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The Youden Index and the optimal cut-point corrected for measurement error.

Random measurement error can attenuate a biomarker's ability to discriminate between diseased and non-diseased populations. A global measure of biomarker effectiveness is the Youden index, the maximum difference between sensitivity, the probability of correctly classifying diseased individuals, and 1-specificity, the probability of incorrectly classifying health individuals. We present an approach for estimating the Youden index and associated optimal cut-point for a normally distributed biomarker that corrects for normally distributed random measurement error. We also provide confidence intervals for these corrected estimates using the delta method and coverage probability through simulation over a variety of situations. Applying these techniques to the biomarker thiobarbituric acid reaction substance (TBARS), a measure of sub-products of lipid peroxidation that has been proposed as a discriminating measurement for cardiovascular disease, yields a 50% increase in diagnostic effectiveness at the optimal cut-point. This result may lead to biomarkers that were once naively considered ineffective becoming useful diagnostic devices.

Biomarkers↗

Validity and clinical utility of sleep laboratory criteria for insomnia.

The sensitivity, specificity, and positive predictive value of two proposed sleep laboratory criteria for the diagnosis of insomnia were evaluated in 375 adults with a primary complaint of insomnia and 150 noninsomniac controls. The two criteria used results in either low sensitivity and moderately strong specificity or high sensitivity and low specificity and, accordingly, in both cases weak positive predictive values (diagnostic accuracy), both for one night and multiple nights of recordings. Further, an empirically optimized criterion also resulted in an unsatisfactory diagnostic accuracy. Finally, the optimized MMPI criteria were superior to optimized sleep criteria in differentiating insomniacs from controls. In conclusion, sleep laboratory recordings provide little relevant information for confirming or excluding the presence of insomnia.

Adolescent↗

[The status of biological risk factors and the optimality concept in diagnosis of early childhood developmental disorders].

In a prospective study the psychomotor development up to the end of the second year of life of 409 preterm and term newborn infants was examined in order to identify which optimality score might be associated with disturbances of normal childlike development. Significant connections between 24 and 55 risk factors and the mortality could be demonstrated, but only 3 factors (sex, apgar, acidosis) exert influence on psychomotor development. The risk loading of the collective was high, not one of the children showed an optimal score. Decreased patients possessed a stronger reduced optimality than survivors. The optimality concept is not suitable for the prediction of later disturbed development of children, because the items are unspecific. The marker of hypoxia, the erythrocytic-density-test, as well as the neuron-specific enolase showed better diagnostic values than the optimality concept.

Brain Damage, Chronic↗

Stratum-specific likelihood ratios of the general health questionnaire in the community: help-seeking and physical co-morbidity affect the test characteristics.

BACKGROUND: In evidence-based medicine, stratum-specific likelihood ratios (SSLRs) are now being increasingly recognized as a more convenient and generalizable method to interpret diagnostic information than an optimal cut-off and its associated sensitivity and specificity. We previously examined the SSLRs of the General Health Questionnaire (GHQ) in primary care settings. The present paper aims to examine if these SSLRs are generalizable to the community settings. METHODS: The Composite International Diagnostic Interview (CIDI) and the GHQ were administered on a representative sample of the Australian population in the Australian National Survey of Mental Health and Well-Being. We first compared the SSLRs of GHQ in urban Australia with the estimates that we had previously obtained from the developed urban centres in the WHO Psychological Problems in General Health Care study. If the SSLRs in the community were found to differ significantly from those in the primary care, we sought for explanatory variables. RESULTS: The SSLRs in urban Australia and in the urban centres in the WHO study were significantly different for three out of the six strata. When we limited the sample to those with physical problems who visited a health professional, however, the SSLRs in the Australian study were strikingly close to those observed for primary care settings. CONCLUSIONS: Different sets of SSLRs apply to primary care and general population samples. For general population surveys in developed countries, the results of the Australian National Survey represent the currently available best estimates. For developing countries or rural areas, the results are less definitive and an investigator may wish to conduct a pilot study.

Adolescent↗

Laboratory automation: trajectory, technology, and tactics.

