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Procalcitonin as a Biomarker in Lower Respiratory Tract Infection and Sepsis
11 Plays6 years ago
In this episode of Critical Matters, we discuss the role of procalcitonin as a biomarker in lower respiratory tract infections and sepsis. Our guest is Dr. David Huang, the primary investigator in the recently published Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infections (ProACT) clinical trial. He discusses lessons learned from this very important study and offers insight into the use of procalcitonin in clinical practice.
ADDITIONAL RESOURCES:
Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infections (ProACT) clinical trial: https://bit.ly/2BTZNsf
A meta-analysis evaluating the effect of procalcitonin-guided treatment on mortality in acute respiratory infections: https://bit.ly/2Un6Lgz
FDA Executive Summary on Procalcitonin assay: https://bit.ly/2EiBN4r
BOOKS MENTIONED IN THIS EPISODE:
7 Habits of Highly Effective People by Stephen R. Covey: https://amzn.to/2Ss0mPq
Partners of the Heart by Vivien Thomas: https://amzn.to/2QC6vLP
Recommended
Transcript
Podcast Introduction and Sepsis Focus
00:00:09
Speaker
Welcome to Critical Matters, a sound critical care podcast covering a broad range of topics related to the practice of intensive care medicine.
00:00:17
Speaker
And now, your host, Dr. Sergio Zanotti.
00:00:22
Speaker
For the last 15 years, an enormous emphasis has been placed on improving the outcomes of patients with sepsis and septic shock.
00:00:29
Speaker
There has been a big push for early identification of sepsis and implementation of time-sensitive therapies, including broad-spectrum antibiotics and fluids.
Antibiotic Resistance Challenges
00:00:38
Speaker
At the same time, growing concerns for increasing antibiotic resistance have led to calls for rationalization of antibiotics and efforts to decrease unneeded exposure to antibiotics in patients who do not have proven infections.
Procalcitonin and FDA Approval
00:00:51
Speaker
In 2017, the FDA approved the use of a procalcitonin assay to help guide the starting and stopping of antibiotic treatment in patients with suspected low respiratory tract infections in the emergency department or hospital.
00:01:05
Speaker
In this episode of Critical Matters, we will discuss this topic.
Guest Introduction: Dr. Wong
00:01:08
Speaker
Our guest is Dr. David Wong.
00:01:11
Speaker
Dr. Wong is an associate professor, Departments of Critical Care Medicine, Emergency Medicine, and Clinical and Translational Science at the University of Pittsburgh Medical School.
00:01:19
Speaker
He is the director of the multidisciplinary acute care research organization, MACRO, the administrative core director of CRISMA Center, and also serves as the associate medical director for the transplant intensive care unit at UPMC Montefiore.
00:01:33
Speaker
Dr. Wang has extensive research experience, and his research focuses on multicenter clinical trials that span the ED and ICU.
Procalcitonin as a Biomarker
00:01:42
Speaker
He served as medical monitor of the PROCESS trial, a leader for the ROSE trial, and was the principal investigator of the Procalcitonin Antibiotic Consensus Trial, PROACT, that was recently published this year and that will be the focus of our discussion.
00:01:57
Speaker
David, welcome to Critical Matters.
00:02:00
Speaker
Thank you, Pedro.
00:02:02
Speaker
So I think that maybe we could start with a very basic kind of approach.
00:02:06
Speaker
explanation of procalcitonin, what happens in health, what happens in acute illness and infection, and how it became of interest for a potential biomarker for infections.
00:02:17
Speaker
Sure.
00:02:20
Speaker
So ordinarily in healthy people, procalcitonin, it's a precursor of the hormone calcitonin, and it's made by the thyroid,
00:02:33
Speaker
and then certain other organs.
00:02:37
Speaker
But when you get sick, forget everything about endocrinology.
00:02:41
Speaker
You shouldn't think of calcitonin or anything.
00:02:43
Speaker
Beat Mueller, arguably the
00:02:56
Speaker
the foremost leader in procalcitonin research sometimes describes it, he's written, he's described it as a hormone kind, like a hormone cytokine in the sense that when somebody gets septic or infected with a bacterial infection, amazingly, procalcitonin seems to be constitutively expressed by almost every tissue type in the body.
00:03:21
Speaker
So I think the first, I think one of the first
00:03:25
Speaker
observations of procalcitonin was around in the early 90s or late 80s, where those authors noticed that, hey, procalcitonin seems to go sky high in general with bacterial infection, but very weirdly is actually low in viral infection.
00:03:46
Speaker
And then the implications for patient care became obvious,
00:03:53
Speaker
with such an observation.
00:03:57
Speaker
And then actually after that, there's relatively few basic science type papers with an extensive record though of human research.
00:04:16
Speaker
And the reason why we think it goes up so acutely and so prominently
00:04:21
Speaker
bacterial infections is because it sounds like LPS or endotoxin is a very potent precursor of the messenger RNA that actually stimulates the production of proclastotonin, is that correct?
00:04:33
Speaker
Yeah, that's one of the main mechanisms at least.
00:04:36
Speaker
And again, it's apparently released by almost every type of tissue in the body, which is quite interesting.
00:04:48
Speaker
And then further basic science papers have noted that, at least in general, viral infections actually suppress the release of procalcitonin.
Procalcitonin Research in Europe vs. USA
00:05:00
Speaker
And I think that that's a good starting point to have an understanding of how what we mostly learned in medical school as a hormone, like you said, also has a cytokine aspect or almost like a dual personality.
00:05:12
Speaker
And in infections, specifically in bacterial infections, has been seen to be secreted in large amounts throughout the body in multiple types of tissue.
00:05:21
Speaker
So for many years, it sounds like procalcitonin has been an
00:05:26
Speaker
heavily studied and utilized in Europe mostly.
00:05:30
Speaker
Obviously, we'll talk about how it came, I mean, to be approved and what led to the PROACT study.
00:05:35
Speaker
But could you give us a little bit of what the literature, I mean, just broad strokes of what the literature has shown in Europe and kind of what served for the basis of your thought process in designing the PROACT study in the last couple of years?
00:05:50
Speaker
Yeah, sure.
00:05:51
Speaker
So, so,
00:05:56
Speaker
A couple years ago I got curious as to how troponin came to replace CKMB.
00:06:04
Speaker
I was a second year resident when I was told, okay, start ordering tropes now.
00:06:11
Speaker
But nobody actually explained to me why.
00:06:15
Speaker
So the history of how troponin replaced CKMB is somewhat analogous.
00:06:20
Speaker
Actually, it's quite analogous to
00:06:24
Speaker
to procalcitonin in the sense that initially it started with a lot of observational studies, both Troponin research and procalcitonin.
00:06:35
Speaker
And so there's a ton of observational studies looking at PCT.
