The Curbsiders (00:00.654) All right, Paul, we'll see how this goes. You know, Paul, ever since I got my lung removed, I'm happy to tell you that I've cut my smoking in half.

The Curbsiders (00:14.926) Nothing? Okay.

The Curbsiders (00:20.974) of Ciders podcast is for entertainment, education and information purposes only and the topics discussed should not be used solely to diagnose, treat, cure or prevent any diseases or conditions. Furthermore, the views and statements expressed on this podcast are solely those of those and should not be interpreted to reflect official policy or position of any entity aside from possibly cash like more hostile and affiliate outreach programs. If indeed there are any, in fact, there are none. Pretty much we aren't responsible if you screw up. You should always do your own homework and let us know when we're wrong.

The Curbsiders (00:44.494) Welcome back to The Curbsiders. I'm Dr. Matthew Francois here with my great friend and America's primary care physician, Dr. Paul Nelson Williams. Paul, how are you doing? You seem to be struggling saying that tonight, Matt. Has something changed? I'm good. How are you? Maybe I'm just still tired from the weekend. I don't really know, but I'm excited, Paul. This is an episode where we are going to review some stories that were featured in recent or.

Future issues of the Digest are our monthly newsletter. So of course, with us, we have a wonderful co -host and I'll let you introduce her in a second, Paul. But first, can you remind people what is it that we do on the Curbsiders? Sure, happy to as always. Typically we are, well, always we are the internal medicine podcast, but typically we use expert interviews to bring you clinical pearls and practice changing knowledge. These episodes are a little bit different. As you mentioned, we go through some of the past and future Digest articles, sort of news you can use or maybe you can't use.

but stuff that's kind of happening out there in the zeitgeist and sort of what you should know and what you need to know to impress your friends out on the words. And as you mentioned, we're joined by the editor of the Digest, the great producer extraordinaire, Dr. Nora Toronto. Nora, how are you? I'm doing well. How are you guys? I'm excited. I am a big fan of your monthly newsletter and it's good to be doing this now in podcast form because I feel like we get to go a little bit more in depth on some of these stories.

and try to figure out if these should or shouldn't change our practice. And when we do this so frequently, I feel like it really does help me keep up with what's happening and remember it better too. I know. I feel like I end up talking about these studies more and I'm always curious what your thoughts are on them. But I feel like it keeps me up to date on everything. Yeah. And I like to run...

all the medical literature through America's primary care physician to get his take on it. So yeah, it's a great idea. I think for everyone. All right. A reminder that this and most episodes are available through VCU health at curbsiders .vcuhealth .org. You can claim CME there. And also, if you're not yet a member, please sign up to join our Patreon at patreon .com slash curbsiders where you can get bonus episodes, ad free episodes.

The Curbsiders (03:01.038) and all sorts of other cool stuff. So check it out at patreon .com slash curbsiders. And now Paul, I wanted to start off with something just for you. We all know that you're a big trial head and a listener named Jess. I'm gonna withhold her last name because I didn't get permission to say her full name on air and I don't wanna embarrass her. But Jess, she wrote us, thank you for all your great work.

I'm a relatively new listener and I've really been enjoying the podcast. In particular, I love the recent episode on antiphospholipid antibody syndrome and the replay of the gut brain access. She said there were some aha moments and she said she thought of us last night when she came across the best slash worst trial name she's seen in a while. The study of the prevention of anal cancer, the spank trial, Paul.

Maybe you already know about it, but if not, you're welcome. And she said, thanks for all the work you do. So what do you think, Paul? Reactions to the trial name? So first of all, thanks to Jess. Any time she wants to send trial names her way, we appreciate it. I like to be thought of. I don't know, dude. It's a peek behind the curtain for our listeners. When we do our idiotic puns at the beginning, there is some agonizing, is this going to offend people? Will this hurt feelings? Is this dismissive of something that is actually a serious problem?

So there is a whole lot of internal vetting as we agnose or there's moronic puns that we actually do. So the Spank trial, I don't know, it feels like it comes from the mindset. If people are talking about it, it's good. But on the other hand, I just find it, considering the seriousness of the topic that it's covering, the name itself just kind of does not sit right with me, so to speak. So I don't know, what was your take on it? I mean, it is from the University of New South Wales in Sydney. So maybe the sense of humor is a bit different. I'm not sure.

Nora, what about you? What did you think about this? And any thoughts on the image that I pasted into the script? Yeah, I mean, I think that the name and the image go well together, and it seems like they have a communal founding principle of just taking it maybe a little bit further than we might. The image is just pretty amazing, and I assume we're going to include it in our show notes for the episode.

The Curbsiders (05:10.542) Yeah, I don't know if we can include the image because of but we will include a link to the website too because the image is The rear end of what I'm assuming is it's a very muscular Naked the rear a rear end of a very muscular naked man with a pink or I don't know red X crossing out over the butt and it's it's Over the anus, I think yes specifically it specifically

Just remind her, the internal medicine podcast. I and I was shocked, Paul, when I looked at it, because I was just trying to look up what the SPANK trial was about. But it turns out, they're basically following people. I think they're going to do three screenings over five years and doing anal pap testing, basically looking for anal cancer, trying to figure out how frequently they should screen people. And so it's obviously an important topic. Yeah, critically important stuff.

