PE Prognostication: Weingart Weighs In
OK friends – it has been an interesting week for me on the blog – lots of discussion about the part 2 of the PE Prognostication podcast. If you haven’t listened to the last 2 podcasts then this episode will sound like an American man who has totally lost his mind, but if you go back and listen to part 1 and 2 of the PE Prognostication podcast then it will sound like pure genius [the two are easily confused I find!]
Don’t worry – I am not going to do a whole PE month – nobody deserves that! I will be releasing a few non-PE posts and cases this week for those of you with a more diverse taste.
Fair to say there was a bit of a twitter shit-storm going on there for a few days and the dust is still settling. I think Minh might have RSI of the thumbs from all his tweeting!
So a little bit of editorial orientation before we get onto today’s podcast. I would like to take a few lines to explain what is going on so that you all have some context for this discussion and the podcast below:
- Dr Anand Senthi is a smart guy who has looked deeply into the PE literature
- There is not much evidence at all to support the “status quo” for low-risk PE work-ups in ED patients. Largely the standard of care is based on expert consensus and the relatively poor volume of quality data available.
- We all know that there is a real risk of over investigation when it comes to PE work-up – especially in the patients that would be described as “low risk” by whatever system you prefer… Wells, PERC, Geneva, Gestalt.
- It is likley that a really conservative approach that attempts to identify every PE that presents to ED will in fact harm more patients than it helps
- Anand is worried about this and would like to change the way we approach these patients.
- Anand has generated an algorithm – a new approach to this group which is based in the evidence that is currently available
- Anand’s approach is at this stage a hypothesis. It is an idea that needs to be tested in a rigorous, randomised trial in order to determine if his approach results in better patient outcomes than the current “standard of care”.
- We are not suggesting that you take this approach and apply it to your patients tomorrow. It is a great idea – but do not lose your job over it!
- Actually that goes for anything you read on this blog! You are a doctor – read widely and make up your own mind.
- This is an idea that is evolving – this is what I love about the FOAM community – through debate and constructive feedback we can refine rough and raw ideas into actual practical and testable hypotheses.
So now that you know what is happening.
In case you don’t know Dr Weingart is an ED Critical Care guy from New York who runs the Emcrit blog / podcast. He is also a man who has written a book about evidence-based medicine, one of the more readable guides to biostatistics that I have encountered! So he is a clinician who understands numbers and decision-making. This makes him a great “devil’s Advocate”, and I really appreciate the time he has taken to point out the logical and clinical problems with the Prognostication algorithm.
Scott [ @emcrit – as if I need to tell you. ] sent me this response to the PE Prognostication podcast. He covers a lot of ideas in rapid fire. So have a listen.
THe blog post review that Scott refers to of contrast-induced nephropathy is here at EDTCC.
I will be having Dr Anand Senthi back on the podcast soon to offer some counterpoint and we will see if the algorithm has evolved in the last few weeks! Let me know what you think on the comments below.
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About The Author
Casey Parker
I am a GP working in Broome, NW of Western Australia. I work as a hospital DMO (District Med Officer) doing Emergency, Anaesthestics, some Obstetrics and a lot of miscellaneous primary care. Also on the web as @broomedocs | + Casey Parker | Contact
Great comments from Scott and I’d like to thank him for taking the time. Look forward to issuing response soon.
thanks Casey for putting this up.
We are testing the issue of post publication peer review of FOAMEd right here!
I want to contest your statement that the “status quo” is non evidence based/poor quality and merely expert consensus opinion.
The 2008 European Guidelines on PE are here
http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-APE-FT.pdf
Take home points of this article in my contention:
1. Level 1 Class A evidence for the “status quo” approach to assess non high risk/low prob PE patients using clinical prediction rules and D Dimer.
2. the support in the first 2 pages for the consideration of DVT and PE as a disease with the same natural history but the caveat that PE is more serious than DVT per se.
3.The support for Scott’s statement that it is the recurrent PE that will lead to serious harm i.e death that makes us prioritise Ax/Rx for suspected PE.
I therefore contest your contention and Anand’s that the current standard of care for Ax of PE patients is causing more harm than good as it lacks good quality evidence.
The European guidelines are not saying we CTPA test everyone with suspected PE . That is NOT the current standard of care.
How many cases of harm have either of you seen from a low risk PE workup in your own ED’s i.e contrast induced death, anticoagulation induced badness?