RCT Design Challenges in Sepsis Research
00:06:42
Speaker
And to summarize all of them, although the overall signal is that procalcitonin
00:06:55
Speaker
outperforms in terms of sensitivity, specificity, whatever performance characteristic you choose, generally seems to outperform other markers such as white blood cell count, IL-6, lactate, CRP, in terms of differentiating bacterial versus viral infection, sepsis versus sterile inflammation, et cetera.
00:07:22
Speaker
Now, not every paper
00:07:26
Speaker
There are certainly papers looking at, for example, aspiration where procalcitrant doesn't do very well in differentiating sterile inflammation versus microbial infection.
00:07:42
Speaker
But if you looked at the last, gosh, there's probably like 1,000 observational studies, in general, that's what the overall findings are.
00:07:56
Speaker
for the observational studies.
00:08:00
Speaker
So then the RCT started.
00:08:04
Speaker
Oh, I shouldn't make one sidebar is that the big advantage that troponin research had was that they had an objective gold standard, which was echo finding.
00:08:20
Speaker
The huge issue with infection and septic research is that there is no gold standard to define infection.
Swiss and European Trials Impact
00:08:29
Speaker
So, for example, as we all know, even in rip-roaring septic shock, a third to half of patients are culture negative.
00:08:40
Speaker
And then for regular old community-acquired pneumonia, there was a New England paper just two or three years ago
00:08:47
Speaker
where even with research-level molecular diagnostics, a significant minority of patients were still microbe negative.
00:08:59
Speaker
So that's a huge, huge problem with infection and sepsis research.
00:09:04
Speaker
And so studies have done stuff like having a clinical adjudication committee of an ID doc, an ED doc, a critical care doc, et cetera,
00:09:15
Speaker
retrospectively look at the entire patient's record and then decide but that's obviously subjective and when you're making a decision on a sick patient right in front of you obviously obviously you don't have you know all the future data so what the swiss pioneers did led by beat mueller who is i thought really clever they did they decided to do an rct
00:09:44
Speaker
where half the patients got pro-calculated care and the other half did not.
00:09:51
Speaker
And then they just looked at the patient outcomes.
00:09:54
Speaker
So then the patient outcome became the gold standard rather than an endless circular debate as to what's the gold standard.
00:10:07
Speaker
And I think that, sorry to interrupt, but I think that's an important point, right?
00:10:10
Speaker
Because one of the challenges we have with sepsis is that it's a syndrome, right?
00:10:15
Speaker
And I like to think about it, infection, with or without organ failure, infection, with or without shock.
00:10:20
Speaker
But ultimately, what we really care as clinicians is does whatever we apply help us not define the syndrome, but improve outcomes?
00:10:29
Speaker
So that, I mean, like you said, is an important distinction and quite a smart move by Mueller and his group of investigators.
00:10:36
Speaker
Yeah, it was really great.
00:10:38
Speaker
It was really great.
00:10:40
Speaker
So then what they, so then they did a series of trials.
00:10:47
Speaker
Most of them centered around emergency department patients with lower respiratory tract infection.
00:10:54
Speaker
So, and in general, actually all of them found reduction in antibiotics
00:11:06
Speaker
And the larger study, ProHAS, published in JAMA in 2009, showed that it was safe in the sense that adverse events in the Brookhouse Stone arm were not higher in the care arm.
00:11:26
Speaker
So those trials were
00:11:34
Speaker
were pretty impressive and really caught the world's attention.
00:11:40
Speaker
And then there were also other trials, of course, like in clinics, a number in the ICU as well.
00:11:58
Speaker
And in terms of what they were showing, I mean, like you said, basically a growing number of trials were showing that if you used procalcitonin-guided therapy and lower tract infections, you could reduce the use of antibiotics and you could safely do it without any increased outcomes in those patients who were in the procalcitonin-guided therapy.
PROACT Trial Design and Rationale
00:12:20
Speaker
And if I'm correct, some of these studies also showed that it was procalcitonin levels, serial levels,
00:12:27
Speaker
were also correlated with prognosis and outcomes, so higher levels associated with either higher progressions to organ failure or shock mortality.
00:12:39
Speaker
So that was also a prognostic value in procalcitonin.
00:12:43
Speaker
And ultimately, I think there were a growing number of European studies that suggested that once you start antibiotics, if you followed a series of percussotonins, and once they went below certain thresholds or a decrease of greater than 80%, you could also start stopping antibiotics without causing any harm.
00:13:01
Speaker
So that was what basically the European experience was showing.
00:13:05
Speaker
Is that correct?
00:13:06
Speaker
Yes.
00:13:08
Speaker
Overall, with just a couple of caveats in the sense that
00:13:12
Speaker
So the ICU trials were really pretty much focused on, so the ED trials were focused both on stopping initiation, like completely, as well as decreasing a number of days.
00:13:31
Speaker
The ICU trials were very understandably mainly focused on just decreasing duration as
00:13:40
Speaker
If you just intubate somebody and they're febrile and on two pressers, 100 out of 100 doctors are going to start antibiotics no matter what.
00:13:49
Speaker
And then the other caveat is that only a couple of the ED and ICU trials were large enough to really be powered for safety.
00:14:07
Speaker
So I think as is common in a lot of what we study and with randomized studies and small trials, even though there was a growing body of literature and you look at different meta-analysis, they were not all necessarily on the same page.
00:14:21
Speaker
And like you said, we didn't have all the answers.
00:14:24
Speaker
So clearly there was also clinical echopoison specific populations.
00:14:28
Speaker
And even though the approval we'll talk about by the FDA came in 2017 for the expanded indications, I presume since PROACT was published last this year, you started it before the FDA had approved it.
00:14:43
Speaker
Can we maybe, before we talk about the FDA approval,
00:14:46
Speaker
dive into the trial.
00:14:48
Speaker
I'm just curious in terms of what was the rationale, how you were thinking about when you said we're going to study this and maybe we can go step by step into what you actually did with your team.
00:15:00
Speaker
Sure.
00:15:00
Speaker
Yeah.
00:15:04
Speaker
So when I and my colleagues at Pitt and elsewhere started really digging into the
00:15:16
Speaker
ED LRTIR trials, you know, it was extremely impressive, very exciting from a patient care point of view.
00:15:26
Speaker
Like, so, you know, I did a residency in emergency medicine, and, you know, it was just exhausting to, you know, hand out antibiotics when in your gut you wonder, do I really need to?
00:15:42
Speaker
Like, I'm...
00:15:44
Speaker
I wonder if there's a test that could sort of help me and help the patients safely decrease antibiotic exposure.
00:15:55
Speaker
But as we started digging into it, we thought there were two key residual questions from the Swiss trials related to the ED-LRTI population.
