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Biomedical subjects

P Winkel

Publications and source records attributed to P Winkel.

At least 19 recordsLinked to original sources

Effect of uncertainty components such as recalibration on the performance of quality control charts.

BACKGROUND: Uncertainty components (recalibration, new reagent lots, etc.) may be the source of random changes in the level of quality control (QC) values, thus causing false alarms. We propose a method for reducing false alarms. MATERIAL AND METHODS: Daily QC measurements of 22 biochemical quantities were recorded over 5 months, while methods and analyser showed no signs of malfunctioning. Each time series of QC values was subdivided according to reagent lot, electrolyte diluent or disposable electrode used. Analysis of variance (ANOVA) was used to examine whether mean levels changed significantly between subseries. For each quantity, the entire time series and each subseries were examined for autocorrelation. An X chart and an exponentially weighted moving average (EWMA) chart (or EWMAST [EWMA for stationary processes] in autocorrelated series) were calculated from the first 50 values of each series or subseries and applied to the whole series. Values falling outside the three standard deviation control limits were noted. RESULTS: In 22 out of 24 time series, the mean level differed significantly between subseries. These changes caused spurious autocorrelation. However, in 51.3 % of all subseries a significant autocorrelation could also be demonstrated. In total, 5.6 % and 29.1 % of all time series values fell outside the control limits of the X charts and the EWMA or EWMAST charts, respectively. These percentages were significantly reduced to 0.44 and 0.70 when the subseries-specific control charts were used. CONCLUSIONS: The mean level may change because of recalibrations or change of electrolyte diluent lot with subsequent false alarms. False alarms may be significantly reduced by revising QC charts when significant changes occur.

Albumins↗

Serial correlation of quality control data--on the use of proper control charts.

BACKGROUND: Biochemical quality control (QC) data have been reported to be autocorrelated. Serial correlation may increase the rate of false alarms if the traditional exponentially weighted moving average (EWMA) control chart to monitoring the process mean is used. False alarms are the focus of this paper, where an alarm is defined as the occurrence of a QC value outside the three standard deviation control limits. METHODS: Daily QC measurements of common biochemical (Vitros 500) and hematological (SF-3000 and Behring Coagulation Timer (BCT)) quantities were recorded during several months while methods and analyzers showed no signs of malfunctioning. The time series were examined for autocorrelation and the performance of the EWMAST chart was compared with that of the EWMA chart when autocorrelation was present. RESULTS: Many of the time series showed significant signs of autocorrelation. Using the EWMA chart to monitor the process mean, false alarms were noted for positively autocorrelated time series, while this was seldom the case when the EWMAST chart was used. For some quantities, the EWMAST chart gave alarms. However, when the process autocorrelation and therefore the limits of the control chart were updated, the alarms given by the EWMAST chart were reduced or disappeared. In some cases the mean level changed over time, which is expected due to calibrations. This problem will be the topic of a subsequent paper. CONCLUSIONS: Positive autocorrelation may be present in QC data. In this case the EWMAST chart should be used in place of the EWMA chart.

Algorithms↗

Automated laboratory protocols.

A protocol is a program which controls, monitors and modifies the requests for laboratory services during the diagnostic work-up and/or monitoring of a patient. A protocol language and an OS/2 based system for the compilation, interpretation and execution of laboratory protocols written in this language is presented. The system is easily interfaced with any patient data base that supports the structured query language (SQL). A compiled protocol may be assigned to a patient and executed as specified in the protocol itself (regularly and/or when certain events such as test requests or arrival of results, occur). In the laboratory protocol language a patient's data are viewed as a set of test procedure groups each comprising data (request time, result, etc.) describing the status of one or more simultaneously made laboratory test requests. A pattern specification is a statement saying that a sequence of test procedure groups of specified types and ages is present in the data. Pattern specifications are linked to Boolean variables. If a pattern matching a pattern specification is found in the patient's database the corresponding Boolean variable is set equal to TRUE. The Boolean variables are utilized in the decision logic of the protocol.

Algorithms↗

Plasma magnesium during human liver transplantation.

