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The Process of Diagnosis: Gordon Guyatt, MD, MSc, discusses "Chapter 14: The Process of Diagnosis" from the Users' Guides to the Medical Literature.
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The Process of Diagnosis: Gordon Guyatt, MD, MSc, discusses "Chapter 14: The Process of Diagnosis" from the Users' Guides to the Medical Literature.
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Language: EN.
Segment:0 .
>> I'm Joan Stephenson, Editor of JAMA's Medical News & Perspectives Section. Today, this JAMAevidence Podcast will focus on the process of diagnosis. Our guest expert is Dr. Gordon Guyatt. Dr. Guyatt, why don't you introduce yourself to our listeners? >> I'm a Professor of Medicine and of Clinical Epidemiology in Biostatistics at McMaster University in Canada. I work clinically as a hospitalist and spend much of my time on research and education related activities.
>> Dr. Guyatt, can you briefly describe the two complementary approaches to diagnosis? >> One approach can be termed pattern recognition. The clinician takes a history, looks the patient over, does a targeted physical examination and the diagnosis is clear. So for instance, a patient presents with a three-day history of pain associated with vesicles appearing in a particular dermatome and the lesions do not cross the midline.
The diagnosis of herpes zoster is secure. On the other hand, patients may present with problems that are much more difficult to diagnose, in which the case the clinician has to generate a differential diagnosis and estimate the probabilities associated with each item in that differential diagnosis. And then undertake further testing to try and narrow the differential diagnosis and ultimately come to a definitive diagnosis.
So for instance the patient presents with non-specific fatigue. There will be many possible diagnoses that enter the physicians' mind and that requires a subsequent investigation where, as new information comes in, the probabilities change and ultimately, hopefully the clinician arrives at the right diagnosis. >> In many physicians' practices the diagnosis is usually self-evident. So how do we know when to go to the effort of making a formal diagnosis on probabilistic grounds? >> Well, my first comment would be to congratulate all those physicians in whom the patient's diagnosis is usually self-evident.
These are clearly exceptional diagnosticians. However, if there was a suggestion that I would have to the situations when you're pretty sure, perhaps on pattern recognition basis, but not absolutely sure and you don't know whether to start generating a differential with probabilities and further investigation, what I would suggest the clinicians do is look at the consequences of a mistake. So for instance, let's say one has a middle aged individual who presents with a 30-pound weight loss over the last six months feeling very fatigued and generally unwell, and a physical examination reveals a hard, knobbly liver.
Well, there's a very, very, very high likelihood that one is looking at a malignancy, either a primary in the liver, or more likely a primary somewhere else that has spread to the liver. However, one would probably be making a mistake to announce to the patient at that moment that that is the diagnosis, because the consequences of being wrong and telling someone they have cancer when they do not have cancer would be very unpleasant for both the patient and physician. And thus, in that situation when the consequences of believing your pattern recognition are potentially damaging, it's probably worthwhile to adopt a probabilistic approach and conduct further investigation.
>> How can a clinician estimate pre-test probabilities? >> Well, one way to do it is on the basis of past experience. So, I'm a general internist and when I get called to the emergency room to see a patient who is short of breath, I know that pneumonia and heart failure are at the top of the list. Chronic obstructive lung disease and asthma are high on the list. And pulmonary embolus is something that I have to think about, but that is lower on the list.
And it's simply seeing many, many patients that has led me to that way of thinking about pre-test probabilities. However, we can all be misled by our experience. We are all subject to making inferences that may not be accurate. And another way to get pre-test probabilities is to use the literature. So, studies that explicitly look at differential diagnosis, they take a patient presenting with syncope or presenting with headache, or presenting with fatigue.
They follow patients up with detailed investigations and sometimes long-term follow up. And at the end they say 20% of the patients had this diagnosis, 15% this diagnosis, and so on. So for instance, one of the things that I bear in mind when I'm seeing a older patient over 65 with anemia, and I wonder about how likely it is that this is iron deficiency, my pre-test probability before other information is available will be around 35% because a study that was actually conducted in my own community found that of such individuals, 35% that is of older people presenting with anemia, 35% of them ended up having iron deficiency.
>> Dr. Guyatt, would you please describe the concepts of test threshold and treatment threshold, and what determines these different thresholds? >> Well, one can think of any patient, their probability of having a particular condition. So, a patient presents with dyspepsia and depending on the nature of the presentation and the patient, it could be gastroesophageal reflux, it could be an ulcer, it could be a cancer, it could be non-specific dyspepsia where investigation would not reveal a particular biologic explanation.
So, one has this pre-test probability and one has to decide what to do. The-- if the probability of a particular diagnosis is sufficiently low, below the test threshold, as we say, one would not pursue that particular diagnosis. If the diagnosis is sufficiently clear, the probability is extremely high above the treatment threshold, we would not do any further testing and we would simply treat the patient.
If the probability is between the test threshold and treatment threshold, then we would conduct further investigations. What determines these thresholds? Well, if the test is very invasive on the test threshold end, that will tend to raise the test threshold in that we are disinclined, we are less inclined, to do tests that are very invasive, such as a pulmonary angiography.
