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Diagnosing the diagnostic process.

Experimental results obtained by examining the diagnostic performance of students and doctors in different medical schools and different cultural environments are presented. The pertinent data were obtained using tests of diagnostic skills based on real cases. The technique requires asking questions (tactics) to obtain the information needed to reach a diagnosis so that the subject becomes an active searcher of information and the final answer is not the only element used to evaluate tactics. The results show significant differences in performance according to medical experience. Experts ask fewer questions than students or less-experienced doctors but maximize the information value by asking them at the proper time in the sequence. New evaluation procedures are described to characterize quantitatively each diagnostic tactic. Experimentally based theoretical considerations are made concerning the prediction and development of diagnostic talent, the structure of diagnostic processes and its training. New approaches to the problem are briefly sketched.

Argentina↗

Plasma inflammatory proteome profiles identify MASLD among children with overweight or obesity.

BACKGROUND & AIMS: Pediatric metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent among children with overweight or obesity, yet its early diagnosis remains a major clinical challenge. This study aimed to identify circulating inflammatory proteins associated with MASLD and to develop a proteomic risk score (ProScore) to improve diagnostic accuracy. METHODS: In this cross-sectional study of 161 children (median age 8.5&#xa0;years) with overweight or obesity, MASLD was assessed by vibration-controlled transient elastography, with 42 cases identified. Plasma concentrations of 92 inflammation-related proteins were quantified using a high-throughput proximity extension assay. The ProScore was compared with eleven conventional anthropometric/metabolic indices (WHtR, METS-IR, SPISE, PNFI, VAI, LAP, TyG, TyG-ALT, TyG-WC, TyG-WHtR, and TyG-BMI) and a genetic risk score (GRS). Six machine learning algorithms were employed and diagnostic performance was assessed using area under the curve (AUC) with fivefold cross-validation. RESULTS: Fifteen proteins were significantly associated with MASLD. A six-protein panel (FGF-21, CDCP1, CD244, OPG, Flt3L, MCP-1) achieved the highest diagnostic accuracy (AUC&#x2009;=&#x2009;0.84), exceeding that of all conventional indices (AUC&#x2009;=&#x2009;0.65-0.78; all P&#x2009;<&#x2009;0.05). ProScore performance remained robust in school-based validation (AUC&#x2009;=&#x2009;0.83), with no substantial improvement when combined with conventional indices. Diagnostic accuracy was higher in children with lower GRS (AUC&#x2009;=&#x2009;0.92) than in those with higher GRS (AUC&#x2009;=&#x2009;0.80; P&#x2009;=&#x2009;0.003). CONCLUSIONS: A proteomic signature of systemic inflammation provides accurate, non-invasive identification of MASLD in at-risk children, outperforming conventional metabolic and genetic tools, and may have utility in clinical and public health settings.

Humans↗

Gynecologic cytology from the perspective of the Laboratory Proficiency Testing Program, Ontario, Canada.

The accumulated test results from annual proficiency testing of approximately 150 cytology laboratories during the period 1977-1992 were analyzed. Several features of the test program are presented, including the adaptability of the uniform diagnostic terminology that was in use throughout. Observations include the impact of screening by a technologist; the better diagnostic performance generally, but not exclusively, in larger-volume laboratories; the degree of reproducibility of reporting in the laboratory; the ease of diagnosis in some diagnostic categories; and patterns observed in "false negative" and "false positive" rates. The follow-up analysis of suboptimal performance is recorded, and remedial and educational aspects are emphasized. The impact of levels of performance on the specific population being screened is correlated with the data on laboratory caseloads and with hospital vs. nonhospital laboratories.

Cytodiagnosis↗

Disturbed right ventricular ejection pattern as a new Doppler echocardiographic sign of acute pulmonary embolism.

