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Computer-assisted diagnosis by a model-free system of direct data analysis.

The basis of the method of data analysis presented is, in the case of any diagnostic test, the automatic compilation of separate frequency distributions for each diagnostic classification. The distinction of different test results for different diseases (the correlation for which the tests are used) can thus be quantitatively monitored. This offers opportunities for more specific control of the accuracy of the data base. Measurements of relative frequencies obtained from the frequency distributions of individuals with and without a given disease can serve as a quantitative handle for the selection of the combination of tests, and for adjustments of individual parameters, which will maximize the discrimination. The usual cutoffs are not used. A data-processing system can serve for the direct incorporation of patient chart data (including test results), and for the automation of the analysis described, with pattern recognition or cluster-seeking techniques. The ability of this system of analysis to minimize some of the problems associated with methods utilizing mathematical models is discussed.

Diagnosis, Computer-Assisted↗

Differentiating new marijuana use from residual drug excretion in occasional marijuana users.

Increases in urine drug concentration that result from changes in urinary output may be mistakenly interpreted as new drug use rather than carryover from previous drug exposure. Normalization of drug excretion to urine creatinine concentration reduces the variability of drug measurement attributable to urine dilution. A specimen ratio of 1.5 or greater between two creatinine normalized positive urine cannabinoid tests was previously proposed as an indicator of new marijuana use. This approach has received wide attention for potential use in treatment and employee assistance programs associated with workplace drug testing. Unfortunately, there has been limited evaluation of the usefulness of this ratio under controlled-dosing conditions with marijuana smokers. A controlled clinical study was conducted to examine the excretion profile of creatinine and marijuana metabolites in a group of six marijuana users who smoked two different doses of marijuana over a 4-week period. A relative operating characteristic curve was constructed from sensitivity and specificity data for 26 different specimen ratios ranging from 0.1 to 2.0. The most accurate specimen ratio (85.4%) for differentiating new use from residual excretion was 0.5. Use of this ratio provided a sensitivity of 80.1%, a specificity of 90.2%, and 5.6% false-positive and 7.4% false-negative predictions. To substantiate the validity of the 0.5 specimen ratio, urine cannabinoid and creatinine data from a controlled clinical trial specifically addressing water dilution as a means of specimen adulteration were evaluated. Sensitivity, specificity, accuracy, and percent false-positive and percent false-negative predictions were 71.9%, 91.6%, 83.9%, 5.4%, and 10.7%, respectively. These data compared favorably with the results from the first clinical study, with the exception of slightly lower sensitivity and higher false-negative percentages in the water dilution study. This would be expected because of the ingestion of large amounts of water and consequent dilution of urine drug concentration. These data indicated that selection of a specimen ratio to evaluate sequential creatinine normalized urine drug concentrations can improve the ability to distinguish residual excretion from new marijuana usage. The selection of an appropriate specimen ratio can be made based on the needs of a specific urine drug-testing program taking into account sensitivity, specificity, and accuracy data.

Adult↗

A comparative study of mobile electronic data entry systems for clinical trials data collection.

PURPOSE: To determine the speed, accuracy, ease of use, and user satisfaction of various electronic data entry platforms for use in the collection of mammography clinical trials data. METHOD AND MATERIALS: Four electronic data entry platforms were tested: standalone personal digital assistant (PDA), Tablet PC, digitizer Tablet/PDA Hybrid (DTP Hybrid), and digital pen (d-pen). Standard paper data entry was used as control. Each of five radiologist readers was assigned to enter interpretations for 20 screening mammograms using three out of the five data entry methods. Assistants recorded both start and stop data entry times of the radiologists and the number of help requests made. Data were checked for handwriting recognition accuracy for the d-pen platform using handwriting verification software. A user satisfaction survey was administered at the end of each platform reading session. RESULTS: Tablet PC and d-pen were statistically equivalent to conventional pen and paper in initial data entry speed. Average verification time for d-pen was significantly less than secondary electronic data entry of paper forms (p-value <0.001). The number of errors in handwriting recognition for d-pen was less than secondary electronic data entry of the paper forms data. Users were most satisfied with Tablet PC, d-pen, and conventional pen and paper for data entry. CONCLUSIONS: Tablet PC and d-pen are equally fast and easy-to-use data entry methods that are well tolerated by radiologist users. Handwriting recognition review and correction for the d-pen is significantly faster and more accurate than secondary manual keyboard and mouse data entry.