It would be more relevant if you actually produced figures/stats/case series of actual cases of the very harm that you claim!
Sorry Minh, but these guidelines are based on the same evidence that Anand and David Newman have discussed – and they are 5 years old – so some new data since then. For example:
from page 2298 of ESC guidelines….
Initial anticoagulation
“Anticoagulant treatment plays a pivotal role in the management of patients with PE. The need for immediate anticoagulation in patients with PE is based on a landmark study which was performed in the 1960s and demonstrated the benefits of unfractionated heparin in comparison with no treatment.280”
Trial referenced 280 = Barrit and Jordan Lancet 1960. That as we know was not really a RCT of PE – it was not a trial that would even be considered for publication after about 1970 – read it, it is on the part 1 blog post.
Now about the recurrent PE causing all the badness. I agree completely with Scott’s statement that the low-risk, stable, normotensive, normal ECHO, trop negative patient is very unlikely to die from “this PE”.
And I completely agree that we should be doing a leg US to double check that there is no “monster clot ” lurking in the thighs. Be patient mate – he next instalment from Anand and a few friends will describe how CUS fits into the workup of the [Well’s< 2, sPESI = 0] patient . BUt... consider this. The sPESI predicted a 30-day mortality of ~ 1% in TREATED PE proven patients. So that either means that: (1) anticoagulation is awesome, OR (2) they were unlikely to die from the recurrent PE / clot lurking in the legs. There is just no good evidence to support (1). Even is they had a 4-fold increase in their post- sPESI mortality through non-treatment, they would still be low risk. There is the guts of the trial that needs to be done, watch this space.... You will have to wait for episode 3 to see how we incorporate the lower limb into the algorithm. Coming soon with a few guests! Casey
Hi there
Really enjoying all the opinions on here. A few comments relating to all 3 podcasts:
1. I’m not sure about applying PERC to the whole population – not what it was designed or validated for (I’m never sure if the UK counts as European or US/Australian risk levels in these discussions) – I’d be more inclined to apply Wells and then PERC to the low risk Wells group?
2. sPESI, as you recognised, only has an evidence base in treated patients. So you could hypothesise that the low risk sPESI group (who aren’t already seriously compromised by their 1st PE) have far more potential to benefit from treatment by preventing their 2nd fatal one. We really need to have the cojones to find this out. It would be good to know the sPESI levels of the patients in the anticoag vs NSAID study.
3. The European guidelines Minh quotes do include class 1A evidence for the status quo diagnostic strategy. However it is only class 1A based on the assumption that finding and treating all PEs is good. We don’t know this – see point 2!
4. I’ll take Scott up on his challenge to really investigate the underlying data. Anyone else?
BW
Kirsty
HI Kirtsy, happy to hear you are enjoying this confusing topic!
1. PERC can be applied to ED patients where a clinician’s guess is they are < 15% likely to have a PE. That roughly equates to an intermediate Well's score (depends which validation you read). So doing Well's then PERC is really very safe. Unfortunately the "risk" is very much in the eye of the beholder! Clinician bias, paranoia or failure to consider it will all effect that! Hence we have limited the discussion to Wells < 2 pts (about half of the PE work-ups. 2. agree, sPESI only looked at treated pts - I did pause on this fact in the podcast. I completely agree - this is where the trial needs to be done - a placebo, controlled RCT of AC vs. placebo. The whole thrust of this exercise is to demonstrate that there is a real clinical question here, that we are at at least equipoise when it comes to the Well's <2, sPESI = 0 patients. There is an ethical imperative to show benefits of anticoagulation in this group whom are potentially at greatest risk of having false + CTPA and potentially being over treated and subsequent complications of therapy for a non-existant disease! 3. The European Guidelines are only as good as the evidence upon which they are based - see other reply to Minh above [or below?]. There is no RCT showing benefit of AC! Consensus for the anticoagulation of proven VTE is not being debated. We are debating the treatment of patients who most probably have a false positive CTPA. So our algorithm aims to identify which patients are at risk of this eventuality and hence should not be investigated further. 4. Awesome - contact Scott pronto! emcrit@gmail.com
thanks!
You have not answered my question of producing even your own case reports or case series of actual patient harm as a result of low risk PE workup. Cite me even one real case that you know.
From Australia, Western Australia.
