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A microcomputer-based clinical trial database incorporated with an 'audit trail' for correction process.

Multicenter clinical trials usually involve several hundred research variables with tens of thousands of records and require mainframe computers for processing. Because of recent advances in hardware and software, it has become possible to support data management and statistical analysis for a complex research project totally on a microcomputer. The Veterans Administration Cooperative Studies Program Coordinating Center (CSPCC) in Hines, IL, U.S.A. has successfully implemented three studies employing the SIR/PC Database Management System (DBMS) on an IBM PC AT. The CSPCC DBMS was designed with a method of verifying data and of updating the database, that leaves a more detailed 'audit trial' of the original data and subsequent modifications than provided by the SIR audit trail facility. Data validation can be done at any time throughout the study to facilitate error identification as early as possible in the data handling process. DBMS operation and maintenance are automated by a system of menus. The utility programs are prestored in a procedure file to optimize performance. The simple design speeds implementation and also reduces the cost of development.

Clinical Trials as Topic↗

Experimental data acquisition and manipulation by microcomputer.

To improve experiment management, we developed a microcomputer system which automatically displays, collects, manipulates and stores data in real-time. Upon completion of all experiments, it automatically performs statistical analysis, prints graphs and stores the results. The components required to accomplish these tasks include: (1) a microprocessor and visual monitor; (2) transducers, each with preamplifier, filter and amplifier; (3) couplers from each amplifier to the computer; (4) software to direct display, manipulation, statistical analysis and storage of data; and (5) hardware to allow real-time graphic and hard copy display. The resulting system allows sampling rates up to 300 Hz and accuracy of 0.20% full scale, 0-200 mm Hg. It provides great flexibility, efficiency and reliability in data management, and thereby facilitates the organization and completion of research protocols. It simplicity of design and operation makes it easy to use, and it is extremely cost effective. We present a method of laboratory microcomputerization as a practical alternative for management of physiological experimentation.

Analog-Digital Conversion↗

Microcomputer-assisted multivariate survival data analysis using Cox's proportional hazards regression model.

We describe a microcomputer program (COXSURV) for proportional hazards multiple regression analysis of survival and other failure-time data generated in clinical trials and in retrospective clinical epidemiology studies. COXSURV is menu-driven and has powerful variable factoring and data exploratory capabilities for multivariate modeling. A batch mode allows automatic uni- or multivariate analyses for confounder summarization. Model selection for predictive purposes is possible through a step-up algorithm. The partial likelihood method used in the program allows the use of either discrete or continuous time scales by treating tied uncensored observations by either the exact method or by a robust approximation method. The program calculates most standard model fitting statistics for either overall or stratified analyses and uses data layout files compatible with those of other related epidemiologic analysis software.

Algorithms↗

Parallelism test on microcomputers for statistically comparing regression lines of bivariate data sets.

Biomedical research is frequently confronted with regression lines that directionally describe the trend of phenomena, each one represented by a set of correlated x and y data. There could be a need to verify whether the regressions lines of two (or more) phenomena are statistically comparable in their slopes and intercepts, in order to draw conclusions about the similarity or dissimilarity of the conditions under scrutiny. The parallelism test the principles and methodology of which are presented here addresses this problem. A program for microcomputers is supplied as a non-profit software that can be freely shared on the understanding that the copyright belongs to the authors of this article.

Analysis of Variance↗

A versatile implementation of the Gauss-Newton minimization algorithm using MATLAB for Macintosh microcomputers.

The present report describes a weighted nonlinear least-squares minimization routine for fitting a wide variety of functions nonlinear in the parameters. The minimization routine is implemented in MacMATLAB, the Macintosh microcomputer version of MATLAB, an interactive program for scientific numeric calculations. Our algorithm makes use of a subroutine that estimates the required derivatives numerically, avoiding the need to differentiate the function under study analytically. We have also implemented two specific subroutines to integrate ordinary differential equations numerically. Therefore, in principle, any kind of nonlinear function can be fitted to a given set of data. The program only requires that the user writes the appropriate equation in a specific subroutine, thus relieving one from knowing and using any 'low-level' code. Other features of the program are: (a) the possibility of using weight to correct for nonuniformity of variance by flexible specification of the error structure; (b) the possibility of checking the parameter values and the residual variance at each iteration; and (c) by the use of the graphic capabilities of MacMATLAB, the possibility of following the improvement of the fitting graphically. One example of nonlinear functions and one example of linear differential equation together with their respective 'function file' and illustrative data are presented to demonstrate the flexibility of our approach and the power of the method used.