You know, we're immature. So there's something called the Spank Trial. We got to talk about it. And they have published. This is a real study. It's worth noting. Worth noting. So, okay. All right. But now on to speaking of cancer, Nora, you are... transition. You are going to present our first article. So please tell us what were you reading? So at Target TP, which looked at...

targeted thrombo prophylaxis in outpatients with cancer who are receiving chemotherapy, looked at whether or not starting low molecular weight heparin or inoxaparin would actually reduce the incidence of venous thromboembolism or arterial thromboembolism in patients who are in the clinic and starting chemotherapy. Now we know that patients with cancer have

an increased risk of clotting of various sorts. And that risk actually differs depending on the type of cancer with in particular gastrointestinal cancers, as well as brain, lung, and ovarian cancer having the highest incidence across different studies. And so trying to figure out what to do in terms of prophylaxing them, like we are prophylaxing patients in the hospital, is why this study was.

The Curbsiders (07:30.702) done, and there have been a couple of other prophylaxis -oriented trials in the outpatient setting over the last five to 10 years that have looked at apixaban and rivaroxaban. But this study actually used a new risk stratification tool, looking at two labs, looking at fibrinogen and then D -dimer, which can easily be obtained in the outpatient setting to try to risk stratify patients into high -risk and low -risk cohorts, even among those patients with

lung and GI cancers. And Nora, per our convention, was this a positive or negative trial? What are the top line results of this? Yeah, so top line results in this cohort of around 300 patients, it was a positive trial. And they found that in the high risk cohort, randomization to an oxaparin or low molecular weight heparin compared to placebo,

decreased the incidence of thromboembolism significantly. And so that was just in the high -risk cohort. And yet again, this is risk stratification based on the D -dimer and fibrinogen levels. In the low -risk cohort, the risk was about what one would expect. Introducing thrombo -prophylaxis or Noxaparin in this cohort, in the high -risk cohort, actually decreased the risk of...

thromboembolism to around the low risk cohort incidence. So it brought the risk down substantially. So you mentioned that this trial used a new risk score, because the one that I had heard of, it's called the CORANA, K -H -O -R -A -N -A score, right? And that goes by like the cancer type, platelet count, hemoglobin, leukocyte count, and their BMI. And then it kind of...

risk stratifies them high, medium, or low based on that. So is that one the one that most people use clinically right now? So this is, I think, why this study is kind of important to talk about. People aren't really prophylaxing in the outpatient setting. They aren't starting patients routinely on prophylactic anticoagulation for patients with cancer unless they have another indication to be on it. And so while we're doing this very routinely in...

The Curbsiders (09:48.846) in the hospital and when patients are admitted for surgery or just admitted generally, they're on something, whether it's an Oxyparin or it's a DOAC, but this really hasn't actually taken hold in the outpatient setting for a variety of reasons probably. So people aren't using the corona score as much as you might think. And then kind of interestingly in the study, if you get into the kind of the discussion,

and the results looking at the nitty gritty of comparing the corona score to the risk stratification they used with the D -dimer and fibrinogen. The patients who had higher corona scores actually didn't, the risk stratification in this population was not actually particularly well stratified by corona score. So patients, even with high...

or higher corona scores had about the same incidence of VTE as the patients with low, whereas the fibrinogen and D -dimer combination seemed to actually predict better whether you in fact have a high risk in the study period or a low risk. It's interesting because the editorial that came along with this, I believe, Corona actually wrote it. Yeah. And it seemed like the...

Maybe there was a little bit of competitive competition there amongst them. But so yeah, that was my take home from this was that the there is a risk score out there. There are guidelines. The editorial was saying that since like 2019, the guidelines have said if people are high risk by the corona score that you should consider putting them on prophylaxis for malignancy while they're, I guess, while they're undergoing chemotherapy. But it's just not really done much right now and needing to figure out a way to like, where do we go from here?

because it seems like it is, you can legitimately prevent harm with it. Yeah, and then the only two other things I'll say, one is that this study, the Target TPE study actually found a significant survival benefit with the prophylaxis group compared to the no prophylaxis, which has not been shown in other studies. And it's quite significant, I think, both from a sheer absolute numbers perspective, but also from...

