stroke misdiagnosis disproportionate in the young says Washington Post

Ehud Zamir ezamir at UNIMELB.EDU.AU
Thu Jun 26 07:43:18 UTC 2014


Dear Dr Jain
Pre test probability is determined subjectively by the doctor. What constitutes high pretest probability for one doctor with a high index of suspicion for a condition will be judged as low pretest probability by another. Therefore I would suggest that clinical competence and diagnostic skill are the solution, rather than over investigation of patients with low pretest probability. We should bear in mind that in the face of truly low pretest probability, even positive results do not push the post test probability very far, unless the test is diagnostic by itself. So I am not sure I agree with your statement that "An incresed awareness thatn a substantial proportion of patients with a given disease, about 10-15 percent, encountered by us  is likely to have low pretest probability." Perhaps the fact that these 15% are CONSIDERED low test probability is simply the root cause of the diagnostic error. It could be argued that a more competent diagnostician would not have regarded these as low PTP, and that the more competent the diagnostician, the more likely their "low pretest probability" judgement is to be a true negative.
It reminds me of the "fever of unknown origin" issue, to which my Professor of Medicine in medical school used to refer to by asking "unknown to whom?"...
Regards
Ehud Zamir


________________________________
From: Jain, Bimal P.,M.D. [BJAIN at PARTNERS.ORG]
Sent: Wednesday, 25 June 2014 9:58 PM
To: IMPROVEDX at LIST.IMPROVEDIAGNOSIS.ORG
Subject: Re: [IMPROVEDX] stroke misdiagnosis disproportionate in the young says Washington Post

Dear Drs. Newman-Toker,Kohn,Gordon,

I have followed your discussions about early diagnosis of stroke in ER with great interest.  I would like to make the following comments about diagnosis in general which may have relevance to diagnosis of stroke.


1.       Since introduction of am probabilistic  model of diagnosis by Lesley and Lusted in 1959 (Science ’59), it has become customary to represent pretest certainty about a disease by its pretest probability.

        2.A pretest probability depends upon a number of independent factors such as symptoms, risk factors, patient’s age, sex etc. which together constitute a clinical presentation. Therefore, a prêt
            est. probability, like any other measure such as height or intelligence quotient, which depends upon a number of independent factors, will tend to be distributed normally in patients with a given
            ease encountered by us (Tao, Best Writing  in Mathematics 2013)

 3.This means most patients with a disease (68 percent) will have intermediate pretest probability (20-79 percent), a few (16 percent) will have low pretest probability (0-19 percent), and other few
             (16 percent) will have high pretest probability(80-100 percent).

         4. This trend towards normal distribution has been observed, for example, in the PIOPED study about diagnosis of pulmonary embolism(JAMA 1990), 67 percent of 252 patients with pulmonary
              Embolism had intermediate pretest probability.

           5. Diagnostic error in general has been found to occur in 10-15 percent patients (Graber 2013).
                In Newman- Toker’s fine study in Diagnosis too, missed diagnosis of stroke in ER was found to be about 13 percent.

          6. The closeness of these diagnostic error rates to the expected percentage of patients with low pretest probability seems to suggest that most if not all diagnostic errors occur in these  patients.

          7. A major cause of diagnostic error in these patients, I suggest, is erroneus interpretation of a low pretest probability which is considered to be minimal evidence for a disease which is ruled out wit
               hout testing in a given, individual patient.

           8. Its correct interpretation, I suggest, is as a distribution, which only indicates a few patients with a disease in a series of similar patients. It does not tell us anything at all about presence or absence
                Of a disease in a given patient.

           9. The presence or absence of a disease in any patient regardless of pretest probability can only be determined by a test result with a high likelihood ratio ( 10 or higher) or a low likelihood ratio
               (0.1 or lower) respectively (Jaeschke 2002).

           10. For widespread use, a test capable of generating such a result needs to be simple and inexpensive. An example of such a test is EKG, which is performed in practically every patient with chest
                 pain seen in ER for evaluation of acute myocardial infarction.

           11. HINTS appears to be such a test for evaluating for stroke in patients with dizziness seen in ER, as suggested by Newman-Toker.

           12.In conclusion, I believe, the following measures could help minimise diagnostic errors.


(a)    An incresed awareness thatn a substantial proportion of patients with a given disease, about 10-15 percent, encountered by us  is likeky to have low pretest probability.

(b)   A disease cannot be ruled out purely from its low pretest probability.

