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Historically, the provision of clinical laboratory services in the United States can be traced to two distinct traditions: clinical pathology originating in the community hospital and laboratory medicine in the academic medical center. Today, there is an increasing need to contain costs and at the same time provide quality error-free laboratory testing. This chapter explores the future practice of laboratory medicine against the background of a rapidly changing healthcare environment. It familiarizes the reader with the historic development of clinical pathology and laboratory medicine in the United States. The chapter encourages an appreciation for the changes taking place in the healthcare environment that influence the future practice of laboratory medicine. Although history taking and physical examination are still identified as the mainstay of clinical practice, practicing physicians rely more and more on the use of technology, in particular imaging and laboratory testing, to solve clinical problems. The trends are in the direction of increasingly complex and costly laboratory molecular techniques designed to aid in the diagnosis and management of equally complex and costly clinical problems. The reaction to the changes that have occurred in the healthcare environment in recent years is essentially twofold: increased efforts to contain costs and increased public demand for appropriate and error-free medical care. Although total elimination of error is unrealistic, decreases in error comparable to those in many industries are now being viewed as within the reach of a number of medical services, including laboratory medicine.

The Academy of Clinical Laboratory Physicians and Scientists conducted a survey of US medical schools to examine the current status of laboratory medicine education, estimate the amount of teaching time available in the curriculum, and identify the most effective teaching practices. Questionnaires were sent to department heads and course directors at 126 US medical schools. Replies were received from 120 schools (95%), 83 of which offered a total of 132 courses in laboratory medicine. Only 68 schools (57%) had required courses. Most of the elective courses (35 of 50; 70%) were in general clinical pathology. Lectures remained the most common teaching format, with or without laboratory sessions and workshops. Computer-assisted instruction was used in only 10 schools. Laboratory medicine courses were offered in all 4 years of medical school, with the majority (70 of 132; 53%) in the second year, often integrated with general pathology. Opinion was divided over the relative importance of laboratory medicine instruction in the preclinical versus clinical years.

The Graylyn Conference Report of the conjoint ACLPS, ASCP, APC, and CAP task force is prompted by the growing realization that without reform of the clinical pathology residency curriculum the future of clinical pathology practice may be in jeopardy. The conclusions reached at the ASCP-sponsored Colorado Springs IV Conference on Clinical Pathology Residency Training laid the groundwork for this report on curriculum reform. The goal is the creation of scientifically oriented clinical pathology practitioners capable of serving as consultants to other physicians of managing laboratory resources, and of playing leadership roles in an increasingly complex health-care system. Recommendations are described under the headings of patient care roles, graduated responsibility, analytical and technical training, laboratory management and informatics, and basic and applied research. In terms of reforming the structure and content of the curriculum, it is recommended that basic laboratory rotations be preceded by either a single didactic general 4- to 6-week orientation, or a series of shorter orientations incorporated into each rotation. The introductory and rotation phase should be 9 to 12 months in duration. It is further recommended that the remaining 6 to 9 months of the 18-month core be an integrated experience in which the resident practices Clinical Pathology by assuming service responsibilities for several laboratory sections simultaneously.

This is the second edition of a text that seeks to blend information on the operating characteristics of laboratory (and other) tests with clinical estimates of pretest probability to provide a rational basis for the use of technology in clinical decision making. The first edition, published in 1991, grew out of an article entitled “Selection and Interpretation of Diagnostic Tests and Procedures: Principles and Applications”, published as a supplement to the Annals of Internal Medicine (1981;94:553–600) by members of the General Medicine Unit at the University of Rochester. This followed the publication of Beyond Normality: The Predictive Value and Efficiency of Medical Diagnosis by Galen and Gambino (New York: Wiley, 1975), the monograph largely responsible for introducing the notion of “predictive value” to the laboratory community. …