Patients with severe liver disease and accompanying malnutrition may exhibit electrolyte disturbances including the magnesium balance. In 18 patients plasma magnesium (p-Mg) was determined at the start of the liver transplantation and during the anhepatic and reperfusion phases of the operation. The blood loss was 6.9 (2.5-8.8) 1 (median and range) and the cumulative transfusion volume was 10.2 (5.0-17.2) 1 of which 5.9 (2.5-14.2) 1 was with fresh frozen plasma. p-Mg was 0.72 (0.58-0.88) mmol.l-1 and it did not change significantly during the operation. Thus, in 4 patients it was at or below the lower reference value of 0.67 mmol.l-1. In 11 patients it changed less than 0.05 mmol.l-1, while in 4 patients the concentration was rose, and in 3 patients we noted a fall in each of 0.08 mmol.l-1. There was no correlation between p-Mg and the blood loss or the administered volume of fresh frozen plasma. In 10 randomly chosen fresh frozen plasma units, the p-Mg was 0.64 (0.61-0.71) mmol.l-1. These observations do not support a need for close monitoring or substitution of magnesium during human liver transplantation. On the other hand, the finding of a low value in 4 of 18 patients suggests that plasma magnesium should be monitored and eventually corrected while the patient is on the waiting list.

Adolescent↗

Application of time series analysis in the clinical setting.

A growth curve time series model is characterized by a biological growth pattern with random deviations added to this basic pattern. Various types are reviewed including the homeostatic model which is a special and simple type characterized by zero growth. The limitations to the use of time series analysis in the clinical setting include lack of initial baseline values and difficulties in specifying in quantitative terms a relevant hypothesis alternative to the one postulated by the time series model. Some ongoing research addressing these problems is discussed.

Biomarkers, Tumor↗

Artificial intelligence within the chemical laboratory.

Various techniques within the area of artificial intelligence such as expert systems and neural networks may play a role during the problem-solving processes within the clinical biochemical laboratory. Neural network analysis provides a non-algorithmic approach to information processing, which results in the ability of the computer to form associations and to recognize patterns or classes among data. It belongs to the machine learning techniques which also include probabilistic techniques such as discriminant function analysis and logistic regression and information theoretical techniques. These techniques may be used to extract knowledge from example patients to optimize decision limits and identify clinically important laboratory quantities. An expert system may be defined as a computer program that can give advice in a well-defined area of expertise and is able to explain its reasoning. Declarative knowledge consists of statements about logical or empirical relationships between things. Expert systems typically separate declarative knowledge residing in a knowledge base from the inference engine: an algorithm that dynamically directs and controls the system when it searches its knowledge base. A tool is an expert system without a knowledge base. The developer of an expert system uses a tool by entering knowledge into the system. Many, if not the majority of problems encountered at the laboratory level are procedural. A problem is procedural if it is possible to write up a step-by-step description of the expert's work or if it can be represented by a decision tree. To solve problems of this type only small expert system tools and/or conventional programming are required.(ABSTRACT TRUNCATED AT 250 WORDS)

Artificial Intelligence↗

A novel method for monitoring high-risk breast cancer with tumor markers: CA 15.3 compared to CEA and TPA.

BACKGROUND: An early and reliable diagnosis of metastatic spread has increased interest in serum tumor markers. This study investigated the ability of CA 15.3, CEA, and TPA to identify, predict, and exclude metastases in bone/viscera during adjuvant treatment and follow-up of high-risk breast cancer. METHODS: Ninety females with high-risk breast cancer were included in the study. Response evaluation was based upon clinical examination, x-rays or histology and elaborated marker criteria. RESULTS: During the marker monitoring period, metastases in four patients were confined to skin or lymph nodes, 21 developed metastases to bone/viscera, and 65 females had no evidence of metastases. CA 15.3, CEA, and TPA correctly classified 48%, 10%, and 19% of the patients with metastases in bone/viscera, and 100%, 94%, and 98% without. Following CA 15.3, CEA, and TPA recurrence, 100%, 33%, and 60% of the patients developed metastases in bone/viscera. Metastases in bone/viscera were excluded in 86%, 76%, and 79% of patients without CA 15.3, CEA, and TPA recurrence. CONCLUSION: Only CA 15.3 gave reliable information about recurrence. Metastases in bone/viscera were identified in 10 of the 21 patients with CA 15.3. There was no false-positive CA 15.3 information on the 65 patients without clinical recurrence. The PVneg (86%) indicated that when CA 15.3 did not signal recurrence, metastases to bone/viscera were not likely.

