires a systematic approach to screen patients for PES risk factors and a standardized test to evaluate that risk. This retrospective study of adult subjects was based on quality assurance data including standardized surveillance screening criteria and a volume-based cuff leak test (CLT) to evaluate PES risk among predominantly surgical-trauma and neurotrauma subjects. Data characterizing PES subjects also were collected. Data were collected between May 2010-December 2017 for all intubated subjects in our surgical-trauma, neurotrauma, and medical ICUs. Respiratory therapists were trained in performing both PES risk assessment surveillance and a volume-based CLT. A pre hoc cutoff leak volume of < 110 mL defined a true positive test result when associated with PES, and a leak ≥ 110 mL defined a true negative test if PES was absent. Multiple comparisons were analyzed by Kruskal-Wallis tests and dichotomous variables assessed by Fisher exact tests. Alpha was set at 0.05. In 681 pre-extubation CLTs ∼85% produced true-negative results and 15% consisted of true-positive (∼4%), false-negative (∼5%), and false-positive (∼6%) results. Positive and negative predictive values were 0.42 (0.32-0.54) and 0.94 (0.92-0.96), respectively. The PES likelihood ratio was 7.0, and correct classification was 89%. Of the 115 PES incidences occurring in 112 PES cases, 67% were female and 48% had suffered acute brain injury. Among predominantly surgical-trauma and neurotrauma subjects with a CLT, leak volume of ≥ 110 mL was associated with a PES risk of ∼6%, whereas the risk of PES was 7 times greater when the leak volume was < 110 mL.

The test characteristics of a biased or ignorant diagnostician

BackgroundA human diagnostician may harbour a special bias towards favourable positive or negative test results. The aim of the present analysis is to describe in quantitative terms how bias can affect the test characteristics of a human tester.MethodsWhereas an unbiased tester would give absolute (100%) preference to true positive or true negative test results, and no (0%) preference to any false positive or false negative test results, a biased tester may harbour some preferences towards false positive or false negative tests. Such bias can be phrased in terms of a separate sensitivity–specificity matrix. The bias matrix multiplied with the original test matrix yields the biased test matrix. Similarly, the extent of ignorance by a human tester about the diagnosis is modelled as a separate sensitivity–specificity matrix, which captures the concordance between positive and negative diagnoses made by an ignorant and expert diagnostician.ResultsIncreasing bias or ignorance result in decreasing test performance with decreasing positive predictive values until the test completely loses its discriminatory power. With more pronounced bias towards false test results, any positive test outcome may even become misinterpreted as predicting the non-existence of a given diagnosis.ConclusionsThe proposed model helps to understand in quantitative terms, how bias and ignorance can alter a diagnostician’s interpretation of test outcomes and result in diagnostic errors.

Comparative field study of Rapid-Antigen Detection (RAD) with Multiplex Real Time-PCR for COVID-19 diagnosis

RT-PCR is a gold standard test for the diagnosis of SARS-CoV2 (Covid-19) infection; however, it is an expensive, time consuming and technical demanding technique. Rapid antigen detection immunoassay (RAD) is cost-effective, quick as well as can be performed and interpreted easily. The rapid diagnosis of COVID-19 patients is essential to reduce cost and control the disease spread; however, the real world data of these tests must be validated with RT-PCR before they can be used at large scale. The objective of this study was to determine the sensitivity and specificity of PanbioTMCOVID-19 Ag-Rapid test device (Abbot) with multiplex RT-PCR. METHODS: A total of n=3509 samples were tested for SARS-CoV-2 RAD and RT-PCR at Institute of Biomedical and Genetic Engineering, Islamabad. The rapid antigen tests were performed by PanbioTMCOVID-19 Ag-Rapid test device (Abbott) and compared with RT-PCR performed on Thermo Fisher (ABI) Quant Studio 5 using CDC 2019-nCoV RT-PCR protocol. RESULTS: Total (n=3509), n=458 (7.60%) samples were reported positive by rapid antigen out of which n= 445 RT-PCR positive (13 false positive by rapid antigen), n=3051 (92.4%) were negative. True antigen negative tests n= 3051) were repeated with RT-PCR among these, n=25 were observed RT-PCR positive (rapid antigen false negative). The threshold cycle (CT) for the RT-PCR tests of these samples was &gt;30. CONCLUSION: PanbioTMCOVID-19 Ag-Rapid test devices (Abbott) showed a sensitivity ratio 94.6% compared to RT-PCR. The PanbioTMCOVID-19 Ag-Rapid test device (Abbott) is reliable and can be used for screening and isolation of positive patients from the population.