(c)    In a given patient with low pretest probability, a disease can only be ruled out if a test result with low likelihood ratio (0.1 or lower) is observed.







Bimal P Jain MD

Pulmonary-Critical Care

Northshore Medical Center

Lynn, MA 01904





From: David Newman-Toker [mailto:toker at JHU.EDU]
Sent: Friday, June 20, 2014 10:50 AM
To: IMPROVEDX at LIST.IMPROVEDIAGNOSIS.ORG
Subject: Re: [IMPROVEDX] stroke misdiagnosis disproportionate in the young says Washington Post

Thanks David. I’ve copied the ListServ because I think this sort of discussion might be interesting to others --- it is the messy real-world business of doing diagnosis in clinical practice! For those interested, see David G.’s excellent points in the trail below.

In response to each of your four points:

1a) OTTAWA SAH RULE IN PRINCIPLE --- Personally, I wouldn’t tap every patient over 20 with a new headache peaking in less than an hour – if they had a very compelling migraine story (e.g., classic visual aura), and it peaked progressively over 55 minutes (or anything over 30, probably), and they were in the correct age group for migraine onset (e.g., 15-40), and didn’t have a personal/family history of aneurysm/SAH, and had none of the dangerous Ottawa SAH rule features, I wouldn’t even CT them.  Nevertheless… I totally understand your perspective, and doing CT-LP in all of the patients in their series (using their entry criteria rather than their final rule) might be slightly simpler than following their rule; it would, however, increase the fraction of headache patients who got (presumably unnecessary) CT/LP by ~15%, which, back of the napkin, is probably at least 30,000 excess CTs a year in the US at a cost of about $10M/year… it may be a drop in the healthcare bucket, but, for that amount, we could do some really nice diagnostic research to refine decision rules to increase performance, usability, and buy in. :)

1b) OTTAWA SAH RULE IN PRACTICE --- I think there is a wider evidence-practice gap in average community ED practice than might be imagined… only 2% of US headache patients undergo an LP (Goldstein, Cephalalgia, 2006) --- that includes all the suspected meningitis and SAH cases; I think most people believe that at least 2% of the total (probably more) have one or the other (meningitis or SAH) as a cause… so 2% is probably a lot fewer LPs than we should be doing, if we consider the asymmetric risk associated with LP vs. missed meningitis/SAH. So I would venture a guess that the average community ED physician is not being as thorough about looking for missed SAH as you are being in your practice… unfortunately, probably none of them are reading this ListServ to benefit from your thoughtful perspective.

2) HINTS --- Agree it is operator dependent, and some of this may go away when devices become more ubiquitous… BUT… how should we respond --- knowingly miss 35% of all the strokes using a bad decision-making approach that is standard practice… or seek out training to learn to do HINTS properly? Maybe ‘ok’ HINTS is still better than ‘great’ ABCD2/vascular risk stratification?

3) WHEN TO APPLY DECISION RULES --- This is an under-discussed but critical problem; one I spoke about in my commentary about JJ Perry’s SAH decision rule; but these rules are developed with fairly strict entry criteria, so I think that applying them in practice is mostly about pattern matching to the study methods in the paper (which, unfortunately, is probably rarely done in practice). I agree it can be tough, though, even if you try hard. I was giving grand rounds at Cornell earlier this week, and they took me to see an acute patient in the ED with dizziness --- it took some skill just to know whether HINTS should be applied or not… and you probably couldn’t have acquired that skill simply by reading the article. I think the co-symptoms issue is less problematic --- whatever the allowable co-symptoms were in the study are what’s relevant, and the determination is made based on the patient’s chief symptom/complaint --- I realize that this is not a perfectly reliable measure (and we have done studies that prove that inter-observer variation is more common than you’d like), but it is certainly a familiar enough one to all physicians… and, until computers are taking all of our histories from patients for us, it will likely remain part of our ‘art.’

4) ISCHEMIC STROKE MECHANISMS IN THE YOUNG --- I believe that we are getting fatter and more diabetic at a younger age, but, honestly, I’m not worried about strokes being missed in patients who are 35 that have HTN, DM, high cholesterol, chronic renal insufficiency, peripheral vascular disease, and a history of 2 prior MIs. No one will ignore all that just because of age. I remember a normal weight guy with no PMH who was 35 and presented with episodic blurred vision and confusion… he was sent home as suspected migraine… came back with turned out to be the proband for a family with undiagnosed familial hypercholesterolemia. So there will be some cases where stroke is the index event that discloses a patient’s (previously unknown) vascular risk and are tricky (esp. those who are non-obese)… but most of the ones we miss will likely be dissections, cardiac emboli, and ‘cryptogenic’ --- I think we should focus our attention on solving the diagnostic problems for those patients.

