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PubMed1985

Toxicity modeling and prediction with pattern recognition.

Empirical models can be constructed relating the change in toxicity to the change in chemical structure for series of similar compounds or mixtures. The first step is to translate the variation in structure to quantitative numbers. This gives a data table, a data matrix denoted by X, which then is analyzed. The same type of the models can be used to relate the variation of in vivo data to the variation of a battery of in vitro tests. A single data analytical model cannot be applied to a set of compounds of diverse chemical structure. For such data sets, separate models must be developed for each subgroup of compounds. The data analytical problem then partly is one of classification, pattern recognition (PARC). The assumption of structural and biological similarity within each subset of modeled compounds is then essential for empirical models to apply. PARC is often used to classify compounds as active (toxic) or inactive. The data structure is then often asymmetric which puts special demands on the data analysis, making the traditional PARC methods inapplicable. Depending on the desired information from the data analysis and on the type of available data, four levels of PARC can be distinguished: (I) the data X are used to develop rules for classifying future compounds into one of the classes represented in X; (II) same as I, but the possibility of future compounds belonging to "unknown" classes not represented in X is taken into account; (III) same as II, plus the quantitative prediction of one activity variable (here toxicity) in some classes; (IV) same as III, but several quantitative activity (toxicity) variables are predicted.

Mathematics↗
PubMed1991

Integrated approach for designing medical decision support systems with knowledge extracted from clinical databases by statistical methods.

In clinical research data is often studied by a particular method without previous analysis of quality or semantic contents which could link clinical database and data analytical (e.g. statistical) procedures. In order to avoid bias caused by this situation, we propose that the analysis of medical data should be divided into two main steps. In the first one we concentrate on conducting the quality, semantic and structure analyses. In the second step our aim is to build an appropriate dictionary of data analysis methods for further knowledge extraction. Methods like robust statistical techniques, procedures for mixed continuous and discrete data, fuzzy linguistic approach, machine learning and neural networks can be included. The results may be evaluated both using test samples and applying other relevant data-analytical techniques to the particular problem under the study.

Artificial Intelligence↗
PubMed1990

Psychotherapy process research: progress, dilemmas, and future directions.

The first several decades of psychotherapy process research have produced advances in measure development and substantive findings of process-outcome relations. A recent paradigm shift toward sequentially patterned, significant change episodes is described, emphasizing segmentation of process by meaningful patterns wherever they occur. Theoretical, psychometric, and data analytic dilemma are reviewed. Strategies are offered that may enhance future research efforts. These include greater attention to construct validity of measures, the relation of process to phase-specific outcome criteria, and the continuing development of multivariate data analytic strategies that take into account Patient X Treatment interactions as well as the sequential dependency of process data. The development of a national archive of significant change events is recommended to advance modeling of the change process, segmentation, construct validation of measures, integration of qualitative and quantitative approaches, and development of a cross-theoretical language for therapy process.

Follow-Up Studies↗
PubMedDate not supplied

[Complementary artificial nutrition in kidney failure].

Denutrition of the uremic patient is a substantial contributing factor to the high rate of morbimortality. At the present time there are no resources which slow the catabolic situation conditioned by humoral or hormonal factors, but resources are available which act on the nutritional factors. The aim of this paper is to study the effect of additional administration of a complete enteral diet, but high in calories and in proteins, on the nutrition of dialysis patients. Six patients undergoing periodic hemodialysis and without metabolic illness were selected: 236 ml of the solution was administered orally on a daily basis for two months. They were studied statistically using the SIGMA Program, with application of the comparison of paired averages, the variations of anthropometric and analytical data and urea kinetics. The results revealed a significant body weight increase, from 58 to 60 kg, and of the tricipital fold from 10 to 12 cm: both variations were statistically significant (p < 0.01). There were no variations in the analytical data, or in the urea kinetics (the PCR was 0.8 g/kg/day and the Kt/V was 0.8). It is concluded that it significantly improves the nutritional state, there are no side effects and it does not detract from the efficacy of the dialysis. Therefore, and although the indication for which it was designed was for predialysis patients, we think that those under periodic hemodialysis--and, form the same reasons, acute kidney failure patients--might be areas for the use of this product.

Adult↗
PubMed1976

Doping control in Japan. An automated extraction procedure for the doping test.