Prolonged SARS‐Cov‐2 shedding with rapid IgG antibody decay in a COVID‐19 patient: A case report

BackgroundThe coronavirus disease 2019 (COVID‐19) epidemic is still spreading rapidly around the world. Recent cases with prolonged severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) RNA detection have been successively reported, and the phenomenon of false‐negative real‐time polymerase chain reaction (RT‐PCR) results of SARS‐CoV‐2 RNA or “repositive” was also described in COVID‐19 patients.MethodsWe report a 69‐year‐old female patient with hypertension, suspected lung tumor, and previous history of total hysterectomy for hysteromyoma who presented with moderate COVID‐19 symptoms and was positive for SARS‐CoV‐2 RNA by RT‐PCR when she traveled from the USA to China.ResultsThe patient required second and third re‐hospitalizations due to “repositive” SARS‐CoV‐2 throat swab test results during post‐charge solitary isolation and observation, and serum SARS‐CoV‐2‐IgG decayed rapidly before disappearing on illness Day 139 when the throat swab was still positive. The virus shedding lasted for at least 146 days (the last positive throat swab test result was on illness Day 146, and the first true‐negative test result was on illness Day 151) since her initial positive test.ConclusionProlonged SARS‐CoV‐2 RNA viral shedding is prone to occur in an immunocompromised host, wherein changes in the host immune status can lead to repeated positive SARS‐CoV‐2 detection. Moreover, the SARS‐CoV‐2‐IgG may decrease rapidly and disappear before virus removal, indicating there may be certain limitations on the protective effect of the SARS‐CoV‐2 antibody, which deserves clinical attention.

Autoimmune Antibody in Encephalopathic Patients: A Pilot Study

Objective: To investigate the specificity of the antibodies related to autoimmune encephalitis and to identify possible associated factors with the false-positive result. Materials and Methods: The present study was a prospective observational study, conducted at the Ramathibodi Hospital between June and December 2019. All patients, who had acute to subacute encephalopathy from any causes, were recruited to the study. Their serum or cerebrospinal fluid (CSF) were taken to analyze for autoimmune encephalitis assays and anti-thyroid antibodies. The authors did not interfere with the primary physicians on any management of the patients. Clinical and laboratory data were systematically reviewed and collected from medical records. The clinical outcome was evaluated one month after the onset. Results: Fifty-one patients were recruited. Only one patient had autoimmune encephalitis related to anti-CV2/CRMP5 antibody. Seventeen out of the remaining fifty patients had positive tests for anti-thyroid antibodies of which five had Hashimoto’s thyroiditis and one of them did not have the document of thyroid status. Eleven remaining patients appeared to have false-positive test since their medical conditions were all clearly explained by other causes. Comparison of clinical and laboratory data between patients with false-positive test and patients with true negative test did not show any significant difference except the duration of the symptoms, which was significantly shorter in the false-positive group. Conclusion: False-positive anti-thyroid antibodies appear to be common in patients with acute encephalopathy. The occurrence of serum/CSF antibody in acute encephalopathy may be a true association, but it may not be the cause of encephalopathy. Therefore, the diagnosis of autoimmune encephalopathy based on anti-thyroid antibodies should be carefully made and excluded from all other possible causes. Keywords: Autoimmune encephalitis; Metabolic encephalopathy; Hashimoto’s encephalopathy; False positive

Clinical characteristics of hospitalized patients with false-negative severe acute respiratory coronavirus virus 2 (SARS-CoV-2) test results.

