In this episode, we dive into the complex narrative of electronic cigarettes and their role in smoking cessation. Join Josh and Adam as they review research showing e-cigarettes as safer than traditional cigarettes in terms of chemical exposure while also examining the risks for non-smokers.
We present evidence that nicotine e-cigarettes may outperform traditional nicotine replacement therapies like patches and gums. Supported by sources such as the American Journal of Public Health and Cochrane, we compare e-cigarettes with Chantix (varenicline) for smoking cessation. We highlight clinical outcomes and the under-researched long-term side effects of e-cigarettes.
Engage with us on social media and share your thoughts and suggestions for future episodes. Thank you for joining the Doctor Journal Club podcast!
Learn more and become a member at www.DrJournalClub.com
Check out our complete offerings of NANCEAC-approved Continuing Education Courses.
In this episode, we dive into the complex narrative of electronic cigarettes and their role in smoking cessation. Join Josh and Adam as they review research showing e-cigarettes as safer than traditional cigarettes in terms of chemical exposure while also examining the risks for non-smokers.
We present evidence that nicotine e-cigarettes may outperform traditional nicotine replacement therapies like patches and gums. Supported by sources such as the American Journal of Public Health and Cochrane, we compare e-cigarettes with Chantix (varenicline) for smoking cessation. We highlight clinical outcomes and the under-researched long-term side effects of e-cigarettes.
Engage with us on social media and share your thoughts and suggestions for future episodes. Thank you for joining the Doctor Journal Club podcast!
Learn more and become a member at www.DrJournalClub.com
Check out our complete offerings of NANCEAC-approved Continuing Education Courses.
Welcome to the Dr Journal Club podcast, the show that goes under the hood of evidence-based integrative medicine. We review recent research articles, interview evidence-based medicine thought leaders and discuss the challenges and opportunities of integrating evidence-based and integrative medicine. Continue your learning after the show at www. drjournalclub. com.
Dr. Joshua Goldenberg:Please bear in mind that this is for educational and entertainment purposes o nly. Talk to your doctor before making any medical decisions, changes, etc. Everything we're talking about that's to teach you guys stuff and have fun. We are not your doctors. Also, we would love to answer your specific questions on drjournalclub. com. You can post questions and comments for specific videos, but go ahead and email us directly at josh at drjournalclub. com. That's josh at drjournalclub. com. Send us your listener questions and we will discuss it on our pod. Hello everyone, this is Dr Joshua Goldenberg and Dr Adam Sadowski. Josh and Adam, your buddies for evidence evaluation and critical eval of the medical literature. And today, for God knows what reason, A adam has us reviewing an electronic cigarettes research article. I think this is the second electronic cigarettes research article you had us do. I think we did one a couple years ago.
Dr. Adam Sadowski:So what do you mean? For God knows what reason
Dr. Joshua Goldenberg:Are people still smoking?
Dr. Adam Sadowski:A lot of people still smoke.
Dr. Joshua Goldenberg:People still can't be smoking.
Dr. Adam Sadowski:Yes, J osh, not only are a lot of people still smoking, but the youths, the youths are smoking.
Dr. Joshua Goldenberg:The youths, yeah, the youths.
Dr. Adam Sadowski:These crazy millennials. These dag nabbit.
Dr. Joshua Goldenberg:That can't be a thing.
Dr. Adam Sadowski:These dag nabbit Gen Zersers
Dr. Joshua Goldenberg:They're not smoking. No one's smoking anymore.
Dr. Adam Sadowski:They're smoking e-cigs.
Dr. Joshua Goldenberg:Oh, e-cigs?
Dr. Adam Sadowski:It's like they're like pacifiers. Man, I'm not even joking.
Dr. Joshua Goldenberg:Well, I think the last one we did was on on the potential dangers of e-cigs. I think, for these concerns that people are going to smoke that instead of smoking something else.
Dr. Adam Sadowski:It was a Dr. Journal Club video. People should check it out actually, because a lot of people are kind of like.
Dr. Joshua Goldenberg:Oh, it was pre-pod. It was pre-pod, that's right.
Dr. Adam Sadowski:It was pre-pod. Yeah, yeah, it was pre-pod. I think people should check it out. It was a good video. I liked the article a lot. Basically with that article you know too long didn't read Spark notes of that study was that e-cigs apparently appear to be safer from a quote-unquote toxicity standpoint like regards to chemicals you're exposed to than than cigarettes.
Dr. Joshua Goldenberg:Right.
Dr. Adam Sadowski:I mean we still. They're still new, right. There's still a lot to learn from them.
Dr. Joshua Goldenberg:Right.
Dr. Adam Sadowski:But the data is so clear that cigarettes are not good for you.
