Flexible combination of multiple diagnostic biomarkers to improve diagnostic accuracy

In medical research, it is common to collect information of multiple continuous biomarkers to improve the accuracy of diagnostic tests. Combining the measurements of these biomarkers into one single score is a popular practice to integrate the collected information, where the accuracy of the resultant diagnostic test is usually improved. To measure the accuracy of a diagnostic test, the Youden index has been widely used in literature. Various parametric and nonparametric methods have been proposed to linearly combine biomarkers so that the corresponding Youden index can be optimized. Yet there seems to be little justification of enforcing such a linear combination. This paper proposes a flexible approach that allows both linear and nonlinear combinations of biomarkers. The proposed approach formulates the problem in a large margin classification framework, where the combination function is embedded in a flexible reproducing kernel Hilbert space. Advantages of the proposed approach are demonstrated in a variety of simulated experiments as well as a real application to a liver disorder study

Diagnostic Accuracy of Five Serologic Tests for Strongyloides stercoralis Infection

Background:The diagnosis of Strongyloides stercoralis (S. stercoralis) infection is hampered by the suboptimal sensitivity of fecal-based tests. Serological methods are believed to be more sensitive, although assessing their accuracy is difficult because of the lack of sensitivity of a fecal-based reference ("gold") standard.Methods:The sensitivity and specificity of 5 serologic tests for S. stercoralis (in-house IFAT, NIE-ELISA and NIE-LIPS and the commercially available Bordier-ELISA and IVD-ELISA) were assessed on 399 cryopreserved serum samples. Accuracy was measured using fecal results as the primary reference standard, but also using a composite reference standard (based on a combination of tests).Results:According to the latter standard, the most sensitive test was IFAT, with 94.6% sensitivity (91.2-96.9), followed by IVD-ELISA (92.3%, 87.7-96.9). The most specific test was NIE-LIPS, with specificity 99.6% (98.9-100), followed by IVD-ELISA (97.4%, 95.5-99.3). NIE-LIPS did not cross-react with any of the specimens from subjects with other parasitic infections. NIE-LIPS and the two commercial ELISAs approach 100% specificity at a cut off level that maintains ≥70% sensitivity.Conclusions:NIE-LIPS is the most accurate serologic test for the diagnosis of S. stercoralis infection. IFAT and each of the ELISA tests are sufficiently accurate, above a given cut off, for diagnosis, prevalence studies and inclusion in clinical trials.Fil: Bisoffi, Zeno. Sacro Cuore Hospital; ItaliaFil: Buonfrate, Dora. Sacro Cuore Hospital; ItaliaFil: Sequi, Marco. Istituto Di Ricerche Farmacologiche Mario Negri; ItaliaFil: Mejia, Rojelio. National Institute Of Allergy And Infectious Diseases; Estados UnidosFil: Cimino, Rubén Oscar. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Albonico, Marco. Sacro Cuore Hospital; ItaliaFil: Gobbo, Maria. Sacro Cuore Hospital; ItaliaFil: Bonafini, Stefania. Sacro Cuore Hospital; ItaliaFil: Angheben, Andrea. Sacro Cuore Hospital; ItaliaFil: Requena-Mendez, Ana. Universidad de Barcelona; EspañaFil: Muñoz, José. Universidad de Barcelona; EspañaFil: Nutman, Thomas B.. National Institute Of Allergy And Infectious Diseases; Estados Unido

Diagnostic accuracy of myocardial perfusion imaging with czt technology. Systemic review and meta-analysis of comparison with invasive coronary angiography

OBJECTIVES: This study sought to summarize the evidence on stress myocardial perfusion imaging (MPI) using cadmium-zinc-telluride (CZT) technology for the diagnosis of obstructive coronary artery disease (CAD). The CZT cameras are newly introduced, and comparative data with the conventional Anger technology (Anger-MPI) are lacking. BACKGROUND: The diagnostic accuracy of Anger-MPI for detection of angiographically significant CAD is well established; however, less evidence is available on the diagnostic accuracy of CZT-MPI. METHODS: Clinical studies comparing CZT-MPI and invasive coronary angiography were systematically searched and abstracted. Calculations of diagnostic accuracy, including sensitivity, specificity, likelihood ratios, and diagnostic odds ratio, were obtained with fixed and random effects, reporting point estimates and 95% confidence intervals. RESULTS: Based on our search, a total of 16 studies (N = 2,092) were included. The sensitivity of CZT-MPI was 0.84 (95% confidence interval [CI]: 0.78 to 0.89), whereas the specificity of 0.69 (95% CI: 0.62 to 0.76) was significantly reduced. The positive likelihood ratio was 2.73 (95% CI: 2.21 to 3.39), the negative likelihood ratio was 0.24 (95% CI: 0.17 to 0.31), and the diagnostic odds ratio was 11.93 (95% CI: 7.84 to 17.42). At subgroup and meta-regression analyses, the diagnostic accuracy between D-SPECT and Discovery cameras was similar (p = 0.711) and not impacted upon by smaller sample size studies (p = 0.573). CONCLUSIONS: CZT-MPI has satisfactory sensitivity for angiographically significant CAD, but its suboptimal specificity warrants further development and research