To determine clinical characteristics associated with false-negative severe acute respiratory coronavirus virus 2 (SARS-CoV-2) test results to help inform coronavirus disease 2019 (COVID-19) testing practices in the inpatient setting. A retrospective observational cohort study. Tertiary-care facility. All patients 2 years of age and older tested for SARS-CoV-2 between March 14, 2020, and April 30, 2020, who had at least 2 SARS-CoV-2 reverse-transcriptase polymerase chain reaction tests within 7 days. The primary outcome measure was a false-negative testing episode, which we defined as an initial negative test followed by a positive test within the subsequent 7 days. Data collected included symptoms, demographics, comorbidities, vital signs, labs, and imaging studies. Logistic regression was used to model associations between clinical variables and false-negative SARS-CoV-2 test results. Of the 1,009 SARS-CoV-2 test results included in the analysis, 4.0% were false-negative results. In multivariable regression analysis, compared with true-negative test results, false-negative test results were associated with anosmia or ageusia (adjusted odds ratio [aOR], 8.4; 95% confidence interval [CI], 1.4-50.5; P = .02), having had a COVID-19-positive contact (aOR, 10.5; 95% CI, 4.3-25.4; P < .0001), and having an elevated lactate dehydrogenase level (aOR, 3.3; 95% CI, 1.2-9.3; P = .03). Demographics, symptom duration, other laboratory values, and abnormal chest imaging were not significantly associated with false-negative test results in our multivariable analysis. Clinical features can help predict which patients are more likely to have false-negative SARS-CoV-2 test results.

The use of pulse-echo ultrasound in women with a recent non-vertebral fracture to identify those without osteoporosis and/or a subclinical vertebral fracture: a pilot study

Screening with portable devices at emergency departments or plaster rooms could be of interest to limit referrals for dual X-ray absorptiometry (DXA) and vertebral fracture assessment (VFA). We calculated the number of negative tests for osteoporosis and/or subclinical vertebral fractures (VFs) using pulse-echo ultrasonometry (P-UE) at different thresholds. In this cross-sectional study, 209 consecutive women of 50-70years with a recent non-vertebral fracture (NVF) were studied at the Fracture Liaison Service (FLS) of one hospital. All women received DXA/VFA and P-EU (Bindex®) assessments. Various P-EU thresholds (based on the density index (DI, g/cm2)) were analyzed to calculate the best balance between true negative (indeed no osteoporosis and/or subclinical VF) and false negative tests (osteoporosis and/or subclinical VF according to DXA/VFA). Eighty-three women had osteoporosis (40%) and 17 women at least one VF (8%). Applying the manufacturer's recommended P-EU threshold (DI 0.844g/cm2) being their proposed cut-off for not having hip osteoporosis resulted in 77 negative tests (37%, 31% true negative and 6% false negative tests). A DI of 0.896g/cm2 resulted in 40 negative tests (19.3%) (38 true negative (18.3%) and 2 false negative tests (1.0%)). The application of P-EU enables the identification of a substantial proportion of women with recent non-vertebral fractures at the FLS who would not need a DXA/VFA referral because they had no osteoporosis and/or subclinical vertebral fractures. The most conservative P-EU threshold resulted in 18.3% true negative tests verified by DXA/VFA against 1% false negative test results.

Multiple Compounds Recognition from The Tandem Mass Spectral Data Using Convolutional Neural Network.

Mixtures analysis can provide more information than individual components. It is important to detect the different compounds in the real complex samples. However, mixtures are often disturbed by impurities and noise to influence the accuracy. Purification and denoising will cost a lot of algorithm time. In this paper, we propose a model based on convolutional neural network (CNN) which can analyze the chemical peak information in the tandem mass spectrometry (MS/MS) data. Compared with traditional analyzing methods, CNN can reduce steps in data preprocessing. This model can extract features of different compounds and classify multi-label mass spectral data. When dealing with MS data of mixtures based on the Human Metabolome Database (HMDB), the accuracy can reach at 98%. In 600 MS test data, 451 MS data were fully detected (true positive), 142 MS data were partially found (false positive), and 7 MS data were falsely predicted (true negative). In comparison, the number of true positive test data for support vector machine (SVM) with principal component analysis (PCA), deep neural network (DNN), long short-term memory (LSTM), and XGBoost respectively are 282, 293, 270, and 402; the number of false positive test data for four models are 318, 284, 198, and 168; the number of true negative test data for four models are 0, 23, 7, 132, and 30. Compared with the model proposed in other literature, the accuracy and model performance of CNN improved considerably by separating the different compounds independent MS/MS data through three-channel architecture input. By inputting MS data from different instruments, adding more offset MS data will make CNN models have stronger universality in the future.