The Curbsiders (12:11.842) statistically. And so one thing that they want they mentioned in the discussion of this study, they need to follow up on this because other studies in this domain have not demonstrated that. But if that is in fact the case, that kind of confers even more power to to this notion that we should be doing it. And yeah, and then I guess the only other thing is just keeping in mind that whereas the the other studies that have looked at this have looked at kind of bigger populations with not just

GI and lung cancer. This study does focus on those two. So I think it's somewhat generalizable, but not to everything. It's the two cancers you're seeing the most. So it's not. Yeah, yeah. Exactly. It's just that population. Yeah. And then the only other thing is just to keep in mind that kind of this notion of patients being high risk at the beginning of their diagnostic and therapeutic journey. That.

risk does change. And so there is some thought about and uncertainty about kind of how long do patients need to be on prophylaxis. And this window of time where they're actually starting chemotherapy seems to be kind of one of the higher risk windows in other studies. So how do you see this playing out in the future? Like if Paul's seeing patients in primary care, do you think primary care doctors will think of this? Or do you think the oncologists are going to start people on?

on medication in three to six months or something while they're going on therapy and then reevaluate every three to six months? Yeah. I mean, I could see, I'm curious what your guys' thoughts are, but I could see it playing out in both ways because I think the oncology visit for patients who are on chemotherapy is often just really focused on like how they're doing from the toxicity perspective or what the toxicities of chemotherapy will be, which can include...

clot. But so I could imagine this might actually fall through the cracks. And that may, in fact, be a piece of why the uptake on this hasn't been all that good. And so it may be kind of in between domains of oncology and the primary care. But I also think there are a lot of important questions that need to be answered about the duration of anticoagulation and how that risk changes over time, which is probably going to just be a collaboration between.

The Curbsiders (14:34.414) Everyone. Paul, what do you think? I mean, this is the eternal survivorship debate, right? Like it's, it's who's somebody. It's just, I think one assumes the other is in charge of something and it's just going to fall through the cracks. And I, I don't think this will be taken up by primary care doctors primarily. I think it might prompt a conversation like reaching out to oncology being like, Hey, should we be talking about this or not? But you know, I think most PCPs will think, well, this person trained in hematology at some point in their career, they would probably know if this person needs anticoagulation or not and sort of trust that the right thing is being done. But hopefully.

If anything, this study will hopefully drive conversation so that there's more uptake among these high -risk groups to actually prevent harm. Yeah. And then one last question, Nora. You said that they were using the low dose, like the 40 milligrams in oxaparin in this one. But with DOACS, is it the low dose of like apixaban or rivaroxaban that would be used for this? Yeah. And I think the data is the strongest with the apixaban.

I think it was the 2 .5 milligrams twice daily of the Apixaban. And then I think also that, yeah, the 10 of the River Oxaban. Yeah. Okay. All right. So any final thoughts on this or recommendations to the audience? No, I mean, I think exactly what Paul said. Like, this is something that sometimes can be overlooked. And in the inpatient to outpatient transition also is probably worth, like if you're a hospitalist or working on the inpatient side with these patients,

saying, oh, we did this while they were here. Like, is this something we should continue since they're going to be starting therapy soon? So. All right. So, you know, speaking of an inpatient and outpatient topic, Paul, COPD, I always struggle with COPD exacerbation. Who needs steroids? Who needs antibiotics? Do you have anything to tell us about this? Do you struggle with that? I was actually open by asking that. So it's the the article I'll be talking about is this.

blood eosinophil guided oral prednisolone for COPD exacerbations in primary care in the UK, AKA the STAR -2 trial, that's two Rs and star, so making it all piratey. And this is a non -inferiority trial and we'll talk about that. That basically what the investigators were looking at. So it's, we know that treating COPD in patients who have eosinophilio with inhaled corticosteroids has benefit. Like we used eosinophilio as a guide who actually gets inhaled corticosteroids, but we have not.

The Curbsiders (16:59.726) typically used eosinophilia as a way to determine who gets systemic steroids during acute exacerbations of COPD. So the investigators, looks like had done some prelim work that suggested that the outcomes were not inferior or maybe even superior using this approach of looking at peripheral eosinophilia as a means to determine whether or not a patient would actually warrant steroids or not. Does that make sense so far? Yeah. Yeah. So let's do the top line results and we'll ask some follow up questions.

So the top line of this is that if you use peripheral eosinophilia as your marker to guide who gets steroids, it's not inferior to just kind of firing off steroids to every patient who you think is an acute exacerbation of COPD. So the patients don't seem to do any better if they don't have eosinophilia, if you just don't treat them with systemic corticosteroid. So that's the bottom line of this trial, which I found kind of surprising. So to get into the nitty -gritty of it, goodbye, Ellie. And Paul, one thing I was going to say, like a big upfront, not necessarily limitation, but a...

Practical limitation of this one is they were using point -of -care eosinophil testing, which I did not know You know, I don't really know that that's available any place that I've ever worked Yeah, you're jumping to my limitations. But yeah, so they're using as whether or not this will be practice changing I think that certainly plays into it They were also using point -of -care CRP testing as well And that's exactly right and then the outcome that that they were looking at in terms of whether or not the treatments were effective Or not was this is at 30 days the primary outcome?

that they're looking at is that 30 days they're looking at treatment failure, which is defined as needing re -treatment. So you had to go back and get them more steroids and more antibiotics or hospital admission or death, which is really the ultimate treatment failure at 30 days. And they did secondary outcomes that included the things that I'm actually kind of interested in, which like health care related quality of life and symptom scores and actually even some spirometric measurements as well.