Clinical Trials as Topic↗

The precision of NMR structure ensembles revisited.

Biomolecular structures provide the basis for many studies in research areas such as structure-based drug design and homology modeling. In order to use molecular coordinates it is important that they are reliable in terms of accurate description of the experimental data and in terms of the overall and local geometry. Besides these primary quality criteria an indication is needed for the uncertainty in the atomic coordinates that may arise from the dynamic behavior of the considered molecules as well as from experimental- and computational procedures. In contrast to the crystallographic B-factor, a good measure for the uncertainty in NMR-derived atomic coordinates is still not available. It has become clear in recent years that the widely used atomic Root Mean Square Deviation (RMSD), which is a measure for the precision of the data, overestimates the accuracy of NMR structure ensembles and therefore is a problematic measure for the uncertainty in the atomic coordinates. In this study we report a method that yields a more realistic estimate of the uncertainty in the atomic coordinates by maximizing the RMSD of an ensemble of structures, while maintaining the accordance with the experimentally derived data. The results indicate that the RMSD of most NMR structure ensembles can be significantly increased compromising neither geometric quality nor NMR data. This maximized RMSD therefore seems a better estimate of the true uncertainty in the atomic coordinates.

Crystallography, X-Ray↗

[Risk assessment of environmental carcinogenesis using WBC DNA adducts].

Environmental carcinogens are enzymatically activated to form intermediates that can react with cellular DNA and form DNA adducts. Several kind of carcinogens bind to several sites of DNA. The measurement of WBC DNA adducts is a useful indicator for environmental carcinogen exposure monitoring. The 32P-Postlabeling method is a most popular and very sensitive method for DNA adduct analysis. We can analyze 1 adduct/10(8) nucleotides. In this review, I show some data of DNA adduct analysis for PAH exposure. These results demonstrated that inter-individual variation was very large. There were some confounding factors, such as metabolism or repair variations. I also showed some limitations of DNA adduct analysis. The method of adduct analysis is very complicated with several steps. We need to improve the accuracy. Do the data from WBC explain the target organ, such as the lung or liver? Almost all previous studies have been cross-sectional. We need a large-sized cohort study to evaluate whether adducts are a predictor of cancer. DNA adducts should be an important factor in gene-environment interaction.

Carcinogens, Environmental↗

Accuracy of patient encounter and billing information in ambulatory care.

BACKGROUND: This study examined the degree of accuracy of billing data in an academically affiliated family practice. METHODS: The progress notes from 1253 consecutive visits were independently reviewed by two family physicians, and the diagnoses, use of procedures, and level of service were determined for each visit. Discrepancies between the reviewers were resolved by consensus. These data were compared with the data on the corresponding billing form that had been completed by the care providers (ie, physicians on the faculty, physicians in training, family nurse practitioners, and nurses). RESULTS: There was poor agreement between the billing form and progress note on level of service and number of diagnoses (kappa = 0.37 and kappa = 0.28, respectively). The progress note usually indicated that a higher level of service should have been billed for a visit than actually was billed. Underreporting of the number of diagnoses was substantial; the billing forms listed only 69% of the diagnoses identified in the progress notes. In 60% of visits, each diagnosis on the billing form had a matching diagnosis in the progress note. This could be improved to 78% of visits if broad categories of disease were used. Residents were similar to faculty in the accuracy of reported level of service and types of diagnoses, but were more likely to underreport the number of diagnoses. CONCLUSIONS: Ambulatory care data from computerized billing files may not be sufficiently accurate for proper reimbursement of physician services or for use in research.