Diagnostic accuracy of sonohysterography vs hysteroscopy in benign uterine endocavitary findings

OBJECTIVE: To compare diagnostic accuracy of sonohysterography vs hysteroscopy in patients with benign uterine endocavitary findings. PATIENTS AND METHODS: This retrospective study evaluated 202 patients submitted to sonohysterography after transvaginal ultrasound examination suspicious for uterine endocavitary findings. Cytological sample was taken and analyzed from the fluid used to distend the uterine cavity. Of 202 patients enrolled for this study, 86 patients underwent gynaecological surgery, of whom 77 were treated with operative hysteroscopy and 9 with other gynaecological surgical techniques. Statistical analysis was performed to evaluate diagnostic agreement between sonohysterography vs hysteroscopy and cytology vs histology. RESULTS: Diagnostic concordance between sonohysterography and hysteroscopy was significant (k value 0.87). The correlation between cytological and histological findings had a moderate level of concordance (k value 0.49).CONCLUSIONS: Sonohysterography provides a diagnostic accuracy as well as hysteroscopy, therefore, it could be considered an alternative procedure in the diagnosis of benign uterine endocavitary findings

Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis

Introduction: Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis. Materials and methods: Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N = 66) and prostatitis patients (N = 36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed. Results: Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (P < 0.001). Urinary bacteria count allowed for discriminating prostatitis patients from HV (P < 0.001). Total amount of biantennary structures (urinary 2A/MA marker) was significantly lower in prostatitis patients compared to HV (P < 0.001). Combining the urinary 2A/MA marker and urinary WBC count resulted in an AUC of 0.79, 95% confidence interval (CI) = (0.70-0.89) which was significantly better than urinary WBC count (AUC = 0.70, 95% CI = [0.59-0.82], P = 0.042) as isolated test. Conclusions: We have demonstrated the diagnostic value of urinary N-glycosylation profiling, which shows great potential as biomarker for prostatitis. Further research is required to unravel the developmental course of prostatic inflammation

Ventilator-Associated Pneumonia and PaO2/FIO2 Diagnostic Accuracy: Changing the Paradigm?

BACKGROUND: Ventilator-associated pneumonia (VAP) is associated to longer stay and poor outcomes. Lacking definitive diagnostic criteria, worsening gas exchange assessed by PaO2/FIO2 ≤ 240 in mmHg has been proposed as one of the diagnostic criteria for VAP. We aim to assess the adequacy of PaO2/FIO2 ≤ 240 to diagnose VAP. METHODS: Prospective observational study in 255 consecutive patients with suspected VAP, clustered according to PaO2/FIO2 ≤ 240 vs. > 240 at pneumonia onset. The primary analysis was the association between PaO2/FIO2 ≤ 240 and quantitative microbiologic confirmation of pneumonia, the most reliable diagnostic gold-standard. RESULTS: Mean PaO2/FIO2 at VAP onset was 195 ± 82; 171 (67%) cases had PaO2/FIO2 ≤ 240. Patients with PaO2/FIO2 ≤ 240 had a lower APACHE-II score at ICU admission; however, at pneumonia onset they had higher CPIS, SOFA score, acute respiratory distress syndrome criteria and incidence of shock, and less microbiological confirmation of pneumonia (117, 69% vs. 71, 85%, p = 0.008), compared to patients with PaO2/FIO2 > 240. In multivariate logistic regression, PaO2/FIO2 ≤ 240 was independently associated with less microbiological confirmation (adjusted odds-ratio 0.37, 95% confidence interval 0.15-0.89, p = 0.027). The association between PaO2/FIO2 and microbiological confirmation of VAP was poor, with an area under the ROC curve 0.645. Initial non-response to treatment and length of stay were similar between both groups, while hospital mortality was higher in patients with PaO2/FIO2 ≤ 240. CONCLUSION: Adding PaO2/FIO2 ratio ≤ 240 to the clinical and radiographic criteria does not help in the diagnosis of VAP. PaO2/FIO2 ratio > 240 does not exclude this infection. Using this threshold may underestimate the incidence of VAP.info:eu-repo/semantics/publishedVersio