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Using the job-exposure matrix for elaborating job histories.

A first software (JHS) for the elaboration of job histories oriented toward risks was designed and results published In an article "A software for the elaboration of Job Histories". This article presents a second software (JES), based on the use of a job-exposure matrix designed for one company. The matrix is essentially a database, an organized gathering of information concerning the company. The two softwares are inter-faced and both run on a PC. When properly exploited, the two softwares can serve as an asset for epidemiological studies dealing with occupational health.

Database Management Systems

Computer-assisted rheological evaluation of microsamples of mucus.

Dynamic viscoelasticity measurements are required in many studies on biological fluids and they can be performed by determining the corresponding strain when a sinusoidal shear stress is applied to a sample. In several circumstances the amount of fluid that can be obtained for analysis in physiological conditions does not exceed microliters. In this context, the microrheometer technique is a useful approach to determine the dynamic rheological profile of the samples. However, the manual calculation of the desired parameters is tedious and time-consuming. This paper describes a menu-oriented program in order to facilitate its use by non-experts. The comparison between manual and computer-aided calculations demonstrated that the program reduced the time of measurement, and reduced intra- and interobserver variations. The program was developed on an IBM compatible PC in Microsoft C 5.1, and tested in a blind study to check the advantages in terms of time and reproducibility of the system verified by the concordance of two independent observers (interobserver influence) in two different occasions (intraobserver influence).

Bronchi

The determination of the absolute bioavailability for drug substances with long elimination half-lives (with PC-programs for the method of truncated areas).

A survey is given of the methods for the determination of the absolute bioavailability for drug substances with long elimination half-lives. All methods depend on the assumption of linear pharmacokinetics. Emphasis is laid on Urso and Aarons' regression method of truncated areas-under-the-curve (AUC) to obtain estimates of the absolute bioavailability, F, and the absorption rate constant, ka, without obeying the otherwise general rule of following blood or plasma levels for at least three times the terminal half-life. It is shown by simulation when the linear and when the logarithmic trapezoidal rule is to be used for the calculation of the AUC. Two PC-programs for the regression method of truncated areas are presented: one program (SIMF&KA.EXE) simulates, based on tentative pharmacokinetic parameters, whether a blood sampling scheme, together with the precision of the analytical assay, is adequate to obtain accurate and precise estimates of F and ka; the method is insensitive to large variations in the tentative value of the elimination half-life. The other program (ESTF&KA.EXE) provides estimates of F and ka, with standard deviations of the estimates, from empirical data.

Biological Availability

A scanning system for digital analysis of cineangiography films.

A system for scanning and digital analysis of cinefilms is presented and its performance is compared with entirely digital radiographic equipment. Apart from the difference between logarithmic and linear gray-scale representation, a higher noise level was found in the scanning system. When its spatial resolution was assessed visually, it was comparable to that of the digital system, although lower than when the cinefilming and scanning steps were evaluated separately. Algorithms for the correction of varying exposure and geometric ("pin-cushion") distortion are also presented. It is concluded that digital analysis after scanning of cinefilms can be a useful alternative to completely digital cineradiographic studies.

Algorithms

Computer quantitation of saturation impairment time as an index of oxygenation during sleep.

The measurement of oxygenation during sleep has become a standard procedure in the assessment of hypoxemia in patients with various disorders. However, an accepted method for quantitating this hypoxemia is not available. This study describes the development of computerized data acquisition and analysis programs to quantitate nocturnal hypoxemia in patients with sleep and breathing disorders. The acquisition program samples the voltage output from pulse oximeters used to measure oxyhemoglobin saturation (SpO2) and stores this on an IBM PC or compatible computer. The analysis program integrates the SpO2 over time below the patient's pretest baseline as well as the integral below 90, 80, 70, 60 and 50% saturation. We refer to each integral as Saturation Impairment Time or SIT. In order to compare these integrals between patients or between the same patient but different studies, the integral is divided by the total sleep study time. We refer to each of these integrals, corrected for sleep study time, as the SIT index. Evaluation of the SIT index in 10 consecutive patients referred for various sleep disorders revealed acquisition program detection and deletion of 48 of 57 (86%) oximeter probe artifacts (mean duration of 3 seconds for undetected artifacts). There were no significant artifacts in the analysis program calculation of the SIT index in these same patients. In conclusion, computer programs were developed to measure and quantitate oxygen saturation measured by oximeters. Preliminary results reveal an accuracy of measurement which should prove acceptable in further clinical evaluations.

Diagnosis, Computer-Assisted

EMSA: a SAAM service for the estimation of population parameters based on model fits to identically replicated experiments.

This paper presents a new technique for the aggregation of models to produce population parameter estimates based on a set of identically replicated experiments. After describing the theoretical basis for the technique we discuss tactical and strategic issues associated with its implementation in the SAAM software. Finally, we demonstrate its utility in the aggregation of models fitted to four simulated experiments.

Algorithms

Intuitive user interfaces (IUI): a CASE starting point for design and programming.