Abstracting and Indexing↗

Tactual picture identification by blind and sighted people: effects of providing categorical information.

Four experiments examined the influence of categorical information and visual experience on the identification of tangible pictures, produced with a raised-line drawing kit. In Experiment 1, prior categorical information aided to accuracy and speed of picture identification. In a second experiment, categorical information helped subjects when given after the examination of each picture, but before any attempt at identification. The benefits of categorical information were also obtained in another group of subjects, when the superordinate categories were named at the start of the experiment. In a third experiment, a multiple-choice picture recognition task was used to eliminate the difficulty of naming from the picture-identification task. The multiple-choice data showed higher accuracy and shorter latencies when compared with identification tasks. A fourth experiment evaluated picture identification in blindfolded sighted, early, and late blind participants. Congenitally blind subjects showed lower performance than did the other groups, despite the availability of prior categorical information. The data were consistent with theories that assume that visual imagery aids tactual perception in naming raised line drawings. It was proposed that part of the difficulty in identification of raised line pictures may derive from problems in locating picture categories or names, and not merely in perception of the patterns.

Adult↗

Assessment of an on-line computerized perinatal data collection and information system.

An on-line maternity data collection system has been designed to provide the information required for perinatal audit and to allow many of the letters and forms required for effective communication in pregnancy to be produced automatically. The system meets the requirements of the Korner Committee on Health Services Information and has been approved by the Computer Policy Committee. Pregnancy is followed prospectively from the first antenatal clinic visit until the file is closed 28 days after delivery. Data are entered by midwives and secretaries onto a network of microcomputers placed at convenient points in the maternity unit. The system has been fully operational with no significant problems since the beginning of 1984 and has led to improved communication between hospital and the community. Analysis of 253 consecutive case notes showed a high level of accuracy of the data recorded on computer. Reports and clinical audit are readily available both from the system locally, from standard programmes on the regional mainframe computer and via a mainframe computer at London University.

Computer Systems↗

Accuracy of glucose meters in measuring low blood glucose levels.

BACKGROUND: Hypoglycemia is an emergency condition requiring treatment as soon as possible. Therefore, rapid and reliable blood glucose measurements are necessary. There are 2 systems of glucose meters (GMs), the reflectance photometer system (RPS) and the electrochemical biosensor system (BSS). GMs are widely used in monitoring blood glucose (BG) in patients with diabetes. BG values measured by GMs have been confirmed to be accurate especially in measuring normal and high BG levels. However, the data on the accuracy of GMs in measuring low BG levels are limited. OBJECTIVE: To compare accuracy and reliability of different systems of GMs in the measurement of low BG values. PATIENTS AND METHOD: Venous and capillary whole blood specimens were collected from patients who were investigated for pituitary dysfunction. The patients underwent an insulin-induced hypoglycemia test by intravenously administering human regular insulin. The low BG level was defined as having venous plasma glucose (PG) of less than 60 mg/dl (mean +/- SD = 36.59 +/- 9.19, n = 54). Capillary blood samples were obtained from fingertips. Venous BG (vBG) and capillary BG (cBG) were measured by GMs. Venous PG which considered a reference value was measured by the glucose dehydrogenase method. RESULTS: The correlation coefficient (r) between vBG measured by GMs-RPS and PG was 0.86 (p < 0.001), whereas, that between vBG by GMs-BSS and PG was 0.75 (p < 0.001). Similarly, the r between cBG by GMs-RPS and PG was 0.73 (p < 0.001), whereas, that between cBG by GMs-BSS and PG was 0.69 (p < 0.001). The mean difference between vBG by GMs-RPS and PG values was 0.01 +/- 4.90 mg/dl, whereas, that between vBG by GMs-BSS and PG values was 10.50 +/- 7.07 mg/dl which was significantly greater than the former (p<0.001). Moreover, the mean difference between cBG by GMs-RPS and PG values was 14.45 +/- 8.76 mg/dl, whereas, that between cBG by GMs-BSS and PG values was 23.87 +/- 9.48 mg/dl which was also significantly greater than the former (p < 0.001). These results demonstrated that vBG measured by GMs-RPS was comparable to PG values. In addition, cBG values by GMs-RPS and GMs-BSS were approximately 14 mg/dl or 38 per cent and 24 mg/dl or 65 per cent greater than PG values, respectively. CONCLUSION: In measuring low blood glucose levels, glucose meters using the reflectance photometer system are more accurate than those using the electrochemical biosensor system.