Laboratory automation is in its infancy, following a path parallel to the development of laboratory information systems in the late 1970s and early 1980s. Changes on the horizon in healthcare and clinical laboratory service that affect the delivery of laboratory results include the increasing age of the population in North America, the implementation of the Balanced Budget Act (1997), and the creation of disease management companies. Major technology drivers include outcomes optimization and phenotypically targeted drugs. Constant cost pressures in the clinical laboratory have forced diagnostic manufacturers into less than optimal profitability states. Laboratory automation can be a tool for the improvement of laboratory services and may decrease costs. The key to improvement of laboratory services is implementation of the correct automation technology. The design of this technology should be driven by required functionality. Automation design issues should be centered on the understanding of the laboratory and its relationship to healthcare delivery and the business and operational processes in the clinical laboratory. Automation design philosophy has evolved from a hardware-based approach to a software-based approach. Process control software to support repeat testing, reflex testing, and transportation management, and overall computer-integrated manufacturing approaches to laboratory automation implementation are rapidly expanding areas. It is clear that hardware and software are functionally interdependent and that the interface between the laboratory automation system and the laboratory information system is a key component. The cost-effectiveness of automation solutions suggested by vendors, however, has been difficult to evaluate because the number of automation installations are few and the precision with which operational data have been collected to determine payback is suboptimal. The trend in automation has moved from total laboratory automation to a modular approach, from a hardware-driven system to process control, from a one-of-a-kind novelty toward a standardized product, and from an in vitro diagnostics novelty to a marketing tool. Multiple vendors are present in the marketplace, many of whom are in vitro diagnostics manufacturers providing an automation solution coupled with their instruments, whereas others are focused automation companies. Automation technology continues to advance, acceptance continues to climb, and payback and cost justification methods are developing.

Automation↗

Optimization of automated quantification of 123I-IBZM uptake in the striatum applied to parkinsonism.

UNLABELLED: Evaluation of therapies for parkinsonism by dopamine receptor SPECT requires a reproducible, optimized quantitation technique. This study presents a new, objective, automated technique for semiquantitative analysis of dopamine receptor density, as applied to the differential diagnosis of parkinsonism. METHODS: Dopamine receptor density measured by 123I-iodobenzamide (IBZM) SPECT was retrospectively analyzed in nonidiopathic parkinsonism (NIPS), in Parkinson's disease (PD), and in healthy volunteers (n = 19, 38, and 13, respectively). A mean template was created from coregistered control studies. Registration errors were assessed using studies with simulated binding deficits. Patient studies were registered to the mean template, and striatal binding was calculated from a corresponding map of 3-dimensional regions of interest (ROIs). The striatal binding ratio and deficits determined by voxelwise comparison with the normal template were investigated and tested with various 3-dimensional ROI sizes and positions. Separation of patient groups was determined by tscore after automatically processing all studies. Results were compared with manual ROI analyses. RESULTS: The automatic method was completely reproducible in 64 of 70 cases. The best diagnostic discriminator was the minimum binding ratio of the 2 striatal nuclei, with the following values: NIPS, 1.33+/-0.13; PD, 1.50+/-0.12; healthy volunteers, 1.49+/-0.08 (+/-SD). The deficit size from voxelwise analysis was: NIPS, 20.5+/-8.2 mL; PD, 9.5+/-8.3; healthy volunteers, 8.9+/-6.0 (+/-SD). The accuracy, measured by receiver operating characteristic areas, was 0.85+/-0.05, 0.77+/-0.06, and 0.80+/-0.06 (+/-SE) for the optimal predictor (automated) and 2 blinded observers (manual), respectively. CONCLUSION: A new 3-dimensional, automated technique has been developed to semiquantitate receptor density that dramatically improves reproducibility. The optimal diagnostic discriminator of parkinsonism determined by the automatic technique has good accuracy compared with the manual technique.

Benzamides↗

Diagnostic criteria for carotid duplex sonography.

Optimal criteria for the duplex sonographic diagnosis of carotid artery stenosis have not yet been defined. We studied 205 vessels in 105 patients with both duplex sonography and angiography. Four diagnostic groups were defined on the basis of Doppler flow characteristics. Receiver-operating-characteristic curves were used to compare diagnostic criteria at significant stenosis levels, and to select threshold values that emphasize specificity as well as sensitivity. Peak systolic velocity, systolic velocity ratios, and end-diastolic velocity were all shown to be equivalent predictors of significant disease. We chose peak systolic velocity in the internal carotid artery as our best parameter because of its ease of measurement. The use of combined parameters offered no significant statistical advantage over the use of a single parameter. The real-time assessment of stenosis and ulceration was not found to be reliable. ROC curves should be used to select Doppler criteria with desired sensitivities and specificities to maximize the benefit in each clinical setting.

Angiography↗

[Use of a new culture procedure in the diagnosis of vaginal mycoses--a contribution on the improvement of diagnosis].