“Inferring overdiagnosis by observing epidemiological trends has limitations because the evidence is derived from administrative data (coding on discharge records and death certificates) with imperfect accuracy, insufficient clinical detail, and lack of standardisation across institutions”
“The answer is not simply to do less testing—clinicians should continue to have a low threshold for considering pulmonary embolism—but to test (and subsequently treat) more selectively and to consider alternative tests such as VQ scanning and ultrasonography when appropriate.”
excerpts from this good discussion paper http://www.bmj.com/content/347/bmj.f3368
no mention of sPESI!
But agrees with need for prospective controlled trial of Rx of subsegmental PE
Note advice to use other imaging as per Scott and Anand too.
Great comments all.
The problem with the ESC guidelines is as described by Casey and Kirsty – based on a flawed unproved assumption. Also outdated – no mention, no taking into account new contrast data and no mention of PERC.
Re sPESI=0, this is an attempt to provide a little more confidence to clinicians wanting to exclude patients from testing. It is not actually required – Wells <2 is below the TT in any case.
Everything else to be answered/discussed in the response to Weingart podcast coming soon.
thanks Anand
there is still the 2012 NICE guideline
http://www.nice.org.uk/nicemedia/live/13767/59720/59720.pdf
Which has no mention of sPESI and your suggestion of it ,is as an unproved assumption as the very evidence you criticise
I refer to pages 15 onwards of the NICE guideline and there is mention in subsection 1.1.13 of discharging patients after risk stratification with Wells, D Dimer +|- CTPA, without treatment
But nothing about discharging pts with suspected PE and Wells unlikely.
Of course if you want to make a clinical decision and say I dont think this person has a PE and not even cite doing a Wells score, then I think thats ok as long as you are prepared to accept a level of risk and the patient understands this.
But if you consider PE as possible, and use the wElls score, I dont think you can avoid using the existing established peer reviewed standard of care guidelines,
Are you able to cite any real cases where you have witnessed true harm to patients as a result of being worked up for low risk PE?
Hi Minh
Here’s the US adverse event reporting on warfarin bleeding
999 deaths
http://classic.muhealth.org/outcomes/development/Bleeding%20Complications%20with%20Warfarin%20Use.pdf
Lets assume at least a few of these were on warfarin for CTPA “proven” PE in low risk group.
WA study in MJA showed 500% increase in CTPA requests in last 10 years without any decrease in PE mortality. But a big increase in diagnosed PE.
There are lots of case reports of warfarin badness
I cannot cite you a personal case for confidentiality reasons
I think we all agree that putting a patient on warfarin etc carries real risk, inconvenience and has impact on their life. The point being we should balance their risk against the small risk if VTE bad outcome.
Putting every patient on AC despite their individual risk is one extreme. There had to be a balance point in the middle
That is the point Anand is trying to identify
You dont have to give specific case details. Just how many cases you know of over what period of time.
I know of 1 case of warfarin related lethal bleeding in my 18 yrs of clinical practice.
and that was for AF!
None I know of for PE.
. At the very least justify your contention from your own clinical experience.
Minh
We cannot base our practice on anecdotes. We need to use large studies and reviews to find the good and bad outcomes when it comes to relatively uncommon events.
The point being that both the harms of CTPA / AC and the benefits from investigating / treating low risk patients are uncommon.
Rare enough that as Scott says – you cannot base it on just your own practice – you need a broad-based evidentiary justification for what you do with the individual patient.
Can you recall a single patient who got renal failure from a CTPA? I cannot, but I only order 3 a year! So it would take me about 200 years to find one, or I could follow 2000 patients through multiple EDs to show the downside – as did Kline in the paper we discussed (Mitchell and Kline)
Wait for response soon on the podcast
C
Minh,
re the AC we don’t need anecdotes, we have meta-analyses showing almost 3% risks of major haemorrhage and 0.4% risk of death in patients being treated for VTE.
re contrast risk – will discuss in the response podcast
Kirsty,
Sorry I forgot to address one of your comments. Yes from a risk point of view I think you should group the UK along with Australia, US etc as countries who have inherited the english tort law system and all its problematic negligence cases. However obviously the US is significantly further along the medicolegal risk curve then the UK. Australia having inherited some US culture is probably somewhere in between. Mainland Europe I understand is very different – with their civil law systems it is much much harder to sue people so it appears they practice more like real docs should … in the patient’s interests not because of fear of litigation.