The acceptance of a software product depends to a considerable extent on the user interface. The class of graphic-oriented user interfaces that are called Intuitive User Interfaces (IUI) is described. These interfaces allow the user to learn to operate software programs quickly. In the following the graphical layout put to use in an IUI is elaborated. All images the layout consists of are created with the aid of a paint program. Using these images, a procedure for creating, programming and linking an IUI to software applications is discussed and recommendations are made concerning software and hardware demands for easily creating IUIs. Practical experience of the authors with this procedure, mainly in the medical area, is described.

Computer Graphics

On the assessment of bioequivalence in a two-period cross-over design.

The results obtained with Meineke and De Mey's algorithm for posterior probability distributions in the nonparametric evaluation of two-period cross-over bioequivalence studies are critically discussed. Suggestions for improvement of their program NEWPARM are given. It is shown that this program in its present form cannot handle the results from bioequivalence studies in which more than 15 subjects participated. For larger study sizes, conversion to a more powerful programming language capable of handling large three-dimensional arrays, is mandatory. An alternative algorithm, allowing large sample sizes to be analysed nonparametrically without program conversion, is offered. A general bioequivalence program written by the author, into which this alternative algorithm is implemented, has been in use by a number of pharmaceutical companies and drug regulatory agencies since February 1990; its most recent update is Version 3.7 (BIOEQV37.EXE) of October 1990.

Algorithms

APIS: a software for model identification, simulation and dosage regimen calculations in clinical and experimental pharmacokinetics.

APIS is a software package based on mathematical modelling which provides a reliable approach in optimizing drug therapy. It was designed to assist clinicians in interpreting blood drug levels so that drug therapy may be better and more cost-effective. It is a methodological approach to describe, predict and control the kinetic behaviour of a drug. This software incorporates the principle of Bayesian procedures, i.e. one can use all available patient information (population) to determine patient-specific parameter estimates. These estimates can then be used to design an optimal and individualized drug regimen. APIS is an attractive and useful tool for clinical and experimental pharmacokinetics. APIS may be used on any IBM compatible computer using the Microsoft-Windows environment. The software is menu driven to provide a very user-friendly tool for analysing pharmacokinetic data and for designing dosage regimens.

Amikacin

A microcomputer program for determining turnover rates during non-steady state conditions: application to monoamine turnover.

A program to calculate the turnover rate of monoaminergic neurotransmitters was written for use on microcomputers. The program is based on non-steady state models, i.e., measuring the rate of change of levels of neurotransmitters or their metabolites after pharmacological inhibition of synthetic or degradative enzymes. Methods have been developed to estimate monoamine turnover by measuring the rate of decrease of catecholamine levels after treatment with alpha-methyl-p-tyrosine (AMPT), a tyrosine hydroxylase inhibitor, or the increase in serotonin levels after pargyline, an inhibitor of monoamine oxidase. This program is suitable for examining either linear increases or exponential decreases in monoamine levels. The program has been tested in our laboratory for the determination of serotonin, dopamine or norepinephrine turnover after hormonal or pharmacological manipulations. The program is readily adaptable for calculation of the turnover rate of other biological molecules under non-steady state conditions.

Biogenic Monoamines

Preoperative assessment and prediction of postoperative results in an artificial arterial network using computer simulation.

A computer model has been developed that can be used to describe the human arterial system mathematically. It simulates the complex relationship of morphology and hydraulics in the vessel network. After entering patient data into a standard vessel model, the mean flow velocity, the flow direction, and the blood pressure at each specified point of the flow network can be calculated. The vessel picture can be altered and modified with the help of a graphic editor. Localized or diffuse stenoses, bypasses with simple or multiple anastomoses, end-to-end anastomoses, end-to-side anastomoses, etc., can be studied in terms of the hydraulic effects on the local situation or on the entire vessel system. Experimental results of ultrasonic mean flow data in vessel systems of leg and cerebral arteries of patients are compared with calculated values. The predicted and measured flow velocities show a mean difference of about 10% indicating that such a computer model may be successfully used in the optimal planning of bypass operations.

Arteries

Hydrophobic neighboring homology (HNH) dotplot: an approach for assessing structurally similar motifs in proteins.

Structural biology needs sensitive tools to detect homology between proteins of low sequence identity, but with closely related 3-D structures. Using a conventional dotplot method, we therefore introduced 2 concepts to improve the search for similarities between secondary structures of analyzed proteins: 'hydrophobic neighboring homology' (HNH) and 'amino acid degeneracy classes'. The amino acids are grouped into 3 subsets: hydrophobic, hydrophilic and mimetic. A 'Neighboring Similarity Index' (NSI) is calculated for every residue pair and quantifies its neighbor homology. By thresholding the homology matrix and filtering the dotplot, the homologous patterns are extracted. We have evaluated the efficiency and limits of the method using 21 protein pairs extracted from the Protein Data Bank (PDB), or selected from the recent literature. Globally, we again find the homologous structures (alpha-helices and beta-strands) of these pair proteins. The introduction of neighbor residue hydrophobicity in the conventional dotplot improves the alignment of proteins with low sequence identity (< 25%). HNH, written in standard ANSI C with the graphic library X11, under UNIX, is available on request.

