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Item Clinical comparison and agreement of PCR, antigen, and viral culture for the diagnosis of COVID-19: Clinical Agreement Between Diagnostics for COVID19(Elsevier, 2022) Agard, Amanda; Elsheikh, Omar; Bell, Drew; Relich, Ryan F.; Schmitt, Bryan H.; Sadowski, Josh; Fadel, William; Webb, Douglas H.; Dbeibo, Lana; Kelley, Kristen; Carozza, Mariel; Lei, Guang-Shen; Calkins, Paul; Beeler, Cole; Medicine, School of MedicineThe aim of this study is to compare the COVID-19 nasopharyngeal PCR (NP PCR) to antigen, nasal PCR, and viral culture. One-hundred-and-fourteen risk-stratified patients were tested by culture, nasal PCR, NP PCR, and Ag testing. Twenty (48%) of the high risk and 23 (32%) of the low risk were NP PCR positive. Compared with NP PCR, the sensitivity of nasal PCR, Sofia Ag, BinaxNOW Ag, and culture were 44%, 31%, 37%, and 15%. In the high risk group, the sensitivity of these tests improved to 71%, 37%, 50%, and 22%. Agreement between tests was highest between nasal PCR and both antigen tests. Patients who were NP PCR positive but antigen negative were more likely to have remote prior COVID-19 infection (p<0.01). Nasal PCR and antigen positive patients were more likely to have symptoms (p = 0.01).Item Clinicians’ Use of Quantitative Information when Assessing the Rate of Functional Progression in Glaucoma(Elsevier, 2022) Gardiner, Stuart K.; Kinast, Robert M.; De Moraes, Carlos Gustavo; Budenz, Donald L.; Jeoung, Jin Wook; Lind, John T.; Myers, Jonathan S.; Nouri-Mahdavi, Kouros; Rhodes, Lindsay A.; Strouthidis, Nicholas G.; Chen, Teresa C.; Mansberger, Steven L.; Ophthalmology, School of MedicinePurpose: Clinicians use both global and point-wise information from visual fields to assess the rate of glaucomatous functional progression. We asked which objective, quantitative measures best correlated with subjective assessment by glaucoma experts. In particular, we aimed to determine how much that judgment was based on localized rates of change vs. on global indices reported by the perimeter. Design: Prospective cohort study. Participants: Eleven academic, expert glaucoma specialists independently scored the rate of functional progression, from 1 (improvement) to 7 (very rapid progression), for a series of 5 biannual clinical printouts from 100 glaucoma or glaucoma suspect eyes of 51 participants, 20 of which were scored twice to assess repeatability. Methods: Regression models were used to predict the average of the 11 clinicians' scores based on objective rates of change of mean deviation (MD), visual field index (VFI), pattern standard deviation (PSD), the Nth fastest progressing location, and the Nth fastest progressing of 10 anatomically defined clusters of locations after weighting by eccentricity. Main outcome measures: Correlation between the objective rates of change and the average of the 11 clinicians' scores. Results: The average MD of the study eyes was -2.4 dB (range, -16.8 to +2.8 dB). The mean clinician score was highly repeatable, with an intraclass correlation coefficient of 0.95. It correlated better with the rate of change of VFI (pseudo-R2 = 0.73, 95% confidence interval [CI, 0.60-0.83]) than with MD (pseudo-R2 = 0.63, 95% CI [0.45-0.76]) or PSD (pseudo-R2 = 0.41, 95% CI [0.26-0.55]). Using point-wise information, the highest correlations were found with the fifth-fastest progressing location (pseudo-R2 = 0.71, 95% CI [0.56-0.80]) and the fastest-progressing cluster after eccentricity weighting (pseudo-R2 = 0.61, 95% CI [0.48-0.72]). Among 25 eyes with an average VFI of > 99%, the highest observed pseudo-R2 value was 0.34 (95% CI [0.16-0.61]) for PSD. Conclusions: Expert academic glaucoma specialists' assessment of the rate of change correlated best with VFI rates, except in eyes with a VFI near the ceiling of 100%. Sensitivities averaged within clusters of locations have been shown to detect change sooner, but the experts' opinions correlated more closely with global VFI. This could be because it is currently the only index for which the perimeter automatically provides a quantitative estimate of the rate of functional progression.Item Dentists Clinical Decision-Making for Erosive Tooth Wear: An Online Study(Elsevier, 2020) Goldfarb, Micah B.; Maupomé, Gerardo; Hirsh, Adam T.; Carvalho, Joana C.; Eckert, George J.; Hara, Anderson T.Objective: Erosive tooth wear (ETW) is an irreversible loss of dental hard tissue. This pilot study examined dentists’ ability to diagnose and manage ETW relative to sound and caries-affected teeth. Methods: Dentists recruited through the Indiana Dental Association (N=36) participated in an internet-based survey, containing twenty-two standardized images of buccal and occlusal surfaces of teeth (sound, ETW, or caries). For each image, they provided diagnosis (presence and differentiation) of dental condition, confidence in their judgment, management need, and likelihood to recommend specific management strategies. Dentists made these