You are right about the risk of using PERC on everyone. In low risk cohorts like many in the US the PERC would probably work well applied to all your patients. It wouldn’t in Europe and I’m unsure about the UK. The safest thing is to apply it to patient’s that you the clinician believe are low risk for PE (<15%). If you wish to use Wells Score to find that low risk group that's fine, but one shouldn't feel they are restricted to only using Wells to identify this gestalt low risk group.
my point in relation to actual clinical experience is that I DO KNOW of at least 4 cases of missed Fatal PE
How many missed fatal PE do you know of? esp when you and I have never seen an actual case of contrast/CTPA induced death?
what you don’t know for your 4 anecdotes is whether or not missing that PE did any harm to that patient because you don’t know if treating them would have helped or harmed them, or whether investigating them my have harmed them from contrast,
If you want anecdotes, I have plenty of anecdotes of people dying from anticoagulation and I’m sure you do too.
How do you weight these different risks? That is what this approach we are speaking of is trying to do.
The point is as Casey states, that anecdotes are extremely unhelpful. You have to consult the data which is what we are doing.
Anyway, that’s all on this particularly issue. The rest will be on the response podcast.
thanks Anand
As I stated in earlier comment I know of 1 case of warfarin related lethal bleeding in 18 yrs of clinical practice.
You cite “plenty ” of anecdotes of AC related death. Be more specific..how many?
You nor CAsey have cited an actual case of contrast/CTPA related death as you keep going on about it. Have either of you personally beeen aware of a single case of contrast/CTPA related death?
The trouble with your citation of meta-analyses of adverse events is that it doesnt necessarily apply to you , in your population , to your clinical practice , does it? You assume once again we are all the same, treat everything the same and so get the same results.
As for my 4 anecdotes of missed PE..those were all fatal outcomes. I know because death is a pretty clear endpoint at autopsy!
“Inferring overdiagnosis by observing epidemiological trends has limitations because the evidence is derived from administrative data (coding on discharge records and death certificates) with imperfect accuracy, insufficient clinical detail, and lack of standardisation across institutions”
“The answer is not simply to do less testing—clinicians should continue to have a low threshold for considering pulmonary embolism—but to test (and subsequently treat) more selectively and to consider alternative tests such as VQ scanning and ultrasonography when appropriate.”
excerpts from this good discussion paper http://www.bmj.com/content/347/bmj.f3368
no mention of sPESI!
But agrees with need for prospective controlled trial of Rx of subsegmental PE
Note advice to use other imaging as per Scott and Anand too.
Thanks for that paper Minh
I think you are agreeing with Anand?
The conclusion of the paper is that we need to learn which small PEs do not require treatment (i.e those who will do well with no AC, or run the risk of AC harm without possible benefits)
This is Anand’s point – a patient with sPESI = 0 [a new concept to the BMJ and most of the ED world ] is possibly the cohort that represents the “small PEs that need no treatment”. The algorithm merely identifies the group of patients who just might fit the bill for “good news! you don’t have a big PE, you have no DVT, so go home… carry on living”!
So we need a trial of these patients – randomised to AC vs. no AC to answer this question. To refute the following hypothesis: “sPESI = 0 patients will benefit from anticoagulation.”
That is the way forward – an RCT of this cohort is very much ethical as we have lots of administrative and observational data to suggest they are getting more harm than benefit from the current strategy of Ix and Rx.
In fact the authors cite a few papers that actually suggest trying to identify patients in whom AC should not be considered – and they pretty much come up with a list of criteria that = a negative sPESI and a clear leg Doppler – which is exactly where we are going with the next podcast… so hold ya horses.
Casey
The NICE guideline development group depresses me – looking at the full guideline (http://www.nice.org.uk/nicemedia/live/13767/59711/59711.pdf), not a single emergency physician, and only 1 GP.
However, they do manage to say (section 7.3) “Following the initial diagnosis of VTE a clinical decision is required whether the benefit of anticoagulation outweighs potential risks, such as bleeding”.
Also, to support Scott’s logic “The purpose of anticoagulation is to prevent recurrence of VTE and its consequences. However, the treatment carries a risk of bleeding. Therefore, anticoagulation should normally continue only if the risk of recurrent VTE, or its consequences, outweighs the risk of bleeding (or other adverse effects) due to anticoagulant therapy.”
They discuss at some length the threshold for continued anticoagulation in terms of risk of VTE recurrence vs bleeding. I’m not sure why they don’t apply the same threshold for initial anticoagulation!