Transthoracic echocardiography (TTE) is frequently performed in patients with suspected acute pulmonary embolism (APE) to search for right ventricular (RV) pressure overload. We prospectively assessed the diagnostic value of a new Doppler echocardiographic sign of APE based on the disturbed RV ejection pattern ("60/60 sign") and compared its diagnostic performances with that of the presence of RV pressure overload, as well as with "McConnell sign" based on RV regional wall motion abnormalities. We assessed 100 consecutive patients with clinical suspicion of APE, including those with previous cardiorespiratory diseases. After TTE, all of the patients underwent reference diagnostic tests for APE. The 60/60 sign required RV acceleration time of <or=60 ms in presence of tricuspid insufficiency pressure gradient <or=60 mm Hg. APE was ultimately confirmed in 67 of 100 patients. In 17 of 67 patients, 60/60 sign correctly suggested APE, whereas 2 false-positive results were noted: in pulmonary fibrosis and in acute respiratory distress syndrome following lung resection. McConnell sign was fully specific but was noted in only 13 of 67 patients. Sensitivity and specificity were 81% and 45% for "RV-pressure overload" signs, 25% and 94% for 60/60 sign, and 19% and 100% for McConnell sign. When combined, the 2 latter signs were 94% specific and 36% sensitive in diagnosing APE. Thus, RV overload at echocardiography is not specific for APE. The 60/60 and McConnell signs are insensitive, but are reliable and helpful in bedside diagnosis of APE when direct visualization of the pulmonary arteries is impossible. Combining these 2 signs may increase the sensitivity without compromising the specificity of echocardiographic diagnosis of APE.

Acute Disease↗

Performance of RVGui sensor and Kodak Ektaspeed Plus film for proximal caries detection.

OBJECTIVE: A high-resolution charge-coupled device was used to compare the diagnostic performances obtained with Trophy's new RVGui sensor and Kodak Ektaspeed Plus film with respect to caries detection. STUDY DESIGN: Three acquisition modes of the Trophy RVGui sensor were compared with Kodak Ektaspeed Plus film. Images of the proximal surfaces of 40 extracted posterior teeth were evaluated by 6 observers. The presence or absence of caries was scored by means of a 5-point confidence scale. The actual caries status of each surface was determined through ground-section histology. Responses were evaluated by means of receiver operating characteristic analysis. Areas under receiver operating characteristic curves (A(Z)) were assessed through analysis of variance. RESULTS: The mean A(Z) scores were 0.85 for film, 0.84 for the high-resolution caries mode, and 0.82 for both the low resolution caries mode and the high-resolution periodontal mode. These differences were not statistically significant (P =.70). The differences among observers also were not statistically significant (P =.23). CONCLUSION: The performance of the RVGui sensor in high- and low-resolution modes for proximal caries detection is comparable to that of Ektaspeed Plus film.

Analysis of Variance↗

Progress on the CSE diagnostic study. Application of McNemar's test revisited.

The authors describe an extension of McNemar's test that can be used to compare diagnostic performance when multiple statements are obtained from computer analysis or visual interpretation of the ECG. If two or more diagnostic statements are made, by definition only one can be correct for the cases in the CSE pilot database, which were selected for single, clinically well documented, abnormalities. If one statement stood out from others as being made with the highest degree of certainty, that was accepted as the single interpretation, right or wrong. However, when two or more statements were made with the same degree of certainty and only one statement was correct, then in the previous application of McNemar's test that interpretation was given credit for being correct. In the extension of the method presented in this article, such an interpretation is given partial credit for the one correct statement and partial discredit for any incorrect statement, thereby reporting the results more properly in the sensitivity and specificity statistics for the different diagnostic categories.

Algorithms↗

NS1 protein secretion during the acute phase of West Nile virus infection.

