User's Guide to the Surgical Literature: How to Use an Article About
Contents
1. or long term follow up to every patient By independent we mean that the individual interpreting the ref erence standard should be unaware of or blind to the results of the test and that the individual interpreting the test should be unaware of the results of the reference standard To the ex tent that this blinding is not achieved the investigation is likely to overestimate the diagnostic power of the test In the study by Lijmer et al lack of blinding resulted in a significant overestimation of the test performance relative diagnostic odds ratio 1 3 95 confidence interval 1 0 1 9 p lt 0 05 For example surgeons who detect a hip fracture with use of nuclear bone scanning or magnetic resonance imaging are more likely to identify a previously undetected fracture line on plain radiographs In one study evaluating the use of plain radi ography and magnetic resonance imaging for the detection of osteonecrosis following a hip fracture the investigators did not report independent assessments of plain radiographs and mag netic resonance images Thus the investigators who identified changes on magnetic resonance images at two months may have been more suspicious of the findings on the plain radiographs which initially appeared normal but ultimately were classified as abnormal USER S GUIDE TO THE SURGICAL LITERATURE HOW TO USE AN ARTICLE ABOUT A DIAGNOSTIC TEST Another way in which a lack of independence can be misle2. Fig 1 Diagram illustrating diagnostic thresholds risk to the patient and may be extremely valuable for ruling in or ruling out infection a complication of total hip arthro plasty that is devastating if left untreated Resolution of the Scenario The patient in the scenario at the beginning of this report had a pretest probability of infection of 20 Her negative C reactive protein test likelihood ratio 0 04 decreased her probability of infection to 1 The patient did not undergo a surgical procedure but required close follow up At the two week follow up appointment the white blood cell count was normal and the patient was afebrile Further examination of radiographs and computed tomographic scans of the lumbar spine revealed right lateral recess stenosis Conclusion Application of the guides presented in this article can allow surgeons to critically assess studies about a diagnostic test Surgeons are continuously exposed to a variety of new and in novative diagnostic tests and to the studies describing their di agnostic properties Determining the validity of these studies the study results and the applicability of these results to your patients are three fundamental steps toward choosing and in terpreting diagnostic tests Mohit Bhandari MD MSc Victor M Montori MD Gordon H Guyatt MD MSc Department of Clinical Epidemiology and Biostatistics McMaster Univer sity Health Sciences Center 1200 M
3. a study indicates that a test is highly reproducible two possibili ties are likely either the test is quite simple and easy to apply to patients or the investigators involved in the study were highly skilled in applying the diagnostic test to the study pa tients If the latter is true the diagnostic test may not be useful in a setting in which nonskilled interpretation of the test is likely to occur Another important issue to consider is the similarity of USER S GUIDE TO THE SURGICAL LITERATURE HOW TO USE AN ARTICLE ABOUT A DIAGNOSTIC TEST your patient to those in the study The properties of a diagnos tic test can change with different disease severities see the dis cussion on the use of an appropriate spectrum above For instance the test may not perform as well in a community practice where less complicated cases will have to be distin guished from multiple competing diagnoses On the other hand in the study by Spangehl et al the patients were as sessed in a referral practice setting a university hospital In that setting surgeons were more likely to encounter patients with more severe or complicated disease in whom the diag nostic test the C reactive protein level was likely to perform better likelihood ratio gt gt 1 In that setting alternative diag noses may have already been explored and ruled out Likeli hood ratios tend to move away from the value of 1 when all patients who have the target disorde