This is all premised on the single Barritt 1960 study – as discussed earlier.
The NPSA quotes 2% major bleeding risk in 3/12 for patients anticoagulated for VTE (http://www.nrls.npsa.nhs.uk/EasySiteWeb/getresource.axd?AssetID=60022&… with 600 patient safety incidents and 92 deaths.
The NNH for CTPA (in terms of cancer caused) has been quoted as 330 at age 20 and 640 at age 40 (Arch Int Med 2009;169:2081). In terms of contrast nephropathy, at Jeff Kline’s centre (where I suspect they aren’t overscanning!), for 174 CTPAs they found 12 PEs and caused 25 cases of CIN (Acad EM 2012;19:618).
I don’t think we know the answers yet but the “obvious” benefit of finding and treating all PEs certainly isn’t proven.
Hi Casey,
Many thanks to you, Scott and Anand for all of the well-argued thought-provoking FOAMy goodness. Our collective metaphorical Guinness pint glass veritably doth runneth over with proteinaceous bubbles.
Three things:
1. Delineate / separate the two distinct questions of (a) current PE vs. (b) risk of next PE
I’ve just listened to Scott’s response, and he made this point beautifully. I could not agree more. When we see a patient in ED with possible PE, we should break our inquiry into two questions. Does the patient have a PE right now? If so, is it causing enough trouble for me to care about any imminent threat to their well-being? (<– I'm claiming artistic license here and calling that one question, by the way; given my sample size of 3 things, 1 = 2 is well within the boundaries of a 95% CI). And secondly, even if I'm happy the PE I think is in their lungs is not a major problem today, if there is a PE there, what is the risk of the _next_ PE being haemodynamically or mortally significant, and what should I do about it?
Frustratingly for the "Avoid CTPA" camp (and in the interests of full disclosure, I'm pitching my own tent firmly on their patch of turf), the answer to the first question does somewhat inform the answer to the second one. What I would love to know, is just how much does one's risk of a fatal/crippling/"bad" PE in a given time period (say, the next 12 months) increase if one has a haemodynamically irrelevant or subsegmental PE today? Even answering the posterior, converse question would be handy: for those patients who have a "bad" PE, how many of them have a sentinel/warning smaller PE that was symptomatic enough to bring them to hospital?
If the answer to both of those sub-questions is "not very much", then the more relaxed our quest to answer the first big question can afford to be. If I know that missing a subsegmental PE in a patient who is low-risk according to clinical decision rules will only result in say a 0.1% absolute risk increase for "bad" PE in the next 12 months, I will be much happier not ordering that CTPA. If, on the other hand, I know that 10% of "bad" PEs are preceded by an ED-presentation-inducing sentinel subsegmental PE, or that there's an annual increased absolute risk of "bad PE" of say 5%, then there is a more pressing need to find or exclude the current possible PE.
As we all know, it's bloody easy to confidently exclude a clinically significant current PE using nothing more exotic than vital signs, ultrasound, ECG and Dr Weingart's patented Looks Like Shit ™ or LLS score. (I'd love to do a prospective trial of the LLS score for massive/submassive/lysable PE, by the way). Unfortunately, until we get a better handle on how a non-haemodynamically significant PE affects the attributable risk of future "bad" PE, we just don't have enough information to make a fully informed decision regarding how hard to look for that small current PE.
Being nearly 3am and running, as I am, on dark mint chocolate and tea, I hereby invoke the conceptual model of "Serial Schrodinger's Cats":
– The existence of the current small PE is represented by the mortal state of the cat in box #1. The probability of the atom decaying, the poison being released and killing the cat is ~20% (i.e. roughly the incidence of PE in those presenting to ED with what we think is ?PE)
– Doing the CTPA opens the box, collapses the probability waveform, and tells us if there's a PE (i.e. if the cat is now, to paraphrase Monty Python, an ex-cat).
– The occurrence of a "bad" PE in the next 12 months is represented by the state of the cat in box #2.
– The discovery of a dead cat in box #1 cascades to alter the probability waveform of box #2. (We presume that the probability of a dead cat #2 was close to zero to begin with, but the reality of a dead cat # 1 puts his counterpart at greater risk).
– We NEVER OPEN the second box, unless the patient presents with a lethal PE some time after we missed the initial one, or they have a massive PE whilst already anticoagulated. This is a consequence of _everybody_ being anticoagulated immediately if we find a dead cat in box # 1.