00:16:11
Speaker
First is, will it work in the United States?
00:16:14
Speaker
So ProHosp, the largest trial, they very forthrightly state in the paper that they use enforcement methods in order to enforce physician adherence to the protocol.
00:16:32
Speaker
So what that meant was that if the physician wanted to overrule the ProCalcitonin guideline, so for example, give antibiotics even though the ProCalcitonin was low, then they had to call
00:16:45
Speaker
the research center and asked for permission.
00:16:51
Speaker
In addition, the treating doctors in the middle of their ED shift actually enrolled the patients into the study, as they forthrightly state in their method section.
00:17:07
Speaker
So, you know, I just didn't, I think even my
00:17:12
Speaker
best friends from my emergency medicine residency, I don't think that they would do either one for me in the middle of a really busy shift.
Translating Trials into Practice
00:17:29
Speaker
So that basic question, will it work with a different design that at least I feel is more realistic to you as practice
00:17:44
Speaker
really, really popped out.
00:17:46
Speaker
And I think, David, that's an important point because we often...
00:17:51
Speaker
translate results of clinical trials, right, to clinical practice very quickly, at least clinicians like to, and we extrapolate.
00:17:58
Speaker
But you're very, very, very, very on point there where this was basically almost a protocol that was dictated and enforced, right?
00:18:08
Speaker
Whereas, I mean, it's a lot harder to do that in the outside of the confines of a very controlled clinical trial and practice, right?
00:18:15
Speaker
Physicians ultimately have the authority and autonomy to order or not order the antibiotics.
00:18:21
Speaker
And I think that's what you were trying to capture in your clinical trial, correct?
00:18:26
Speaker
Yes, yes.
00:18:29
Speaker
And besides the autonomy issues, there were differences in background care.
00:18:37
Speaker
So the length of stay was really long.
00:18:40
Speaker
So, for example, in pro-hosp for community-acquired pneumonia, it was...
00:18:45
Speaker
10 to 12 days, versus on average it's about five to six in the United States.
00:18:52
Speaker
And their antibacterial was also really long.
00:18:54
Speaker
It was about 11 days.
00:18:56
Speaker
Now, in their defense, their reference was the 2001 IDSA and ATS CAP guidelines, which were much bigger about antibacterial than the most current one, the 2008 ones, which are
00:19:15
Speaker
which really pushed trying to use a shorter course.
00:19:23
Speaker
So that was the first question.
00:19:24
Speaker
Will it work in contemporary care in the U.S. and elsewhere?
00:19:32
Speaker
And honestly, elsewhere where you don't have such enforcement and you don't have such long antibiotic duration.
00:19:41
Speaker
And the second question was, is it safe?
00:19:46
Speaker
you know, anytime you don't give antibiotics, at least I always worry, you know, is that the right call?
00:19:56
Speaker
And they used a somewhat wide, it's called a non-inferiority margin, and their point estimate for mortality was, it wasn't stats significant, but it was numerically a bit higher.
00:20:12
Speaker
So I felt like the,
00:20:16
Speaker
the safety issue wasn't entirely wrapped up.
00:20:20
Speaker
So for those two reasons, does it work and is it safe, those are really the two core reasons why we wanted to do PRO-X.
PROACT Execution and Guidelines
00:20:33
Speaker
So tell us a little bit, I mean, just in a summary, kind of what did you actually do?
00:20:38
Speaker
I mean, obviously, the PROAC study was published earlier this year in the Journal of Medicine.
00:20:43
Speaker
There will be a link attached to the show notes.
00:20:45
Speaker
But tell us, I mean, how you set it up, I mean, with these two questions and, I mean, main questions in mind.
00:20:51
Speaker
And it is the largest study that's been done in North America, for sure.
00:20:54
Speaker
I don't know if it's larger than the European studies, but it is the most recent and largest clinical trial that has looked at this problem, right?
00:21:05
Speaker
Yeah, sure.
00:21:06
Speaker
So you want me to just sort of summarize the overall in a few minutes?
00:21:10
Speaker
Yeah, that'd be great.
00:21:12
Speaker
Okay.
00:21:13
Speaker
So just conceptually, PRO-ARCT was designed to answer a basic clinical question.
00:21:20
Speaker
Can procalcitonin help clinicians safely decrease antibiotic use in lower respiratory tract infection?
00:21:31
Speaker
So it was a two-arm trial, usual care versus procalcitonin, 14 US hospitals, mostly urban tertiary care academic centers.
00:21:42
Speaker
All of them had done very well with the old Joint Commission pneumonia core measures, and none of them routinely used procalcitonin.
00:21:54
Speaker
And we had two aims, which basically mirrored the two questions.
00:21:58
Speaker
Will it work?
00:21:59
Speaker
Is it safe?
00:22:01
Speaker
So we enrolled adult patients with a primary clinical diagnosis of acute LRTI.
00:22:11
Speaker
And then really importantly, where there was diagnostic and decision-making uncertainty, in the sense that the clinician was willing to consider procalcitonin in their antibiotic thinking and decision-making.
00:22:30
Speaker
And the rationale there was because if a patient has purulence coming out of multiple orifices, why would you order procalcitonin?
00:22:42
Speaker
Waste of money.
00:22:43
Speaker
Obviously, you're giving them lots of antibiotics.
00:22:45
Speaker
And conversely, if the, oh, here's Mr. Jones again, well-known as manic, he comes in every two months, especially when he's gardening, okay, obviously, you're not going to give that person
00:22:57
Speaker
Obviously, you're not giving that person antibiotics either.
00:23:01
Speaker
So we wanted to capture patients where an additional test might actually help guide management as opposed to just be a waste of money.
00:23:13
Speaker
We enrolled them in the ED, and then we excluded really sick patients because we felt that, such as endotracheal intubator or impressors, because we felt that
00:23:26
Speaker
basically nobody is going to stop initiation of antibiotics on a patient who's really sick.
00:23:34
Speaker
So these were non-critically ill emergency department LRTI patients.
00:23:40
Speaker
And then we also worked hard to disseminate national antibiotic guidelines, such as CDC and pretty much
00:23:54
Speaker
that for acute bronchitis, you shouldn't give antibiotics for uncomfortable bronchitis.
00:24:03
Speaker
Because past procalcitonin papers trials have been criticized by saying, oh, well, sure, you reduced antibiotic use.
00:24:11
Speaker
That's because in usual care, patients were getting Z-packs like M&Ms.
00:24:17
Speaker
So we wanted to at least do our best to constrain that type of gross antibiotic abuse.
00:24:27
Speaker
So then the intervention was just making sure that the doctors in the ED and the hospital looked at the ProCalcetotin value and recommendation, and then they could do whatever they wanted to do.
00:24:44
Speaker
And we worked pretty hard at implementing the protocol.