Algorithms↗

A microcomputer-based interactive cough sound analysis system.

The occurrence and nature of cough sounds, especially those occurring in asthma in young children, is of considerable interest to workers in paediatrics and general practice. To facilitate our research into the characteristics of such sounds, we have developed a microcomputer-based analysis system, which we call COFF. In this paper we discuss the design and implementation of the system, emphasising its user-friendly, interactive features, and the manner in which it efficiently manages the large amounts of data that research into sounds incurs. We illustrate the operation of the system with examples of spectrograms computed from cough sounds recorded simultaneously at the mouth and through the chest wall.

Asthma↗

Fluxplus, a microcomputer program for interactive calculation of 'in vitro' solute fluxes, uptakes and accumulations in studies of intestinal transport.

A new microcomputer program for interactive comparisons, analysis and calculation of in vitro solute transepithelial fluxes and nutrient uptakes and accumulations by intestinal tissues is described. The program is written in Microsoft GWBASIC for the widely distributed IBM-PC. Flux, uptake and accumulation values are obtained by computation from initial sequential data files and stored in sequential or random-orgaized files, depending on the specific process. Computed unidirectional fluxes are saved together with their associate electrical variables. The program calculates univariate statistics for unidirectional and net fluxes, and allows comparisons between selected groups of experiments by using the Student's t-test. An homocedasticity test is also provided. Active uptake or accumulations of solutes are calculated by substracting the predicted diffusive values at a determined concentration to total uptake or accumulation and from this, kinetic parameters are computed. The program was designed to be user-friendly and includes several functions to permit the user to manage and examine stored data. Examples of outputs illustrate applications of the program.

Animals↗

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↗

A combined one- and two-way analysis of variance microcomputer program.

A simple microcomputer program in BASIC is designed to compute both the one-way and two-way analysis of variance. The program is an interactive one and can be easily and promptly used for statistical analysis of biomedical data. The applicability of the program is illustrated by data obtained from the percutaneous absorption of dihydroergotamine into the excised skin of rabbits.

Analysis of Variance↗

Meta-analysis of clinical trials based on censored end-points: simplified theory and implementation of the statistical algorithms on a microcomputer.

Meta-analysis is increasingly being used in clinical research. While the meta-analytical algorithms for pooling the results of studies using non-censored end-points are now sufficiently standardized, the management of trials based on censored end-points is still controversial, and specific algorithms of meta-analysis are still needed (for example, censored end-points are commonly used in survival studies of cancer patients). In the present article we review the various algorithms that have thus far been utilized to perform a meta-analysis based on censored end-points, and we propose a new and original approach that combines two of the existing algorithms. Our approach is designed to formulate any meta-analysis of survival studies in terms of the calculation of an odds ratio. The meta-analytical odds ratio proposed here is called the 'log-rank' odds ratio of meta-analysis. A microcomputer program is described that implements the various methods of meta-analysis that can handle clinical trials based on censored end-points. Some examples are presented to illustrate the use of the program.

Algorithms↗

A microcomputer based lung sounds analysis.

The use of a microcomputer in lung sound-analysis is described. The system was used experimentally in order to evaluate automated auscultation as a mean for improving the sensitivity of pulmonary health mass screening. The sound signals from four custom-made piezoelectric transducers, affixed at specific locations on the chest wall, and the breathing flow signal produced by a pneumotachograph were amplified, filtered and digitized simultaneously at 4000 Hz per channel for 512 ms. The acoustic data were transformed to the frequency domain to enable the calculation of the power spectra. Those were averaged over successive runs and displayed as log power vs. frequency. The operator could assess the convergence of the spectral pattern using the on-line graphics and calculated parameters, and store the data once the noise level had reached a preset level. This procedure was repeated during expiration, inspiration and on breath arrest. The results of the off-line analysis of the lung sounds, combined with pulmonary function tests and a questionnaire, were used to identify lung pathology.