So to get into this trial, you had to be over the age of 40. You had to be either a current user of tobacco or have used tobacco in the past, I think at least 10 pack years if I remember correctly, and had at least one COPD exacerbation within the past year. And they basically randomized these patients one -to -one into two different groups. And one group got the standard of care at that time, which is also important. And then the other group was the eosinophilia guided therapy. And within that group, if they had elevated peripheral eosinophils, then they were given...

The Curbsiders (19:12.814) steroids and if they did not, then they were not. So everyone in the standard group received Prednisolone 30 milligrams for a total of 14 days. Does this make sense so far? Yep. And I guess the first thing that jumped out at me as I'm sort of looking at this is 14 days worth of treatment I don't think is what most of us are doing these days. No. And I calculated, uh, you can, cause I like math, Paul. So was so much surprises. Yeah. The Prednisolone and Prednisone are a one to one, right? So, and they were giving,

30 milligrams for 14 days. So that's a total dose of 420 milligrams over those two weeks. And then what we typically give is 40 milligrams for five days, 200 milligrams. So more than twice the dose of steroid that we usually give in the U .S. Thank you for doing that. I meant to, and I was just too lazy to, but I knew that I had you as backup. But I think the important thing here is that we're, the whole reason to go through this whole rigmarole is because we know.

systemic corticosteroid exposure comes with its own set of harms. And they actually make a lot of hay out of the number needed to harm is actually lower than the number needed to treat looking at prior meta -analysis. So this aggressive treatment with prolonged courses of steroids is probably doing more harm than good. They were presupposing. So the idea is to limit as much exposure as possible. But meanwhile, this trial is designed where the actual intervention was not the way that we actually treat COPD these days and was with a prolonged treatment course over 14 days. I think the other thing that was interesting is,

regardless of what group you're into, you also got 200 milligrams of doxycycline for seven days. And this was, regardless of sort of the symptoms that you had, just recall that typically the treatment of CBD exacerbations with antibiotic therapy at least warrants you have to have pure elements of sputum or increased dyspnea or I increased volume of sputum. You have to meet some of these sort of criteria to suggest using it. You don't just sort of shotgun everyone with antibiotics. So I - Yeah, Paul, the cardinal symptoms, right? You gotta have two or three. Yeah. And did he -

They didn't use the CRP testing because that was one of the other things. The gold guidelines actually mentioned that the point of care CRP testing is being looked at to see if you should pull the trigger on antibiotics based on CRP, which so far... that was not used. It was just if you were in the trial, you got yourself some doxycycline. Yeah. It's a shame because, Paul, we want one of these tests that just like, give me these tests. How great would that be, Paul? You get a point of care CRP, get a point of care eosinophils, and then it just tells you what to do.

The Curbsiders (21:32.654) I don't think that's gonna happen. It's probably not gonna happen. That, which I guess raises the other. So there's lots of things. I already told you the sort of the outcome. So let me talk to you about the limitations here and I actually just recap the outcome first if I can. So basically at the end of the day, there were fewer treatment failures in the patients who had eosinophilia, who were treated with steroids than those who had eosinophilia, who were not treated with steroids. And there was no real difference.

if you did not have elevated eosinophils, whether or not you were treated or not. So which is to say the patients who benefited the most from steroid therapy, not surprisingly had elevated eosinophils. So great, good, makes sense. I'm kind of on board, but the limitations I think in this trial were numerous and it was described by an accompanying editorials landmark trial, which I think is a bold statement to say. But first of all, during the study, they actually had a significant randomization error where that affected 60 patients where basically what they found was that,

they were just misallocating treatments to the different treatment groups. And they actually had to sort of stop, take stock, do some cystical finagling. And the trial was initially designed to be a superiority trial. And unfortunately they had to sort of backstep and be like, okay, this is actually, we're gonna have to make this non -inferiority. And they did modified intention to treat. So that's one. We mentioned the Prolonged Antibiotic Course, that's two. The definition of a COPD exacerbation was actually the clinicians in the trial. So this was done at primary care sites, which I think is fantastic.

but the decision to treat was by someone who's like, yep, that person probably needs steroids or not. And I do wonder if that didn't create some kind of unconscious bias towards only treating sicker patients because you knew that you were doing this study. And I, again, this, I don't think this is a bad bias. I don't think it invalidates their findings necessarily, but I do think it kind of skews the results a little bit. And then other stuff, the sort of the antimicrobial therapy, regardless of sort of symptoms or not. And then the, the outcome measurement at 30 days, not really.

Just, which is fine, I think. Actually, I guess I won't comment on one so much. Yeah, I that one was fine. Yeah. The one question I had about that was that, I guess, how it related to the fact that patients could be re -randomized if they had another exacerbation after six weeks. And so part of me wonders whether the fact that after six weeks, if they're having another exacerbation, which I think a good number of these patients were in fact re -randomized.

The Curbsiders (23:48.238) whether or not those patients in fact had somehow failed the therapy that we kind of initially thought they had benefited from. So it just made me a little bit kind of confused and uncertain of whether or not these were truly separate events and independent events when they're being randomized.