judgments for teeth with no, initial, moderate, or severe ETW/caries. Results: Dentists demonstrated poor detection of ETW compared to sound teeth and caries at each level of severity. The dentists were less confident, less able to correctly diagnose and manage ETW, and less likely to recommend most management strategies for ETW than caries at each level of severity. Conclusions: Dentists had difficulty correctly diagnosing (both detection and differentiation) and managing ETW, across all severity levels and particularly in early stages. These difficulties were particularly apparent when compared to caries. The current results are clinically relevant given the importance of early diagnosis for ETW management.Item Imaging ligands targeting glypican-3 receptor expression in hepatocellular carcinoma(e-Century, 2022-08-20) Grega, Shaun D.; Zheng, David X.; Zheng, Qi-Huang; Radiology and Imaging Sciences, School of MedicineHepatocellular carcinoma (HCC) is the third leading cause of cancer mortality. Early detection of HCC is important since potentially curative therapies exist in the initial stages of HCC; no curative therapies exist for late-stage HCC. However, the initial detection of HCC remains challenging due to the lack of symptoms during the early stage of the disease. Other methods of screening and detecting HCC, including blood serum tests and conventional imaging methods, remain inadequate due to genetic differences between patients and the high background activity of liver tissues. Thus, there is a need for an accurate imaging agent for the diagnosis, staging, and prognosis of HCC. Glypican-3 (GPC3) is an oncofetal receptor responsible for regulating cell division, growth, and survival. GPC3 is a clinically relevant biomarker for imaging and therapeutics, as its expression is HCC tumor-specific and absent from normal and other pathological liver tissues. The development of novel GPC3-targeting imaging agents has encompassed three classes of biomolecules: peptides, antibodies, and aptamers. These biomolecules serve as constructs for diagnostic imaging (demonstrating potential as positron emission tomography [PET], single-photon emission tomography [SPECT], and optical imaging agents) and HCC treatment delivery. More than 20 unique ligands have been identified in the literature as showing specificity for the GPC3 receptor. Although several ligands are currently under clinical investigation as therapies for HCC, clinical translation of GPC3-targeting ligands as imaging agents is lacking. This review highlights the current landscape of ligands targeting GPC3 and describes their promising possibilities as imaging agents for HCC.Item Performance of TEM-PCR vs Culture for Bacterial Identification in Pediatric Musculoskeletal Infections(Oxford Academic, 2018-05-22) Wood, James B.; Sesler, Cheryl; Stalons, Donald; Grigorenko, Elena; Schoenecker, Jonathan G.; Creech, C. Buddy; Thomsen, Isaac P.; Pediatrics, School of MedicineImproved diagnostics are needed for children with musculoskeletal infections (MSKIs). We assessed the performance of target-enriched multiplex polymerase chain reaction (TEM-PCR) in children with MSKI. TEM-PCR was concordant with culture in pathogen identification and antibiotic susceptibility testing, while increasing the overall yield of pathogen detection. This technology has the potential to inform judicious antimicrobial use early in the disease course.Item Repurposing MALDI-TOF MS for effective antibiotic resistance screening in Staphylococcus epidermidis using machine learning(Springer Nature, 2024-10-15) Ren, Michael; Chen, Qiang; Zhang, Jing; Engineering Technology, Purdue School of Engineering and TechnologyThe emergence of Staphylococcus epidermidis as a significant nosocomial pathogen necessitates advancements in more efficient antimicrobial resistance profiling. However, existing culture-based and PCR-based antimicrobial susceptibility testing methods are far too slow or costly. This study combines machine learning with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to develop predictive models for various antibiotics using a comprehensive dataset containing thousands of S. epidermidis isolates. Optimized machine learning models utilized feature selection and achieved high AUROC scores ranging from 0.80 to 0.95 while maintaining AUPRC scores up to 0.97. Shapley Additive exPlanations were employed to analyze relevant features and assess the significance of corresponding protein biomarkers while also verifying that predictive power was derived from the detection of proteins rather than noise. Antimicrobial resistance models were validated externally to evaluate model performance outside the original data collection site. The approaches and findings in this study demonstrate a significant advancement in rapid, cost-effective antimicrobial resistance profiling, offering a promising solution for improving treatments for nosocomial infections and being potentially applicable to other microbial pathogens in the future.