On the basis of our good experiences with the application of the spoon culture procedure in the quantitative bacteriological urine diagnostics, we tested the applicability of the plastic spoon in the diagnostics of vaginal mycoses. Our investigations show that the spoon culture procedure means an optimization and rationalization in mycological diagnostics due to omission of several stages of work and of the risks of transport, and due to improvement of diagnostic reliability and acceleration of the transmission of findings.

Bacteriological Techniques↗

Assessment of fine-needle aspiration sampling technique in thyroid nodules.

BACKGROUND: A prospective two-yr study was undertaken to assess the heterogeneity of thyroid nodules using the fine-needle aspiration (FNA) technique of systematic regional sampling. In addition, we determined the number of regions to be sampled to minimize non-diagnostic results, and to optimally characterize thyroid nodules. DESIGN: FNA was performed on 74 nodules > or = 1.5 cm. in diameter in five distinct regions in sequence (center, then four quadrants starting at 12:00, clockwise). Slides from each region were coded, randomized, subjected to blind review, and categorized as non-diagnostic (ND), benign (B), indeterminate (ID), suspicious/neoplastic (S/N), or malignant (M). Final cytologic diagnosis (CD) was made from all slides of each nodule. RESULTS: The ND rate for center FNAs alone was 16%, but addition of the 12:00 region decreased it to 5.3%. With 3, 4, or 5 sequential sites the nondiagnostic rates were 4, 2.6, and 2.6%. The center region diagnosis was identical to the final CD in 71% of the cases. Addition of the 12:00 region increased the concordance to 88%. Three sequential regions equaled the CD in 93% of cases, and 4 regions equaled the CD in 99% of cases. All nodules characterized as M or S/N were resected as were 76% of the ID nodules. Of the 43 nodules characterized as B, 3 were resected, 24 involuted, 6 were unchanged, and 10 were lost to follow-up. All 3 M nodules proved malignant by histology, as did 7/10 S/N, 0/17 ID, and 0/43 B nodules; 3/10 S/N, 1/17 ID and 1/43 B were adenomas. Likelihood ratios for diagnosing neoplasia were ND:0, B:0.10, ID:0.21, S/N:infinity, M:infinity. CONCLUSIONS: Sampling of at least four distinct regions accurately assesses thyroid nodules while minimizing ND results. Regional sampling also addresses intranodular heterogeneity.

Biopsy, Needle↗

A contribution to the establishment of diagnostic reference levels in CT.

CT has become the major source of population exposure to diagnostic X-rays. CT dose index (CTDI) and dose-length product (DLP) have been proposed as the appropriate dose quantities for the establishment of diagnostic reference levels for optimizing patient exposure. Dose measurements on 27 CT scanners in Northern Greece involving six routine CT examinations have been performed in order to compare their performance with the currently proposed European reference dose values and to produce a preliminary set of data for the establishment of local diagnostic reference levels. All measurements were performed using a pencil shaped ionization chamber introduced into polymethyl methacrylate cylindrical head and body phantoms. The results revealed significant discrepancies in dose values among the CT scanners, which can be mainly attributed to variations in the examination protocols and the different kinds of scanners. Significant overdosing compared with the European reference levels has not been observed, with the exception of the routine head examination, where 47% of the scanners exceeded the corresponding CTDI(w) value. CT scans in the trunk region result in the higher effective doses, which can reach estimated maximal values of the order of 15 mSv.

Humans↗

Strategy for identifying primary malignancies with inaugural bone metastases.

The diagnosis of primary tumors with inaugural bone metastases is a serious and difficult problem commonly encountered in rheumatology. Helpful information can be derived from the radiologic appearance of the metastases, history of the patient, clinical findings, chest film, standard laboratory tests, imaging studies, serum marker assays, and histologic findings. Based on our personal experience and on previously published data, we have developed a decision tree aimed at enhancing the efficacy of the diagnostic process while ensuring optimal patient comfort and containing costs.

Adult↗

Diagnostic imaging evaluation of benign prostatic hyperplasia.