– All of our efforts and discussions to this point therefore revolve around finding a way to AVOID OPENING BOX # 1.
A bit like Gene Hackman's advice to Tom Cruise in "The Firm" when handing him a sealed envelope containing his new job offer and salary details, "A good attorney wouldn't have to ask what's in the envelope", we strive to divine as accurately as possible the state of health of cat #1 without cheating and peeking in the box. But the _only reason_ we care about cat #1 is the effect his or her demise has on cat #2. However, anticoagulation destroys the quantum entanglement that links the two cats, and prevents us from determining the conditional probabilities upon which to base our estimates of how cat # 1 is doing, without looking in the box.
The point is: We need to start opening box #2, to confidently determine when it's safe not to open box #1.
*(There is a more complex model, involving a 3rd cat representing the harms of CTPA + anticoagulation, but… we're just not going there tonight… )
2. All gestalts are not created equal.
Yes, gestalt (or a combination of gestalt + clinical decision rule (CDR)) outperforms CDRs alone. But I can't help but think that we should simply abandon the idea of clinical gestalt being a separate entity. For what is clinical gestalt? It is a set of factors or criteria, present or notably absent in our patient's history and examination findings, which alters our notional pre-test probability of the patient having the pathology of interest, in this case a PE. What is a CDR or risk-stratification-tool (such as Wells or Geneva)? I submit that they are precisely the same thing, with one notable qualitative difference: Wells, Geneva, etc. are an explicitly defined and consistent subset of all of the myriad variables we might consider when estimating that pre-test probability. Clinical gestalt is much more a moving feast; it is a highly user-dependent, non-uniform and undefined collection of some of those same, and some different, variables found in the CDRs.
This is important, because even though overall when averaged across many physicians and many patients, gestalt might come out looking pretty good in the wash, there is likely to be much higher physician to physician and patient to patient variability in the accuracy of the assigned pre-test probability than there is with consistent application of a rigidly defined set of criteria. Thus, by employing gestalt, there will be a larger number of "outlying" patients who are either under or over-investigated and/or treated which by definition causes greater overall harm.
This is one of the reasons I favour Geneva over Wells (when used in this context), as it seems a bit recursive and self-referential to include, essentially, "Do I reckon this is probably a PE?" as one of the highest scoring components of a CDR which I am employing specifically to help me estimate the probability that this might be a PE. Geneva, at least, is more objective and consequently more reproducible across different observers/scorers.
The point is that all of these estimations use criteria that significantly overlap. So, I fret that the logic in saying things like:
"Gestalt has superior predictive power than CDR 1 or CDR 2, and gestalt + CDR 1 is even better!"
…when that essentially means, for discrete criteria {a,b,c…n} :
(a+b+c+d+e+f+x+y+z) is better than (a+b+c+d) or (a+c+d+f+g+h)
…and…
(a+b+c+d+e+f+x+y+z) + (a+b+c+d) is better than (a+c+d+f+g+h)
…is a wee bit flawed, and we can probably do better. I admit that real world effects of synergism and the fact that the addition of risk factors is not a zero-sum game mandate that we must somewhat laboriously conduct large prospective trials of each subset of criteria that takes our fancy, rather than just applying Boolean logic to simplify the problem (though the idea does have some merit), but I suggest that there must be some way of more rigidly quantifying what it is that makes up our individual clinical gestalt guesstimations, other than waving our hands vaguely and ascribing it to "using the force".
If and when we can get a handle on a well-defined set of variables that in reality are what we actually use (even if not explicitly or "out loud") to tip us over that critical "Hey, you know what, I reckon this just might be a PE… aww, crap!" point, we will be one step closer to a more rational evidence-based approach to estimating pre-test probability in a less volatile and noisy manner, so that practice will be more consistent and fewer patients will be unnecessarily harmed by "gestalt variation".
3. Let's do an RCT. No… really.
Sick of a lack of high quality evidence undermining your lovingly crafted prognostic algorithms? Tired of the unquestioned acceptance of dogma from a bygone era bursting your bubble of hope for a more objective predictive model? Take heart, for you are not alone!
Is anyone interested in seriously looking into the possibility of setting up a prospective RCT for this? Ethics approval is clearly a major issue given the ingrained nature of universal anticoagulation, but I suspect it is not unthinkable that a strong enough case can be made, on solid evidential grounds (or predominantly the lack of evidence, really), to crack on and actually learn something that will probably change practice.