Blood Glucose↗

Estimation of anomalous signal in diffraction data.

It is difficult to judge objectively the amount and resolution limit of the anomalous signal present in diffraction data. While several criteria can be used for this purpose, the usefulness of these indicators varies and depends on factors such as the data redundancy, the accuracy of the estimation of intensities and their uncertainties, and the properties of the anomalously scattering atoms in the crystal. Various indicators give an approximate measure of the anomalous signal, but do not provide a reliable guarantee that the crystal structure will be solved. The ultimate criterion of the anomalous signal is a successful structure solution. The current data-acquisition and phasing methods are so advanced that it is often possible to phase reflections and obtain preliminary electron-density maps in a few minutes, while the crystal still resides at the experimental station and further data can be collected if necessary.

Crystallization↗

Pharmacokinetics in low dose extrapolation using animal cancer data.

Data on rodents exposed to carcinogens indicate that their tumor probabilities are proportional to effective concentrations of parent compound or metabolites at the target tissues. This proportionality suggests that observed nonlinear dose-response curves reflect dose-dependent kinetics between applied dose rate and effective concentrations. Therefore low dose extrapolation procedures that include pharmacokinetic data could improve extrapolation accuracy. To test such procedures, we simulated bioassay and pharmacokinetic "data." Then, ignoring the mechanisms generating the data, we used four extrapolation procedures to estimate tumor probability at a low applied dose rate. Two of the procedures use a pharmacokinetic model and simulated pharmacokinetic data, and two do not. The pharmacokinetic model used for extrapolation was only an approximation to the one used to generate the pharmacokinetic data. The procedures that include pharmacokinetics often performed better and never did much worse than those that ignore them, regardless of the relations used to generate the data, the amount of experimental error in the pharmacokinetic data, and the appropriateness of the pharmacokinetic and extrapolation models used. Moreover they performed substantially better when effective concentration and tumor probability were concave-up functions of applied dose rate.

Animals↗

Clinical applications of risk-assessment protocols in the management of individual patients.

BACKGROUND: Cardiac surgical databases are typically used to compare performance rather than to predict performance. Application of analytic techniques to representative clinical data allows for the creation of highly reliable prediction models for outcomes such as mortality after coronary artery bypass grafting. METHODS: The Northern New England Cardiovascular Disease Study Group collects clinical data from the six regional cardiac institutions. The four basic components of the one-page clinical data form are demographic information, comorbidity data, severity of illness data, and outcomes. From these, a mathematical model predicts the likelihood of inhospital mortality after coronary artery bypass grafting. RESULTS: The Northern New England Cardiovascular Disease Study Group mortality prediction rule was validated and found to predict and discriminate well. It is updated yearly based on the most current data. At Dartmouth-Hitchcock Medical Center, the rule has been combined with other decision-support tools based on American College of Cardiology/American Heart Association indications for coronary artery bypass grafting. These data are compared with data supplied by patients on their expectations for operation and their assessments of acceptable mortality risk. By expanding the database to include variables such as 5-year survival and additional outcomes, and additional interventions, an "electronic second opinion" is made available to clinicians. CONCLUSIONS: Although experience with decision-support tools has been positive, prediction rules have certain limitations. Their accuracy depends on data that are consistently tracked; thus, transfer to other patient populations must be approached with caution. The challenge for the future is to develop and validate similar techniques that apply to more difficult clinical situations.