Dr. Joshua Goldenberg:Well, but it's like this, interesting. Okay, so it's been years and and, Michele, um, we're going to get you the link so you could put it in the show notes to that Dr Journal Club review. But I kind of remember a discussion about if it's compared to regular cigarettes yeah, safer, but the fear is well, what if people are picking up the habit from doing nothing? That's not good. And then to look at that net, how does that? How does that net out, I guess, across society?
Dr. Adam Sadowski:Yeah, and that the A american academy pediatrics, way back when, did have an article on this as well. Where they come basically? Uh, you know they were looking at at adolescents who had no motivation or, you know, any interest in actually picking up cigarette smoking, and I think it was a cohort study, if I'm not mistaken, cohort or cross-sectional, I think it was cohort and basically what happened was those who were not ever motivated to start smoking cigarettes but did use the e-cigarettes. Again, this is in adolescents who aren't using e-cigarettes for smoking cessation. It's a different topic altogether. There was, I think, a fourfold increased risk in the then going on to actually picking up a smoking habit.
Dr. Joshua Goldenberg:Yeah, so that's interesting that's interesting.
Dr. Adam Sadowski:So you know, if you're not doing it, don't do this, don't start if you're doing it. But if you're smoking cigarettes and the question is, hey, doc, you know, should I? Yeah, because this was this came up all the time of hey, should I go from smoking cigarettes to you know, uh, these vapes and there were so many people who were saying like no, smoking cigarettes is safer, which is the dumbest thing I've ever heard.
Dr. Joshua Goldenberg:What oh, because it's quote, unquote, natural or something like that. Is that the idea?
Dr. Adam Sadowski:I don't know, but I don't know, but it really annoyed me and there's really high-level evidence in Cochrane papers that support the transition from cigarettes to e-cigarettes. Now, granted, ideally you come off of e-cigarettes, but the whole goal is to get people to stop smoking.
Dr. Joshua Goldenberg:It's interesting. Have you ever smoked? No, I smoked for a while. Really, I smoked a while when I was 18. I remember thinking I'm going to be cold. Were you the?
Dr. Adam Sadowski:Marlboro man, did you walk around with a cowboy hat?
Dr. Joshua Goldenberg:I was Marlboro Lights. They were gold or something.
Dr. Adam Sadowski:So they were safer for you.
Dr. Joshua Goldenberg:I remember people having that conversation when I was hanging out with the hippies. They'd be like, well, I only smoke. I can't remember the name of the. There's like a native american brand or something. It's like all natural american spirits, american spirits, and that was the theory. Is that, like that was the healthy cigarette? I'm like you've got to be kidding, you realize. Like we're all lying to ourselves, right? Um, anyway, but so you know what actually got me to quit smoking. I was thinking about this when I was reading the paper. I was like it was so freaking hard, right, like I knew how. First of all I was like why are we doing this? No one smokes anymore. And then I was like, well, it was really kind of hard to quit.
Dr. Adam Sadowski:Like I can see how it would be helpful I think you need to dip back into primary care and get a little dose of reality.
Dr. Joshua Goldenberg:I know that's that's I were going to say that you knew you were going to say that You're going to be like, well, you have to stop dealing with folks with SIBO all the time, and that's all you see, because you're right. I have no sense of what reality is, but anyway, I've got pretty good self-control, but it was impossible to quit. It was so freaking hard and I remember like um, I remember like getting so frustrated with myself and like breaking the cigarettes and throwing them in the trash and then, like you know, not making this up then lighting a trash on fire and having a big old bonfire of cigarettes I should have, because I would go back.
Dr. Joshua Goldenberg:I and I taped them together, adam, like it was. So such a powerful addiction it it's crazy. And the only thing that worked is I did my little hippie trip off to Central America for like I don't know. I think I was gone a half year or something like that and I was on a farm in Costa Rica with no access to anything, miles from the town. You couldn't go and there was no store and I ran out of cigarettes and I couldn't do anything for like a number of weeks and that's how I quit. Right, it was like you physically need to be in a jungle somewhere and have no access to cigarettes, Josh, because apparently that's the level of self control that you have and that I mean that was really telling to me. This is powerful addiction stuff that we're talking about here.
Dr. Adam Sadowski:Yeah, yeah. No, it's very tough. I've, you know, I've worked with people who use pretty intense illicit substances and they, you know, they say that the hardest thing to quit for them was the cigarettes.
Dr. Joshua Goldenberg:That's crazy. I've heard that before, but that's like crazy that anecdotally you've been hearing that as well like poor Josh back in the day, have tried to quit smoking, even did a clinical trial to quit smoking and failed were unsuccessful, and now we're like trying yet again. So these are people who are desperate to stop and they need help, and that was the recruitment goal for this one.
