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Library of Congress Cataloging-in-Publication Data
Names: Gleadle, Jonathan, author. | Li, Jordan, author. | Yong, Tuck, author.
Title: Clinical investigations at a glance / Jonathan Gleadle, Jordan Li, Tuck Yong.
Other titles: At a glance series (Oxford, England)
Description: Chichester, West Sussex : John Wiley & Sons, Ltd.,
2017. | Series: At a glance series | Includes bibliographical references and index.
Identifiers: LCCN 2016009162 (print) | LCCN 2016011193 (ebook) | ISBN
9781118759325 (pbk.) | ISBN 9781118759301 (pdf) | ISBN 9781118759318 (epub)
Subjects: | MESH: Diagnostic Techniques and Procedures | Handbooks
Classification: LCC RC71.3 (print) | LCC RC71.3 (ebook) | NLM WB 39 | DDC
616.07/5—dc23
LC record available at http://lccn.loc.gov/2016009162
A catalogue record for this book is available from the British Library.
Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.
Cover image: ©David Heinrich
We have written this book to try to improve the understanding of clinical investigations in medicine. It has arisen as a response to many students asking “What test should I do?” “What do I do about this incidental finding?” “Why was this test wrong?” Our patients asking “What is this test for?” “What does this test mean?” “Will it hurt?” And our medical colleagues referring patients with “The scan has shown a cyst, what do I do now?”
It was also written in part because of the growing recognition that many people are overdiagnosed, undergo too many tests and are overtreated for a wide range of conditions. There are a bewildering and growing array of tests that doctors can request in attempting to establish diagnosis and prognosis. Whilst many have provided powerful improvements in the accuracy of diagnosis, many carry with them the risk of incidental findings, significant cost and potential for harm. Understanding the role of such tests, their interpretation and how to deal with such asymptomatic discoveries is an increasing part of modern medical practice. Screening the general population for disease with tests is an increasingly difficult area and it is essential to consider whether patients are likely to benefit and whether any test will affect the patient’s outcome or management.
All clinical investigations are an adjunct to thorough clinical history and examination but not a substitute, and nor do they treat patients. Investigations should be ordered if they are of benefit in diagnosis, management, prevention and prognosis. This book is intended to assist clinicians develop evidence-based use of clinical investigations and interpret results of these investigations properly. We hope that this book will contribute to the better use of clinical investigations, improve diagnostic accuracy and reduce unnecessary tests or harm.
Jonathan Gleadle
Jordan Li
Tuck Yong
We are grateful to the many colleagues and students who have improved this book, provided images or edited the text and would particularly like to thank Elizabeth Johnston for helping to initiate this project.
We would like to thank the following for their expert reviews and provision of images.
Dr Marc Agazarian
Consultant Radiologist
Department of Medical Imaging
Flinders Medical Centre
Dr Justin Ardill
Consultant Cardiologist
Department of Cardiology
Flinders Medical Centre
Dr Virginia Au
Consultant Radiologist
Department of Medical Imaging
Flinders Medical Centre
Dr Jir-Ping Boey
Senior Registrar
Department of Haematology
Flinders Medical Centre
Dr Jeff Bowden
Consultant Respiratory Physician
Department of Respiratory and Sleep medicine
Flinders Medical Centre & Flinders University
Lynn Brown
Chief Cardiac Sonographer
Department of Cardiology
Flinders Medical Centre
Dr Joseph Frasca
Consultant Neurologist
Department of Neurology
Flinders Medical Centre
Ashley Gaw
Medical student
School of Medicine, Flinders University
Dr Zbigniew Gieroba
Consultant Geriatrician
Department of Aged Care
Flinders Medical Centre
Professor David Gordon
Consultant Infectious Disease Physician
Department of Microbiology & Infectious Diseases
Flinders Medical Centre & Flinders University
Lucy I-Ning Huang
Medical student
School of Medicine, Flinders University
Dr Neil Jones
Consultant Radiologist
Department of Medical Imaging
Flinders Medical Centre
Associate Professor Sonja Klebe
Consultant Surgical Pathologist
SA Pathology
Flinders Medical Centre & Flinders University
Dr Su Yin Lau
Senior Registrar
Department of Gastroenterology and Hepatology
Flinders Medical Centre
Jonathon Jing-Ping Liu
Medical student
School of Medicine, Flinders University
Dr Anand Rose
Consultant Respiratory Physician
Department of Respiratory and Sleep Medicine
Flinders Medical Centre & Flinders University
Dr Mark Siddins
Consultant Urologist
Flinders Private Hospital
Dr Magdalena Sobieraj-Teague
Consultant Haematologist
Department of Haematology and Genetic Pathology
Flinders Medical Centre & Flinders University
Dr Chrismin Tan
Senior Registrar
Department of Medical Imaging
Flinders Medical Centre
Dr Tilenka Thynne
Consultant Endocrinologist and Clinical Pharmacologist
Departments of Endocrinology and Clinical Pharmacology
Flinders Medical Centre & Flinders University
Dr Yew Toh Wong
Consultant Vascular Surgeon
Department of Vascular surgery
Flinders Medical Centre & Flinders University
Investigations are tests to determine more about a person’s health, illness or prognosis. A variety of types of investigations can be undertaken, including: blood tests (e.g. biochemistry, haematology, immunology – Figure 1.1), radiology (e.g. plain X-rays, CT scans, ultrasounds, nuclear medicine tests, MRI scans – Figure 1.2), tests utilising electrical activity (e.g. ECG, EEG or nerve conduction – Figure 1.3), biopsies (tissue obtained for histological and cytological analysis – Figure 1.4), analysis of other biological fluids/specimens (e.g. urine, stool, cerebrospinal fluid – Figure 1.5), genetic testing (e.g. analysing for a DNA mutation that might cause disease – Figure 1.6) and tests for infection (e.g. attempts to culture an organism, detect DNA or an antibody response – Figure 1.7).