The optimal evaluation of the patient with symptomatic BPH should include the diagnostic testing necessary to supplement the clinical examination and select a suitable medical, surgical, or interventional therapeutic option. A variety of imaging modalities offer unique but often unnecessary, superfluous, or very expensive information. Rarely is therapeutic intervention for symptomatic BPH denied a patient because of lesions detected with screening imaging tests; it may be only delayed rather than withheld. Virtually all pretreatment IVUs in patients with BPH are normal. Estimates range from 73 to 93 per cent of the studies as normal or having only insignificant findings. Significant pathology, either life-threatening or sufficient to alter or delay treatment, is found between 0.5 and 10 per cent of the time. Upper tract hydronephrosis is the most common finding (3 to 13 per cent). Renal or urothelial cancer prevalence in the patient population with BPH is really no different than in the general population. If signs or symptoms are not present to alert the clinician to some risk factor other than the symptoms of BPH, there is no benefit for routine urography solely for upper tract cancer detection. Furthermore, with the growing use of nonionic contrast media for elderly patients, the cost of the preoperative routine IVU will increase even further as the added charge for contrast ($100 or more) is tacked onto the cost of the study. Azotemic patients are best served by diagnostic ultrasound or by Foley catheter drainage prior to urography when indicated. Ultrasound remains an operator-dependent and technology-limited examination that cannot measure renal function, but the sensitivity and specificity, as well as the overall diagnostic accuracy, are equal to or greater than those of urography for the detection of hydronephrosis, cystic renal masses, and bladder or prostate abnormalities. False-positive ultrasound scans do occur secondary to reflux caused by bladder diverticula, megacalicosis, or other congenital abnormalities. However, these lesions are distinctly rare. Sensitivity for urothelial malignancy is not good, but endoscopic, clinical, and laboratory evaluations should provide adequate pretherapy diagnostic screening. In spite of the preoperative comfort that a normal IVU may give the patient and the operating surgeon, routine intravenous urography for all BPH patients should no longer be considered necessary. Diagnostic ultrasound, either transabdominal or transrectal, also offers the ability to evaluate the kidneys, ureters, and bladder, effectively replacing routine intravenous urography.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗

Optimization of dose and image quality for computed radiography and digital radiography.

The surface doses to patients during chest, abdomen and pelvis radiography were measured over a period of 3 years, during which time computed radiography (CR) and digital radiography (DR) systems were introduced to replace film-screen systems. For film-screen and CR the surface doses were measured with thermoluminescent dosimeters. For DR the surface doses were calculated from the dose-area product (DAP) meter readings. Measurements were made for each type of examination and detector type on 10 average-size patients. Measurements were made immediately after the new systems were introduced, and subsequently as adjustments were made to optimize dose and image quality. Published diagnostic reference levels were used as target values in this optimization. Initially, CR doses were the same as or higher than for film-screen, and the doses were lower for DR compared to film-screen. Subsequent clinical experience with the systems led to changes in the technique used for chest examinations both for CR and for DR. For CR, it was possible to change the algorithm and decrease the dose to one quarter of the initial value with acceptable image quality. For DR, it was decided to reduce noise by increasing the dose by a factor of two. No changes were made to abdomen or pelvic imaging techniques for either CR or DR. The final patient surface doses using CR were similar to published diagnostic reference doses; for DR, all patient doses were less than published reference levels.

Algorithms↗

The AAPM/RSNA physics tutorial for residents. X-ray interactions.

The diagnostic information in a radiograph or fluoroscopic image is largely the result of the quantity of x rays that are not removed from the incident x-ray beam. The information content of the image is delivered by the percentage of noninteracting photons that are successfully recorded. There are four major x-ray interactions: Rayleigh (coherent) scattering. Compton scattering, photoelectric absorption, and pair production. The degree of attenuation and the predominant mechanisms involved in the interactions are influenced by the x-ray energy and tissue composition. In the diagnostic energy range, photoelectric absorption and Compton scattering are the predominant modes of attenuation. One of the challenges in diagnostic imaging is to optimize image acquisition by controlling x-ray attenuation to obtain the appropriate contrast between the tissues while minimizing patient dose and scattered radiation in the image. Imaging techniques such as use of contrast material and dedicated mammography equipment exploit the differences in these types of x-ray interactions to improve the quality and diagnostic utility of the examination. Rayleigh scattering and pair production are presented but do not occur to any significant degree in diagnostic radiography.

Scattering, Radiation↗

Neoadjuvant chemotherapy for the management of ovarian cancer.