00:24:52
Speaker
I had pre-launch education during the trial.
00:24:55
Speaker
There was a lot of live education by the coordinators, then at faculty meetings.
00:25:03
Speaker
And then I reviewed every instance of ProCal Stone and guideline non-adherence and then reviewed each instance with each site PI for each site, trying to try and do
00:25:20
Speaker
a feedback boost.
00:25:25
Speaker
So before we go further, I just want to share with our listeners, I mean, and I have it here from your publication, the actual guideline.
PROACT Outcomes and Insights
00:25:33
Speaker
So I think that gives a frame of reference, right?
00:25:36
Speaker
So basically, like you said, you shared with all the clinicians the current guidelines for community-acquired pneumonia, COPD, asthma, cuprochitis, educated everybody.
00:25:47
Speaker
And like you said at the beginning, these are already high-performing institutions.
00:25:52
Speaker
that had very good data based on CMS and JCO compliance with pneumonia bundles.
00:25:59
Speaker
So in terms of the guideline that you offered, you had three columns, procalcitonin level, the likelihood of bacterial etiology, and then a recommendation that was linked to a clinical behavior.
00:26:13
Speaker
So if the procal level was below 0.1 micrograms per liter,
00:26:18
Speaker
you thought the guideline would say that it was very unlikely to be bacterial and that antibiotics were strongly discouraged.
00:26:26
Speaker
If it was between 0.1 and 0.25 micrograms per liter, the likelihood of bacterial etiology was unlikely and the antibiotics were discouraged.
00:26:36
Speaker
If it was between 0.25 and 0.5, the likelihood of bacterial etiology was thought as likely, and at that point, antibiotics were recommended.
00:26:46
Speaker
And if it was above 0.5 micro-rounds per liter, it was very likely to be bacterial, and the recommendation was that antibiotics be strongly recommended.
00:26:55
Speaker
So that is basically the instructions that the clinicians had paired to the levels, correct?
00:27:04
Speaker
Yes, and we didn't make up this guideline.
00:27:08
Speaker
It's the same guideline used in the Swiss trials and the same guideline that was approved by FDA last year.
00:27:15
Speaker
Okay.
00:27:16
Speaker
So this is kind of like what's considered the standard from that perspective.
00:27:22
Speaker
Yeah.
00:27:24
Speaker
Okay.
00:27:25
Speaker
Yep.
00:27:27
Speaker
So tell us what you found.
00:27:29
Speaker
Yeah.
00:27:30
Speaker
So...
00:27:33
Speaker
So I'll preface by saying that as a doctor, I was very disappointed because I really hoped that it would be a so-called positive trial.
00:27:50
Speaker
But as an investigator, the data are what the data are.
00:27:58
Speaker
That's how we do a study, right?
00:28:01
Speaker
Yeah.
00:28:01
Speaker
That's why we do the study.
00:28:05
Speaker
Yeah.
00:28:07
Speaker
So what we found?
00:28:09
Speaker
So unfortunately, what we found, as I'm sure you already know, is that there really was no overall difference.
00:28:19
Speaker
If you look at... So first of all, we implemented the protocol well in the sense that almost every time
00:28:33
Speaker
the intervention was done correctly, and that the ProCalS-Totent level was drawn, measured, and quickly made available to the treating doctors, versus in usual care where only 2% had any testing.
00:28:51
Speaker
So there was definitely a separation in terms of administered treatments between arms.
00:29:00
Speaker
there was no difference in the overall primary outcome of number of antibiotic days by day 30.
00:29:08
Speaker
4.2 versus 4.3 mean antibiotic days, with very similar results no matter how you analyze, whether intention to treat, per protocol, sensitivity analysis, et cetera.
00:29:23
Speaker
And then similarly, there were no differences in adverse outcomes by day 30.
00:29:27
Speaker
So in other words,
00:29:30
Speaker
It didn't work, and unsurprisingly, it appeared safe.
00:29:38
Speaker
In secondary outcomes, though, there was a possible signal in the sense that antibiotic prescription in the eMERGE department for acute bronchitis was cut in half, 32% in usual care, 17% in the ED.
00:29:53
Speaker
And this was
00:29:59
Speaker
And this finding was robust to a very strict, what's called a Bonferroni correction, which is when you correct for what's called multiple comparisons.
00:30:12
Speaker
So basically, if you look at 30 outcomes, the possibility of you finding something with the magic P less than 0.05 is much higher than if you just look at one outcome.
00:30:24
Speaker
But this finding for acute bronchitis, even though it survived
00:30:29
Speaker
rigorous bonferonic correction is a secondary outcome of a subgroup.
00:30:35
Speaker
So hard to call it necessarily truth, per se.
00:30:42
Speaker
And I think that, David, I mean, and I know that there's been follow-up letters to the editor not too long ago, I mean, and you've answered those.
00:30:51
Speaker
And one of the letters actually pointed out about the Q bronchitis population, which is a population that has been more heavily
00:31:01
Speaker
present in some of the European studies, right?
00:31:04
Speaker
And which maybe, like you said, is an area where there's more overprescribing of antibiotics.
00:31:09
Speaker
So that's one question.
00:31:11
Speaker
But the other question that I also had was what happened specifically with the people who we thought had pneumonia?
00:31:17
Speaker
Was there any differences there?
00:31:19
Speaker
Any comments you can make on the pneumonia population?
00:31:23
Speaker
No, there was no signal for pneumonia.
00:31:28
Speaker
antibiotic reduction in pneumonia.
00:31:35
Speaker
And one of the things that I think are important is, in general, people will read an abstract or take a quick look at a study, okay, say it's a negative study, right?
00:31:45
Speaker
But I think that, like you said, it is negative in terms that it didn't show a positive decrease in the use.
00:31:53
Speaker
But also, I think that what it actually tells us
00:31:58
Speaker
a bit more nuanced than just somebody saying, well, I don't believe in precocitonin, and David's study shows it doesn't really work.
00:32:06
Speaker
Can you comment on that a little bit more?
00:32:08
Speaker
Yeah, absolutely.
00:32:13
Speaker
So in October 2017 was when we finally unblinded.
00:32:19
Speaker
And after basically a decade of planning and thinking about PROACT, I finally saw
00:32:28
Speaker
the results.
00:32:31
Speaker
So after going through the seven stages of grief, I completely deleted and trashed my blank tables and figures, which I had drawn up for expecting a so-called positive trial.
00:32:52
Speaker
And then I really went to work on
00:32:55
Speaker
try and understand this surprise finding.
00:33:00
Speaker
You know, this might amuse you and your listeners, but prior to unblinding, I surveyed the entire team, including all the site PIs, and everybody except one expected to find antibiotic reduction.