The diagnosis of acute myocardial infarction (AMI) in the early postoperative period may be quite difficult in certain patients. Electrocardiograms fail to be diagnostic of AMI in as many as one third of patients with myocardial injury found at autopsy. Enzyme patterns commonly used to diagnose AMI in patients admitted to coronary care units are obscured by muscle injury, medications, cardioversion, surgical manipulation, and blood transfusion. The MB isoenzyme of creatinine phosphokinase (CPK) has been described as a specific indicator of myocardial injury. Therefore the CPK-MB isoenzyme level was evaluated as a potential aid in the diagnosis of AMI in the early postoperative period. Thirty patients undergoing cardiac surgery and 7 patients undergoing thoracic surgery not involving the heart were studied. CPK-MB isoenzyme was present in the serum in 10 of 30 patients after cardiac surgery but in none of 7 patients after thoracic surgery. The presence of CPK-MB isoenzyme was found to be a valuable adjunctive indicator in the diagnosis of AMI in the early postoperative period.

Algorithmic testing strategies for various clinical problems, such as myocardial infarction, hypothyroidism, and hepatic disease, are presented. The strategies, although based on Bayesian statistics and clinical decision analysis, are descriptive in that, for the most part, clinicians appear to adopt the same ideas and principles.

Hypoglycemia recently has become somewhat of a fad diagnosis, often misguidedly used to explain such vague complaints as chronic anxiety and lack of pep. True symptomatic hypoglycemia is of two types: reactive, which may follow gastric surgery, and fasting, most commonly associated with alcoholism, hepatic disease, pituitary or adrenal insufficiency, or tumor. Test strategies for documenting hypoglycemia, differentiating the two types, and identifying the cause are presented here.

gamma-Glutamyl transpeptidase (GGTP) is a sensitive but nonspecific index hepatobiliary disease. In infectious mononucleosis (IM) or the mononucleosis-like disease attributable to cytomegalovirus (cytomegalovirus-induced IM), GGTP reverted to normal later than aspartate aminotransferase and alkaline phosphatase. In three cases elevated serum GGTP activity persisted for up to 24 months -- raising the question of persistent 'post-IM' hepatitis. Such prolonged GGTP activity was unusual in other late IM specimens. Possible, but unlikely, causes for such persistent GGTP activity are an unusual degree of hepatic damage during acute IM, excessive induction of microsomal enzyme system activity by drugs, or unusual Epstein-Barr virus carrier state activation that might contribute to ongoing hepatic structural damage. Other markers of chronic hepatocellular disease including aspartate aminotrasferase, alkaline phosphatase, and bilirubin were normal in late specimens from these 3 patients. The cause of their persistent elevated GGTP activities remains unknown.

This is a prospective study of the value of the creatine kinase (CK) isoenzyme determination in the early diagnosis of acute myocardial infarction. The presence or absence of the MB isoenzyme was correlated with electrocardiogram and standard enzymes. The frequency of falsely positive and falsely negative results for CK-MB, electrocardiogram and each standard enzyme was calculated and, using the elements of conditional probability theory, their predictive values for the diagnosis of acute myocardial infarction were determined. Results indicate that CK-MB combines the best attributes of the electrocardiogram and standard enzyme tests: detectable MB isoenzyme activity by acrylamide slab electrophoresis has a predictive value for the diagnosis if acute myocardial infarction comparable to that of a positive electrocardiogram; absence of MB isoenzyme activity, in the 24 hour period following the onset of symptoms, excludes the diagnosis of acute myocardial infarction with a probability equivalent to that provided by normal standard enzyme results.

A clinically useful test is one that, indirectly, leads to better management results. Decision analysis and benefit-risk models are discussed as means by which performance standards can be set to determine when to treat or not to treat a patient. The difficulties involved in such an assessment are probed.