The West Nile virus (WNV) nonstructural protein NS1 is a protein of unknown function that is found within, associated with, and secreted from infected cells. We systematically investigated the kinetics of NS1 secretion in vitro and in vivo to determine the potential use of this protein as a diagnostic marker and to analyze NS1 secretion in relation to the infection cycle. A sensitive antigen capture enzyme-linked immunosorbent assay (ELISA) for detection of WNV NS1 (polyclonal-ACE) was developed, as well as a capture ELISA for the specific detection of NS1 multimers (4G4-ACE). The 4G4-ACE detected native NS1 antigens at high sensitivity, whereas the polyclonal-ACE had a higher specificity for recombinant forms of the protein. Applying these assays we found that only a small fraction of intracellular NS1 is secreted and that secretion of NS1 in tissue culture is delayed compared to the release of virus particles. In experimentally infected hamsters, NS1 was detected in the serum between days 3 and 8 postinfection, peaking on day 5, the day prior to the onset of clinical disease; immunoglobulin M (IgM) antibodies were detected at low levels on day 5 postinfection. Although real-time PCR gave the earliest indication of infection (day 1), the diagnostic performance of the 4G4-ACE was comparable to that of real-time PCR during the time period when NS1 was secreted. Moreover, the 4G4-ACE was found to be superior in performance to both the IgM and plaque assays during this time period, suggesting that NS1 is a viable early diagnostic marker of WNV infection.

Animals↗

Duplex ultrasound criteria for the identification of carotid stenosis should be laboratory specific.

BACKGROUND AND PURPOSE: Published criteria for the determination of carotid stenosis have been widely applied by vascular laboratories. We compared two vascular laboratories and their duplex ultrasound (DU) machines in terms of their overall diagnostic performance and the optimal criteria to identify patients who have a 70% to 99% stenosis of the internal carotid artery. METHODS: Measurements of stenosis by DU and angiography were compared for 123 carotid arteries (60 arteries, laboratory A; 63 arteries, laboratory B). Receiver operating characteristic (ROC) curves were created, and the areas under the ROC curves and the optimal criteria for determining a 70% to 99% stenosis were compared. Multiple regression analysis was used to measure the effect of laboratory on the relationship between angiographic stenosis and DU velocity parameters. RESULTS: Areas under the ROC curves were similar for both laboratories (0.89 to 0.90, laboratory A; 0.90 to 0.92, laboratory B). However, the optimal criterion for the identification of a 70% to 99% carotid stenosis was different for each laboratory. For most velocity parameters, based on regression analyses, the predicted percent angiographic stenosis for laboratory A was significantly greater than that for laboratory B. In addition, performance differed between the laboratories when established criteria from the literature were applied. CONCLUSIONS: Two vascular laboratories with similar diagnostic accuracy by ROC analysis have markedly different "optimal" DU criteria. For a given angiographic stenosis, velocities in one laboratory were consistently greater than those in the other laboratory. Laboratory-specific criteria rather than published criteria should be used to identify patients with internal carotid artery stenoses.

Aged↗

Combined determination of plasma MMP2, MMP9, and TIMP1 improves the non-invasive detection of transitional cell carcinoma of the bladder.

BACKGROUND: Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play a major role in the maintenance of extracellular matrix homeostasis and are involved in the process of tumour invasion and metastasis in several malignant tumour entities. The goal of this study is to evaluate the diagnostic value of various circulating MMPs and TIMPs in blood plasma for a non-invasive detection of transitional cell carcinoma of the bladder (TCC). METHODS: In this study the concentrations of MMP1, MMP2, MMP3, MMP9, their inhibitors TIMP1, TIMP2, and the MMP1/TIMP1-complex (MTC1) were quantified in blood plasma with the sandwich enzyme-linked immunosorbent assay (ELISA). Blood plasma samples were investigated from 68 patients (non-metastasized, n = 57 and metastasized, n = 11) with TCC of the bladder and from 79 healthy controls. The mROC program was used to calculate the best two- and three- marker combinations. The diagnostic values for all single markers and the marker combinations were estimated both by the overall diagnostic performance index area under the ROC curve (AUC) and the sensitivity and specificity at cutoff limits with the highest diagnostic accuracy and at the 90% and 95% limits of sensitivity and specificity, respectively. RESULTS: The median MMP2 concentration was elevated in blood plasma in all patient groups with TCC in comparison to the controls (p < 0.001). The concentrations of TIMP1, TIMP2, and MTC1 in plasma probes were significantly lower from patients with non-metastasized TCC compared to the controls. MMP2 tested alone reached the highest sensitivity and specificity at 75%, respectively. The sensitivity and specificity increased when tested in combination with MMP9 and TIMP1 (97%, 94%, respectively). The combination of MMP9 and TIMP1 also showed an improved sensitivity (80%) and specificity (99%) than tested alone. CONCLUSION: MMP2 is a statistically significant marker in blood plasma for bladder cancer detection with an increased diagnostic value in combination with MMP9 and TIMP1. This study showed that the highest sensitivities and specificities are not obtained by testing each marker alone. As shown by the best two-marker combination, which includes MMP9 and TIMP1, the optimized combination does not always include the best single markers.