00:33:24
Speaker
So this was a huge surprise to everybody.
00:33:29
Speaker
But so then we went to work very hard to try and understand.
00:33:34
Speaker
And I think we understand it now.
00:33:39
Speaker
And yes, this stuff is in the manuscript text, but it's not in the abstract in much detail because of word limitations.
00:33:51
Speaker
So I think the first interesting thing was, so we measured procalcitonin in the usual care group.
00:33:58
Speaker
We just didn't show it.
00:34:01
Speaker
So the first most compelling thing is that procalcitonin levels were associated with emergency department antibiotic prescription rates in both groups.
00:34:15
Speaker
So nothing like
00:34:18
Speaker
about three-quarters of the patients presented with really low procalcitonin levels.
00:34:23
Speaker
So there was ample opportunity in the patient cohort for procalcitonin to work, so to speak.
00:34:30
Speaker
But in those three-quarters of patients, whether or not the doctors saw the procalcitonin level, antibiotic prescription was basically the same.
00:34:44
Speaker
It was basically only about one-third in each arm.
00:34:49
Speaker
And then if you go on the other extreme, you look at the patients with really high procalcitonin levels, you saw the exact same phenomenon.
00:34:59
Speaker
Whether or not the doctors saw the procalcitonin level, three-quarters of them in each arm got antibiotics.
00:35:09
Speaker
And in the middle, with the middle two tiers, yeah, maybe you start to see some differences.
00:35:18
Speaker
But the vast, some differences in antibiotic prescription between arms, but the vast majority of patients presented in either the lowest or the highest tier.
00:35:30
Speaker
So to me, that was sort of suggestive that good doctors can sort of almost sense what the procalcitonin value is.
00:35:46
Speaker
And then
00:35:48
Speaker
And then once we saw that, I decided to look at clinical signs and outcomes and correlate them with procalcitonin level.
00:36:02
Speaker
So in 2008, we did an observational study of procalcitonin and community-acquired pneumonia, and I found that in general, as procalcitonin level rose, so too did
00:36:17
Speaker
severity scores, and outcomes.
00:36:20
Speaker
And we found the exact same signal here.
00:36:22
Speaker
So for example, in the lowest procalcitonin tier, number of service criteria was one, actually 0.9, but then as you rose to the highest tier, it doubled to 1.7.
00:36:37
Speaker
So I think in that context where procalcitonin is associated with how the patient looks and how the patient ultimately does, procalcitonin probably only provided
00:36:48
Speaker
modest incremental information to guide clinician decisions.
00:36:54
Speaker
And that's why we saw that for emergency-partum antibiotic prescription, whether or not you saw the procalcitonin, your actions were pretty similar.
FDA Approval Context and Recommendations
00:37:06
Speaker
So that's, I think, an important point, right?
00:37:08
Speaker
I mean, and I think that it also speaks to the evolution of care.
00:37:13
Speaker
And you were involved with the process trial as well, right?
00:37:16
Speaker
But I think that's another example of when you compare a trial that was done a decade earlier, right?
00:37:23
Speaker
right, like the Swiss trials with some different design issues.
00:37:27
Speaker
And then you do a different study like PROACT almost 10 years later.
00:37:32
Speaker
Not only, I mean, the design is different, but also the clinical behavior has changed, right?
00:37:37
Speaker
I mean, people have molded their practices in different ways.
00:37:39
Speaker
And it seems that at least in the two extremes of those groups, it seems like the doctors were doing a better job and being congruent in terms of being coherent in their approach to either give or not give antibiotics.
00:37:53
Speaker
Yeah, I think so.
00:37:55
Speaker
At least in these 14 academic, there's like, yeah, at least in these 14 tertiary care centers.
00:38:04
Speaker
But exactly.
00:38:05
Speaker
So if you look at the control groups of ProAct and ProHosp, we had much less antibiotic use.
00:38:12
Speaker
Now ProHosp did have a sicker population with more pneumonia than we did.
00:38:20
Speaker
But that said, it's pretty dramatic.
00:38:22
Speaker
So ProAct control,
00:38:24
Speaker
Antibiotic duration was 4.3 days and pro hosp was double 8.7.
00:38:28
Speaker
Yeah, but you know Pro hosp finished enrolling 10 years ago and then since then as we all know, this is huge movement towards shorter courses Yeah, so clinical practice is changing.
00:38:40
Speaker
I mean is evolving as we go along Absolutely.
00:38:44
Speaker
Yeah, and then also, you know, so These these emerge departments were not handing out the packs like candies
00:38:54
Speaker
which is a common criticism of not only EDs, but PCPs and everybody for acute bronchitis.
00:39:01
Speaker
So in PROACT, less than a third of patients with acute bronchitis got antibiotics, but nationally, it's more like 70%.
00:39:11
Speaker
So these 14 hospitals were relatively judicious in their antibiotic use.
00:39:20
Speaker
And I think that a lot of the issues that we discussed also speak to the limitations that these large randomized trials have.
00:39:27
Speaker
I mean, running these trials are not easy.
00:39:30
Speaker
Designing them is not easy.
00:39:31
Speaker
And everything you decide to include, it means that you exclude something else and everything has...
00:39:36
Speaker
probably unintended consequences.
00:39:38
Speaker
So it's very difficult to foresee all of this.
00:39:41
Speaker
But I mean, like you said, I mean, the design, I think the design was phenomenal.
00:39:46
Speaker
I mean, you're trying to address important questions and our listeners can look at the study themselves, but the compliance with what was intended to be done and the follow-up was phenomenal.
00:39:56
Speaker
So I think that, like you said, at the end of the day, whether you were hoping for something positive and dramatic or not,
00:40:04
Speaker
the data is the data, right?
00:40:06
Speaker
And you have to kind of report that and kind of try to understand that.
00:40:10
Speaker
Yeah, exactly.
00:40:14
Speaker
Exactly.
00:40:15
Speaker
So I think that, David, and I know that a lot of the emphasis was on, like you said, LRTIs and the ED, but still very important for our critical care audience and for obviously our ED audience.
00:40:27
Speaker
But I do think that just to kind of bring together
00:40:31
Speaker
what your experience with the trial is just to remind, I mean, our listeners that at kind of the same time that you were finishing your trial in 2017, what the FDA really did is expand the approval of the procalcitonin assay to include an
00:40:50
Speaker
to be utilized as a clinical tool in conjunction with clinical findings for decisions regarding starting and stopping of lower respiratory tract infections and for
00:41:05
Speaker
for the stopping of antibiotics or antibiotics in patients with sepsis, which is not the same, right?
00:41:13
Speaker
So there's no really FDA approval to decide, like you said, on a patient that comes in and is in multi-organ failure, is this high lactic acid, maybe a vasopressor, and you don't have a source, you think, oh, should I give or not antibiotics?