Yeah, and I do think the benefits of steroid therapy that we've seen so far are not these like huge mortality reductions. They're not like the lungs don't get magically better. Like it's these short -term outcomes like reductions in hospital stay and people not getting admitted to the hospital, which admittedly was included in part of these outcomes. But I just think empirically, which I know is not the best way to base your judgment to treat, but like the patients that I treat for severe exacerbations feel better within a matter of days and like sort of follow up in 14 days at the minimum. Like I just, I wonder that sort of the role of recall, like if there are some harder outcomes like hospitalizations and death.

which obviously matter. But like, I just, you know, I don't know. I think there's sort of enough that made me scratch my head a little bit. And then also, Matt, as you mentioned, the practicality of having a point of care complete blood count with a differential device and offices to help make this determination also seems like I don't just foresee this changing practice anytime in the next years, really, at this point. I mean, I guess if the technology gets cheaper and it gets widespread enough. I would love a stat diff.

which this is basically what that is. So, yeah, so I'm excited about it. All right. So let's move on because we have a couple more things to talk about. So I wanted to talk about subclinical atrial fibrillation. Paul, do you have a clear concept of what that is in your head? Subclinical AFib? You do. Yeah, I screen all my patients for it. As for recommendations. No, I don't know what that means. I feel like atrial...

Yeah, I had to learn some new vocab. Yes, okay. So I will go through the terminology. So there's two terms that, and we'll just use them interchangeably, but if you're reading the literature, there is atrial high -rate episodes, which are these episodes of high atrial rate that are device detected. So these are people with a pacemaker, defibrillator, some sort of implanted cardiac device that's detecting these high -rate episodes.

The Curbsiders (25:59.694) And those actually have to be adjudicated, meaning someone has to look at them and see if they're AFib or if they're artifact or something else. But a lot of the times they are AFib and these are asymptomatic episodes of AFib. So they are subclinical and they're these often short -lived, but it's pretty common in somebody that has a device. And now with wearables, people are probably presenting with them even if they don't have an implanted device, because you can capture it with your

whatever your smartwatch is. So it's come up that what do we do with this subclinical atrial fibrillation, these atrial high rate events, especially if they're very brief. Less than five minutes, the guidelines, the most recent guidelines from ACC AHA say you don't have to do anything about it, Paul. So less than five minutes, you know, that number, I don't know if that's, have you heard that cited before, but apparently we can just ignore it if it's less than five minutes.

Do you find that reassuring? Yeah, sure. I mean, that's great. And that might stop watch out. So that's good news. Yeah. So of course, the big question is the people that have more than five minutes, what do we do with them? So I guess the best figure I found to sort of think about how to do this is in the ACC AHA. It's figure 12. It's in their 2023 guideline. And basically,

As their burden of subclinical AFib goes up, meaning the more frequently they have it and the longer the duration, um, the more likely you are to recommend anticoagulation. And of course, as their risk factor for stroke goes up, so as their CHADS VAS score gets above, uh, two for men or three for women, you know, that kind of puts you in the higher risk group where it would be reasonable to prescribe anticoagulation like you would for clinical AFib where someone has symptoms or.

It's been actually captured on an EKG. But what I will say is there were two big trials, the NOAA AFNET trial and the ARTESIA trial, which came out in the fall of 2023, looking at people who had between five and 24 hours of subclinical AFib captured on a device. And in one trial, the NOAA AFNET, they gave you doxaban and in ARTESIA, they gave a pixaban. And they were looking at...

The Curbsiders (28:27.182) does this decrease the risk of stroke? And they had slightly different end points, but essentially they were interested in stroke and they were interested in the incidence of bleeding. Any questions so far, comments, concerns? No? Okay. No, I'm just thinking through, in terms of the actual initial capture, I think is interesting. So, let's exclude wearables for a hot second. But in terms of picking this up initially on someone who has some sort of implantable device, I feel like if you have...

a pacer or an ICD in place already, the chances of you having a low ChAS VASC score seems small. You know what I mean? Like you probably have risk factors for cardiovascular disease already. So it's just, it seems like an already at risk patient population. So I'm just trying to sort of wrangle my brain around how I would make, which I guess is why you need more information to decide who to treat and who not to. So this is me just trying to keep up with you Matt. So I mean, the NOAA AFNET and the Artezia trial took people with...

Chad's vast score of at least two or three. So, you know, people that you would consider treating if they had clinical AFib and they followed them out and they, and the NOAA AFNET trial was actually a negative trial. It was stopped early because there was major bleeding as you would expect with edoxaban more so than with placebo, which isn't surprising, but they did not find a reduction in stroke. The artesia trial using a pixaban versus aspirin, it actually did find a reduction in stroke.

It also did find more bleeding with a pixaban, which was expected. And the number needed to treat in that stuff was about 217 in artesia and the number needed to harm was 130. But the point the authors make is that they cut the risk of like disabling stroke like in half. So, you know, it's not super clear even though, because the bleeding is often reversible and they didn't see more intracranial hemorrhage.

or more fatal bleeding necessarily. So it's still a little bit unclear how you would proceed. So any comments on that? Questions? I see Paul is like, Paul, you don't look reassured by any of this. Well, I mean, what do do with that information? Sort of the eternal question. Like, granted, I know this sort of the old saw, well, you can always get more blood, but like that's still, it's still not nothing. So I just don't, yeah, I don't quite know what to do with that necessarily. It does not.