Cardiovascular Diseases↗

High-definition freehand 3-D ultrasound.

This paper describes a high-definition freehand 3-D ultrasound (US) system, with accuracy surpassing that of previously documented systems. 3-D point location accuracy within a US data set can be achieved to within 0.5 mm. Such accuracy is possible through a series of novel system-design and calibration techniques. The accuracy is quantified using a purpose-built tissue-mimicking phantom, designed to create realistic clinical conditions without compromising the accuracy of the measurement procedure. The paper includes a thorough discussion of the various ways of measuring system accuracy and their relative merits; and compares, in this context, all recently documented freehand 3-D US systems.

Calibration↗

Protein flexibility and intrinsic disorder.

Comparisons were made among four categories of protein flexibility: (1) low-B-factor ordered regions, (2) high-B-factor ordered regions, (3) short disordered regions, and (4) long disordered regions. Amino acid compositions of the four categories were found to be significantly different from each other, with high-B-factor ordered and short disordered regions being the most similar pair. The high-B-factor (flexible) ordered regions are characterized by a higher average flexibility index, higher average hydrophilicity, higher average absolute net charge, and higher total charge than disordered regions. The low-B-factor regions are significantly enriched in hydrophobic residues and depleted in the total number of charged residues compared to the other three categories. We examined the predictability of the high-B-factor regions and developed a predictor that discriminates between regions of low and high B-factors. This predictor achieved an accuracy of 70% and a correlation of 0.43 with experimental data, outperforming the 64% accuracy and 0.32 correlation of predictors based solely on flexibility indices. To further clarify the differences between short disordered regions and ordered regions, a predictor of short disordered regions was developed. Its relatively high accuracy of 81% indicates considerable differences between ordered and disordered regions. The distinctive amino acid biases of high-B-factor ordered regions, short disordered regions, and long disordered regions indicate that the sequence determinants for these flexibility categories differ from one another, whereas the significantly-greater-than-chance predictability of these categories from sequence suggest that flexible ordered regions, short disorder, and long disorder are, to a significant degree, encoded at the primary structure level.

Amino Acid Sequence↗

Evaluation of linked cancer registry and hospital records of breast cancer.

BACKGROUND: Information on the treatment of women with breast cancer in Australia is generally available only from special surveys. Analysis of routinely collected datasets may be more timely and cost effective, if the data are sufficiently accurate and complete. OBJECTIVE: To evaluate the accuracy and completeness of data on treatment in linked records of breast cancer from two routinely collected datasets. METHODS: The NSW Department of Health linked NSW Central Cancer Registry (CCR) records for 2,636 women diagnosed with breast cancer in NSW in 1992 to all hospital admission records in the NSW In-patient Statistics Collection (ISC) from January 1991 to June 1994. We queried the original paper records of subsets of women to identify missing or miscoded information and cases not notified to the CCR. We also compared the treatment data with data collected independently from the medical records of 19% of the women. RESULTS: ISC records linked to 89% of the CCR records. The CCR had identified 94.9% of women with breast cancer treated as hospital in-patients and 83% of these women had surgical treatment recorded in the ISC. The linked dataset under-estimated the percentage of women having breast-conserving therapy (-4%) and slightly over-estimated the percentage having mastectomy (+1%). We estimated that 42% of women treated surgically for breast cancer had actually had breast-conserving surgery, compared with 39% in the original dataset. There was no evident bias by age or by urban or rural residence in the under-recording of breast conservation. There was 94% agreement on the type of surgery between the linked dataset and the independent dataset.

Adult↗

Identification of 3D shape from texture and motion across the visual field.