A typical urine pregnancy test with the enzyme-linked immunoassay for human chorionic gonadotropin (Tandem Icon human chorionic gonadotropin) was performed as was a qualitative serum radioimmunoassay for human chorionic gonadotropin when the positive cutoff for the latter was set at 30 IU/L. There was 99.5% concordance between the two methods when performed on 871 simultaneous urine and serum specimens. Although the serum radioimmunoassay can detect levels of human chorionic gonadotropin as low as 10 IU/L, in this study the majority of patients with serum levels between 10 and 30 IU/L were not pregnant on clinical follow-up. Of nine patients with adequate clinical follow-up, a negative urine pregnancy test result, and a serum human chorionic gonadotropin level between 10 and 30 IU/L, only one proved to be pregnant. The Tandem Icon human chorionic gonadotropin urine test is sufficient for routine pregnancy testing and to rule out the need for immediate intervention in cases of ectopic pregnancy

The critical role of expert judgment in clinical decision support has been accommodated in a class of approaches termed knowledge based systems. These, have arisen from work in artificial intelligence on expert performance. Some of the perspectives and insights that have been gained from these approaches are briefly discussed.

Modified patient management problems were administered to senior medical students in pre- and postexamination formats to evaluate the effects of systematic instruction in laboratory medicine on clinical problem solving performance. Significant improvements were noted on several of the derived performance measures studied. Most improvements could be attributed to the course of instruction, some were problem dependent, and students with some prior clinical experience exhibited more improvement than did their less experienced colleagues. Evidence is presented to suggest that poor problem solving performance, as evident from pre-examination results, reflects not any inherent problem solving deficiency, but a specific lack of knowledge. The greater degree of improvement exhibited by inexperienced students toward greater hypothesis specificity and higher diagnostic goal indices leads us to speculate that inexperienced students structure knowledge differently from their experienced counterparts. It is concluded that systematic instruction aimed at improving laboratory utilization is capable of evaluation and, at least in simulated format, leads to improved clinical problem solving. The implications are discussed.

Enzyme determinations are among the most commonly ordered laboratory tests and are valuable diagnostic aids. For the results to be useful, the sample must be processed and stored properly and patient variables, including age, sex, medication history, and exercise status, must be considered. Isoenzyme determinations are helpful in specific situations.

We evaluated a new 2-hour latex agglutination-inhibition tube test, designed to detect a minimum of 200 ng of morphine (or structurally related compounds) per milliliter of either serum or urine. It was compared with a more sensitive radioimmunoassay procedure, by use of 159 addict urines (radioimmunoassay-positive) and 506 selected (radioimmunoassay-negative) urines. Our results were negative for 99.6% of the radioimmunoassay-negative specimens, including many from addicts taking several drugs other than opiates, and for 94.3% (33 of 35) of radioimmunoassay-positive specimens from addicts, containing only 40-99 ng (morphine equivalents) per milliliter. Positive test results were recorded for 108 of 110 specimens containing 200 or more nanograms (morphine equivalents) per milliliter. The test is technically and instrumentally simple and has a clearcut negative endpoint. Because glucuronide-conjugated morphine is readily detected, this test can be used before chromatography to eliminate those specimens that have no significant concentrations of narcotics (i.e., give a negative latex tube test) and thus obviate timeconsuming hydrolysis before chromatography.

The increased utilization of diagnostic procedures has prompted interest in cost-effective laboratory testing. Clinically useful tests-useful in the sense that the patient benefits-are cost effective. The choice of test(s) is determined by the risks and benefits of proposed management. In practice, the first step in cost-effective laboratory testing is to define the clinical problem; the next step is to choose the test(s) that minimize the risks of making a false diagnosis. The choice will depend on whether sensitivity, specificity, or both are needed to decrease diagnostic uncertainty to the extent that management does more good than harm.

Fasting plasma glucose determination is the test of choice for diagnosis of diabetes. Glucose tolerance testing should be reserved for patients with borderline fasting values or possible diabetic complications and those suspected of having gestational diabetes. Strict attention to patient variables is essential if glucose tolerance testing is to be of value. The diagnosis of diabetes should be reserved for those patients with symptoms and unequivocal hyperglycemia, those with fasting plasma glucose values of 140 mg/dl or more repeatedly, and those with glucose tolerance test values of 200 mg/dl or more at two hours and at least one other time.

Appropriate use of test strategies requires not only an appreciation of analytic considerations and the ability of the tests to confirm or exclude the hypotheses, but also an understanding of the underlying pathophysiology and clinical features of the problems to be addressed. This discussion covers disease definition, pathophysiology, analytic considerations, and strategies for diagnosis and management.