The Curbsiders (30:49.102) It would not leave me anticoagulating with wild abandon is what I would say. Yeah. Okay. Noor, any comments or questions before I get to my final take home? There were a couple secondary end points that I was a little bit surprised seemed to actually favor from a bleeding perspective, a pixivan, even though the sheer number of events was higher with the pixivan. And so that made me a little bit more open to thinking about.

anticoagulation in these patients, but I agree. It feels like you're kind of stuck between a rock and a hard place with from a stroke and bleeding perspective, which I guess is all of AFib. So, yeah, I mean, I think as primary care, we're probably going to be more working with a cardiologist, like, because usually we're not the one interrogating the device. But if patients are coming to us with a wearable or something, and I guess in the future, if we're the one getting that information about

how long or how much AFib they have, and it's between five minutes and 24 hours, then it would kind of be a ball in our court whether or not we did this. But with these subclinical AFib, it does have a lower risk, about 1 % per year of stroke compared to patients with clinical AFib, where they're symptomatic or it's lasting longer.

So the annual risk is 1 % with the subclinical versus something like 3 % annual risk for people with a comparable score and clinical AFib. So the editorialist that was, you know, wrote the editorial accompanying the artesia trial basically said, you know, you're gonna have to just manage bleeding risk, manage the risk for AF—risk factors for AFib. Paul, remember we talked about the pillars, you know, lifestyle and there's—

rate control, rhythm control, all those kind of things, the pillars for managing AFib. But basically, the lifestyle risk factors, us in primary care, is what we can manage to try to minimize the risk of AFib. Because AFib can progress and it does progress from subclinical to clinical and it can progress from paroxysmal to permanent AFib. We've seen that happen in our patients. So it's really gonna be a very individualized decision for the patient, you know. How high is the risk for stroke? How high is the risk for bleeding?

The Curbsiders (33:02.862) how well can you manage their risk factors and deciding with the patient whether or not they want to receive anticoagulation for this subclinical AFib. But not an easy one. I imagine there'll be more risk calculators and risk stratifiers and it'll just become more and more nuanced as more and more data rolls in. It'll also be very interesting to see how the Apple Watch and or other devices that are not actually internal, not like pacemakers or the implantable cardiac monitors.

actually change both the population you're seeing this in, but also like the risk stratification. Yeah. I just got very excited because I realized I have a chance to be that guy and say, well, I really think this is where AI will come in in the future. AI is the future. OK. So moving on to another cancer topic, Nora, from you, genetic testing in breast cancer. I heard there's new recommendations on that.

Amazing. Yeah, and this one will be quick, just as important to highlight since I think actually this will come up in primary care quite a bit. And this follows the episode on breast cancer updates that just came out, I think today, actually. But this is looking at the new American Society of Clinical Oncology and Surgical Oncology expert guidelines and updated recommendations on genetic testing in breast cancer.

And this consensus update was published in the setting of lots of new data on the risk of breast cancer that's stratified by many different genetic mutations that have been discovered over the last 20 years. Also in the setting of new drugs actually that can target some of these and in particular BRCA1 and 2.

And so in the setting of new drugs and new information, as well as a lot of ongoing uncertainty from patients about what tests to get, how many tests to get, when to get them, and what to do with family history, the panel wanted to reissue and reassess what the data showed and to formulate some recommendations. So that's kind of the

The Curbsiders (35:25.386) reason for this guideline update. The guideline update, which was just published in the Journal of Clinical Oncology and was covered by Dr. Alyssa Mancini in Digest 49, made a bunch of different recommendations, and we'll just focus on the top line ones. And the top line number one recommendation was that all patients who are newly diagnosed with breast cancer who are 65 or under,

should be offered BRCA1 and 2 testing. So this is a blanket recommendation based on age, which has not actually been used before across these guidelines. Can I ask a potentially dumb question about this? When someone has a procedure or surgery for breast cancer, do they always test the tumor for BRCA mutations? No. So that's actually not a dumb...

This is talk, this, this recommendation is actually related to germline testing. So inherited testing and not actually looking at the tumor tissue itself, which those mutations that we look for are called somatic mutations. So those are not inherited. Those are just in the tumor, in the tumor cells that opens a whole nother can of worms that we won't get into here and that the guidelines don't address. They, there are.

You can actually test tumors for BRCA1 and 2, but what we're talking about here is actually the inherited BRCA1 and 2 mutations that do actually confer the higher risk of breast cancer in the family tree. Yeah. So -called germline mutations, right? Yeah, exactly. OK. So, Matt, that was actually a great question. Allow me to ask a dumb question, Nora, before you move on. I love it. I just, I do, the wording of the recommendation itself feels a little bit mealy -mouthed to me in terms of offering testing as opposed to patients should be tested. Is there a...