Dr. Adam Sadowski:Yeah, and it's also very clinically relevant because, you know, oftentimes people have tried more than once to try quitting tobacco use, and so this is it's not an unreasonable inclusion criteria or population that we're dealing with, like the main thing is like okay, this is relatively homogenous patient population in that it's people from Finland and that it's people from Finland. The fact that these are people who have tried to quit in the past and failed, and are ready to go again is very much clinically relevant.
Dr. Joshua Goldenberg:I thought so too. I'm trying to remember. The inclusion criteria Was something like 30-pack year history. They had to be moderate or severe level nicotine addiction.
Dr. Adam Sadowski:Yeah, they were smoking on a daily basis and willing to quit, and these are people who were recruited back from 2003 to 2009 in that previous trial and basically, if they were still smoking, were then allowed to come into this trial, and they had to be between the ages of 25 to 75 years of age, smoking daily for longer than 10 years with at least 10 cigarettes per day. There's 20 cigarettes in a pack, so they're smoking at least a half a pack a day.
Introducer:Wow.
Dr. Adam Sadowski:And they had to have been smoking at least a half a pack a day for the past five years and they had to have a carbon monoxide level of 15 parts per million or greater when they were doing exhale like exhale testing. And the reason for that is because the primary outcome was not only self-reported smoking cessation success but also parts per million of the carbon monoxide and basically, if it was like under a certain threshold, then you can say like yes, you have been, you have not been smoking. We can confirm biologically that that what you're saying is truthful.
Dr. Joshua Goldenberg:Yeah, it's always nice to have that objective marker. Um, well, let's, let's zoom back out again. I mean we're we're kind of jumping in a little bit, but we did a pretty decent job. So so that was the. I think we did a good job with the inclusion criteria. So these are, like you said, very clinically relevant population. Um, and then, yeah, yeah, let's talk about the arms. There was some, it was a cool design.
Dr. Adam Sadowski:There is a three-arm trial well, before we get into that.
Dr. Joshua Goldenberg:I mean I I did read the introduction to this just always assume you didn't and move on, but go ahead yeah well.
Dr. Adam Sadowski:I mean again, sometimes I like to read it if it's an interesting topic or something that like, if, if the introduction reads well, I will kind of pay attention to it. Sometimes they're just like way out there and I'm like, okay, this is, this is going somewhere I don't want to get involved with. But basically what they're saying is that you know, they cited previous evidence that there is high certainty evidence that uh, e-cigarettes that contain nicotine are associated with increased conventional cigarette smoking abstinence rates compared with nicotine replacement therapy. So that would be like your nicotine gums, your nicotine lozenges, patches, etc. Etc.
Dr. Joshua Goldenberg:So hold on pause on that, like that's crazy to me. So you've got. Let me just like. Let's just highlight that. First of all, very, very, very few things in medicine have high certainty evidence like that's already very, very rare and that's that's like grade level high. And so nicotine. So these are e-cigarettes with nicotine and they have increased, first of all, your increased absence from cigarettes. So that's even surprising to me, and even more so than nicotine replacement therapy.
Dr. Adam Sadowski:That's great, that's impressive yeah, and the evidence they cited was from the American Journal of Public Health and Cochrane, so not like little tiny trials, but pretty reputable journals, so that's impressive.
Dr. Joshua Goldenberg:Okay, so we know that these e-cigarettes with nicotine are excellent for abstinence from regular cigarette smoking. Okay Deal, keep them going.
Dr. Adam Sadowski:Yep. And then they, you know, continue to say like, hey, there's not a lot of, there's no reported short-term adverse effects with it. But we do know that adverse effect reporting in clinical trials is miserable, and these just haven't been around long enough to develop, you know, a solid database of long-term side effect profile of e-cigarettes. And so what they said was in this study the one that we're going to be podcasting about was basically a 52-week follow-up where they looked at both effectiveness and harms of electronic cigarettes for smoking cessation, compared to varenicline, which is brand name Chantix, in adults who were long-term smokers of conventional cigarettes and for, basically, for people who don't know. Typically, when it comes to medical therapy for smoking cessation, there aren't very many options. You have the nicotine replacement therapy, which can be like gums, lozenges, patches, a combination of those. You have bupropion, which can be used, and then you also have varenicline, which is a brand name Chantix. Chantix is known for causing vivid dreams and there used to be concern.
Dr. Joshua Goldenberg:Oh yeah.
Dr. Adam Sadowski:There used to be concern that it could cause or, you know, induce or result in psychosis, and so it kind of had this like oh. Yeah, For a second there. It had a black box warning.
Dr. Joshua Goldenberg:That's not good.
Dr. Adam Sadowski:But then after the Eagles trial, which actually looked to investigate this, the FDA then subsequently removed that psychosis black box warning. They showed that there was actually no significant increased risk in the development of that with Chantix used compared to placebo. So then they removed that label.
Dr. Joshua Goldenberg:Good background Okay.