4. and pus in the joint On the other hand the white blood cell count will almost never be elevated in healthy controls However its di agnostic utility is very poor in patients like the one in the sce nario described above who may have early septic arthritis but who also may have another condition that elevates the white blood cell count such as viral pharyngitis a urinary tract in fection or recent trauma The use of carcinoembryonic antigen for the detection of colorectal cancer provides a striking example of the variable utility of a diagnostic test in populations with different disease severity Fletcher reported that carcinoembryonic antigen levels were elevated in thirty five of thirty six patients with estab lished cancer and were much lower in patients without cancer However in an another study in which carcinoembryonic anti gen testing was applied to patients with less advanced stages of 1135 THE JOURNAL OF BONE amp JOINT SURGERY JBJS ORG VOLUME 85 A NUMBER 6 JUNE 2003 colorectal cancer the test results were similar enough to those in patients without cancer that the ability of the test to distinguish the two groups declined Accordingly the use of carcinoembry onic antigen in the diagnosis of cancer was abandoned Spangehl et al included a wide spectrum of patients with low moderate and high levels of clinical suspicion of infection We can therefore conclude that the authors assem bled an appr
5. de Velde CJ The value of fine needle aspiration biopsy in pa tients with nodular thyroid disease divided into groups of suspicion of malig nant neoplasms on clinical grounds Arch Intern Med 1990 150 113 6 The PIOPED Investigators Value of the ventilation perfusion scan in acute USER S GUIDE TO THE SURGICAL LITERATURE HOW TO USE AN ARTICLE ABOUT A DIAGNOSTIC TEST 14 15 16 IT 18 pulmonary embolism Results of the prospective investigation of pulmonary embolism diagnosis PIOPED JAMA 1990 263 2753 9 Fagan TJ Letter nomogram for Bayes theorem N Engl J Med 1975 293 257 Parvizi J Wayman J Kelly P Moran CG Combining the clinical signs im proves diagnosis of scaphoid fractures A prospective study with follow up J Hand Surg Br 1998 23 324 7 Hoffman JR Mower WR Wolfson AB Todd KH Zucker MI Validity of a set of clinical criteria to rule out injury to the cervical spine in patients with blunt trauma National Emergency X Radiography Utilization Study Group N Engl J Med 2000 343 94 9 Teefey SA Hasan SA Middleton WD Patel M Wright RW Yamaguchi K Ultrasonography of the rotator cuff A comparison of ultrasonographic and arthroscopic findings in one hundred consecutive cases J Bone Joint Surg Am 2000 82 498 504 Rubinstein RA Jr Shelbourne KD McCarroll JR VanMeter CD Rettig AC The accuracy of the clinical examination in the setting of posterior cruciate ligament injuries Am J Sports
6. fine needle aspira tion biopsy underwent a further reference standard examina tion with surgical resection and pathological analysis That study is likely to have overestimated the power of the test in excluding malignancy Verification bias was also a potential problem in the landmark study of the value of the ventilation perfusion lung scan in the diagnosis of pulmonary embolism the PIOPED study Patients whose ventilation perfusion scans were in terpreted as normal near normal and low probability were less likely to undergo pulmonary angiography than those with more positive ventilation perfusion scans specifically 69 of the patients in the former group and 92 of those in the latter group underwent angiography This finding is not surprising as clinicians might be reluctant to subject patients who have a low probability of pulmonary embolism to the risks of angiography In this case however the investigators dealt successfully with the bias by constructing an alternative reference standard for patients who did not undergo angiog raphy They followed these untreated patients for one year to ensure that they remained free of evidence of pulmonary em bolism during this period of time The methods section of the article by Spangehl et al in dicates that all patients underwent frozen section analysis as well as intraoperative gram staining and culture of specimens from the surgical site Thus the results of the C re
7. ligament injury virtually certain Sensitivity and specificity have drawbacks In calculat ing sensitivity and specificity important information is often discarded to collapse the data to fit the 2 x 2 table format Moreover multiple recalculations of sensitivity and specific ity are often necessary at each potential cut point or division when one is considering a continuous variable for example blood pressure or a test result that is reported as one of a number of categories such as a high intermediate or low probability ventilation perfusion scan Finally there is no convenient nomogram that allows us with knowledge of sen sitivity specificity and a particular test result to convert pre test probability to posttest probability However one can translate these measures into likelihood ratios Similar draw backs affect the calculation of predictive values Table II Will the Results Help Me in Caring for My Patients Having assessed the validity of the article and performed the necessary simple calculations to understand its results you can ask yourself whether these results will help you in caring for your patient The value of a diagnostic test often depends on its re producibility when applied to patients If a test requires much interpretation e g electrocardiograms or pathological speci mens or involves the use of laboratory assays e g stains or biochemical assays variation in test results can occur If
