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Serum Olink Proteomics Reveals Novel Biomarkers for Early Diagnosis of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly prevalent malignant tumor in China, and early diagnosis critically affects the prognosis. Current imaging and pathological biopsy techniques have limitations, including high invasiveness and limited accessibility, while the insufficient sensitivity of serum biomarkers (such as AFP) restricts their use in early screening. In this study, using the Olink proteomics platform based on the proximity extension assay (PEA), we screened for hepatocellular carcinoma-related differentially expressed proteins (DEPs) and constructed a multiprotein diagnostic model. In the discovery cohort, we included 15 patients with newly diagnosed HCCs and 16 healthy controls. DEPs were identified using Olink, and their diagnostic performance was analyzed to identify the candidate biomarkers. In an independent validation cohort, including 116 HCC patients (50 early stage, 66 late stage) and 83 healthy controls, we further validated the expression levels and diagnostic performance of identified proteins─C1QA and GFER. The C1QA and GFER expression levels were significantly higher in the serum of patients with early and late HCC stages compared to healthy controls. By constructing a multiprotein diagnostic model, we identified C1QA, GFER, and AFP as the optimal diagnostic combination, demonstrating a combined diagnostic AUC of 0.92 and 0.99 for early-stage and advanced-stage HCC, respectively.

Humans↗

Malaria rapid diagnostic devices: performance characteristics of the ParaSight F device determined in a multisite field study.

Microscopic detection of parasites has been the reference standard for malaria diagnosis for decades. However, difficulty in maintaining required technical skills and infrastructure has spurred the development of several nonmicroscopic malaria rapid diagnostic devices based on the detection of malaria parasite antigen in whole blood. The ParaSight F test is one such device. It detects the presence of Plasmodium falciparum-specific histidine-rich protein 2 by using an antigen-capture immunochromatographic strip format. The present study was conducted at outpatient malaria clinics in Iquitos, Peru, and Maesod, Thailand. Duplicate, blinded, expert microscopy was employed as the reference standard for evaluating device performance. Of 2,988 eligible patients, microscopy showed that 547 (18%) had P. falciparum, 658 (22%) had P. vivax, 2 (0.07%) had P. malariae, and 1,750 (59%) were negative for Plasmodium. Mixed infections (P. falciparum and P. vivax) were identified in 31 patients (1%). The overall sensitivity of ParaSight F for P. falciparum was 95%. When stratified by magnitude of parasitemia (no. of asexual parasites per microliter of whole blood), sensitivities were 83% (>0 to 500 parasites/microl), 87% (501 to 1,000/microl), 98% (1,001 to 5,000/microl), and 98% (>5,000/microl). Device specificity was 86%.

Animals↗

Optimization of semi-quantification in metabolic PET studies with 18F-fluorodeoxyglucose and 11C-methionine in the determination of malignancy of gliomas.

The treatment of the glioma patient depends on the nature of the lesion and on the aggressiveness of the tumor. The management of gliomas continues to be a challenging task, because morphological neuroimaging techniques do not always differentiate them from nontumoral lesions or high grade tumors from low grade lesions. Positron Emission Tomography (PET) offers the possibility of the in vivo quantitative characterization of brain tumors. Despite decades of useful application of PET in the clinical monitoring of gliomas, no consensus has been reached on the most effective image analysis approach for providing the best diagnostic performance under heavy-duty clinical diagnostic circumstances. The main objective of the present study was to find and validate optimal semi-quantitative search strategies for metabolic PET studies on gliomas, with special regard to the optimization of those metabolic tracer uptake ratios most sensitive in predicting histologic grade and prognosis. 11C-Methionine (11C-Met, n = 50) and/or 18F-Fluorodeoxyglucose (18F-FDG, n = 33) PET measurements were performed in 59 patients with primary and recurrent brain gliomas (22 high grade and 37 low grade tumors) in order to correlate the biological behavior and 11C-Met/18F-FDG uptake of tumors. Data were analyzed by region-of-interests (ROI) methods using standard uptake value calculation. Different ROI defining strategies were then compared with each other for two of the most commonly used metabolic radiotracers, 18F-FDG and 11C-Met, in order to determine their usefulness in grading gliomas. The results were compared to histological data in all patients. Both ANOVA and receiver operating characteristic (ROC) analysis indicated that the performance of 18F-FDG was superior to that of 11C-Met for most of the ratios. 18F-FDG is therefore suggested as the tracer of choice for noninvasive semi-quantitative indicator of histologic grade of gliomas. 11C-Methionine has been suggested as a complimentary tracer, useful in delineating the extent of the tumor. The best diagnostic performance was obtained by calculating the ratio of the peak 18F-FDG uptake of the tumor to that of white matter (p < 0.001; ANOVA). This metabolic tracer uptake ratio is therefore suggested as an easily obtained semi-quantitative PET indicator of malignancy and histological grade in gliomas.