The other thing is the consequences of missing the particular diagnosis. And if the consequences are if we missed the diagnosis it would be a very bad thing. That will lower the test threshold. We have to be very sure before we conclude that the patient doesn't have the condition of interest. On the other hand, the same factors affect the treatment threshold but differently. The more invasive the test, the more we will lower the treatment threshold and be ready to treat rather than test further because of the possible adverse consequences of the test.
And the other thing is the consequences of a false positive. If we treated the patient, if the treatment is particularly toxic, that is going to raise the treatment threshold. We have to be very sure before we abandon further testing. >> What if I were a physician who sees patients intermittently and episodically over the years? How would I organize my practice so that I can take advantage of that fact and revisiting old diagnoses and making new ones in those patients and in others like them?
>> Well, the big advantage to me of seeing patients repeatedly over years is that one understands their values and preference as well. And in terms of the test and treatment thresholds that I just described, the test and treatment thresholds are actually going to differ between patients. So consider the patient presenting with dyspepsia and the choice being whether to go and do an endoscopy, or give the patient a trial of an anti-acid drug, such as an H2 antagonist or a proton pump inhibitor.
There may be some patients whose values are such that they definitely want to know what is going on, they are unsatisfied by the uncertainty that comes when you don't do an invasive test, and they are ready to undergo an endoscopy. There may be other patients for whom the endoscopy is much more aversive and who are much more ready to tolerate some uncertainty in whom a trial of a acid-suppressing intervention would be what would be best for those individuals.
>> Is there anything else that JAMAevidence users should know about diagnosis? >> Well, potentially there is a lot that they could know. So within the User's Guide to the Medical Literature, there are chapters on differential diagnosis, which I alluded to in how one gets one's pre-test probabilities. There's a chapter on diagnostic test, which deals with risk of bias in diagnostic tests. And there are chapters on advanced topics in diagnosis, including and particularly most important likelihood ratios, which are a very powerful way to interpret diagnostic test results and clinical prediction rules, which are more and more available, and again are another tool for generating pre-test probabilities.
Also, JAMA users may be very interested in the Rational Clinical Examination. All items of clinical examination are best conceptualized as diagnostic tests and the Rational Clinical Examination is extremely powerful in providing you with the evidence and guidance for how to use items of physical examination in making diagnoses or leading you toward diagnoses and delivering optimal patient care. >> Thank you, Dr. Guyatt, for this overview of the process of diagnosis.
This has been Joan Stephenson of JAMA interviewing Dr. Gordon Guyatt about the process of diagnosis for JAMAevidence.
Segment:0 .
>> I'm Joan Stephenson, Editor of JAMA's Medical News & Perspectives Section. Today, this JAMAevidence Podcast will focus on the process of diagnosis. Our guest expert is Dr. Gordon Guyatt. Dr. Guyatt, why don't you introduce yourself to our listeners? >> I'm a Professor of Medicine and of Clinical Epidemiology in Biostatistics at McMaster University in Canada. I work clinically as a hospitalist and spend much of my time on research and education related activities.
>> Dr. Guyatt, can you briefly describe the two complementary approaches to diagnosis? >> One approach can be termed pattern recognition. The clinician takes a history, looks the patient over, does a targeted physical examination and the diagnosis is clear. So for instance, a patient presents with a three-day history of pain associated with vesicles appearing in a particular dermatome and the lesions do not cross the midline.
The diagnosis of herpes zoster is secure. On the other hand, patients may present with problems that are much more difficult to diagnose, in which the case the clinician has to generate a differential diagnosis and estimate the probabilities associated with each item in that differential diagnosis. And then undertake further testing to try and narrow the differential diagnosis and ultimately come to a definitive diagnosis.
So for instance the patient presents with non-specific fatigue. There will be many possible diagnoses that enter the physicians' mind and that requires a subsequent investigation where, as new information comes in, the probabilities change and ultimately, hopefully the clinician arrives at the right diagnosis. >> In many physicians' practices the diagnosis is usually self-evident. So how do we know when to go to the effort of making a formal diagnosis on probabilistic grounds? >> Well, my first comment would be to congratulate all those physicians in whom the patient's diagnosis is usually self-evident.
These are clearly exceptional diagnosticians. However, if there was a suggestion that I would have to the situations when you're pretty sure, perhaps on pattern recognition basis, but not absolutely sure and you don't know whether to start generating a differential with probabilities and further investigation, what I would suggest the clinicians do is look at the consequences of a mistake. So for instance, let's say one has a middle aged individual who presents with a 30-pound weight loss over the last six months feeling very fatigued and generally unwell, and a physical examination reveals a hard, knobbly liver.