Horse racing in Japan consists of two systems, the National (10 racecourses) and the Regional public racing (32 racecourses) having about 2,500 racing meetings in total per year. Urine or saliva samples for dope testing are collected by the officials from thw winner, second and third, and transported to the laboratory in a frozen state. In 1975, 76, 117 samples were analyzed by this laboratory. The laboratory provides the following four methods of analysis, which are variously combined by request. (1) Method for detection of drugs extracted by chloroform from alkalinized sample. (2) Methods for detection of camphor and its derivatives. (3) Method for detection of barbiturates. (4) Method for detection of ethanol. These methods consist of screening, mainly by thin layer chromatography and confirmatory tests using ultra violet spectrophotometry, gas chromatography and mass spectrometry combined with gas chromatography. In the screening test of doping drugs, alkalinized samples are extracted with chloroform. In order to automate the extraction procedure, the authors contrived a new automatic extractor. They also devised a means of pH adjustment of horse urine by using buffer solution and an efficient mechanism of evaporation of organic solvent. Analytical data obtained by the automatic extractor are presented in this paper. In 1972, we started research work to automate the extraction procedure in method (1) above, and the Automatic Extractor has been in use in routine work since last July. One hundred and twnety samples per hour are extracted automatically by three automatic extractors. The analytical data using this apparatus is presented below.

Animals↗
PubMed1990

[Contents and batch-dependent variations of mineral substances in milk formula for premature infants and possible effects on renal acid burden].

The mineral contents of Na, K, Ca, Mg, Cl and P was determined in different batches of 5 preterm formulas. The purpose of this study was 1st to investigate whether the analytical data are in agreement with the specifications of the manufactures and 2nd whether there are large variations between different batches of the same formula. For each analyzed mineral we found marked differences between the specifications and our measurements in at least one of the formulas. In these cases the differences between the labels and the medians of the analytical data were larger than half of the range of all determinations of the respective formula. Without exception the mean values for K were all clearly lower than the specifications of the producers. In 4 of the 5 premature formulas variation coefficients greater than 10% were observed for at least one mineral. The results show that coincidental variations of mineral contents in different batches can result in a disadvantageous mineral composition because of synergistic effects on metabolism. In this context the importance of the sum of Na and K over Cl in premature formulas is stressed with regard to renal acid excretion. The introduction of more stringent quality standards is proposed.

Acid-Base Equilibrium↗
PubMed1986

Statistical approaches to suicidal risk factor analysis.

Suicide research is a particularly difficult area primarily because of the base rate problem and inadequate case finding. Traditional item-analytic and multiple regression or discriminant function data-analytic methods in suicide research are criticized on several technical grounds, including capitalization on chance, failure to cross-validate, and confusion of the degree of relationship with its statistical significance. These errors are further confounded when the research data base misrepresents the very low true base rate. However, the most serious defect in item-analytic and both conventional and stepwise multiple regression procedures is their failure to take into account the causal structure of suicide risk factors. Setwise hierarchical multiple regression/correlation analysis is offered as an effective tool for suicide research. It capitalizes on the powerful general data-analytic features of regression analysis, but does so in a way that represents the causal structure of the putative risk factors. The more complex methods of causal models analysis are also recommended. I do not believe, however, that progress in the understanding of suicide lies mainly in the improvement of the statistical procedures employed. Even with optimal procedures, the amount by which we can expect to increase the predictability of suicidality using psychosocial risk factors is not likely to be large. Recent research in the biochemistry of suicide offers some hope. If to the psychosocial factors now employed we can add relevant biological factors and their interactions with psychosocial factors, we may be able to develop the causal models necessary for the understanding, prediction, and prevention of suicide.

Depressive Disorder↗
PubMed1986

On robust partial discriminant analysis as a decision-making tool with clinical and analytical chemical data.

Classification is one of the fundamental goals of science and is basic to the diagnosis of disease. Unfortunately, classifying objects (e.g., patients) on the basis of clinical and/or laboratory experimental observations into various groups can be difficult when the groups overlap or contain outlying points. Recently, Broffitt, Randles, and co-workers proposed a procedure, robust partial discriminant analysis (RPDA) for dealing with such problems, but testing of the procedure was limited to Monte Carlo simulation. In this study, RPDA was applied to real data, in order to compare its effectiveness with ordinary discriminant analysis, as well as to determine if RPDA was a suitable procedure to use to classify chemical compounds on the basis of experimental observations and as a tool in the diagnosis of disease (in particular, multiple sclerosis and thyrotoxicosis), with data based on experimental and clinical observations. The resulting RPDA classifications were an improvement over those obtained from ordinary discriminant analysis.