Cluster Analysis

A method for quantitative image assessment based on redundant feature measurements and statistical reasoning.

Advances in computer graphics and electronics have contributed significantly to the increased utilization of digital imaging throughout the scientific community. Recently, as the volume of data being gathered for biomedical applications has begun to approach the human capacity for processing, emphasis has been placed on developing an automated approach to assist health scientists in assessing images. Methods that are currently used for analysis often lack sufficient sensitivity for discriminating among elements that exhibit subtle differences in feature measurements. In addition, most approaches are highly interactive. This paper presents an automated approach to segmentation and object recognition in which the spectral and spatial content of images is statistically exploited. Using this approach to assess noisy images resulted in correct classification of more than 97% of the pixels evaluated during segmentation and in recognition of geometric shapes irrespective of variations in size, orientation, and translation. The software was subsequently used to evaluate digitized stained blood smears.

Algorithms

A SAS macro for residual deviance of ordinal regression analysis.

In this paper, a SAS macro is described for calculating the likelihood of the 'saturated' model in the analysis of ordinal regression. The outcome variable is multinomial on an ordinal scale, while the explanatory variables can be nominal or ordinal. Several ordinal regression models may be fitted to the data. One method of testing for the goodness of fit of these regression models is by comparing the residual deviance with the chi 2 distribution. In SAS, PROC LOGISTIC may be used to fit this type of data with proportional odds model. Unfortunately, the residual deviance is not available from the output. Our SAS macro will supplement the SAS output so that the residual deviance test may be carried out. The data from an ongoing HIV study is used as an illustration.

Bias

The pragmatics of clinical hypermedia: experiences from 5 years of participatory design in the MEDEA project.

To explore a medical hypermedia design process where requirements engineering and participatory design are used in a naturalistic setting, 5 years of participatory action research (PAR) have been performed in the development of a hypermedia system to be used in primary care practice. In PAR, the participating organizations cooperate with the researchers in deciding and later evaluating organizational actions, and the results are concluded cooperatively. A new type of system emerged from the study, in that the resulting design has its focus on the management of large volumes of hypermedia material, the traceability of authority in the documents, and teamwork support. Regarding the participatory design process, it was found to be essential to deal with social and organizational issues in the design group and its surroundings--and not to cover these over. For instance, an agreement was reached with the managers responsible for health care in the county where the design process took place, whereby the design activity was also given priority at the highest local administrative level. Since health care is a practice organization, there is a potential market for similar systems if only ways of organizing design and marketing the products of participatory design are further developed. Modified versions of structured product specification methods could be a valuable complement. The conclusion of the study is that the development and spread of hypermedia systems in health care may require considerable changes in current design routines and organizations.

Administrative Personnel

Structuring the patient record: NUCLEUS (customisation environment for multi-media integrated patient records).

The NUCLEUS project (AIM A2025) develops a prototype of a multi-media integrated patient record, based on the concepts of intelligent act management as conceived in RICHE (Esprit 2221). Moreover, NUCLEUS creates facilities for the customisation of such patient record according to the requirements of the health professionals (physicians, nurses, therapists, etc.) who operate and consult the patient record. Health professionals retain full control of the patient record contents:--NUCLEUS offers facilities to structure any significant patient record, subject to the specifications of the health professionals involved. Finally, NUCLEUS implements its results in the practical clinical conditions of the three leading European hospitals.

Europe

ORATEL: telematic system for quality assurance in oral health care (AIM Project A2029).

ORATEL is a 3-year project with the ultimate objective of improving oral health through use of appropriate computerized information systems. These tools will promote quality assurance and development in oral health care by using common quality indicators/standards. The project has completed its first phase, during which two European surveys were made, one on quality assurance clinical practices, and another on existing computerized information systems in oral health care. Pan European consensus was reached on 3 and 4 September 1992 when quality assurance indicators for oral health care services were endorsed. A manual on quality assurance indicators in oral health care has also been issued by the project.

Computer Communication Networks

SETH: an expert system for the management on acute drug poisoning in adults.

The aim of SETH is to give end-users specific advice concerning treatment and monitoring of adult drug poisoning. SETH is developed with an off the shelf expert system shell (KBMS) and runs on a microcomputer. Technical choices were done according to this analysis, financial considerations and portability. Currently, the database contains 1000 French drugs from 75 different toxicological classes. The SETH expert system simulates the expert reasoning, taking into account for each toxicological class delay, signs and dose. Two phases of evaluation were performed. The experimental implementation of Seth began in April 1992 in our Poison Control Centre. Since then, 1100 cases inputted by residents were analysed by SETH. The extension of the knowledge base to child poisoning began in March 1993.

Acute Disease