Adolescent↗

Analytic validation and clinical evaluation of the STA LIATEST immunoturbidimetric D-dimer assay for the diagnosis of disseminated intravascular coagulation.

To evaluate the diagnostic performance of a quantitative, immunoturbidimetric D-dimer assay and compare it with other components of the proposed International Society on Thrombosis and Haemostasis disseminated intravascular coagulation (DIC) diagnostic algorithm, we retrospectively analyzed the D-dimer, platelet count, prothrombin time, and fibrinogen results for all eligible hospitalized patients (n = 241) who had a D-dimer assay ordered during a 12-month period. A receiver operating characteristic (ROC) curve constructed from the maximum D-dimer measurement for all patients was significant (P < .001) with an area under the curve (AUC) of 0.94. The ROC curves of the other tests were each significant (P < .001), but the AUCs of the prothrombin time (0.74), fibrinogen level (0.70), and platelet count (0.67) did not approach that of the D-dimer. A D-dimer cutoff of 8.2 microg/mL (8,200 microg/L) optimized sensitivity and negative predictive value for the total population and patients with a predisposing condition. Validation against 286 additional patients in a separate analysis verified the diagnostic performance of the aforementioned cutoff. A sensitive, immunoturbidimetric D-dimer assay, by itself provides excellent sensitivity and negative predictive value for the diagnosis of DIC.

Adult↗

[Indications, performance and complications of bronchofibroscopy in the aged].

Bronchofibroscopy is a widely used exploration for the diagnosis of several pulmonary processes. However, its use in aged patients, these being considered a high risk group, is still a controversial issue. The aim of this study was to analyze the indications, diagnostic performance and complications of the bronchofibroscopy in the elderly and to determine if there are any differences with respect to the adult population. A retrospective case control study was conducted, taking as cases those patients with 70 or more years of age, and as controls, those patients with less than 70 years. The study period was 1 year, with 54 bronchofibroscopies performed in 49 patients from the study group and 149 in 145 patients from the control group. The indications were similar in both groups, except for the study of opportunistic infections, these being more frequent among the control group. Diagnostic performance and complications did not show any differences between both groups. Indications, performance and complications of bronchofibroscopy in aged patients are similar to those in the adult population. Hence, the age in itself should not be a limiting factor for the indication of this exploration.

Adult↗

The role of pattern analysis and the ABCD rule of dermoscopy in the detection of histological atypia in melanocytic naevi.

BACKGROUND: Clinical features of melanocytic naevi correlate poorly with the presence, histopathologically, of architectural disorder and cytological atypia, making the detection of histological atypia by means of macroscopic appearance unreliable. OBJECTIVES: The aim of this study was to investigate the diagnostic effectiveness of dermoscopy in the non-invasive detection of histological atypia in naevi. METHODS: Observers blinded for histological diagnosis classified a series of 168 melanocytic naevi as common or atypical on the basis of their clinical features and on their dermoscopic profile. The diagnostic performance of both methods compared with the true (histopathological) diagnosis was assessed. RESULTS: Dermoscopy using pattern analysis showed better results than clinical examination in the non-invasive detection of naevi with architectural disorder with or without cytological atypia (diagnostic accuracy 45% vs. 28%). A statistically significant difference in the frequency of dermoscopic parameters between atypical and common naevi was found for atypical pigment network (39% vs. 17%, P = 0.001) and dermoscopic regression structures (13% vs. 2%, P = 0.008). Dermoscopic features, which best predicted histological atypia in naevi, were regression structures (white scar-like areas or peppering), irregular vascular pattern and grey-blue areas (positive predictive values 83%, 83% and 73%, respectively). In contrast, no statistically significant difference in the mean values of the ABCD score between common and atypical naevi was found. The best diagnostic performance of dermoscopy by means of the ABCD rule (cut-off point of 4.0 of total dermoscopy score) was not dissimilar to that of clinical diagnosis (diagnostic accuracy 30%). CONCLUSIONS: Dermoscopy by means of pattern analysis enhances the diagnostic accuracy of dermatologists in the prediction of histological atypia in melanocytic naevi as compared with clinical examination alone.