Auscultation↗

PCS: an IBM-compatible microcomputer program for the analysis and display of voltage-clamp data.

A program for IBM-compatible microcomputers is described which facilitates the analysis and manipulation of voltage-clamp data. PCS accepts pCLAMP acquired data as well as data from a more generalized binary data file. This cursor-driven program permits four modes of analysis: peak detection, averaging, integration and curve fitting, with direct graphical feedback of the results. Graphs of analysis results, such as current versus voltage relations (I-V curves), with tabulated data can be concisely printed using a HP Laserjet III. Selected current traces may also be plotted using the HP Laserjet III or exported to an ASCII comma and quotation mark delimited file suitable for import to a spreadsheet program.

Animals↗

The J. Otto Lottes Health Sciences Library and the Microcomputer Learning Laboratory.

Opened in 1985, the J. Otto Lottes Health Sciences Library at the University of Missouri-Columbia has adapted to changes in information technology by installing a fiber optic backbone, establishing local area networks and file servers with databases and software programs, establishing a microcomputer learning laboratory, and responding to the needs of a problem-based learning curriculum. The library works cooperatively with the Medical Informatics Group, which is housed in the library and runs the micro laboratory, to support student and faculty computing.

CD-ROM↗

Design of crossover microcomputer program and application on drug bioequivalence data.

A simple microcomputer crossover program in BASIC is designed for the purpose of drug bioequivalence studies and other related fields of statistical investigation. An illustration of the application of the program is presented to compare the bioavailability of ibuprofen when administered alone or followed by colestipol hydrochloride or by cholestyramine.

Analysis of Variance↗

Microcomputer-based monitoring of cardiovascular functions in simulated microgravity.

A microcomputer-based system for non-invasive monitoring of cardiovascular system in simulated microgravity is described. The system evaluates automatically, accurately and interactively heart beat intervals, beat-to-beat non-invasive finger arterial blood pressure (systolic, diastolic, mean and pulse pressure) using a Finapres device and beat-to-beat changes of thoracic blood volume using impedance changes. In addition, beat-to-beat evaluation of cardiac mechanical function including left ventricular ejection time, diastolic time, systolic time intervals, left ventricular ejection fraction estimate and several other contractility parameters, left ventricular volume, stroke volume and cardiac output estimates are performed with high degree of automaticity.

Blood Pressure↗

Microcomputer analysis of cortical power spectrum: calibration and correlates of behavioral artifacts.

Cortical power spectrum (CPS) is a quantitative estimate of EEG spectral power density. The CPS provides suitably precise data for quantification and statistical inference compared to the qualitative evaluation of EGG when interpreted by clinicians or researchers. In the past decade, the CPS has been applied to the studies of cognitive functions, memory, psi phenomena, speech laterality, and states of consciousness including coma, sleep, anesthesia, pathophysiology and pain state. However, few systematic evaluations of CPS methodology have been reported, rendering cross-laboratory comparisons difficult and external validity of experimental results uncertain. This report first describes a calibration procedure employing a microcomputer system for measuring the functional relationship between input signals and output cortical powers. Second, we examine controlled behavioral artifact effects on the CPS. The behavioral artifacts observed in the CPS can provide a measurement anchor for less ambiguous interpretation of CPS experiments conducted in clinical or laboratory settings.

Cerebral Cortex↗

An IBM-PC and Commodore 64 microcomputer-based system for elicitation and recording of eyeblink reflexes.

The eyeblink reflex is well suited for the study of habituation, sensitization, reflex modification and classical conditioning in humans. A microcomputer-based system for elicitation and recording of the eyeblink reflex is described. The system consists of three functional units: (1) an air-pressure bottle and pressure-reducing valves for delivery of air puffs to the eye in order to elicit the eyeblink reflex, and a CBM 64 computer for presentations of auditory stimuli in conjunction with air puffs; (2) a pair of light-emitting diodes and photocells placed in a pair of goggles placed on the subject for detection of eyeblinks; (3) an IBM-compatible personal computer, equipped with the ASYSTANT + software for eyeblink data acquisition and overall control of experiment and parameters. The system is presently in use in our laboratory, and technical details about the system can be obtained by writing to the first author.

Acoustic Stimulation↗