Aldehydes↗
PubMed1988

Serum levels of carcinomedin (1-keto-24-methyl-25-hydroxycholecalciferol) as an indicator of the progression of cancer. Preliminary results of a prospective study.

The serum levels of the cholesterol derivative 1-keto-24-methyl-25-hydroxycholecalciferol found in patients with cancer varies after surgical, chemical or radiotherapy treatments. The serum level associated with the vitamin profile has a predictive value for evaluating progress of the disease and therapeutic efficacy. The detection, identification and assay of a vitamin D3 derivative, 1-keto-24-methyl-25-hydroxycholecalciferol, named carcinomedin by us, in the serum of cancer patients was described in prior work. Also, the assay of carcinomedin, combined with those of serum levels of vitamin A, beta-carotene and alpha-tocopherol indicated a statistically significant correlation between these parameters and the localization of the primary neoplastic mass. In spite of the probable connection between carcinomedin and the presence of a neoplastic mass, several questions remain unanswered. In particular, it may be asked if the stage and progression of the tumor, surgical, chemotherapeutic or radiotherapeutic treatments may be related with any type of change in the serum levels of carcinomedin and fat soluble vitamins? To verify and respond to these questions, patients with various cancers (stomach, esophagus, breast, ovaries, uterus, etc.) were followed for three years. Clinical data were compared to analytical data supplied by assays of carcinomedin and the fat soluble vitamins.

Adult↗
PubMed1992

Transferability of clinical laboratory data within a health care region.

Analytical data for S-Creatinine and S-Urate are presented from seventeen laboratories in the Swedish Uppsala-Orebro regional quality assessment program. The bias and imprecision as well as the instability of the measurement procedures in the participating laboratories were estimated over three 14-week periods. Bias was estimated by a linear least squares fit of the difference between measured and assigned values vs. assigned values, and expressed in absolute and relative terms. Instability of the measurement procedures was estimated by comparing slope and intercept of regression lines of measured vs. assigned values from three fourteen week periods. According to our experiences we recommend regression analysis to describe the performance of the analytical methods of a laboratory over time. The results show that most laboratories fell within the limits of +/- 15% bias for S-Creatinine above 100 mumol l-1 and +/- 17% for S-Urate at concentrations above 250 mumol l-1. Various steps to reduce the inter-laboratory variability are suggested, including numerical correction of individual laboratory results using correction functions. In a few laboratories, instability was too high to allow for numerical corrections of analytical results.

Bias↗
PubMed1992

EDMUS, a European database for multiple sclerosis.

EDMUS is a minimal descriptive record developed for research purposes to document clinical and laboratory data in patients with multiple sclerosis (MS). It has been designed by a committee of the European Concerted Action for MS, organised under the auspices of the Commission of the European Communities. The software is user-friendly and fast, with a minimal set of obligatory data. Priority has been given to analytical data and the system is capable of automatically generating data, such as diagnosis classification, using appropriate algorithms. This procedure saves time, ensures a uniform approach to individual cases and allows automatic updating of the classification whenever additional information becomes available. It is also compatible with future developments and requirements since new algorithms can be entered in the programme when necessary. This system is flexible and may be adapted to the users needs. It is run on Apple and IBM-PC personal microcomputers. Great care has been taken to preserve confidentiality of the data. It is anticipated that this "common" language will enable the collection of appropriate cases for specific purposes, including population-based studies of MS and will be particularly useful in projects where the collaboration of several centres is needed to recruit a critical number of patients.

Database Management Systems↗
PubMedDate not supplied

Importance of analytical methods in pharmacokinetic and drug metabolism studies.

Pharmacokinetic and drug metabolism studies first request that good analytical data are available. The various methods that permit unchanged drugs and their metabolites to be separated, identified and quantitatively assayed are briefly reviewed. The present importance of gas chromatography/mass spectrometry is emphasized, as well as the limits of immunological assays. The sensitivity of the analytical assay has a direct impact on the validity of the pharmacokinetic model which is built up from plasma concentration data. The precision and accuracy of the assay is also critical, and it is not always easily estimated. A new significant parameter is the speed of analysis, and the resulting massive production of analytical data. New drugs coming from biotechnology, and new dosage forms, like targeted drugs, will create new analytical problems in the future. They will probably call for the development of new biological or pharmacological assay procedures, in addition to the physicochemical means of analysis.