Is this one of those informed decisions? Like, obviously, all decisions are sure to your decision making. But like, what can you sort of get into exactly how strong the recommendation is? Yeah. I mean, I think this is actually one of the stronger recommendations in looking at the other guidelines and other society recommendations that have been published over the last like 10 years. So they all have a lot of slightly ambiguous should be offered, should be counseled, should be risk stratified.

The Curbsiders (37:51.85) language in them. And I think a big part of that is exactly what you were saying, which is that this is a shared decision that doesn't only affect the patient, it affects their kids, it affects their siblings, their parents, and kind of informs a lot more. And so I think historically, a lot of the language has been more like this, the language here. And that's one of the reasons that there hasn't been a blanket age recommendation in general.

with some exceptions that the NCCN did have a lower age blanket recommendation. So this is just expanding to a bigger cohort of just breast cancer patients who are under a certain age. And I believe the guideline also says if I'm seeing a woman, even if she's now 70, but she had breast cancer when she was 55 and she wants to be tested,

you know, she can also be, they also would recommend testing that person, correct? Yeah, and they kind of caveat it even more, as I'm sure you noticed. They say, if it will inform personal or family risk, and they say that with a lot of the other recommendations as well. And the kind of long and short of it, and the reason they don't say that with the newly diagnosed breast cancer patients who are 65 or under is because in fact,

there are some kind of surgical and therapy decisions that actually are informed by the result. And that's because whether or not you're getting a unilateral mastectomy, lumpectomy, or a bilateral mastectomy can be informed by whether or not you have a BRCA one or two mutation. People decide differently based on that. And so it actually is something that they think about in surgical planning. And then also if they have high risk disease,

prior to surgery and or right after surgery, there are actually medications that we, the drugs that target the BRCA mutations that you would give to patients. So - These are the PARP inhibitors? The inhibitors, yeah, exactly. So like Olaparib and Talazaparib, you may hear about them or see -

The Curbsiders (40:07.63) see ads for them. This is the first I really heard of them and I had to look up what they were. I was looking up the mechanism because I was interested, you know, because they were mentioned multiple times in here. Yeah. And that's that's because over the last like five years, we've had some landmark trials that have actually found benefit.

to these agents, not even just in the advanced setting, the metastatic setting, but also in the earlier stage, breast cancer setting. And so I think that's a big part of why the expert panel decided actually we're gonna say all these patients who are under 65 should be tested because it may actually change the medications that they receive. Paul, do you have any worries about the logistics or the practicality of this recommendation as a primary care physician?

people coming in your office asking you to send bracket testing. Yeah, I mean, that's always, that's a low grade terror for me in general, Matt. So yeah, I do think it requires you to know more, which I don't think is necessarily a bad thing, but it does. It'll open avenues to sort of longer complicated conversations, which I don't think is necessarily bad, but it will make life a little bit more challenging. Are you guys actually sending it in clinic? I'm always curious. I don't. I refer to a genetics counselor. Okay.

Fortunately, the past few places I've worked at have had one, so I always just refer to them. Got it. Yeah, and I think that depending on where you live or where you're practicing, there will be more or less resources from that perspective. And so the guidelines also recommend, if you're ever unsure essentially about family history risk or any of this, like what tests to send even.

than refer to a genetics counselor or a genetics provider. But that can be easier said than done. Well, that recommendation terrified me. So I feel better having talked to you about it. I feel like I understand where it's coming from a bit better now. I feel like that type of testing specifically falls squarely in the domain of like, I will not know what to do with the results when they come back. Right. Like you say, Matt, that's where having the counselor there is really, really helpful. I can order this stuff. But that means I'll also be getting the results. And at that point, then all bets are off.

The Curbsiders (42:20.526) Yeah. And the only other thing to mention, which I found really interesting, was that the different panels can test for different things. And so like one test for BRCA1 -2 from 10 years ago was actually testing likely for different variants, different genetic variants than the tests are testing now. They're more inclusive now. And so, and then...

Notably, a lot of the direct -to -consumer tests actually don't include all of the different variants. And so you may only be looking at the variants that were in the Ashkenazi Jew population, as opposed to the many other variants that we now know are actually important. And so I would say using the kind of standard ones that the genetic counselor is recommending is better. Yeah. OK. Well.

We are gonna, Paul, we started with talking about anal cancer. We're gonna end talking about STIs and HPV testing, okay? Because Alyssa Mancini wrote about a home STI kit that is now available. We don't necessarily have to say the brand name here, Paul, but the FDA granted marketing authorization for the first at -home test for chlamydia and gonorrhea.

And it's available over the counter for adult patients. It uses vaginal swabs and urine specimens. And after purchase, you activate the kit online. I actually watched a video about how to do this. They show you how to collect your own urine, mix the sample, and you send it off to a lab. And Paul, what do you think happens if you have a positive result? Great question. I have to imagine, is it like some sort of patient portal you sign up for, and that's how get the result back? Yeah, Paul.

So the initial kit costs something like $149 and the physician consultation, which is available in some, but not all states, I guess some states don't allow telehealth, telemedicine, it's a $39 consultation. The physician will prescribe you antibiotics and you can go pick them up. They can either mail them to you or send them to your local pharmacy. So that's a thing. What do you think, Paul? I mean, I think it's a positive.