8. nearly 0 and you would not conduct fur ther testing for periprosthetic infection You may wish to apply different numbers here the treatment and test thresh olds are a matter of values ideally the patient s values and they differ among conditions depending on the risks of ther apy ie if the therapy is associated with severe side effects you may want to be more certain of your diagnosis before rec ommending it and the danger of the disease if left untreated i e if the danger of missing the disease is high as it is in the case of pulmonary embolism you may want your posttest probability to be very low before abandoning diagnostic test ing Fig 1 Finally you can ask yourself if your patient will be better off having had the test A test becomes more valuable when it has acceptable risks the target disorder has major conse quences if left untreated and the target disorder can be readily treated if diagnosed C reactive protein testing poses minimal 1139 THE JOURNAL OF BONE amp JOINT SURGERY JBJS ORG VOLUME 85 A NUMBER 6 JUNE 2003 USER S GUIDE TO THE SURGICAL LITERATURE HOW TO USE AN ARTICLE ABOUT A DIAGNOSTIC TEST Probability of Diagnosis 0 Test Treatment 100 Threshold Probability below Probability between test Probability above treatment test threshold and treatment threshold threshold NO FURTHER no further testing further testing warranted TESTING WARRANTED warranted START TREATMENT
9. the diagnostic utility of fine needle aspiration biopsy in the determination of malignancy in patients with nodular thyroid disease Patients who had benign lesions on fine needle aspiration biopsy did not have surgical resection of the thyroid nodule for definitive pathological diagnosis whereas those 1136 THE JOURNAL OF BONE amp JOINT SURGERY JBJS ORG VOLUME 85 A NUMBER 6 JUNE 2003 USER S GUIDE TO THE SURGICAL LITERATURE HOW TO USE AN ARTICLE ABOUT A DIAGNOSTIC TEST TABLE II Likelihood Ratios for a Positive and Negative C Reactive Protein Test Periprosthetic Infection C Reactive Protein Test Yes No Total Positive gt 10 mg L 25 True Positive a 9 False Positive b 34 Negative lt 10 mg L 1 False Negative c 107 True Negative d 108 Total 26 116 Sensitivity a a c 25 26 96 Specificity d b d 107 116 92 Positive predictive value a a b 25 34 74 Negative predictive value d c d 107 108 99 Accuracy a d a b c d 132 142 93 Prevalence a c a b c d 26 142 18 Likelihood ratio for positive test a a c b b d sensitivity 1 specificity 25 26 9 116 0 96 0 077 12 5 Likelihood ratio for negative test c a c d b d 1 sensitivity specificity 1 26 107 116 0 038 0 92 0 041 The data are from the study by Spangehl et al who had malignant or uncertain lesions on
10. 1133 COPYRIGHT 2003 BY THE JOURNAL OF BONE AND JOINT SURGERY INCORPORATED CURRENT CONCEPTS REVIEW UsErR s GUIDE TO THE SURGICAL LITERATURE How To USE AN ARTICLE ABOUT A DIAGNOSTIC TEST By MOHIT BHANDARI MD MSc VICTOR M MONTORI MD MARC F SWIONTKOWSKI MD AND GORDON H GUYATT MD MSc gt The primary issues to consider in determining the validity of a diagnostic test study are how the authors assem bled the patients and whether they used an appropriate reference standard for all patients to determine whether the patients did or did not have the target condition gt Likelihood ratios are key to the interpretation of diagnostic tests as they link estimates of pretest probability to posttest probability gt Sensitivity is the property of the test that describes the proportion of individuals with the disorder in whom the test result is positive gt Specificity is the property of the test that describes the proportion of individuals without the disorder in whom the test result is negative Clinical Scenario You are an orthopaedic surgeon who is asked to evaluate a sixty five year old woman in the emergency department be cause of new onset right hip pain that started one week ago Seven months previously the patient had had a right total hip arthroplasty for the treatment of osteoarthritis The pain radi ates to the thigh and buttocks The patient reports that she slipped on a kitchen floor a few days ago b
11. Med 1994 22 550 7
12. active pro tein test did not influence the decision to conduct reference standard investigations in these patients What is less clear is whether the investigators interpreting the reference standard had access to the results of the C reactive protein test What Are the Results The starting point for any diagnostic process is to determine the probability that the target disease is present in a given pa tient group before the next diagnostic test is performed Let us consider two patients 1 a sixty five year old woman with diabetes who presents six months after total hip arthroplasty with a fever an elevated white blood cell count and a painful hip with an erythematous wound and 2 a sixty year old otherwise healthy woman who presents one year after arthro plasty with intermittent hip pain normal findings on physical examination and an elevated white blood cell count Most surgeons would consider the probability of an infection about the prosthesis to be different for these two patients The prob ability referred to as the pretest probability of periprosthetic infection in the sixty five year old patient with hip pain and fever is much higher than the probability of infection in the sixty year old patient even before additional diagnostic tests are conducted How can surgeons estimate pretest probability Litera ture on the probability of disease given a certain presentation for example reports discussing the probability of