Animals↗
PubMed1990

Individual-differences assessment of the relationship between change in and initial level of adult cognitive functioning.

Methodological factors may have been partially responsible for the inconsistency in findings from previous investigations into the relationship between change in, and initial level of, adult cognitive functioning. An alternative data-analytic procedure is proposed and applied to data from 277 men (25-76 years of age at initial testing) over 3 measurement occasions (interwave intervals of 6.7 years). Performances on both the Benton Revised Visual Retention Test (BVRT) and the Wechsler Adult Intelligence Scale (WAIS) Vocabulary subtest were analyzed. The findings demonstrate that the significant negative relationships between change and initial status, found on both tests, were partially a function of measurement error. Once adjustments were made for errors of measurement, the previously significant negative relationship for the BVRT data became significantly positive, whereas for the WAIS the relationship remained significantly negative, although to a lesser degree. The importance of accounting for errors of measurement is discussed.

Adult↗
PubMed1989

Receiver operating characteristic (ROC) methodology: the state of the art.

Receiver operating characteristic (ROC) methodology has been increasingly used in medical applications in the last 10 years. The text by Swets and Pickett has popularized the technique and the journal Medical Decision Making (1981--) provides a forum for further methodologic issues. In this article, I will (1) describe the nature of the data generated by ROC studies; (2) evaluate the choices of summary indices of performance (accuracy); (3) outline the data-analytic techniques used, and how to incorporate data from multiple observers and multiple "readings"; (4) review proposed alternatives to the commonly used binormal ROC model; and (5) discuss issues, such as verification bias, and challenges, such as multicenter comparative imaging studies and the difficulty of obtaining "truth data", which need to be addressed when adapting ROC methods to medical contexts.

ROC Curve↗
PubMed1977

[Central accounting as a model of laboratory diagnosis].

From the experiences in the field of scientific organisation of the last years results a laboratory-diagnostic model with an automatic laboratory, a district laboratory and larger central units, so-called coordination laboratories which work together with about 10 to 20 laboratories and guarantee an up-to-date diagnostic spectre for the whole territory. Apart from the increasing investigation frequency, a constant dilatation of the diagnostic spectre and improved quality control of structural conditions must be taken into consideration. The constructed model which demands the collaboration of all institutions meets these critical problems. A central balancing should also extend to the personal and technical apparative capacity. Apart from this the system is to be extended by further automation in the sense of a machine activity with improvement by control and regulation processes. An electronic data processing improves the functional capacity only when the analytic data processing has achieved a high level. The cooperation in the field of laboratory diagnostics is not only a task in scientific organisation, but in the same way also scientific problems are solved together. The requirements increasing in qualitative and quantitative respect may optimally be fulfilled only by the two partners, clinic and laboratory. With increasing independence the laboratories should in scientific and organizational respect remain a place of meeting for laboratory scientist and physician.

Clinical Laboratory Techniques↗
PubMed1976

Medical economics survey-methods study: design, data collection, and analytical plan.

This paper describes the background, methodology, data collection, and analytical plan of a pilot investigation conducted under contract for the National Center for Health Statistics during 1975. The objective was to determine the cost effectiveness of a variety of strategies under consideration for national application to develop previously unavailable information on utilization of, and the costs and payments for, health care. Detailed data on health care utilization and expenditures were collected periodically from a panel of 691 Maryland households over a six-month interval. Issues to be tested through a random experimental design include whether periodicity (monthly vs bimonthly interviews) and type of contact (in-person vs telephone) are significant factors in the cost effectiveness of this type of survey. An extensive record check involving all providers and third-party payers identified in the household survey was carried out. Record information will be used to 1) provide a basis for measuring accuracy of household data, 2) fill gaps in household knowledge, and 3) determine whether a subset of the record sources can provide adequate information for correcting household data. The household survey resulted in an initial response rate of 77.5 per cent with a subsequent attrition rate over six months of 13.6 per cent. Signed permission to access record data was obtained for 84.9 per cent of the individuals completing the entire survey. The most intensive survey strategy, monthly, mostly in-person contact, resulted in the lowest participation. The analytical plan presents details of the approaches to be taken in making judgments on the relative accuracy and completeness of data obtained by the various survey strategies and the contribution made by availability of data from record sources.

Adolescent↗