2238. Evaluation of Adjuvant Interferon-Gamma-Level Assessment to Improve the Performance of Procalcitonin Testing in Hospitalized Bacteremic Patients

BackgroundAlthough procalcitonin-guided antimicrobial stewardship has had proven utility in emergency and ICU settings, it is still not widely adopted outside these areas. One limitation to a more universal uptake has been the unreliable performance in discriminating bacterial infected from uninfected individuals. Viral infections have been noted to suppress procalcitonin (PCT) levels through Interferon-gamma (IFN-G)-mediated inhibition of procalcitonin release from parenchymal cells. Unfortunately, clinical application algorithms do not assess INF-G levels at the time evaluation thus treating providers are unable to distinguish a true-negative test from a false-negative test resulting from INF-G-mediated procalcitonin suppression This undermines the performance of PCT, particularly in patients with bacterial and viral co-infections. We hypothesized that adjuvant interferon gamma testing could improve the performance of PCT. To test this hypothesis we prospectively enrolled bacteremic hospitalized patients along with culture-negative controls and then assessed the performance of PCT with adjuvant IFN-G testing.Methods69 hospitalized patients with bacteremia and 32 culture-negative controls were enrolled. Demographic and clinical parameters were compared between groups alongside INFG and PCT levels Parametric and non-parametric statistical tests were performed where appropriate. Test performance was evaluated by constructing receiver operator curves (ROCs) for PCT, INF-G, and a combination of PCT+INF-G.ResultsOf 101 patients enrolled, the mean age was 49.46 ± 13.6 years with 47% being female. The following were comparative statistics between the culture-positive vs. culture-negative group: mean age 52.1 ± 15.7 vs. 46.4 ± 14.2 years, P = 0.56; WBC 11.9 ± 9.5 vs. 9.5±5.1, P = 0.170; ANC 8,466 ± 5,686 vs. 8,189 ± 4,769, P = 0.907; eGFR 73.2 ± 23 vs. 74.5 ± 26.1, P = 0.644; PCT 2.79 ± 5.87 vs. 0.71 ± 1.79, P = 0.03. Of these 57 patients had INF-G and PCT values available and their corresponding ROCs are shown in figure.ConclusionOur interim results indicate adjuvant INF-G testing may not improve the performance of procalcitonin in hospitalized bacteremic patients. The additional samples are being analyzed to confirm these findings. Disclosures All authors: No reported disclosures.

Decision Aids for Prostate Cancer Screening Choice

US guidelines recommend that physicians engage in shared decision-making with men considering prostate cancer screening. To estimate the association of decision aids with decisional outcomes in prostate cancer screening. MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL were searched from inception through June 19, 2018. Randomized trials comparing decision aids for prostate cancer screening with usual care. Independent duplicate assessment of eligibility and risk of bias, rating of quality of the decision aids, random-effects meta-analysis, and Grading of Recommendations, Assessment, Development and Evaluations rating of the quality of evidence. Knowledge, decisional conflict, screening discussion, and screening choice. Of 19 eligible trials (12 781 men), 9 adequately concealed allocation and 8 blinded outcome assessment. Of 12 decision aids with available information, only 4 reported the likelihood of a true-negative test result, and 3 presented the likelihood of false-negative test results or the next step if the screening test result was negative. Decision aids are possibly associated with improvement in knowledge (risk ratio, 1.38; 95% CI, 1.09-1.73; I2 = 67%; risk difference, 12.1; low quality), are probably associated with a small decrease in decisional conflict (mean difference on a 100-point scale, -4.19; 95% CI, -7.06 to -1.33; I2 = 75%; moderate quality), and are possibly not associated with whether physicians and patients discuss prostate cancer screening (risk ratio, 1.12; 95% CI, 0.90-1.39; I2 = 60%; low quality) or with men's decision to undergo prostate cancer screening (risk ratio, 0.95; 95% CI, 0.88-1.03; I2 = 36%; low quality). The results of this study provide moderate-quality evidence that decision aids compared with usual care are associated with a small decrease in decisional conflict and low-quality evidence that they are associated with an increase in knowledge but not with whether physicians and patients discussed prostate cancer screening or with screening choice. Results suggest that further progress in facilitating effective shared decision-making may require decision aids that not only provide education to patients but are specifically targeted to promote shared decision-making in the patient-physician encounter.