Little is known about the perception of 3D shape in the visual periphery. Here we ask whether identification accuracy in shape-from-texture and shape-from-motion tasks can be equated across the visual field with sufficient stimulus magnification. Both tasks employed 3D surfaces comprising hills, valleys, and plains in three possible locations, yielding a 27 alternative forced-choice task (27AFC). Participants performed the task at eccentricities of 0 to 16 deg in the right visual field over a 64-fold range of stimulus sizes. Performance reached ceiling levels at all eccentricities, indicating that stimulus magnification was sufficient to compensate for eccentricity-dependent sensitivity loss. The parameter E(2) (in the equation F = 1 + E / E(2)) was used to characterize the rate at which stimulus size must increase with eccentricity (E) to achieve foveal levels of performance. Three parameter models (mu, sigma, and E(2)) captured most of the variability in the psychometric functions relating stimulus size and eccentricity to accuracy for all participants' data in the two experiments. For the shape-from-texture task, the average E(2) was 1.52, and for the shape-from-motion task, it was 0.61. The E(2) values indicate that sensitivity to structure from motion declines at a faster rate with eccentricity than does sensitivity to structure from texture. Although size scaling with F = 1 + E / E(2) eliminated most eccentricity variation from the structure-from-motion data, there was some evidence that E(2) increases as accuracy decreases in the shape-from-texture task, suggesting that there may be more than one eccentricity-dependent limitation on performance in this task.

Adult↗

Corneal wave aberration from videokeratography: accuracy and limitations of the procedure.

A procedure to calculate the wave aberration of the human cornea from its surface shape measured by videokeratography is presented. The wave aberration was calculated as the difference in optical path between the marginal rays and the chief ray refracted at the surface, for both on- and off-axis objects. The corneal shape elevation map was obtained from videokeratography and fitted to a Zernike polynomial expansion through a Gram-Schmidt orthogonalization. The wave aberration was obtained also as a Zernike polynomial representation. The accuracy of the procedure was analyzed. For calibrated reference surface elevations, a root-mean-square error (RMSE) of 1 to 2 microm for an aperture 4-6 mm in diameter was obtained, and the RMSE associated with the experimental errors and with the fitting method was 0.2 microm. The procedure permits estimation of the corneal wave aberration from videokeratoscopic data with an accuracy of 0.05-0.2 microm for a pupil 4-6 mm in diameter, rendering the method adequate for many applications.

Cornea↗

Eponyms and the diagnosis of aortic regurgitation: what says the evidence?

BACKGROUND: Chronic aortic regurgitation can lead to significant morbidity and mortality. For more than a century, numerous eponymous signs of aortic regurgitation have been described in textbooks and the literature. PURPOSE: To compare current textbook content with the peer-reviewed literature on the eponymous signs of aortic regurgitation and to assess the role of these signs in clinical practice. DATA SOURCES: 11 textbooks, MEDLINE (1966 through October 2002), and bibliographies of textbooks and relevant papers. STUDY SELECTION: English-language reports that were related to the properties of a sign on physical examination, incorporated more than 10 adults, and did not involve prosthetic heart valves or acute aortic regurgitation. DATA EXTRACTION: Three investigators independently analyzed relevant textbook extracts and 27 reports, using predetermined qualitative review criteria. Data relating to diagnostic accuracy and properties of the index test were also extracted. DATA SYNTHESIS: Twelve eponymous signs were described as having varying degrees of importance by textbook authors. Only the Austin Flint murmur, the Corrigan pulse, the Duroziez sign, and the Hill sign had sufficient original literature for detailed review. Most reports were low quality, with varying sensitivities for all signs. Except for the Hill sign, specificity tended to be poor. Evidence for the Hill sign also suggested a correlation between the popliteal-brachial gradient and aortic regurgitation severity. CONCLUSIONS: Prominent textbook support of the eponymous signs of aortic regurgitation is not matched by the literature. Clinicians and educators should update and improve the evidence for these signs to ensure their relevance in current medical practice.

Aged↗