00:41:26
Speaker
That's not what we're talking about.
00:41:28
Speaker
We're talking about basically the population you studied, right, which is basically lower respiratory tract infections, and that includes COPD, asthma, acute bronchitis, and pneumonia.
00:41:39
Speaker
Or in those who are start antibiotics with sepsis, there are protocols that over time can
00:41:45
Speaker
If the ProCal drops below a certain level, usually below 0.3 or 0.25, you can safely stop the antibiotic.
00:41:53
Speaker
Or if there's a drastic reduction of greater than 80%, also can help you shorten the duration.
00:41:59
Speaker
Any comments from that perspective and how you see the use today?
00:42:03
Speaker
Yeah, so when FDA approved it in 2017, I...
00:42:13
Speaker
I thought that was quite interesting.
00:42:17
Speaker
And I read the transcript of the meeting, which was very helpful.
00:42:26
Speaker
So they approved procalcitonin.
00:42:29
Speaker
The FDA approved procalcitonin based on a meta-analysis submitted by the manufacturer of procalcitonin.
00:42:41
Speaker
And the FDA did forthrightly state that the primary limitation associated with the meta-analysis was the lack of US trial sites.
00:42:53
Speaker
But the overall feel was that antibiotic resistance is such a huge problem.
00:43:03
Speaker
And they stated that although there's two US trials running,
00:43:11
Speaker
PROACT and then a different one, they're not finished yet and they needed to make a decision.
00:43:21
Speaker
So I think it was understandable given the enormous worldwide problem of antibiotic resistance as to why FDA approved PCT.
00:43:36
Speaker
What was your second question, Serge?
00:43:54
Speaker
In order for us to say we're going to do this on 100,000 ICU patients or a large number of patients, the evidence has to be top-notch, right?
00:44:02
Speaker
I mean, you really have to, in order to mandate something, you have to feel very comfortable.
00:44:06
Speaker
I think there's still, I mean, there's a lot of good signals and good evidence, but I still, we're not there yet with patients.
Procalcitonin's Role in Antibiotic Resistance
00:44:13
Speaker
mandating procrastinate on everybody.
00:44:15
Speaker
And I think that current guidelines like the Surviving Sepsis Campaign and other institutions are moving along those lines and saying that there is evidence, this is what the evidence shows, if you're going to be an early adopter, there are certain things that you should consider, right?
00:44:30
Speaker
So they're not saying that everybody should do it, but I also think a lot of people are measuring their institutions procrastinate.
00:44:35
Speaker
I think it's important for them
00:44:37
Speaker
to understand how to utilize it best if they choose to utilize it.
00:44:42
Speaker
So from your perspective, David, are there any specific recommendations you can give our clinicians in terms of if they're gonna use prospective patent, when and how to use it?
00:44:52
Speaker
Yeah, sure.
00:44:53
Speaker
So why don't we talk just a little bit about the ICU trials.
00:44:58
Speaker
Excellent, yep, yep, yep.
00:45:00
Speaker
Yeah, so there's been a large number of ICU trials
00:45:07
Speaker
But a lot of them were single center, you know, like less than 100 patients.
00:45:16
Speaker
Two of the largest ones were ProRata, about 600 odd patients in France, and SAPS in the Netherlands, that was about 1,600 patients.
00:45:29
Speaker
And there are other decently large studies as well.
00:45:36
Speaker
So first of all, yeah, so most of them were relatively small studies, except for Prorata, Saps, and one or two others.
00:45:48
Speaker
Most of the ICU trials were in medical patients.
00:45:53
Speaker
They did have logical exclusions, such as immunosuppression, endocarditis, et cetera.
00:46:01
Speaker
And then they all used different
00:46:06
Speaker
cutoffs.
00:46:08
Speaker
So the ED-LRTI trials pretty much all use the same guidelines that PROACT used.
00:46:15
Speaker
But all the ICU ones are all over the place.
00:46:18
Speaker
So some of them use less than one microgram per liter.
00:46:21
Speaker
Some of them use less than 0.25.
00:46:24
Speaker
Some of them use the decrease from the baseline peak.
00:46:27
Speaker
It's really sort of a mixed bag.
00:46:29
Speaker
And then
00:46:32
Speaker
And then the overall, so there was a couple of meta-analyses, but one of them basically said, both actually, all of them basically said that if you look at them all together, the average effect size is something like saving one to do antibiotic days, which is great.
00:46:59
Speaker
Well, no, I would say it's good.
00:47:04
Speaker
But what really matters is decreasing antibiotic resistance.
00:47:11
Speaker
That's really the societal goal.
00:47:13
Speaker
So if you take somebody from, say, an eight-day course to a six-day course, certainly you're saving money.
00:47:26
Speaker
And certainly that's a good thing, assuming it's safe, which it probably is.
00:47:32
Speaker
But it's actually unknown if saving two days will actually reduce antibiotic resistance, as opposed to an ED where what I and I assume every other ED trialist was after was if you can convert somebody from a five-day Z-PAC to nothing, then you can take it as a matter of faith that, yes, you reduced antibiotic resistance.
00:48:02
Speaker
So I think that's probably my overall concern with procalcitonin's true utility in the ICU.
00:48:11
Speaker
Are you really going to move the needle on resistance?
00:48:15
Speaker
And I think it's a very fair point.
00:48:17
Speaker
I mean, the difference between decreasing the number of days versus a binary exposure, yes or no, right?
00:48:25
Speaker
That might be a big difference.
00:48:27
Speaker
And it might take maybe a much bigger effect if it is the case that it doesn't make a difference.
00:48:33
Speaker
But we have no proof that that is the case, which is, I think, a very good point.
Clinical Interpretation of Procalcitonin
00:48:39
Speaker
Yeah.
00:48:40
Speaker
So I think –
00:48:42
Speaker
So that's my interpretation, at least, of the ICU evidence.
00:48:45
Speaker
So overall, I kind of agree with what the current SSC guidelines say, which it was something like we suggest that PCT can be used to shorten duration.
00:48:59
Speaker
It was one of those weak recommendations, but it wouldn't be crazy to use it.
00:49:05
Speaker
Yeah, so I have them here, so I'll just share them with the audience.
00:49:08
Speaker
So they had two recommendations on PCT and PCT.
00:49:11
Speaker
One, like you said, David, we suggest that measurement of procalcitonin levels can be used to support shortening the duration of antimicrobial therapy in sepsis patients.
00:49:20
Speaker
And as you stated, it's a weak recommendation with low quality of evidence.
00:49:24
Speaker
And the second one, number 15, says we suggest that procalcitonin levels can be used to support discontinuation of empiric antibiotics in patients who initially appear to have sepsis but subsequently have limited clinical evidence of infection.