13. ading is if the test under evaluation is a component of the reference standard For example in one study investigating the utility of the serum and urinary amylase test in the diag nosis of pancreatitis the investigators constructed a reference standard that consisted of a series of tests including the serum and urinary amylase test This incorporation of the test under evaluation into the reference standard is likely to overestimate the utility of the test Thus clinicians should make sure that the test under evaluation and the reference standard are inde pendent of each other In the study by Spangehl et al all patients underwent measurement of the C reactive protein level and testing to de termine the presence or absence of infection The authors did not describe clearly whether the assessments were performed in an independent and blinded fashion The investigators de fined infection as the presence of an open or draining sinus communicating with the hip joint the detection of purulent fluid within the joint during surgical exploration or a positive result on at least three other investigations intraoperative cul ture preoperative aspiration frozen section analysis determi nation of the C reactive protein level and determination of the erythrocyte sedimentation rate The inclusion of the di agnostic test in question the C reactive protein test as a component of this reference standard raises a serious con cern This in
14. ain Street West Hamilton ON L8N 3Z5 Canada E mail address for M Bhandari bhandari sympatico ca Marc F Swiontkowski MD Department of Orthopaedic Surgery University of Minnesota Box 492 Delaware Street N E Minneapolis MN 55455 The authors did not receive grants or outside funding in support of their research or preparation of this manuscript They did not receive pay ments or other benefits or a commitment or agreement to provide such benefits from a commercial entity No commercial entity paid or directed or agreed to pay or direct any benefits to any research fund foundation educational institution or other charitable or nonprofit organization with which the authors are affiliated or associated References 1 Spangehl MJ Masri BA O Connell JX Duncan CP Prospective analysis of preoperative and intraoperative investigations for the diagnosis of infection at the sites of two hundred and two revision total hip arthroplasties J Bone Joint Surg Am 1999 81 672 83 2 Jaeschke R Guyatt G Sackett DL Users guides to the medical literature Ill How to use an article about a diagnostic test A Are the results of the study valid Evidence Based Medicine Working Group JAMA 1994 271 389 91 3 Lijmer JG Mol BW Heisterkamp S Bonsel GJ Prins MH van der Meulen JH Bossuyt PM Empirical evidence of design related bias in studies of diag nostic tests JAMA 1999 282 1061 6 4 Fletcher RH Carcinoembryonic a
15. at describes the propor tion of patients with the disorder in whom the test result is posi tive Specificity is the property of the test that describes the proportion of patients without the disorder in whom the test result is negative Using the rules provided in Table II we can calculate the sensitivity and specificity of the C reactive protein test in detecting infection To calculate sensitivity we divide the total number of patients who had a proven infection and a posi tive test true positives n 25 by the total number of patients who had a proven infection true positives false negatives n 26 Thus the sensitivity is 96 To calculate specificity we di vide the total number of patients who had a negative C reactive protein test true negatives n 107 by the total number of pa tients who had no infection true negatives false positives n 116 Therefore the specificity is 92 Tests with high sensitivity are useful for ruling out dis ease and tests with high specificity are useful for ruling in dis ease For example since almost all patients with a scaphoid TABLE III Pretest Probabilities Likelihood Ratios and Posttest Probabilities Pretest Likelinood Posttest Probability Ratio Probability Negative test 80 high probability 0 04 14 50 0 04 3 8 30 0 04 1 8 10 low probability 0 04 0 4 Positive test 80 high probability 12 5 98 50 12 5 93 30 12 5 84 10 intermediate probabil