Diagnosis, Differential↗

Conventional film-screen versus computed storage phosphor radiography. Simulated miliary lung disease in an anthropomorphic phantom.

RATIONALE AND OBJECTIVES: In this experimental study, the authors examined whether laser printed hardcopies from digital storage phosphor radiographs yield diagnostic performance equal to conventional film-screen radiographs in the detection of simulated miliary disease, using a standardized object. METHODS: A commercially available anthropomorphic chest phantom was used for radiographic evaluation. Miliary disease was simulated by superimposing one to four sheets of millet seeds on the lungs, resembling a miliary disease pattern with varying degrees of detectability. An observer study (receiver-operating characteristic) with eight radiologists was conducted to compare the reader performance using hardcopies of computed storage phosphor radiography versus the conventional film-screen system, optimized for chest x-rays. The digitally generated images were presented as a double-image hardcopy, with a conventionally adopted version and an edge enhanced image version. RESULTS: When analyzed separately, one out of the eight observers performed slightly better using the conventional films. When treated as a group, analysis of the areas under the receiver-operating characteristic curves demonstrated no significant difference in reader performance for each of the systems under investigation (t = 0.286). The Wilcoxon test could not prove a statistical difference. CONCLUSION: Storage phosphor technology is a method that yields equal diagnostic performance as conventional film in evaluating miliary disease of the chest.

Adult↗

Clinical performance of the urine-based TERT promoter AbsoluteQ Digital PCR for non-invasive detection of bladder cancer.

Bladder cancer (BC) is the ninth most common cancer worldwide, with urothelial carcinoma accounting for approximately 90% of all cases and presenting predominantly as non-muscle-invasive disease. Due to its high recurrence rate and the need for long-term surveillance, BC is associated with the highest lifetime treatment costs per patient among all cancers, making its effective management a significant clinical and economic challenge. The most frequently identified variants in the TERT gene promoter are c.-124C>T (C228T) and c.-146C>T (C250T), located within a region characterized by high guanine-cytosine (GC) content, which makes amplification challenging. We aimed to validate the AbsoluteQ Digital PCR assay for the detection of urine-based TERT promoter variants for the diagnosis of urothelial bladder cancer and to assess its diagnostic performance in comparison with standard methods. Urine samples were collected from patients with histopathologically confirmed bladder cancer (n&#x2009;=&#x2009;58) and compared with a control group (n&#x2009;=&#x2009;55). The C228T and C250T variants were tested using the AbsoluteQ Digital PCR assay. Sensitivity, specificity, and predictive values were calculated to evaluate the performance of the assessed method. The AbsoluteQ Digital PCR demonstrated superior diagnostic performance compared to conventional Sanger sequencing for detecting TERT promoter variants, achieving a sensitivity of 89.65% (95% CI: 78.16-95.72) and a specificity of 100% (95% CI: 91.87-100), with no false positives observed. Given its robustness and clinical relevance, AbsoluteQ Digital PCR is emerging as a promising tool for non-invasive molecular diagnostics targeting TERT promoter variants.

Humans↗

Accuracy of diagnostic imaging techniques in the diagnosis of aseptic loosening of the femoral component of a hip prosthesis: a meta-analysis.