00:49:37
Speaker
weak recommendation, low quality of evidence.
00:49:39
Speaker
So again, like they're saying is you could use it, but we're not saying that everybody should use it and there are some caveats to it.
00:49:48
Speaker
Yeah, exactly.
00:49:49
Speaker
So if you ask me what should somebody do right now in the ICU, first of all, as an academic, I have to
00:50:08
Speaker
state that now I'm switching hats and speaking as a doctor because everything I'm saying now is speculation of course but I think I think first of all you shouldn't order it like all the time it shouldn't be done routinely and but I could imagine a strong doctor who's already done the basics the history the physical I've looked at everything else and
00:50:38
Speaker
and it's still kind of uncertain.
00:50:41
Speaker
You could imagine that in certain situations, it's sort of like swans.
00:50:46
Speaker
So there's been now, what, 10 negative trials of swans, but we still swan some people.
00:50:54
Speaker
And it's kind of hard to quantify exactly when a good doctor will swan, but certainly nobody is saying we should just throw swans in the garbage.
00:51:06
Speaker
So I think there are situations where a strong doctor could reasonably, as an early adopter, as you said, Sergio, order a procalcitonin.
00:51:20
Speaker
But then also, you have to be ready to act on it.
00:51:24
Speaker
So it's a bit like the Choosing Wisey campaign.
00:51:27
Speaker
And I saw an editorial on viscoelastic testing, so TEGs, and the title was something like
00:51:36
Speaker
It's not the test, it's the action.
00:51:40
Speaker
Which again, immediately reminded me of the great swan debates from about 15 years ago.
00:51:49
Speaker
What changes with the information?
00:51:50
Speaker
That's the real question, right?
00:51:53
Speaker
Yeah, exactly.
00:51:54
Speaker
So if on a select non-routine patient you decide to order it, then you have to be, yeah, like with anything.
00:52:03
Speaker
Like, is it worth sending this intubated patient
00:52:06
Speaker
an 80% antenna peep down the hall to the CT scan.
00:52:11
Speaker
Well, it is if you're going to change management, but if you're not going to change management, you better not get that scan.
00:52:18
Speaker
Yeah, I agree.
00:52:22
Speaker
And, and what about incorporating your PCT use into a antibiotic stewardship program?
00:52:27
Speaker
There's been a lot of discussion and some of the letters to the editor also talked about that.
00:52:33
Speaker
Any comments on that?
00:52:36
Speaker
Yeah, so I remember when the stewardship program was first introduced at Pitt.
00:52:44
Speaker
And at first, I mean, I'll just speak personally, at first I was like, what?
00:52:51
Speaker
What is this hoop that we have to jump through?
00:52:54
Speaker
But then gradually I saw that this is a wonderful thing.
00:53:00
Speaker
It really is.
00:53:02
Speaker
First of all, it's almost like a curbside consult for ID.
00:53:09
Speaker
But overall, yeah, I think we need to be restricted.
00:53:15
Speaker
So one of the letters to the editor basically said, how come you didn't combine it with a stewardship program?
00:53:24
Speaker
And I basically said, because that would be testing two interventions, which is
00:53:31
Speaker
completely different design and a really heavy... So number one, it's a completely different design and doing two interventions is much bigger in scope than one.
00:53:46
Speaker
But if you already have an antibiotic stewardship program, then you might imagine that folding ProCalStone into it might be more effective.
00:53:59
Speaker
And there's some papers
00:54:03
Speaker
that suggests that that's true.
00:54:10
Speaker
So one thing that we didn't touch on, but I guess would be valuable since we're talking about
00:54:14
Speaker
potential clinical application based on the evidence and what you learned from the trial.
00:54:21
Speaker
There are certain conditions that are associated with elevations in the baseline procalcitonin that are not related to infection, right?
00:54:28
Speaker
And those, I think, were exclusions in your study.
00:54:32
Speaker
Can you mention some of those, David?
00:54:34
Speaker
Sure.
00:54:35
Speaker
So this is not an exhaustive list, but in the study, I chose to exclude relatively common conditions
00:54:45
Speaker
where PCT can be high without infection.
00:54:50
Speaker
So, for example, chronic dialysis.
00:54:53
Speaker
And again, not every paper says this, but certainly at least the time when I designed the trial with my colleagues, there was enough to make me nervous enough to exclude them.
00:55:04
Speaker
So, I'm sorry, what I mean by high is greater than 0.25.
00:55:13
Speaker
microgram.
00:55:15
Speaker
So they would compromise the lower extreme which is the one that's useful in saying don't give antibiotics.
00:55:22
Speaker
That's right.
00:55:24
Speaker
High in the ED may be low in the ICU.
00:55:27
Speaker
Correct.
00:55:30
Speaker
So chronic dialysis, metastatic cancer and then recent surgery.
00:55:40
Speaker
So if you were being an early adopter
00:55:42
Speaker
and you nonetheless decide to order procalcitonin in these conditions, particularly surgical patients, you have to recognize that their baseline level is going to be higher than somebody else's.
00:55:56
Speaker
And then there's also certain types of thyroid cancer where procalcitonin is high.
00:56:03
Speaker
Not every type of thyroid cancer, though.
00:56:10
Speaker
Well, I think that this is obviously still an unsettled topic.
00:56:15
Speaker
I think that because it's already available and people use it or misuse it, maybe we're going to probably hear more about it.
00:56:22
Speaker
But I think that, like, one of the first, I mean, thank you for your time, but also for the effort of trying to study this in a very...
00:56:30
Speaker
scientific way and even though the the sometimes the findings are not what we expect or what we hope for like you said I mean understanding the data is the key of really doing evidence-based medicine so that was very very useful but one of the things that we like to do in our podcast David is at the end kind of ask some questions that are not related to a specific topic and just tapping into the wisdom of our of our guests would that be okay
00:56:56
Speaker
So the first question is, what book has influenced you the most or what book have you gifted most often to others?
00:57:05
Speaker
I think there's two books that stand out.
00:57:10
Speaker
The first is The Seven Habits of Highly Effective People.
00:57:15
Speaker
I think from that book, the single most important message is that we don't spend enough time in what the
00:57:23
Speaker
what Dr. Covey calls the type two quadrant of activities, which is important but non-urgent.
00:57:31
Speaker
So here's an exercise in the book where he says, write down three activities that you know if you did consistently for the next year, so like a New Year's resolution perhaps, given that it's December 6 right now, you know would improve your life.
00:57:50
Speaker
And it's always stuff like,
00:57:52
Speaker
exercising more, flossing more, spend more time with my family.
00:57:59
Speaker
So all those things are important, but they're not urgent, like a cardiac arrest or a grant deadline or whatever.
00:58:08
Speaker
So it's very easy to not do important things.