Neoadjuvant chemotherapy refers to the administration of chemotherapy before definitive surgery is performed; this approach was introduced into the management of ovarian cancer approximately one decade ago, initially for use in women who were medically unable to tolerate aggressive cytoreductive surgery. Subsequently, neoadjuvant chemotherapy was employed in women who, by diagnostic imaging analysis, were unlikely to undergo successful optimal cytoreductive surgery. Only very limited data are available on the use of neoadjuvant chemotherapy in the management of women with apparent advanced ovarian cancer; these data are derived mainly from single institution experiences and suggest that this approach may increase disease-free survival but does not improve overall survival for the patient. However, it has consistently enhanced the feasibility of optimum surgical cytoreduction once neoadjuvant chemotherapy has been administered. Reduced blood loss, and shorter operations, intensive care unit stays and overall hospitalizations have been well documented. The methods for selecting candidates for neoadjuvant chemotherapy vary among institutions. Non-optimal surgical cytoreducibility has been assessed on the basis of diagnostic imaging studies, laparoscopic assessment and/or laparotomies. Currently, neoadjuvant chemotherapy is most beneficial for women who are medically impaired and unable to tolerate aggressive cytoreductive surgery and for women who are found to have such aggressive cancers that optimal cytoreductive surgery does not appear by diagnostic imaging or direct visualization to be possible.

Antineoplastic Agents↗

Use of biochemical markers of infarction for diagnosing perioperative myocardial infarction and early graft occlusion after coronary artery bypass surgery.

STUDY OBJECTIVES: Perioperative myocardial infarction (PMI) during coronary artery bypass grafting (CABG) is an important clinical problem because it is closely associated with increased morbidity and mortality. The diagnosis of PMI is, however, associated with several problems. Due to the surgical trauma, the usual indicators of myocardial infarction (pain, ECG changes, and elevated biochemical markers of infarction) have uncertain diagnostic value. The primary aim of this study was to illustrate the levels of the biochemical markers after uncomplicated bypass surgery defined as no clinical or ECG evidence of PMI, and no graft occlusion at 7 days by repeat angiography; and secondarily, to establish biochemical diagnostic discrimination limits for detection of in-hospital graft occlusion. METHODS AND RESULTS: One hundred three patients undergoing elective CABG were closely monitored by serial measurements of creatine kinase (CK)-MB mass, myoglobin, troponin T, and troponin I, and underwent a repeat angiography before discharge. Seven patients had ECG evidence of PMI. Peak troponin T and CK-MB values were significantly higher in these seven patients, although the diagnostic performances of the optimally chosen cutoff levels for diagnosing AMI were fair. Twelve patients had at least one occluded graft shown by repeat angiography. Peak values of CK-MB and troponin T were significantly higher in patients with graft occlusion (52.2 microg/L vs 24.7 microg/L, p = 0.01; and 3.7 microg/L vs 1.0 microg/L, p = 0.05, respectively). By multivariate analysis, a diagnostic discrimination level of 30 microg/L for CK-MB did not reach statistical significance; however, the independent diagnostic value of a cutoff level for troponin T at 3 microg/L reached a level of significance (p = 0.06). DISCUSSION: We have suggested normal values of four different biochemical markers of infarction after uncomplicated coronary bypass surgery. Patients with in-hospital graft occlusion had higher peak CK-MB and troponin T values. However, the overlap with patients without graft occlusion is substantial, and the patency status in the individual cannot be reliably predicted from these noninvasive tests.

Adult↗

Cystic adventitial disease of the popliteal artery: diagnosis and treatment.

PURPOSE: This paper represents the presentation of a case of cystic adventitial disease of the popliteal artery and an exhaustive review of the literature with an emphasis on optimal means for diagnosis and treatment of this unusual disease. METHODS: We collect all reported cases of cystic adventitial disease of the popliteal artery since the last review in 1987 with an additional review of these cases reported in the U.S. since the initial description of the disease. RESULTS: We found 264 cases of cystic adventitial disease (CAD) of the popliteal artery from 1954 to 1995, with 38 reported in the U.S. Fifty-eight new cases of CAD have been reported since the last review in 1987; 11 of these were reported in the U.S. Diagnosis of the disease has improved in the last few years with non-invasive techniques. Duplex color scanning followed by T2-weighted MRI now appears to be the best diagnostic choice. Various therapeutic methods have been described for the treatment of CAD. The recommended treatments are excision of the cyst with the cystic wall when the artery is stenotic and resection of the affected artery, followed by an interposition graft, when the artery is occluded. CONCLUSION: Claudication in young, healthy patients resulting from popliteal artery stenosis or occlusion is a leading symptom of CAD. This disease affects males in a ratio of approximately 5:1 and appears predominantly in the fourth and fifth decades. The incidence is approximately 1 in 1200 cases of claudication or 1 in 1000 peripheral arteriograms. The predominance of reported cases is found in Japan and Europe. Optimal diagnostic techniques include duplex color scanning and T2-weighted MRI. The lesions can be effectively treated by resectional or non-resectional means depending on the presence or absence of complete arterial occlusion.

Adult↗