David


David E. Newman-Toker, MD, PhD
Associate Professor, Department of Neurology
Johns Hopkins Hospital, Meyer 8-154; 600 North Wolfe Street, Baltimore, MD 21287
Email: toker at jhu.edu<mailto:toker at jhu.edu>; 410-502-6270 (phone); 410-502-6265 (fax)
Web address: Johns Hopkins Neurology (David Newman-Toker)<http://www.hopkinsmedicine.org/neurology_neurosurgery/specialty_areas/vestibular/profiles/team_member_profile/516F40C024FCA3D4B4B633D0E080FE1B/David_Newman-Toker>


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From: David Gordon, M.D. [mailto:davidc.gordon at duke.edu]
Sent: Thursday, June 19, 2014 5:03 PM
To: David Newman-Toker
Subject: RE: [IMPROVEDX] stroke misdiagnosis disproportionate in the young says Washington Post

Hi David,

Thanks for highlighting these articles. So some specific and then general comments:


1)      Ottawa SAH rule--- This is interesting because I have to say, while this rule is a good teaching tool for highlighting the red flags of headache, it would not personally impact my practice pattern.  If I have anyone 20 or older ( the rule uses 15) with “new severe nontraumatic headache reaching maximum intensity within 1 hour” that alone is enough for me to cross over the diagnostic threshold  for ruling out SAH.  The other variables in the rule don’t mean much at that point for testing purposes. I would venture to say most emergency physicians would acknowledge this as the culture of their training. So in the patients with missed SAH in your recent study, it would be very interesting to know the specifics of their presentation. Did they have an atypical presentation for SAH that not even the rule would capture or would this rule if employed by the physician as a diagnostic aid have appropriately steered them towards work-up they neglected to pursue. Need to see this rule studied prospectively.

2)      HINTS- compelling CDR but I would venture to say limited by operator dependence—at least until the devices are widely available and employed.  I personally would not feel confident in my current proficiency in assessing eye movements. You alluded to this in the article, but it seems this has been employed mainly by specialists to date. Would the sensitivity change in the hands of less experienced practitioners? As you also alluded to, used indiscriminately, this CDR runs the risk of MRI overuse given that a normal physiologic response is a bad sign in this tool.  So I still think there is more studies to be done before recommending for general use.

3)      This has been echoed before, but applying such rules prospectively in an undifferentiated population could be challenging owing to overlapping spectrum of symptoms. Patients come in with headache alone, headache + dizziness, headache and speech disturbance, no headache and speech disturbance?  Which rule is one to apply?

4)      This discussion of missing strokes in the young covers a broad array of potential etiologies. What exactly is the pathophysiology being missed here? Are we seeing accelerated atheroembolic disease in young patients due to HTN and DM? Or do young people represent a separate physiology from older patients with stroke owing to vertebral dissections and venothrombotic events?  I think the more we understand the pathophysiology at play here, the better we can advise clinicians to either adjust their age threshold for the development of atheroembolic disease or to make sure to consider these alternate disease processes for stroke-like symptoms in the young.

Thanks,
David G


David Gordon, MD
Associate Professor
Undergraduate Education Director
Division of Emergency Medicine
Duke University

From: David Newman-Toker [mailto:toker at jhu.edu]
Sent: Thursday, June 19, 2014 7:37 AM
To: David Gordon, M.D.; Society to Improve Diagnosis in Medicine
Subject: RE: [IMPROVEDX] stroke misdiagnosis disproportionate in the young says Washington Post

Thanks David. So I gather you think that these two CDRs below addressing stroke diagnosis in patients with headache and dizziness, respectively, are lacking some combination of good performance, ease of use, or buy in? (“rule has good performance, easy to use, and is bought into by both emergency physicians and neurologists”)

Perry JJ, Stiell IG, Sivilotti ML, et al. Clinical decision rules to rule out subarachnoid hemorrhage for acute headache. JAMA : the journal of the American Medical Association 2013;310:1248-55.

Newman-Toker DE, Kerber KA, Hsieh YH, et al. HINTS Outperforms ABCD2 to Screen for Stroke in Acute Continuous Vertigo and Dizziness. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine 2013;20:986-96.