An analysis of 1863 cases in a comparative study of 5 immunologic pregnancy tests is presented. 724 of the 1863 urine specimens were specifically selected because of interfering substance in the specimen or because of a clinical state capable of causing such substances to be excreted. The specimens were subjected to 2 hemagglutination-inhibition tube tests (UCG - urine chorionic gonadotropin - and Pregnosticon) 2 latex agglutination-inhibition slide tests (Gravindex and Pregnosticon) and a direct latex agglutination slide test (DAP). Maximum accuracies based on correct test results in uncomplicated first trimester pregnancies and a control group of nonpregnant patients were 98.8% for Pregnosticon tube test 98.6% for the UCG test 96.7% for the Pregnosticon slide test 93.8% for the Gravindex test and 93.2% for the DAP test. These results demonstrate greater sensitivity of tube tests and therefore indicate that tube tests should be used for all patients having elective gynecologic surgery or curettage in the childbearing period. Of the 3 slide tests the Pregnosticon slide test gave the least number of false positive results. Most false positive or inconclusive latex agglutination-inhibition results were related to protein or blood in the urine specimens.

The laboratory of the future will not be exclusively centrally placed in the hospital setting, and Laboratory Medicine will not be hospital-based to the extent it has been in the past. The requirement that Laboratory Medicine support necessary and beneficial clinical care remains. Unless laboratory personnel pay greater attention to all aspects of laboratory performance, including test ordering and reporting, the viability of Laboratory Medicine as a specialty may be jeopardized.

pH and blood gas measurements are used to detect and monitor ventilation, oxygenation, and acid-base disturbances. The blood sample must be drawn anaerobically and transported in ice water to the laboratory. Partial pressure of carbon dioxide in arterial blood (PaCO2) reflects alveolar ventilation; partial pressure of oxygen in arterial blood (PaO2) reflects oxygen loading. The alveolar-arterial PO2 gradient (PA-aO2) distinguishes hypoxemia due to hypoventilation from that due to inefficent pulmonary gas exchange. The demand status of the cardiovascular system and the hemoglobin value reflect oxygen delivery to tissues. The relationship among pH, PaCO2, and bicarbonate concentration, when interpreted in the light of clinical findings, specifies the type and duration of acid-base disturbance.

In Reply.— We believe that the choice of laboratory test, or test regimen, must be made by the physician. The purpose of ordering—or, preferably, requesting—a laboratory test is to confirm or exclude clinical impressions with sufficient certainty to ensure that clinical management does more good than harm. This is the essence of laboratory medicine and in our view is best achieved by consultation between clinical pathologist and practicing physician. In recent years we have come to appreciate the concepts of diagnostic value and clinical usefulness as they apply to laboratory testing. 1 Nevertheless, it is important to realize that test strategy may be rendered meaningless if requests are improperly transmitted, blood samples are improperly obtained, analyses are inaccurate or imprecise, or results are reported incorrectly. To ensure the quality of the foregoing requires well-trained and dedicated medical technologists. We agree with Dr Meyer that in the interest of improving laboratory

We prospectively evaluated the accuracy with which clerical and laboratory staff carried out physicians' written orders for thyroid function testing in 181 patients at two institutions. In 54% of the patients studied, support staff were found to have added or deleted one or more tests from the original written orders. When the ordering physicians were asked to identify the clinical indications for the tests they had ordered, 37% of their orders either lacked an appropriate test or included an unnecessary test request. In contrast, after clerical and laboratory staff had changed orders, only 25% of patients had inappropriate tests performed or necessary tests omitted. Clerical staff using computer-based ordering menus significantly improved the appropriateness of physicians' orders compared with clerks who lacked such guidance. Laboratory technologists who used informal, knowledge-based rules also tended to improve the appropriateness of physicians' orders. We conclude that a substantial proportion of physicians' orders for diagnostic tests may be modified during the test requisitioning process. The use of testing regimens by ward clerks and laboratory technologists may explain their ability to improve on physicians' orders. ( JAMA 1988;259:2549-2552)