Biochemical tests of placental function versus ultrasound assessment of fetal size for stillbirth and small-for-gestational-age infants.

Biochemical tests of placental function versus ultrasound assessment of fetal size for stillbirth and small-for-gestational-age infants.

Performance of Forced Vital Capacity and Lung Diffusion Cutpoints for Associated Radiographic Interstitial Lung Disease in Systemic Sclerosis

Forced vital capacity (FVC) and DLCO are used for screening of systemic sclerosis-associated interstitial lung disease (SSc-ILD). The study purpose was to determine the sensitivity, specificity, and negative predictive value (NPV) (proportion of true negative screening tests) of FVC and DLCO thresholds for SSc-ILD on chest high-resolution computed tomography (HRCT) scans. Patients fulfilling American College of Rheumatology 2013 SSc criteria with a chest HRCT scan and pulmonary function tests (PFT) were studied. A thoracic radiologist quantified radiographic ILD. Optimal FVC and DLCO % predicted thresholds for ILD were identified using receiver-operating characteristic curves. The FVC and DLCO combinations with greatest sensitivity and specificity were also determined. Subanalysis was performed in patients with positive Scl-70 autoantibodies. The study included 265 patients. Of 188 (71%) with radiographic ILD, 59 (31%) had "normal" FVC (≥ 80% predicted), and 65 out of 151 (43%) had "normal" DLCO (≥ 60% predicted). FVC < 80% (sensitivity 0.69, specificity 0.73), and DLCO < 62% (sensitivity 0.60, specificity 0.70) were optimal thresholds for radiographic SSc-ILD. All FVC and DLCO threshold combinations evaluated had NPV < 0.70. The NPV for radiographic ILD for FVC < 80% was lower in patients with positive Scl-70 autoantibody (NPV = 0.05) compared to negative Scl-70 autoantibody (NPV = 0.57). Radiographic ILD is prevalent in SSc despite "normal" PFT. No % predicted FVC or DLCO threshold combinations yielded high NPV for SSc-ILD screening. "Normal" FVC and DLCO in patients with SSc, especially those with positive Scl-70 autoantibodies, should not obviate consideration of HRCT for ILD evaluation.

Decision aids for prostate cancer screening choice: A systematic review and meta-analysis

Importance US guidelines recommend that physicians engage in shared decision-making with men considering prostate cancer screening. Objective To estimate the association of decision aids with decisional outcomes in prostate cancer screening. Data Sources MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL were searched from inception through June 19, 2018. Study Selection Randomized trials comparing decision aids for prostate cancer screening with usual care. Data Extraction and Synthesis Independent duplicate assessment of eligibility and risk of bias, rating of quality of the decision aids, random-effects meta-analysis, and Grading of Recommendations, Assessment, Development and Evaluations rating of the quality of evidence. Main Outcomes and Measures Knowledge, decisional conflict, screening discussion, and screening choice. Results Of 19 eligible trials (12 781 men), 9 adequately concealed allocation and 8 blinded outcome assessment. Of 12 decision aids with available information, only 4 reported the likelihood of a true-negative test result, and 3 presented the likelihood of false-negative test results or the next step if the screening test result was negative. Decision aids are possibly associated with improvement in knowledge (risk ratio, 1.38; 95% CI, 1.09-1.73;I2 = 67%; risk difference, 12.1; low quality), are probably associated with a small decrease in decisional conflict (mean difference on a 100-point scale, −4.19; 95% CI, −7.06 to −1.33;I2 = 75%; moderate quality), and are possibly not associated with whether physicians and patients discuss prostate cancer screening (risk ratio, 1.12; 95% CI, 0.90-1.39;I2 = 60%; low quality) or with men’s decision to undergo prostate cancer screening (risk ratio, 0.95; 95% CI, 0.88-1.03;I2 = 36%; low quality). Conclusions and Relevance The results of this study provide moderate-quality evidence that decision aids compared with usual care are associated with a small decrease in decisional conflict and low-quality evidence that they are associated with an increase in knowledge but not with whether physicians and patients discussed prostate cancer screening or with screening choice. Results suggest that further progress in facilitating effective shared decision-making may require decision aids that not only provide education to patients but are specifically targeted to promote shared decision-making in the patient-physician encounter.