The Curbsiders (44:36.91) Right? I think that physicians, clinicians will say in general, do a miserable job talking to patients about their sexual health. And as a result, patients will often feel scared or ashamed. And also, just access in general is an issue. So I think this is something that has public health implications. And the lower the barrier to access to treatment is and diagnosis, the better off we are. I am troubled, as always, by the fact that we live in a capitalist hellscape, but the fact that this may allow someone to get something diagnosed and treated that they may otherwise

has long -term and potentially serious public health implications and also local implications. You know, their partners could get very sick from it. It's a shame that it is necessary, but also I think the fact that it's necessary, just given what the landscape looks like, is a net positive. So I can't get too mad at it. That was a lot of words. Yeah, well, I think the access is definitely the good part of this. The website is very nicely done. It's, you know, slick design and everything. So I imagine someone thought there was...

money in this. I mean, that's the reason. I think that's the motivation for doing it, but it does have a potential to benefit patients. I worry about the cost for a lot people just don't want to spend, you know, you're going to spend close to $200 to get diagnosed and treated for this when if you had insurance, you know, this wouldn't cost you much out of pocket beyond like your insurance premiums and copay, which I guess you could argue is a lot of money if you had it up over the whole year.

They had, there were two different tests. They had like the standard five and they had the, uh, and then an expanded panel. So even though it said it's chlamydia and gonorrhea, when you go to their website, they're also offering like a bunch of other, um, so the standard five is gonorrhea, chlamydia, HIV, syphilis, and trichomonas. And then the complete eight is, includes those five plus bacterial vaginosis, mycoplasma and urea plasma. And.

So it was interesting. The other thing that's on the horizon that's related to this is home testing, like self swab for HPV, which I think would be a really great, um, a really great thing if it does become available. And, uh, I was just looking it up. There's something called the, um, last mile initiative, which is a, it's, it's basically a big study that's kicking off in 2024 and it's going to look at.

The Curbsiders (46:58.798) home like self collected swabs for HPV that can be done at home. And in studies, there's, there's been a bunch of studies of this and it definitely like increases screening by like 50 % in some of the trials. And it seems like it's, it's definitely very doable. So I do think this is something that would, when that is available, I would be really excited about that for patients. Cause it's, it's one of probably people's least favorite doctor's visits and um,

it would really expand the amount of people who can be screened. I will also say just from personal experience that access to care for this is really challenging even in like a city. And I know a number of friends who like, whose PCPs don't actually do PAPs for whatever reason. And yeah, no, I mean, this is, yeah. And so then getting into C gynecology,

It's difficult. So I think this is I'd be curious to know what the clinician consultation is, because the other thing that occurs to me, Matt, is that a diagnosis of bacterial STI in the past six months is an indication of a conversation about PrEP, right? And I wonder if that conversation is happening, or a conversation about post -exposure prophylaxis, or it looks like you can pony up the money for other STI co -testing, but are people going to necessarily do that? So missing a chance to screen for HIV, or have a conversation about...

safer sex practice says like all the kind of stuff that actually happens with an in -person visit that actually has important implications too. Like it's great there linked to the clinician, but I wonder what that visit looks like and how much counseling is actually given as opposed to, you know, take four of these and call me in the morning. So it's from that standpoint, I do think it represents another missed opportunity as well. So again, I, you know, I think getting these treated quickly and effectively is great, but it does miss a lot of opportunities, which may have broader sort of health implications in the patient's lifetime. Yeah. That's why you're America's primary care physician, Paul. You're always thinking about,

You're always thinking about the patient, patients first. So I think we've come to the end of it. I think we've done great work as usual. And unless you two have anything else, I think we should get to an outro.

The Curbsiders (49:11.79) This has been another episode of the Curbsiders, bringing you a little knowledge food for your brain hole. Yummy.

It's about the right energy. I'm a little slow today. We're all doing great. Still hungry for more? Join our Patreon and get all of our episodes ad free plus twice monthly bonus episodes at patreon .com slash Curbsiders. You can find our show notes at thecurbsiders .com and while there's time for a mailing list to get our weekly show notes in your inbox, that includes the excellent digest reference multiple times today, which recaps the latest practice changing articles, guidelines and news and internal medicine.

And we're committed to high value practice changing knowledge. And to do that, we need your feedback. So please email us at askcurbsiders at gmail .com. It really does help a lot when you subscribe, rate, and review us on YouTube, Spotify, or Apple podcasts. A reminder that this and most episodes are available for CME credit through vcuhealth at curbsiders .vcuhealth .org. Wanted to give a special thanks to the writers for our digest team.

for their help with this episode and to our whole Curbsiders team. Our technical production is done by PodPaste, Elizabeth Proto does our social media, Jen Watto runs our Patreon, Krista Chumanchu moderates our Discord, Stuart Brigham composed our theme music, and with all that, until next time, I've been Dr. Matthew Frank Watto. I've been Dr. Nora Toronto. And as always, I mean, Dr. Paul Nelson -Williams, thank you and goodbye.