Well, there's a very, very, very high likelihood that one is looking at a malignancy, either a primary in the liver, or more likely a primary somewhere else that has spread to the liver. However, one would probably be making a mistake to announce to the patient at that moment that that is the diagnosis, because the consequences of being wrong and telling someone they have cancer when they do not have cancer would be very unpleasant for both the patient and physician. And thus, in that situation when the consequences of believing your pattern recognition are potentially damaging, it's probably worthwhile to adopt a probabilistic approach and conduct further investigation.
>> How can a clinician estimate pre-test probabilities? >> Well, one way to do it is on the basis of past experience. So, I'm a general internist and when I get called to the emergency room to see a patient who is short of breath, I know that pneumonia and heart failure are at the top of the list. Chronic obstructive lung disease and asthma are high on the list. And pulmonary embolus is something that I have to think about, but that is lower on the list.
And it's simply seeing many, many patients that has led me to that way of thinking about pre-test probabilities. However, we can all be misled by our experience. We are all subject to making inferences that may not be accurate. And another way to get pre-test probabilities is to use the literature. So, studies that explicitly look at differential diagnosis, they take a patient presenting with syncope or presenting with headache, or presenting with fatigue.
They follow patients up with detailed investigations and sometimes long-term follow up. And at the end they say 20% of the patients had this diagnosis, 15% this diagnosis, and so on. So for instance, one of the things that I bear in mind when I'm seeing a older patient over 65 with anemia, and I wonder about how likely it is that this is iron deficiency, my pre-test probability before other information is available will be around 35% because a study that was actually conducted in my own community found that of such individuals, 35% that is of older people presenting with anemia, 35% of them ended up having iron deficiency.
>> Dr. Guyatt, would you please describe the concepts of test threshold and treatment threshold, and what determines these different thresholds? >> Well, one can think of any patient, their probability of having a particular condition. So, a patient presents with dyspepsia and depending on the nature of the presentation and the patient, it could be gastroesophageal reflux, it could be an ulcer, it could be a cancer, it could be non-specific dyspepsia where investigation would not reveal a particular biologic explanation.
So, one has this pre-test probability and one has to decide what to do. The-- if the probability of a particular diagnosis is sufficiently low, below the test threshold, as we say, one would not pursue that particular diagnosis. If the diagnosis is sufficiently clear, the probability is extremely high above the treatment threshold, we would not do any further testing and we would simply treat the patient.
If the probability is between the test threshold and treatment threshold, then we would conduct further investigations. What determines these thresholds? Well, if the test is very invasive on the test threshold end, that will tend to raise the test threshold in that we are disinclined, we are less inclined, to do tests that are very invasive, such as a pulmonary angiography.
The other thing is the consequences of missing the particular diagnosis. And if the consequences are if we missed the diagnosis it would be a very bad thing. That will lower the test threshold. We have to be very sure before we conclude that the patient doesn't have the condition of interest. On the other hand, the same factors affect the treatment threshold but differently. The more invasive the test, the more we will lower the treatment threshold and be ready to treat rather than test further because of the possible adverse consequences of the test.
And the other thing is the consequences of a false positive. If we treated the patient, if the treatment is particularly toxic, that is going to raise the treatment threshold. We have to be very sure before we abandon further testing. >> What if I were a physician who sees patients intermittently and episodically over the years? How would I organize my practice so that I can take advantage of that fact and revisiting old diagnoses and making new ones in those patients and in others like them?
>> Well, the big advantage to me of seeing patients repeatedly over years is that one understands their values and preference as well. And in terms of the test and treatment thresholds that I just described, the test and treatment thresholds are actually going to differ between patients. So consider the patient presenting with dyspepsia and the choice being whether to go and do an endoscopy, or give the patient a trial of an anti-acid drug, such as an H2 antagonist or a proton pump inhibitor.
There may be some patients whose values are such that they definitely want to know what is going on, they are unsatisfied by the uncertainty that comes when you don't do an invasive test, and they are ready to undergo an endoscopy. There may be other patients for whom the endoscopy is much more aversive and who are much more ready to tolerate some uncertainty in whom a trial of a acid-suppressing intervention would be what would be best for those individuals.
>> Is there anything else that JAMAevidence users should know about diagnosis? >> Well, potentially there is a lot that they could know. So within the User's Guide to the Medical Literature, there are chapters on differential diagnosis, which I alluded to in how one gets one's pre-test probabilities. There's a chapter on diagnostic test, which deals with risk of bias in diagnostic tests. And there are chapters on advanced topics in diagnosis, including and particularly most important likelihood ratios, which are a very powerful way to interpret diagnostic test results and clinical prediction rules, which are more and more available, and again are another tool for generating pre-test probabilities.
Also, JAMA users may be very interested in the Rational Clinical Examination. All items of clinical examination are best conceptualized as diagnostic tests and the Rational Clinical Examination is extremely powerful in providing you with the evidence and guidance for how to use items of physical examination in making diagnoses or leading you toward diagnoses and delivering optimal patient care. >> Thank you, Dr. Guyatt, for this overview of the process of diagnosis.
This has been Joan Stephenson of JAMA interviewing Dr. Gordon Guyatt about the process of diagnosis for JAMAevidence.
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