00:58:12
Speaker
but not urgent things.
00:58:14
Speaker
And I think that this is super applicable to medicine and healthcare in general today.
00:58:21
Speaker
So we work with a lot of hospital partners throughout the country.
00:58:27
Speaker
And I think that one of the problems with a lot of our hospital administrations, and that occurs in academic centers too, is that there is a tremendous emphasis on what's urgent.
Personal Insights from Dr. Wong
00:58:39
Speaker
the last state can't visit or Jayco's coming next week.
00:58:43
Speaker
And I think that sometimes we undervalue or undermine what's important, which is building quality programs that are going to be everlasting and really move care forward.
00:58:53
Speaker
So I think that we do both, I mean, in general, but I think sometimes the emphasis switches too much to what's urgent.
00:58:59
Speaker
And I think that's a great lesson.
00:59:00
Speaker
And we'll definitely link this book at the end of the show notes.
00:59:04
Speaker
What's the second one?
00:59:06
Speaker
The second one, it's called
00:59:08
Speaker
Partners of the Heart, written by Dr. Vivian Thomas.
00:59:15
Speaker
So very briefly, the famous Blalock-Talzig shunt, so the world's first heart operation, in this case, was for the famous, they call them the Blue Babies, for Tetralogy of Fellow.
00:59:37
Speaker
It should be called the Blalock-Talzig-Thomas shunt.
00:59:41
Speaker
So Blalock was the surgeon.
00:59:43
Speaker
Talzig was the pediatrician, female pediatrician.
00:59:47
Speaker
And Vivian Thomas was the Noel College education, African-American lab technician who did little minor things like create the dog model for Tetralogy of Fallot.
01:00:02
Speaker
And
01:00:06
Speaker
And when Blalock became chair, he actually, it was Thomas who did all the operations in the lab, such that when Dr. Blalock did the world's first heart operation, he literally told Thomas to stand on a step stool behind his right shoulder and told him to walk him through the operation.
01:00:30
Speaker
Yeah, interesting, right?
01:00:33
Speaker
And it's amazing.
01:00:35
Speaker
So HBO did a docudrama on it called Something the Lord Made, based off of a quote where when Dr. Blalock felt the vascular anastomosis that Thomas had made in the dog, it was so smooth that he was like, my God, this anastomosis is like something God made.
01:00:57
Speaker
Wow.
01:00:58
Speaker
And when I saw the docudrama, I was like,
01:01:03
Speaker
this is too crazy to be true.
01:01:05
Speaker
So I heavily researched it, I got biography, and it is 100% true.
01:01:16
Speaker
They changed one little minor historical detail at the end, but the rest is completely true.
01:01:23
Speaker
And yeah, 100% it should be called the Blalock-Towcyk-Thomas shunt.
01:01:31
Speaker
Which is interesting, like how every story has so many layers that we don't necessarily know.
01:01:35
Speaker
And I think that's also something that we learn when we talk with the investigators who run these trials.
01:01:41
Speaker
We read them, but there's a lot of things that go behind scenes, thought process into the whole design that I think it's interesting to understand.
01:01:50
Speaker
So these two will be referenced at the show notes.
01:01:52
Speaker
I mean, I have not read Partners of the Heart, but definitely have an interest in that.
01:01:57
Speaker
So definitely we'll look it up.
01:01:59
Speaker
The second question, David, is what do you believe to be true in medicine or in life that most other people don't believe?
01:02:11
Speaker
Give me a minute here, Sergio.
01:02:19
Speaker
Most other people...
01:02:28
Speaker
Well, and I think that one of the things that you mentioned that would be an extension of the seven habits of highly effective people is the importance of focusing on what is important versus urgent.
01:02:38
Speaker
Right.
01:02:39
Speaker
So figuring out, I guess, a lot of people don't see that.
01:02:43
Speaker
Everybody's always busy with what's urgent, the next emergency.
01:02:46
Speaker
But ultimately, the more energy we spend in that quadrant, probably the better for ourselves and also for the people we're trying to help.
Final Takeaways for Clinicians
01:02:53
Speaker
But I think that that would be kind of an example, I think, of what I consider things that are true, but most people don't believe or they believe it, they don't act on it.
01:03:06
Speaker
Yeah, fair enough.
01:03:07
Speaker
Yep.
01:03:09
Speaker
So what would you want every intensivist who's listening to this podcast to know in closing?
01:03:15
Speaker
Anything in particular could be related to PCT or anything else that is important for you?
01:03:30
Speaker
I think the... Well, I guess related to PCT, I think the Choosing Wisely campaign is probably one of the best things to come out of organized medicine in the last 10, 20 years.
01:03:48
Speaker
It's not another controversial...
01:03:51
Speaker
maintenance of certification exam, but actually something that really is a strong clinical use.
01:04:04
Speaker
And I think choosing when to order Procalcitonin wisely is just a – it fits very well into the overall Choosing Wisely campaign.
01:04:18
Speaker
I agree.
01:04:18
Speaker
And I think in terms of when you choose it, when you order a test, I mean, using that to make meaningful impact on the patient.
01:04:24
Speaker
So I think there are so many data points that we order that cost money, can cause problems that we don't utilize or we're not going to utilize.
01:04:33
Speaker
And I think it's just, I mean, wasteful and low value care for our patients.
Podcast Conclusion and Call to Action
01:04:40
Speaker
Yeah.
01:04:40
Speaker
And, you know, one last thing, like I don't want to be nihilistic about procalciton.
01:04:45
Speaker
And like, if you think about it,
01:04:48
Speaker
You know, so like, you know, we have such an intense troponin envy, but like cardiologists, everybody's still arguing over how to best use troponin in 2018.
01:05:01
Speaker
And heck, we still don't know exactly when and who and how to order mammograms.
01:05:11
Speaker
So the whole area of testing research and how to test the test
01:05:18
Speaker
Procalcitonin is just one small part of that overall clinical and academic struggle of how do you test the test and when should you actually order that test and on who and how often.
01:05:35
Speaker
So it's going to take a lot more both research and clinical experience to figure out when to order prostate-specific antigen, when to SWAN, when to order mammogram, and when to order procalcitonin.
01:05:48
Speaker
And I think that that's a perfect place to stop.
01:05:50
Speaker
I really want to thank you, David, for your time, for being so generous with all your knowledge and walking us through, I mean, a wonderful trial that, even though it's negative, I think taught us a lot about implementation of change in clinical practice.
01:06:05
Speaker
And hope to have you again on the podcast soon.
01:06:09
Speaker
Great.
01:06:09
Speaker
Thanks a lot, Sergio.
01:06:13
Speaker
Thanks again for listening to Critical Matters.
01:06:15
Speaker
Make sure to subscribe to this podcast on iTunes or Google Play.