In this meta-analysis we included 32 English-language articles published between January 1975 and June 2004 on the diagnostic performance of plain radiography, subtraction arthrography, nuclear arthrography and bone scintigraphy in detecting aseptic loosening of the femoral component, using criteria based on the Cochrane systematic review of screening and diagnostic tests. The mean sensitivity and specificity were, respectively, 82% (95% confidence interval (CI) 76 to 87) and 81% (95% CI 73 to 87) for plain radiography and 85% (95% CI 75 to 91) and 83% (95% CI 75 to 89) for nuclear arthrography. Pooled sensitivity and specificity were, respectively, 86% (95% CI 74 to 93) and 85% (95% CI 77 to 91) for subtraction arthrography and 85% (95% CI 79 to 89) and 72% (95% CI 64 to 79) for bone scintigraphy. Although the diagnostic performance of the imaging techniques was not significantly different, plain radiography and bone scintigraphy are preferred for the assessment of a femoral component because of their efficacy and lower risk of patient morbidity.

Arthrography↗

Rapid screening for Schistosoma mansoni in western Côte d'Ivoire using a simple school questionnaire.

The distribution of schistosomiasis is focal, so if the resources available for control are to be used most effectively, they need to be directed towards the individuals and/or communities at highest risk of morbidity from schistosomiasis. Rapid and inexpensive ways of doing this are needed, such as simple school questionnaires. The present study used such questionnaires in an area of western Côte d'Ivoire where Schistosoma mansoni is endemic; correctly completed questionnaires were returned from 121 out of 134 schools (90.3%), with 12,227 children interviewed individually. The presence of S. mansoni was verified by microscopic examination in 60 randomly selected schools, where 5047 schoolchildren provided two consecutive stool samples for Kato-Katz thick smears. For all samples it was found that 54.4% of individuals were infected with S. mansoni. Moreover, individuals infected with S. mansoni reported "bloody diarrhoea", "blood in stools" and "schistosomiasis" significantly more often than uninfected children. At the school level, Spearman rank correlation analysis showed that the prevalence of S. mansoni significantly correlated with the prevalence of reported bloody diarrhoea (P = 0.002), reported blood in stools (P = 0.014) and reported schistosomiasis (P = 0.011). Reported bloody diarrhoea and reported blood in stools had the best diagnostic performance (sensitivity: 88.2%, specificity: 57.7%, positive predictive value: 73.2%, negative predictive value: 78.9%). The study, which is probably the largest of its kind ever undertaken in Africa, revealed a moderate diagnostic performance of questionnaires for identifying individuals and/or communities at high risk from S. mansoni.

Adolescent↗

A new-generation dilute Russell's viper venom time assay system for lupus anticoagulants: evaluation of detection utilising frozen reagents and controls.

The dilute Russell's viper venom time (DRVVT) is one of the most widely used assays to detect lupus anticoagulants (LAs). Variation in diagnostic performance exists between DRVVT reagents from various manufacturers due to a variety of factors such as antibody heterogeneity, reagent phospholipid composition, venom heterogeneity, assay methodology and analytical technique. Recently, a new-generation DRVVT assay system has become available that utilises frozen reagents and controls that offer potential benefits to the diagnostic laboratory in terms of reagent quality and convenience of use. This study evaluates the diagnostic and analytical performance of these CryoCheck reagents and controls on a commonly employed automated coagulation analyser, the Sysmex CA 1500. Sensitivity is assessed by analysis of 60 samples shown to contain LAs by combinations of an alternative DRVVT, LA-sensitive dilute activated partial thromboplastin time and activated seven lupus anticoagulant assay. Specificity is assessed using 30 samples negative for LA, eight plasmas from non-LA orally anticoagulated patients and also immunodepleted factor-deficient plasmas. The CryoCheck reagents generated comparable diagnostic performance data to that previously reported for other reagents. There was a marked improvement in sensitivity when the BCSH recommended percent correction of ratio calculation for assessment of phospholipid dependence was employed in place of the manufacturer suggested test/confirm ratio. Slightly better diagnostic performance was achieved when using a frozen pooled normal control in place of a lyophilised normal control to generate sample/control ratios, giving sensitivity, specificity, positive predictive and negative predictive values of 88.2%, 86.8%, 90% and 85.2%, respectively. The combination of CryoCheck reagents and the Sysmex CA 1500 analyser provides a sensitive and specific LA detection technique comparable to those currently available.