Adult↗

Establishing reference values from adults: recommendation on procedures for the preparation of individuals, collection of blood, and handling and storage of specimens. Committee on Reference Values of the Scandinavian Society for Clinical Chemistry.

The concentrations of blood components are influenced by a number of preanalytical factors, the importance of which varies [1]. Therefore it is necessary to standardize the specimen collection, as was done by the Committee on Reference Values of the Scandinavian Society for Clinical Chemistry and Clinical Physiology, which in 1975 published its recommendation on the production of reference values in clinical chemistry [2]. It was the very first recommendation of its kind. Since then, new information has accumulated, and it has become necessary to revise the part concerning the preparation of subjects for blood collection, the collection procedure itself, and the subsequent handling of the specimen. Also, The International Federation of Clinical Chemistry (Expert Panel on Theory of Reference Values) has produced its own recommendation [3]. The recommendation described below replaces pp. 39-44 of the former Scandinavian recommendation [2]. The procedure described below is designed for the collection of specimens for the measurement of the majority of components in blood and specimen collection from the cubital vein is described. It can be easily adapted for the collection of blood from other vessels [4]. Certain laboratory investigations require a special protocol. In that case, the preparation of the subject prior to and during specimen collection as well as the procedure itself should be described in sufficient detail to permit reproduction by adequately trained personnel. In any project designed to produce reference values the same protocol for the preparation of individuals and specimen collection should be used throughout the project. The protocol should be described in detail. Thus, it is not satisfactory to state only that the present recommendation was followed. Each section of the recommendation is followed by a check list for points which should be taken into account.

Adult↗

A programming language and a system for automated time- and laboratory test level dependent decision-making during patient monitoring.

A programming language specifically designed for automated time-dependent decision-making during patient monitoring (obtaining test requests, scheduling of test requests, cancelling of test requests, the issuing of messages to clinician or laboratory) has been developed. The output from a program written in this language is a set of decision rules in tabular form (a patient type), intended to solve a specific problem related to patient monitoring. A system for automated decision-making based on this language utilizes a file of patient types and a patient file. Whenever a new patient record is created, the patient's type is defined and the corresponding patient type is copied from the patient type file and linked to the patient's record. The system is activated, i.e., the decision rules are implemented and the tables of the patient's type updated, when laboratory results are available, when a clinician wants to order tests, and at regular user-defined intervals.

Computer Systems↗

CA 125, placental alkaline phosphatase, and tissue polypeptide antigen in the monitoring of ovarian carcinoma. A comparative study of three different tumor markers.

Three different tumor markers, placental alkaline phosphatase (PLAP), tissue polypeptide antigen (TPA), and cancer antigen 125 (CA 125), were measured in serum samples obtained during chemotherapy in 57 ovarian carcinoma patients. At the start of chemotherapy, 37, 63, and 77% had elevated serum values of PLAP, TPA, and CA 125, respectively. During chemotherapy, changing PLAP serum levels reflected disease regression and, later, progression in only 2 patients. TPA serum levels reflected the disease course in 15 patients and CA 125 in 28 patients. Rising CA 125 values predicted disease progression in 12 patients for a median of 2 months. At second-look laparotomy, all 11 patients with pathological complete response were marker negative. In the remaining 46 patients with residual or progressive disease, 27, 50, and 61% had elevated serum levels of PLAP, TPA, and CA 125, respectively. None of the markers reflected microscopic disease or pure carcinomatosis. For management decisions, CA 125 was clearly the most useful of the markers. In this study no further information was gained from the other two markers.

Alkaline Phosphatase↗

Present and projected consumption of hospital bed-days as a function of terminal days before death.