Adult↗

Specific IgE determination using the CAP system: comparative evaluation with RAST.

The CAP system's main contribution is its solid phase, which consists of a cellulose polymer activated within a capsule (the ImmunoCAP). This solid phase can bind more protein to it, and, in addition, the conditions of reaction seem to make the system more sensitive at detecting antibodies to certain antigens. It is therefore important to assess the new analytical and diagnostic performance in comparison with previous systems. In this context, we studied the reliability and comparison with the RAST and with skin tests carried out on 144 pediatric patients. Skin tests and specific IgE for radioimmunological RAST (radio-allergosorbent test) and for the fluoroimmunological CAP system were performed on all the patients. The RAST/CAP correlation quotients for the different allergens tested varied between 0.971 and 0.991. Diagnostic sensitivity increased for all the allergens studied and specificity remained unchanged. The system provides reliable results, with better diagnostic capacity than RAST, but it must be quantified for each allergen because its results are not interchangeable.

Adolescent↗

A Narrative Review of Urine-Based Human Papillomavirus Screening: Performance, Challenges, and Opportunities to Expand Access in the United States.

BACKGROUND: In the United States, about 12,000 new cases of cervical cancer are diagnosed each year, largely due to limited screening access. Urine-based testing for human papillomavirus (HPV) offers a noninvasive, self-sampling method that could improve access to screening. We conducted a narrative review of urine-based HPV testing, focusing on diagnostic performance and feasibility. METHODS: Studies were identified through PubMed using combinations of search terms including "urine," "screening," "diagnostic tests," and "HPV" from January 1, 2006, to December 31, 2024. Studies reporting test performance for detecting HPV and acceptability of urine-based HPV testing compared with cervical specimens, vaginal specimens, or precancerous lesions were included. Weighted averages for sensitivity and specificity were calculated based on sample sizes. RESULTS: We identified 36 studies (N = 65 to N = 1952) evaluating test performance for detecting HPV in urine specimens. When compared with cervical specimens, vaginal specimens, and CIN2+-confirmed lesions, urine-based testing demonstrated a wide range of sensitivity (44.8%-98.6%) and specificity (61%-100%). Differences in assay technology, genomic target, and clinical context contributed to the variability in findings. Regarding acceptability (n = 10 studies), studies found participants to be comfortable with urine sampling due to its ease of collection. CONCLUSIONS: Urine-based HPV testing is widely accepted but requires further standardization to improve performance and secure Food and Drug Administration approval for broader implementation.

Humans↗

Radiographic detectability of occipital and temporal-parietal fractures induced in cadaver heads.

Diagnostic performance based on a double-blind evaluation of test and control radiographs produced from nine different fractured cadaver skulls was compiled for six radiologists. The data resulting from two different diagnostic tasks were analyzed statistically for accuracy and confirmed interpretability including an assessment of task-related performance differences. Performance was found to be relatively independent of differences among radiologists and lesion location. Little overall correlation was found to exist between demonstrated ability to detect lesions radiographically, and visual confirmation of known lesions from the same films. These results suggest that overall performance was probably limited by a number of undefined clinical factors which influence the amount of meaningful information available from the resulting radiographs. The distribution of these degrading influences was not uniform within the population sampled so that certain radiographs proved to be particularly misleading when considered in terms of their apparent diagnostic value. As a result, even relatively large depressed fractures were in some instances considered radiographically uninterpretable.

Autopsy↗

Human and computer-aided diagnosis of abdominal pain: further report with emphasis on performance of clinicians.