Freezing↗

Analytical performance and diagnostic accuracy of immunometric assays for the measurement of circulating oxidized LDL.

BACKGROUND: Oxidized LDL (ox-LDL) plays an important role in the pathogenesis of coronary heart disease (CHD). Several tests for circulating ox-LDL have been published. We believe it is critical to carefully evaluate these assays because small differences in performance may have profound effects when results are compared; we therefore compared the analytical and clinical performances of 2 assays: one developed in our laboratory and a commercial assay (Mercodia) that uses the same monoclonal antibody (4E6). METHODS: We determined the variance of ox-LDL in both tests, including its longitudinal stability (n = 225; 3 time points per person) and its diagnostic accuracy, by ROC analysis of 95 consecutive CHD patients and 20 controls. RESULTS: The between-person variability was 77% for the in-house assay (with the remaining 23% being within-person and analytical variance) and 74% for the commercial assay. For comparison, previously reported values were 66% for high-sensitivity C-reactive protein and 82% for total cholesterol. The areas under the curves for CHD in the 2 assays were identical (0.85). The odds ratios (logistic regression) for CHD among persons with high ox-LDL (>or=15 mg/L) compared with persons with low ox-LDL were not different: 4.3 (95% confidence interval, 1.4-12) for the in-house assay and 3.3 (1.1-10) for the commercial assay. CONCLUSIONS: The longitudinal stability of ox-LDL, as assessed by multiple measures in people over time, is similar to that of total cholesterol and high-sensitivity C-reactive protein. Both assays tested similarly distinguish between healthy controls and CHD patients.

Adult↗

Systematic review of the effectiveness and cost-effectiveness, and economic evaluation, of myocardial perfusion scintigraphy for the diagnosis and management of angina and myocardial infarction.

OBJECTIVES: To assess the effectiveness and cost-effectiveness of single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy for the diagnosis and management of angina and myocardial infarction (MI). DATA SOURCES: Major electronic databases. REVIEW METHODS: Two reviewers independently extracted data and assessed study quality. A decision tree model was used to model the diagnosis decision and a Markov model was developed for the management of patients with suspected coronary artery disease. Costs for the treatments and interventions within strategies were derived from the literature and expressed in 2001-02 pounds sterling. Quality-adjusted life-year (QALY) weights for the different Markov model states were also obtained from the literature. RESULTS: Twenty-one diagnostic and 46 prognostic studies were included, plus two studies comparing SPECT with electrocardiography (ECG)-gated SPECT and one study comparing SPECT with attenuation-corrected SPECT. The diagnostic values of SPECT were generally higher than those of stress ECG, indicating that SPECT provided a better diagnostic performance. SPECT also provided higher positive and lower negative likelihood ratios than stress ECG but heterogeneity was evident among studies. The subgroup of studies including patients with previous MI tended to report a better diagnostic performance for SPECT than stress ECG, but there were too few studies to assess this reliably. The extent and size of the perfusion defect, and whether reversible or fixed, were important factors in predicting future cardiac events such as cardiac death or non-fatal MI. SPECT may be able to identify lower risk patients for whom coronary angiography (CA) might be avoided. Normal SPECT scans were associated with a benign prognosis and the option of medical rather than invasive management. Four studies of patients post-MI reported SPECT to be valuable in stratifying patients into at-risk groups for further cardiac events. The two studies comparing SPECT with ECG-gated SPECT, one diagnostic and the other prognostic, found in favour of gated SPECT. The study comparing SPECT with attenuation-corrected SPECT reported the latter to be more accurate. The systematic review of economic evaluations indicated that strategies involving SPECT were likely either to be dominant or to produce more QALYs at an acceptable cost. There was less agreement about which of the strategies involving SPECT was optimal. The model suggested that, for low prevalence, the incremental cost per unit of output (true positives diagnosed, accurate diagnosis, QALY) for the move from stress ECG-SPECT-CA and from stress ECG-CA to SPECT-CA might be considered worthwhile. Even after allowing for different values for sensitivity or specificity, the least costly and least effective strategy was stress ECG-SPECT-CA. The sensitivity analysis suggested that the cost-effectiveness of SPECT-CA improved if it was assumed that SPECT results allowed for the adoption of a management strategy without recourse to CA. As the time horizon reduced, the incremental cost per QALY increased (as the cost of initial diagnosis and treatment were not offset by survival and quality of life gains). CONCLUSIONS: There was a considerable variability in terms of measurement of outcomes, management, setting and patient characteristics, however the direction of evidence tended to favour SPECT in terms of test sensitivity, although these conclusions are based on a relatively small number of diagnostic studies. SPECT, in a variety of settings and patient populations, provided valuable independent and incremental prognostic information to that provided by stress ECG and/or CA that helped to risk-stratify patients and influence the way in which their condition was managed. However, all of the prognostic studies were observational studies and may be biased by unknown confounding factors. Although the ECG-gated and attenuation-corrected SPECT findings seem promising, it is difficult to draw conclusions from so few studies. Further research is needed on the effectiveness and cost-effectiveness, diagnostically and prognostically, of (a) gated and attenuation-corrected SPECT compared with standard SPECT, (b) standard SPECT compared with stress echocardiography and (c) the uncertainty surrounding the results presented in the cost-effectiveness analysis.