16. corporation bias may spuriously increase the ap parent utility of the test Having asked the most critical questions that assist in the determination of study validity you can further reduce your chances of being misled by asking an additional question Did the Results of the Test Being Evaluated Influence the Decision to Perform the Reference Standard The properties of a diagnostic test will be distorted if the re sults of the test influence the decision to carry out the refer ence standard This situation called verification bias or workup bias applies when for example investigators only conduct further evaluation with the reference standard for patients who have a positive test result and assume that those who have a negative test result do not have the target condition In prac tice this leads to an overly sanguine estimation of the ability of the test being evaluated to differentiate between patients who have the target condition and those who do not In the study by Lijmer et al the test performance was overestimated twofold in studies in which different reference standards were used for patients who had the target condition and those who did not relative diagnostic odds ratio 2 2 95 confidence interval 1 5 3 3 Generally if a test is invasive surgeons will be less likely to apply the reference standard i e surgical biopsy when the probability of disease is low Verification bias occurred in a study of
17. d ratios The clinician obtains the posttest probability by placing a straight edge that aligns the pretest probability to the likelihood ratio for the diagnostic test For your patient who has a pretest probability of 20 on the basis of history and clinical examination and a negative C reactive protein test LR 0 04 the posttest probability is 1 If the C reactive protein test had been positive LR USER S GUIDE TO THE SURGICAL LITERATURE HOW TO USE AN ARTICLE ABOUT A DIAGNOSTIC TEST 12 5 then the posttest probability of an periprosthetic infec tion would have increased to 76 Table II illustrates how this approach would be applied to the two patients presented earlier the sixty five year old woman with hip pain and overt signs of infection pretest prob ability 80 and the sixty year old woman with hip pain but no fever pretest probability 10 Formally new knowledge posttest probability that is derived from the revision of previ ous knowledge pretest probability on the basis of new infor mation likelihood ratio is an application of Bayes theorem to diagnosis As is evident from the above examples the use of like lihood ratios is key to the interpretation of diagnostic tests However many studies present the properties of diagnostic tests in less clinically useful terms sensitivity and specificity Sensitivity Specificity and Predictive Value see Table II Sensitivity is the property of the test th
18. e target con dition may be healthy or may have one of the competing diag noses in this case hip trauma or pain radiating from the back The credibility believability or validity of a study is only as good as the methods used in its conduct The primary issues to consider in determining the validity of a diagnostic test study are how the authors assembled the patients and whether they used an appropriate reference standard for all patients to determine whether the patients did or did not have the target condition Was There Diagnostic Uncertainty How do you know whether the investigators chose a suitable population or whether their choice threatens the study s valid ity The specific question to ask yourself is whether the sur geons who cared for the patients faced genuine diagnostic uncertainty Tests are able to easily distinguish between se verely affected and healthy patients otherwise they can easily be discarded from use The reason for this excellent diagnos USER S GUIDE TO THE SURGICAL LITERATURE HOW TO USE AN ARTICLE ABOUT A DIAGNOSTIC TEST TABLE Guidelines for Evaluating Studies About a Diagnostic Test Are the results of the study valid Primary guides Did clinicians face diagnostic uncertainty Was there an independent blind comparison with a reference standard Secondary guides Did the results of the test being evaluated influence the decision to perform the reference standard Were the meth
19. e test that indicates the direction and magnitude of this change This characteristic of the test is termed the like lihood ratio The likelihood ratio LR is the characteristic of the test that links the pretest probability to the posttest proba bility that is the probability of the target condition after the test results are obtained What Are the Likelihood Ratios Associated with the Test Results Table II presents results from the study by Spangehl et al al though not in the way that the authors presented them There were twenty five patients who had a proven infection and 107 patients in whom infection was ruled out For all patients the C reactive protein level was classified as positive gt 10 mg L or negative lt 10 mg L How likely is a negative C reactive protein test among patients who have a periprosthetic infec tion Table II reveals that the C reactive protein level was nor mal in one 4 of twenty six patients with an infection and in 107 92 of 116 patients without an infection The ratio of these two proportions 0 04 0 92 is the likelihood ratio for a negative C reactive protein test and is equal to 0 043 Thus a negative C reactive protein test is twenty three times that is 1 0 043 times less likely to occur in patients with a peripros thetic infection than in those without an infection Alterna tively a positive C reactive protein test is 12 5 times more likely to occur in patients with a peripr