Hi Chris
Great comments – a lot of this is covered in the final episode – out soon!
I particularly love the quantum physics analogy – I am actually writing a post on “Diagnostic Decoherence” which has been coming together for the last 6 months in my head.
I don’t want to give too much away, but the concept that we are looking at the current PE risk and missing the “next PE” risk is really a false one… have alisten when we discuss next episode.
Casey
Hi Casey,
Oh, I think we’re all very much considering the “next PE” risk question in our clinical practice, it’s just a question of the way we conceptualise it. If I polled the interns & junior residents as to what we’re interested in, I suspect 95% of them would opt for “Does the pt have a PE?”, which is fine, as knowing the answer helps us estimate the answer to what we really want to know, which is “Are they gonna have a big PE soon?”. So I see it more as a “which way around we think about it” conceptual thing rather than a tangible difference.
The other major issue I didn’t touch on (my comment was long enough…. sorry… the wee hours are a bad time to sit and write stuff online!) is the efficacy (or lack thereof) and risk associated with anticoagulation. Ignoring the detailed answers, I think the big big problem we have is that there are too many uncertain variables at both the diagnostic and treatment ends of the equation.
We have a disease for which we do not know the natural history (coz they all get treated), and for which we do not know the effect of treatment (coz they all get treated).
This kinda sucks. We need a decent RCT or two to reduce those uncertainties.
In the meantime, we are therefore limited to picking away at the lesser problem of “cat #1”, or diagnosing with some certainty the _current_ PE.
Thanks again for all the podcasts, and ongoing discussion. I’m looking forward to the next installment!! 🙂
hey Chris, thanks for the great comments.
– agree gestalt is not ideal and it would be great if we had something totally objective and someone should create this. However until then we must use what we have a best we can.
– gestalt is a combination of all the objective factors as you say but many have not yet been incorporated usefully in a CDR. So for now combining gestalt + some objective data is best for identifying a low risk group.
– I think while gestalt may have greater variability than objective data as you say, this doesn’t automatically imply it is less safe. eg with PE I suspect there may be great variability in what a clinician’s gestalt determines is NOT low risk. However when you look at the group of patients where clinicians have determined ARE low risk in combination with objective data, I suspect there would be less disagreement amongst independent clinicians that these are low risk patients. Whereas I suspect that if you looked at the group of patients that were put in the NOT low risk group, I suspect there would be broad disagreement about who was in this group. This is a suspicion of mine based on the data. In any case we seem to across different countries and cohorts be able to identify a very low risk group by combining gestalt and objective data of PERC and Wells far better than when we use a more detailed but completely objective approach Geneva. In the end, in the absence of anything better, we must proceed with this.
Re risk of recurrent PE, most will be explained in the podcast, especially regarding the first 3 months post PE.
After the first 3 months, all people who have had a PE have a slightly elevated risk of further PE per year for the rest of their lives as I understand. This is very small elevated risk for provoked and a more elevated risk for unprovoked 1st PE. For the former group this recurrent risk is substantially lower than the risk of AC so it would not justify AC. For the latter group this recurrent risk I think is usually not fully known in the individual straight away so often still given a trial off AC after 3-6/12 though I think this very much depends on the physician/haematologist and also on whether any and which thrombophilia disorders are detected on work up.
The vast majority of recurrent PE’s happen in the first 3 weeks – we’ll discuss this in the next response podcast.
Finally – yes I would love to do an RCT … discussed in the next response response podcast.
Kirsty – re AC, the Linkins meta-analysis looking at VTE patients specifically over a 3/12 period had a risk of major haemorrhage of 2.7% and death of 0.4%.
Dr Cole
Schrodinger’s PEs – just brilliant!
I would also be keen to join the RCT.
Dear Chris & Kirsty
Love the quantum physics. Maybe another analogy from the strange world of the tiny we might discuss: Werner Heisenberg’s Uncertainty Principle http://plato.stanford.edu/entries/qt-uncertainty/
Basically the more accurately you measure one variable then the less certain / accurate is the result! You cannot know the mass and the velocity of a particle – measuring one interferes with the result of the other variable
The most supersensitive CTPA would diagnose 99.9999999% of PEs, but we would then be left wondering which of the extras are really a problem. Similar chat re: IST3 a whiles back…
Love it
C
yep agree – Schrodinger’s PE was brilliant!