This paper reports a controlled trial of human and computer-aided diagnosis in a series of 552 patients with acute abdominal pain. The overall diagnostic accuracy of the computer-aided system was 91.5% and that of the senior clinician to see each case was 81.2%. However, the clinician's diagnostic performance improved markedly during the period of the trial. The proportion of appendices which perforated before operation fell from 36% to 4% during the trial, and the negative laparotomy rate dropped sharply. After the trial closed in August 1972 these figures reverted towards their pretrial levels.It is suggested that while computer-aided diagnosis is a valuable direct adjunct to the clinician dealing with the "acute abdomen," he may also benefit in the short-term from the constant feedback he receives and from the disciplines and constraints involved in communicating with the computer.

Abdomen↗

The effect of data sampling on the performance evaluation of artificial neural networks in medical diagnosis.

PURPOSE: To study the effect of data sampling on the predictive assessment of artificial neural networks (ANNs) for medical diagnostic tasks. METHODS: Three statistical techniques were used to evaluate the diagnostic performances of ANNs: 1) cross validation, 2) round robin, and 3) bootstrap. These techniques are different sampling plans designed to reduce the small-sample estimation bias and variance contributions. The study was based on two networks, one developed for the diagnosis of pulmonary embolism (1,064 cases) and the other developed for the diagnosis of breast cancer (206 cases). RESULTS: The three sampling techniques produced different performance estimates for both networks. The estimates varied substantially depending on the training sample size and the training-stopping criterion. CONCLUSION: The predictive assessment of ANNs in medical diagnosis can vary substantially based on the complexity of the problem, the data sampling technique, and the number of cases available.

Breast Neoplasms↗

Receiver operating characteristic analysis of the performance of basal serum hormone profiles for the diagnosis of polycystic ovary syndrome in epidemiological studies.

OBJECTIVE: We have used receiver operating characteristic (ROC) analysis to determine the diagnostic performance of several serum parameters, in order to evaluate their potential usefulness in establishing the diagnosis of polycystic ovary syndrome (PCOS) in epidemiological studies. DESIGN: Prospective study. METHODS: One hundred and fourteen women reporting spontaneously for blood donation were included in the study. Menopausal and oral contraceptive-treated women were excluded. Serum samples were obtained at the moment of donation, independently of fasting, time of day or day of menstrual cycle. Measurements included total testosterone, sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), LH, FSH and estradiol. The free testosterone (FT) concentration and the free androgen index (FAI) were calculated from testosterone and SHBG levels. ROC curves were calculated for all these serum determinations. RESULTS: Eight patients were diagnosed with PCOS, according to the presence of oligomenorrhea, hirsutism, acne and/or hyperandrogenemia, and exclusion of non-classic congenital adrenal hyperplasia, hypothyroidism and hyperprolactinemia. Of the parameters studied SHBG, FAI, FT and DHEAS were considered adequate measures for the diagnosis of PCOS. For example, serum SHBG levels showed an area under the ROC curve of 0.875+/-(S.E.(w))0.045 (95% confidence interval 0.800-0.929). A SHBG decision threshold <37 nmol/l had a sensitivity of 87.5%, a specificity of 86.8%, a positive likelihood ratio of 6.63, and a negative likelihood ratio of 0.14, for the diagnosis of PCOS. CONCLUSIONS: Our present results strongly suggest that decreased SHBG levels, and increased FAI, free testosterone concentration and DHEAS concentrations, are highly effective as single analytical procedures in epidemiological studies for the detection of PCOS in women of reproductive age.

Adult↗

Initial evaluation of the new urinary bladder cancer rapid test in the detection of transitional cell carcinoma of the bladder.