20. infection in patients presenting with pain and fever after arthroplasty similar data derived from the hospital s registry and a sur geon s clinical experience and intuition can help that surgeon to estimate pretest probability Other information that can be used to estimate pretest probability can be found in studies evaluating the utility of a diagnostic test For instance in the study by Spangehl et al 17 thirty five of the 202 hips were found to be infected Returning to your patient you can use the history and clinical examination to arrive at a pretest probability that is the probability of infection before the result of the C reactive protein test was obtained Your patient s elevated white blood cell count and fever are consistent with her recent viral infection However the new onset hip pain raises concern that she may have a periprosthetic infection The wound is neither erythematous nor warm to the touch Indeed this patient is similar to an average patient in the study by Spangehl et al On the basis of this information you estimate that your pa tient has a 20 probability of a periprosthetic infection The next step is to decide how the results of the C reactive protein test change your estimate of the probability of infec tion In other words surgeons should be interested in the char 1137 THE JOURNAL OF BONE amp JOINT SURGERY JBJS ORG VOLUME 85 A NUMBER 6 JUNE 2003 acteristic of th
21. ity 12 5 60 As determined on the basis of the result of the C reactive pro tein test 1138 THE JOURNAL OF BONE amp JOINT SURGERY JBJS ORG VOLUME 85 A NUMBER 6 JUNE 2003 fracture suffer from anatomical snuffbox tenderness a highly sensitive test the absence of such tenderness virtually rules out a scaphoid fracture In patients with a neck injury the absence of five clinical features midline cervical tenderness focal neurological deficit impaired alertness intoxication and history of a distraction injury reduces the probability of an important cervical spine injury to lt 1 In patients sus pected of having a full thickness rotator cuff tear a normal ultrasound rules out a full thickness tear because ultrasonog raphy has a sensitivity of 100 The three examples cited above are all situations in which a high sensitivity test if negative can rule out a target condition The posterior drawer test for the diagnosis of pos terior cruciate ligament injury is highly specific Rubinstein et al conducted a study to determine the diagnostic utility of the posterior drawer test among a varied population of patients including those with normal knees those with anterior cruciate deficient knees and those with posterior cruciate deficient knees Among blinded assessors a specific ity of 99 was reported Thus a positive result on the posterior drawer test makes the diagnosis of posterior cruciate
22. lacing your patient s name on the next day s procedures list for an aspiration the result of the C reactive protein test comes back as 8 mg dL normal lt 10 mg dL This finding raises some question as to tests in the care of surgical patients This article is the fourth in a series designed to help the orthopaedic surgeon use the published literature in practice In the first article in the series we presented guidelines for making a decision about therapy and focused on randomized controlled trials In the second article we focused on evaluating nonrandomized studies that present information about a patient s prognosis In the third article we focused on systematic literature reviews In this article we address the use of articles about diagnostic 1134 THE JOURNAL OF BONE amp JOINT SURGERY JBJS ORG VOLUME 85 A NUMBER 6 JUNE 2003 whether your patient actually has an infection Unsure about the true utility of a C reactive protein test in patients with a suspected infection you decide to find a suitable article to clarify your concerns That evening you conduct an Internet search to identify relevant articles to answer your question The Search In preparation for your search you formulate your question as follows In patients with a previous total hip arthroplasty who are suspected of having an acute infection what is the utility of a C reactive protein test in diagnosing infection You have recentl