Angina Pectoris↗

Non-invasive analysis of melanoma thickness by means of dermoscopy: a retrospective study.

Epiluminescence microscopy (ELM), or dermatoscopy, is a non-invasive technique for the diagnosis of cutaneous melanoma that may play a role in the non-invasive, preoperative assessment of melanoma thickness. This study investigated the correlation between the frequency of appearance of some standard ELM criteria and the histological thickness of melanomas. In addition, the possible role of the total dermoscopic score (TDS) according to ABCD rule of dermoscopy as a predictor of melanoma thickness was analysed. The dermoscopic images of 84 cutaneous melanomas were retrospectively investigated to evaluate the presence of 10 standard ELM criteria, and for each lesion the TDS was established (with observers blinded as to the tumour thickness). A statistically significant association was found between the presence of an irregular pigment network and melanomas with a Breslow index equal to or lower than 0.75 mm (positive predictive value of 68%); in contrast, radial streaming, atypical vascular pattern and grey-blue areas were associated with melanomas > 0.75 mm (positive predictive values of 77%, 65% and 70%, respectively). Of the melanomas thinner than 0.76 mm, 82% showed a TDS lower than 6.80 (optimized cut-off point), while 79% of melanomas thicker than 0.75 mm had a TDS higher than 6.80 (chi2 = 30.815, P < 0.001); the positive predictive value of a TDS > 6.80 in the detection of lesions thicker than 0.75 mm was 79%. In conclusion, a statistically significant correlation does exist between some dermoscopic features and melanoma thickness. Both the mostly used dermoscopic methods (standard ELM pattern analysis and the ABCD rule of dermatoscopy) may provide useful information in the non-invasive assessment of melanoma thickness. However, their diagnostic performance is far from 100%; further studies are needed to investigate whether the combination of dermoscopy with other non-invasive approaches (e.g. sonometry) may result in an overall improvement in the diagnostic performance.

Adolescent↗

Electrical methods in occlusal caries diagnosis: An in vitro comparison with visual inspection and bite-wing radiography.

The aim of this study was to compare in vitro diagnostic performance of three electrical methods for occlusal caries diagnosis with that of visual inspection and bite-wing radiography. One hundred and seven extracted molar and premolar teeth were subjected to the diagnostic methods by 2 operators and subsequently sectioned for histological validation. Electrical measurements were made at site level and at surface level using two different instruments. The diagnostic parameters calculated from the results were: sensitivity, specificity, diagnostic accuracy at a theoretical caries prevalence of 10% and area under the ROC curve. The electrical methods and bite-wing radiography showed higher sensitivity and lower specificity than visual inspection. Diagnostic accuracy was significantly lower for bite-wing radiography and one electrical method than for visual inspection. Overall diagnostic performance of two electrical methods was superior.

Area Under Curve↗

Assessing the responsiveness of functional scales to clinical change: an analogy to diagnostic test performance.