OBJECTIVES: To evaluate the diagnostic performance of the new noninvasive urinary bladder cancer (UBC) rapid test in selected urine voided samples for the detection of transitional cell carcinoma (TCC) of the bladder, and to assess the differential sensitivity of the biomarker regarding the most relevant histologic and clinical parameters of bladder cancer. METHODS: Two hundred sixty-seven subjects were entered into the study and classified into five groups: 111 patients with active TCC of the bladder (group 1); 76 follow-up patients with TCC free from disease as confirmed by cystoscopy (group 2); 25 patients with other benign urologic diseases (group 3); 25 patients with other malignant pathologic conditions (group 4); and 30 healthy subjects (group 5). The UBC rapid test was measured by an immunochromatographic method that qualitatively detects the presence of fragments of cytokeratins 8 and 18 in the urine. UBC rapid test differences regarding stage, grade, tumor size, pattern of growth, focality, and recurrence were also evaluated. RESULTS: The sensitivity in group 1 was 78.4% and the specificity in group 2 was 97.4%. Positive and negative predictive values in groups 1 and 2 were 97.4% and 79.0%, respectively, with a global accuracy of 86.1%. False-positive rates were 20.0% and 44.0% for groups 3 and 4, respectively. The sensitivities of the UBC rapid test were associated with the histologic and clinical characteristics of bladder cancer, but not enough to reach statistical significance. CONCLUSIONS: The UBC rapid test appears to be a promising noninvasive adjunct that might guide the urologist in the decision to perform cytoscopy for the detection of TCC of the bladder. Further studies appear to be merited to assess its potential diagnostic role.

Aged↗

Bead-based ELISA for validation of ovarian cancer early detection markers.

PURPOSE: Efforts to validate ovarian cancer early detection biomarkers with immunoassays are challenged by the limited specimen volumes available. We sought to develop a specimen-efficient assay to measure CA125 in serum, assess its reproducibility, validity, and performance, and test its potential for multiplexing and combining with human epididymis protein 4 (HE4), a promising novel ovarian cancer marker. EXPERIMENTAL DESIGN: Four pairs of commercially available anti-CA125 antibodies and one pair of anti-HE4 antibodies were evaluated for accuracy in measuring known concentrations of antigen on a bead-based platform. The two best pairs were further assessed for reproducibility, validity, and the ability to discriminate between blinded serum samples obtained from ovarian cancer cases (n = 66) and women without ovarian cancer (n = 125). RESULTS: Suitability for use in a bead-based assay varied across CA125 antibody pairs. Two CA125 bead-based assays were highly reproducible (overall correlations between replicates >/= 0.95; coefficients of variation < 0.2) and strongly correlated with the research standard CA125II RIA (correlations >/= 0.9). Their ability to distinguish ovarian cancer cases from non-cases based on receiver operating characteristic analyses (area under the curve, AUC, of 0.85 and 0.84) was close to that of the CA125II RIA (AUC, 0.87). The HE4 bead-based assay showed lower reproducibility but yielded an AUC of 0.89 in receiver operating characteristics analysis. Multiplexing was not possible but a composite marker including CA125 and HE4 achieved an AUC of 0.91. CONCLUSION: Optimization procedures yielded two bead-based assays for CA125 that perform comparably to the standard CA125II RIA, which could be combined with an HE4 bead-based assay to improve diagnostic performance, and requires only 15 muL of sample each.

Adult↗

Wireless networking for the dental office: current wireless standards and security protocols.

Digital radiography has gained immense popularity in dentistry today in spite of the early difficulty for the profession to embrace the technology. The transition from film to digital has been happening at a faster pace in the fields of Orthodontics, Oral Surgery, Endodontics, Periodontics, and other specialties where the radiographic images (periapical, bitewing, panoramic, cephalometric, and skull radiographs) are being acquired digitally, stored within a server locally, and eventually accessed for diagnostic purposes, along with the rest of the patient data via the patient management software (PMS). A review of the literature shows the diagnostic performance of digital radiography is at least comparable to or even better than that of conventional radiography. Similarly, other digital diagnostic tools like caries detectors, cephalometric analysis software, and digital scanners were used for many years for the diagnosis and treatment planning purposes. The introduction of wireless charged-coupled device (CCD) sensors in early 2004 (Schick Technologies, Long Island City, NY) has moved digital radiography a step further into the wireless era. As with any emerging technology, there are concerns that should be looked into before adapting to the wireless environment. Foremost is the network security involved in the installation and usage of these wireless networks. This article deals with the existing standards and choices in wireless technologies that are available for implementation within a contemporary dental office. The network security protocols that protect the patient data and boost the efficiency of modern day dental clinics are enumerated.

Computer Security↗