23. ntigen Ann Intern Med 1986 104 66 73 5 Thomson DM Krupey J Freedman SO Gold P The radioimmunoassay of cir culating carcinoembryonic antigen of the human digestive system Proc Natl Acad Sci USA 1969 64 161 7 6 Kawasaki M Hasegawa Y Sakano S Sugiyama H Tajima T lwasada S Iwata H Prediction of osteonecrosis by magnetic resonance imaging after femoral neck fractures Clin Orthop 2001 385 157 64 7 Kemppainen EA Hedstrom JI Puolokkainen PA Sainio VS Haapiainen RK Perhoniemi V Osman S Kivilaakso EO Stenman UH Rapid measurement 1140 10 11 12 13 THE JOURNAL OF BONE amp JOINT SURGERY JBJS ORG VOLUME 85 A NUMBER 6 JUNE 2003 of urinary trypsinogen 2 as a screening test for acute pancreatitis N Engl J Med 1997 336 1788 93 Begg CB Greenes RA Assessment of diagnostic tests when disease verifi cation is subject to selection bias Biometrics 1983 39 207 15 Gray R Begg CB Greenes RA Construction of receiver operating characteris tic curves when disease verification is subject to selection bias Med Decis Making 1984 4 151 64 Ransohoff DF Feinstein AR Problems of spectrum and bias in evaluating the efficacy of diagnostic tests N Engl J Med 1978 299 926 30 Choi BC Sensitivity and specificity of a single diagnostic test in the presence of work up bias J Clin Epidemiol 1992 45 581 6 Hamming JF Goslings BM van Steenis GJ van Ravenswaay Claasen H Hermans J van
24. ods for performing the test described in sufficient detail to permit replication What are the results Are likelihood ratios of the test being evaluated or data necessary for their calculation provided Will the results help me in caring for my patients Will the reproducibility of the test result and its interpretation be satisfactory in my setting Are the results applicable to my patient Will the results change my management of the patient Will patients be better off as a result of the test tic performance relates to the minimal overlap between the test results for severely ill patients and the test results for healthy volunteers However clinicians are interested in using tests when there is diagnostic uncertainty that is when the test results for patients with the target condition are similar to the test results for patients without the target condition In the latter group diagnoses other than the target condition are re sponsible for the similarity of the test results between groups Lijmer et al in a report on bias in studies of diagnostic tests demonstrated that studies involving patients with severe dis ease and healthy volunteers overestimated test performance threefold relative diagnostic odds ratio 3 0 95 confidence interval 2 0 4 5 For instance the white blood cell count will almost al ways be elevated in patients who present with an obvious hip infection that is associated with a draining sinus
25. opriate spectrum of patients It is important to recognize that the predictive value of a test will change with changes in the prevalence of the disease spectrum already discussed Consider the following situation When a test to diagnose influenza infection the common flu virus is used during an influenza season positive test results are more likely to truly indicate cases of influenza than they are when the same test is used in the same community during the off season This difference occurs because there are more cases i e a higher prevalence of influenza during the influ enza season and not because the diagnostic properties of the test have changed Was There an Independent Comparison with a Reference Standard The accuracy of a diagnostic test is best determined by compar ing it with the truth Truth about whether the disease is present is usually defined by the presence or absence of a pathological finding that represents the condition i e an essential lesion A reference standard that uses that pathological finding is most desirable Conversely a reference standard that does not use an essential lesion is at risk of miscategorizing patients Therefore judgment should be used to decide whether the chosen refer ence is appropriate Accordingly readers must make sure that the investiga tors have applied independently both the test under investiga tion and an appropriate reference standard such as biopsy surgery autopsy
26. osthetic infection than in those without an infection Table IT How can we use the likelihood ratio The likelihood ratio tells us how much the pretest probability increases or decreases For instance a likelihood ratio of 1 0 will not change the pretest probability whereas a likelihood ratio of gt 1 will increase it A rough guide to the interpretation of likelihood ratios is as fol lows likelihood ratios of gt 10 or lt 0 1 generate large and often conclusive changes in the posttest probability likelihood ratios from gt 5 to 10 or from 0 1 to 0 2 generate moderate shifts in posttest probability likelihood ratios from gt 2 to 5 or from gt 0 2 to 0 5 generate small but sometimes important changes in probability and likelihood ratios from gt 1 to 2 or from gt 0 5 to 1 alter posttest probability to a small degree Having determined the likelihood ratios how do we use them to link the pretest probability to the posttest probability A simple but tedious calculation converts the pretest probabil ity to pretest odds odds probability 1 probability The clinician can then multiply the pretest odds by the likelihood ratio to obtain the posttest odds With use of another calcula tion the posttest odds can be converted back to posttest prob ability probability odds 1 odds To save time and avoid computations Fagan proposed a nomogram for converting pretest probability to posttest prob ability with use of likelihoo