David E. Newman-Toker, MD, PhD
Associate Professor, Department of Neurology
Johns Hopkins Hospital, Meyer 8-154; 600 North Wolfe Street, Baltimore, MD 21287
Email: toker at jhu.edu<mailto:toker at jhu.edu>; 410-502-6270 (phone); 410-502-6265 (fax)
Web address: Johns Hopkins Neurology (David Newman-Toker)<http://www.hopkinsmedicine.org/neurology_neurosurgery/specialty_areas/vestibular/profiles/team_member_profile/516F40C024FCA3D4B4B633D0E080FE1B/David_Newman-Toker>


Confidentiality Notice: The information contained in this email is intended for the confidential use of the above named recipient. If the reader of this message is not the intended recipient or person responsible for delivering it to the intended recipient, you are hereby notified that you have received this communication in error, and that any review, dissemination, distribution, or copying of this communication is strictly prohibited. If you have received this in error, please notify the sender immediately by telephone at the number set forth above and destroy this email message. Thank you.

From: David Gordon, M.D. [mailto:davidc.gordon at duke.edu]
Sent: Wednesday, June 18, 2014 9:40 AM
To: Society to Improve Diagnosis in Medicine; David Newman-Toker
Subject: RE: [IMPROVEDX] stroke misdiagnosis disproportionate in the young says Washington Post

David,

A real challenge here is trying to separate the signal from the noise, and when it comes to neurologic complaints, there is unfortunately a lot of noise in emergency departments. Overcrowding and financial pressures further compound the difficulty of who requires the full work-up.

I think risk stratification is key to this issue. We have imperfect but overall good processes and tools in place for the risk stratification of ACS and pulmonary embolism. As an emergency physician, I don't feel I have the same cognitive tools available for independently risk stratifying TIA/stroke. I am fortunate to work in a clinical environment where I have ready access to neurology consultation to assist in the process and an observation protocol for equivocal/intermediate cases, but I gather to say this is far from the norm.

As far as the treatment of neurologic complaints in the emergency setting, we need more evidence. It is going to take prospective analysis of all-comers to the ED with stroke-like symptoms to better understand who needs immediate work-up and who can be safely discharged. Perhaps we will end up with 2 different stratification tools- one for the young and one for the old.

As far as whether diagnostic aids will be utilized or ignored due to CDRs, I think it depends. If the rule has good performance, easy to use, and is bought into by both emergency physicians and neurologists, I do think it would be readily employed - especially if the evidence becomes increasingly convincing that the epidemiology of stroke is changing (or becoming better understood) and young patient's are being misdiagnosed.

-David

David Gordon, MD
Associate Professor
Undergraduate Education Director
Division of Emergency Medicine
Duke University

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________________________________
From: David Newman-Toker [toker at JHU.EDU]
Sent: Tuesday, June 17, 2014 2:56 PM
To: IMPROVEDX at LIST.IMPROVEDIAGNOSIS.ORG<mailto:IMPROVEDX at LIST.IMPROVEDIAGNOSIS.ORG>
Subject: [IMPROVEDX] stroke misdiagnosis disproportionate in the young says Washington Post
Stroke is a major public health problem, and recent work suggests young patients are having more strokes, with rates rising alarmingly in recent years, according to an article in today’s Washington Post…

http://www.washingtonpost.com/national/health-science/strokes-long-on-the-decline-among-the-elderly-are-rising-among-younger-adults/2014/06/16/f1f54538-e5d9-11e3-a86b-362fd5443d19_story.html

They are also much more likely to be misdiagnosed (7-fold greater risk in those 18-45 relative to those >75)…

http://www.degruyter.com/view/j/dx.2014.1.issue-2/dx-2013-0038/dx-2013-0038.xml

Thoughts?

David


David E. Newman-Toker, MD, PhD
Associate Professor, Department of Neurology
Johns Hopkins Hospital, Meyer 8-154; 600 North Wolfe Street, Baltimore, MD 21287
Email: toker at jhu.edu<mailto:toker at jhu.edu>; 410-502-6270 (phone); 410-502-6265 (fax)
Web address: Johns Hopkins Neurology (David Newman-Toker)<http://www.hopkinsmedicine.org/neurology_neurosurgery/specialty_areas/vestibular/profiles/team_member_profile/516F40C024FCA3D4B4B633D0E080FE1B/David_Newman-Toker>


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