Investigations may be undertaken during an acute illness to contribute to making a diagnosis (e.g. a CT scan of the head in someone who is unconscious) or as a screening test in a well individual (e.g. a mammogram) to look for asymptomatic disease. Sometimes tests are undertaken to exclude particular diagnoses, especially if symptoms or signs of that illness can be subtle or nonspecific.
Prior to undertaking investigations in non-emergency settings, a detailed history and physical examination should be performed. Information obtained will often lead to selecting the most appropriate investigations.
When undertaking an investigation it is essential to ensure that it is done on the right person. Identification can be helped by accurate completion of request forms, verification of identity with questions about name, address, date of birth and examination of wrist bands. The use of sticky labels can improve the amount of information on a tube or a request form, but it is easy to mistakenly stick the wrong label on the wrong tube.
The person should have an appropriate understanding of the reason for the test, with consent that includes potential risks and consequences, the possible outcomes of the test and its implications.
When requesting a test, consider how you (or other health professionals) will receive/check/chase the result and how the result will be communicated to the patient (and other relevant health professionals involved in care).
Remember that all test results (and, indeed, even the fact that a patient is undergoing a test) should be regarded as confidential, restricted to the patient or professionals directly involved in their care and only shared with relatives and friends with the patient’s explicit permission and understanding. Similarly, test results and images should be stored in a confidential manner.
In some situations it may be helpful to repeat a test; for example, when following change in an incidentally noted pulmonary nodule on CT scanning or repeating urea, creatinine and electrolytes to monitor response to rehydration. However, be wary of repeating tests too frequently or at too short an interval. Recognise that some abnormalities may take days or weeks to resolve following treatment and that the levels of some blood tests have prolonged half-lives. It is important to recognise that there will be variation in any test because of inter-individual variation and analytical variation.
A perfect diagnostic test would be positive in every patient who has the disease (i.e. have no false negatives). This is the sensitivity of the test. The ideal test would also not be positive in any patient without the disease (i.e. have no false positives). This is the specificity. Diagnostic sensitivity is the proportion of individuals with disease who have a positive test associated with that disease. Diagnostic specificity refers to the proportion of individuals without disease who yield a negative test. A ‘perfect’ test would have both 100% diagnostic sensitivity and specificity. A test with 50% sensitivity and specificity is no better than tossing a coin.
For any test result one can compare the probability of getting that result if the patient truly had the condition with the probability if they were healthy. The ratio of these probabilities is the likelihood ratio (LR), calculated as sensitivity/(1 − specificity).
A receiver operator characteristic curve plots the false-positive rate (FPR = 1 − specificity) versus the true-positive rate (TPR = sensitivity). They assess the diagnostic accuracy of any test. The area under the curve (range: 0.5–1.0) is a quantitative representation of test accuracy, where values from 0.5 to 0.7 represent low accuracy, from 0.7 to 0.9 represent tests that are useful for some purposes, and >0.9 represent tests with high accuracy.
No test is perfect, and after every test the true disease state of the patient remains uncertain. Quantitating this residual uncertainty can be done with Bayes’ theorem. This provides a mathematical way to calculate the post-test probability of disease from three parameters: the pre-test probability of the disease, the test sensitivity and test specificity. Pre-test probability: can be estimated using population prevalence of disease or more patient-specific data.
When interpreting tests it is important to examine the test value with the normal range for that patient. These reference ranges are often derived from a population of ‘normal’ individuals and reflect the prediction interval within which 95% of values fall such that 2.5% of values will be less than the lower limit of this interval and 2.5% of the time it will be greater. However, this assumes a normal distribution of values and may not account for changes with age, gender and other physiological or pathological changes, such as impaired renal function. For some tests, because a large proportion of the ‘normal’ population have values associated with disease risk, a healthy or recommended range is quoted (e.g. vitamin D or cholesterol).
Incidental findings are results that you were not looking for. With increasingly sophisticated testing, very large number of healthy individuals can be found to have ‘abnormalities’ detected. Examples include benign cysts in the liver, detected with CT scans or ultrasounds, and small pulmonary nodules. The interpretation of such incidental findings can be difficult but should be grounded in the pre-test probability, any symptoms or signs and the incidence of such findings in healthy individuals.