27. r have severe disease and they tend to move toward the value of 1 when all patients who have the target disorder have mild disease In general how ever if you practice in a similar setting to that presented in the study and your patient meets the study eligibility criteria you can be confident in applying the results of the study to your patient Once you have decided that the results are in fact ap plicable to your patient you must decide whether they will change your management of the patient Before making any decisions you must have a sense of what probabilities would confirm or refute the target diagnosis For example suppose you are willing to proceed with d bridement and implant re moval without further testing in patients who have a 285 probability of infection realizing that you will be operating on 15 of patients unnecessarily Moreover suppose you are willing to reject the diagnosis of infection if the test probabil ity is 10 In the sixty five year old woman with hip pain and overt signs of infection pretest probability 80 and a negative C reactive protein test the posttest probability of periprosthetic infection would be 14 and you would pro ceed with further testing e g hip aspiration before aban doning infection as a diagnosis However in the sixty year old afebrile woman with hip pain pretest probability 10 and a negative C reactive protein test the posttest probability of in fection would be
28. ut did not think that she had sustained a serious injury In addition she has been recovering from a sinus infection a viral illness for the past ten days She is otherwise healthy except that she takes oral bisphosphonates for the treatment of osteoporosis On examination she has a temperature of 39 C She walks most comfortably with a flexed posture The range of motion of the right hip is normal There is no erythema or draining sinus over the right hip and thigh Anteroposterior radiographs of the pelvis and the right hip reveal a press fit acetabular component and a cemented femoral stem with no evidence of loosening Laboratory evaluations show a white blood cell count of 12 1 cells uL of which 85 are neutro phils Blood cultures are negative You wonder whether the new onset of hip pain is the re sult of a soft tissue injury back pain radiating to the hip pros thetic loosening that is not apparent on radiographs or an infection of the hip joint If the hip is truly infected the pa tient will require an operative procedure for d bridement of the wound and removal of the implants While some of your colleagues would take all such patients to the operating room for exploration of the hip you have been impressed by the number of cases in which you have found no infection Be cause of such concerns your practice is to routinely aspirate the hip in patients in whom an infection is suspected Just as you are thinking about p
29. y learned about the Clinical Queries function in PubMed a quick way to narrow your search to identify articles that focus on diagnosis Therefore using the Clinical Queries search option in PubMed http www ncbi nlm nih gov entrez query static clinical html you choose a narrow scope search specificity option for articles on Diag nosis using the expression C reactive protein AND total joint arthroplasty This search yields a single article entitled Pro spective Analysis of Preoperative and Intraoperative Investi gations for the Diagnosis of Infection at the Sites of Two Hundred and Two Revision Total Hip Arthroplasties by Span gehl et al A quick review of the abstract indicates that it will likely provide the information that you need You obtain the ar ticle from your local hospital library Having decided on a relevant article as is the case with other types of articles therapy prognosis or harm you should ask yourself three questions 1 Are the results of the study valid 2 What are the results and 3 Will the results help me in caring for my patients Table I Are the Results of the Study Valid Investigators studying a diagnostic test hope to establish the power of that test to differentiate between patients who have the target condition i e the disease or health state in this case infection about a hip prosthesis and those who are free of the target condition Patients who are free of th
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