In 1983 the bed-day consumption per year per 1,000 inhabitants was 1,571 for all subjects in the Copenhagen County, and 774, 1,239, and 4,918 for subjects 0-19 years, 20-64 years, and above 65 years of age, respectively. Extrapolating from these data the hospital bed-day consumption per inhabitant is predicted to increase by 20.6% in Denmark by the year 2025 as compared to 1986. The mean hospital bed-day consumption per subject during the last 150 days prior to death in hospital was 25.0 days for males and 29.7 for females. Making the conservative assumption that only subjects who die in hospital consume hospital bed-days during the last 150 days before death, the bed-day consumption during 1983 of 0-64 years old subjects being in the terminal 150-day phase was 5.87% of the total annual bed-day consumption of this age group. For subjects 65 years of age or older, it was 18.1%.

Adolescent↗

Variability in plasma oestrogen concentrations in men with a myocardial infarction.

Several studies have reported high levels of oestrogens--especially oestradiol--in plasma in men surviving an acute myocardial infarction (AMI). We have measured plasma levels of the two major oestrogens, oestrone and oestradiol, for three days during the acute AMI and at three months after discharge. Patients admitted to a coronary care unit with ischaemic heart disease without proof of an infarction and patients without evidence of heart disease served as controls. We found significantly higher oestrone levels during the acute infarction than at three months afterwards and also higher than in men without AMI. Men who died shortly after admission had grossly elevated plasma oestrone concentrations. As oestrone levels were correlated to excretion of catecholamines and cardiac enzyme levels in plasma and as circulating levels of oestrone are influenced by ACTH, the hyperoestronaemia may reflect stress-induced increased adrenocortical activity. Plasma oestradiol concentrations in men with AMI decreased significantly during the first three days after admission. In men given no medication oestradiol concentrations did not differ significantly from those in the control groups. Three months after the infarction, the median plasma oestradiol (but not oestrone) concentrations were significantly elevated, but not if only data from men given no medication were considered.

Adult↗

Multivariate techniques to assess laboratory tests in cancer patients.

In this chapter the application of multivariate techniques for the assessment of laboratory tests in cancer patients has been reviewed. We emphasize that the transformation of laboratory test values into just two categories (normal or abnormal) may entail a considerable loss of information. For instance, correlation between two laboratory tests that may be important for differentiating among various clinical categories of patients may disappear when this procedure is used. When only a single set of laboratory results measured in the same specimen is available for a given patient, we must compare these values to those obtained from other patients or healthy subjects to make inferences about the patient on the basis of the laboratory results. Thus, the analysis of the data must be group based. Discriminant analysis, logistic regression analysis, and survival analysis based on Cox's regression model are the techniques most often used in this situation. By contrast, when previous results are available from the same patient we may compare his or her present values to those previously obtained when we want to make inferences about the patient. Our objective is to make a prediction about the time that will elapse until some specified event (death or recurrence of disease) occurs. Two models that have been applied in this situation--the Markov chain and the autoregressive time series model--were reviewed and examples of specific medical applications presented.

Analysis of Variance↗

Coronary risk factors, development of myocardial infarction, and plasma oestrogens: a prospective case-control study in men.

A number of studies have reported hyperoestrogenaemia in men surviving an acute myocardial infarction (AMI). This has led to speculations that hyperoestrogenaemia might be a coronary risk factor. It is not clear why plasma levels of oestrogens should be elevated in coronary heart disease. To ascertain whether hyperoestrogenaemia might be present before the onset of a myocardial infarction, we performed a prospective study in 252 men above the age of forty who within the following 5 years suffered an AMI and, as controls, 526 men matched for age and coronary risk factors and 329 randomly selected men. Mean plasma concentrations of oestradiol and oestrone did not differ significantly between the groups. This suggests that hyperoestrogenaemia is not a coronary risk factor and thus, if present after the AMI, is more likely develop concurrently with the myocardial infarction.

Adult↗

The application of expert systems in the clinical laboratory.

An "expert system" consists of a knowledge base containing information of a general nature and an inference system that receives data from the user and applies the knowledge base to produce advice and explanations. An expert system stripped of its knowledge base (a tool) may be used to build new expert systems. Existing systems relevant for laboratory medicine are reviewed. The role in the laboratory of expert systems and their integration and evaluation are discussed.

Clinical Laboratory Techniques↗