One characteristic of newer health or functional status scales which has received little attention is their responsiveness over time to clinical change. In part, this is because methods for assessing this characteristic are crude and not well standardized. We suggest that scales be viewed as "diagnostic tests" for discriminating between improved and unimproved patients. With this perspective, one may construct receiver operating characteristic (ROC) curves describing a scale's ability to detect improvement (or failure to improve) using some external criterion. This method is illustrated using data from a study of acute low back pain, comparing the Sickness Impact Profile, its major subscales, and a shorter, more disease-specific scale. The results demonstrate an advantage of the ROC approach over simple pre- and post-treatment score comparisons in assessing scale responsiveness. They also suggest some advantage for a brief disease-specific scale over the lengthier "generic" SIP.

Adult↗

Epiluminescence microscopy. A useful tool for the diagnosis of pigmented skin lesions for formally trained dermatologists.

BACKGROUND AND DESIGN: Epiluminescence microscopy (ELM) is a noninvasive technique that, by employing the optical phenomenon of oil immersion, makes subsurface structures of the skin accessible for in vivo examination and thus provides additional criteria for the clinical diagnosis of pigmented skin lesions. At present, almost all studies about the value and clinical importance of ELM are based on data derived from ELM experts (ie, dermatologists specifically trained in this technique). In the present study, we attempt to determine whether the clinical diagnosis of pigmented skin lesions is significantly improved using ELM and whether ELM-trained individuals and dermatologists not trained in this technique profit equally from this technique. Randomly selected histologically proven pigmented skin lesion specimens, photographed with (ELM) and without oil immersion (surface microscopy) were presented by slide projection to six ELM experts and 13 ELM nonexperts (ie, dermatologists not formally trained in ELM) for diagnosis. To evaluate the diagnostic performance of ELM experts and nonexperts with and without the oil immersion technique (ie, ELM vs surface microscopy), the following parameters were obtained: intraobserver and interobserver agreement by kappa statistics and sensitivity and specificity of diagnostic performance. RESULTS: Our results show that by using the ELM technique the ELM experts reach a substantially better intraobserver agreement than nonexperts (median kappa, 0.56 vs 0.36). The interobserver agreement was markedly increased in the ELM experts group (average gain, 7%) but decreased in the ELM nonexperts group (average loss, 6%). The sensitivity of diagnosis was significantly increased in the ELM experts group (average gain, 10%), but decreased in the nonexperts group (average loss, 10%). Finally, the specificity of diagnosis was excellent in the ELM experts group, both with and without oil immersion (0.91) and was somewhat improved by ELM in the nonexperts group (0.77 vs 0.85). CONCLUSIONS: We conclude that the ELM technique increases sensitivity in formally trained dermatologists, but may decrease the diagnostic ability in dermatologists not formally trained in the ELM technique. Consequently, formal broad-based training in ELM should be offered to the dermatologic community.

Clinical Competence↗

The role of basic science knowledge and clinical knowledge in diagnostic reasoning: a structural equation modeling approach.

PURPOSE: To examine four theories on the role of basic science knowledge and clinical knowledge in diagnostic reasoning. METHOD: In 2000-01, the authors tested the basic science and clinical knowledge and diagnostic performances of 59 family physicians and 184 second- to sixth-year medical students at Maastricht University, The Netherlands. Structural equation modeling was used to analyze the data. Four theoretical models were tested. In the first model only basic science knowledge is involved in diagnostic reasoning; in the second model only clinical knowledge is related to diagnostic reasoning; in the third model, clinical knowledge is related to diagnostic reasoning, but basic science knowledge is integrated in clinical knowledge; and in the fourth model, both basic science knowledge and clinical knowledge independently influence diagnostic reasoning. RESULTS: Forty-four (75%) of the family physicians and 184 (100%) of the students responded. The results indicated that the third model, which is based on the knowledge encapsulation theory, provided the best fit to the data, whereas the models that had directly related basic science knowledge with diagnostic performance did not fit the data adequately. CONCLUSION: The results generally supported the third model by Schmidt and Boshuizen of knowledge encapsulation theory suggesting that basic science knowledge is activated in expert diagnostic reasoning through its relation with clinical knowledge.

Clinical Competence↗