Dr. Adam Sadowski:Yeah, so that's just some background information with regards to that
Dr. Joshua Goldenberg:I think this is right. It's a partial ag like nicotinic receptor agonist, right
Dr. Joshua Goldenberg:? Who cares? Well, I think that's the mechanism. Well, well, just with this thought,
Dr. Joshua Goldenberg:who cares? I knew you were gonna say that no, no, but seriously.
Dr. Adam Sadowski:No, no but seriously. Who, who cares?
Dr. Joshua Goldenberg:well, I mean, it kind of makes sense. You sort of like agonize, agonize. You sort of like tickle the nicotine receptor and it's gonna hey, josh, josh cool, are you still smoking? Nobody cares, nobody cares, stop, you know we have people on this pod who care about mechanism of action. Thank you very much. That's the problem. Problem.
Dr. Adam Sadowski:Stop. Yeah, cool we have. We have mechanisms of actions and like we can use that and be nerdy and like, yes, it is important, but clinically I want you to stop smoking.
Dr. Joshua Goldenberg:Okay, that's fair. That's fair especially with like high level evidence, like I don't know what the evidence level is for shantix. But you know, you know it's one thing to say, okay, we've got like this one tiny little trial, like we're hanging our hat too much on or too little on mechanism of action to to explain it. But if it is solid evidence, like yeah, you're right at the end of the day who right, okay, um, okay, and so then basically what they what they did in the prior trials was looking, I'm gonna have all these benchtop scientists come after us.
Dr. Joshua Goldenberg:Yeah, go ahead all right.
Dr. Adam Sadowski:So come after us, give us your again. Come after us give us your, give us your data you don't want to mess with rat people.
Dr. Joshua Goldenberg:Rat people are serious. I mean, let me tell you I don't know about we could take the elijah people, but you know rat scientists, I'm not sure. I'm not sure.
Dr. Adam Sadowski:All right, keep on going as good as, as good as the rat from uh teenage, uh mutant ninja turtles so this has been killing me.
Dr. Joshua Goldenberg:Is that shredder, or there's shredder and there's um? No sure, I thought shredder was the bad dude okay, so that's why I couldn't remember there was a bad dude and a's no.
Dr. Adam Sadowski:I thought Shredder was the bad dude. Okay, so that's why I couldn't remember there was a bad dude and a good dude. Yeah, the good one takes in the Teenage Mutant.
Dr. Joshua Goldenberg:Ninja Turtles Right, but that's not Shredder. It was Shredder, but there was another S name, it wasn't Sadowski. That's what we'll call you, adam the Shredder Sadowski. You, adam the shredder Sadesk. Talk to Adam the shredder Sadesk.
Dr. Adam Sadowski:Okay, we're going on a tangent. We're going on a tangent, okay.
Dr. Joshua Goldenberg:I hit the tangent. Did you like that? Normally we tangent at the beginning. This is an interpod tangent to fool our listeners. Okay, go ahead, keep on going, okay.
Dr. Adam Sadowski:So the primary outcome of that last trial where they recruited these patients from, the primary outcome was seven-day smoking abstinence. So self-reported of hey, I haven't smoked in the past week, which is great. And then they also confirmed it with carbon monoxide on exhalation and that was at the 26-week mark.
Dr. Adam Sadowski:So basically after six months of follow, follow-up so solid, solid outcomes yeah, and then for for this trial, because there was no previous randomized controlled trials that looking at e-cigarettes compared to chantix or varenicline and we don't get any sort of compensation for for saying it. It's just easier to say chantix and that's what most people know it by yeah.
Dr. Adam Sadowski:So we're not, we're not getting uh sponsored by by big chantix here we're not part of the chantix lobby and so what they hypothesized in this trial was that if veroniclean or chantix therapy were to be combined with motivational interviewing, um, then the success rate of smoking cessation would increase compared to nicotine-containing e-cigarettes combined with motivational interviewing. So they're kind of comparing Chantix plus motivational interviewing to e-cigarettes plus motivational interviewing.
Dr. Joshua Goldenberg:Which is standard of like I would imagine you tell me you're the primary care doc, but like that would be standard, right? Like we know, motivational interviewing technique works, I assume, and that's sort of like you add that to whatever other intervention you're doing. So it's not like they were trying to get this thing to win, they were like setting it up as it would be in real life.
Dr. Adam Sadowski:Yeah, yeah, and and again, because they're they're really trying to maximize therapeutic benefit here. So, uh, ideally you're doing motivational interviewing with your patients, but reality sets in and sometimes you can't.
Dr. Joshua Goldenberg:Wait, wait. Did the placebo groups also get the motivational interviewing?
Dr. Adam Sadowski:Yeah, they got.
Dr. Joshua Goldenberg:Oh, they got it too Okay.
Dr. Adam Sadowski:Yep, they got placebo in this trial. They got placebo Chantix, placebo e-cigarettes, plus motivational interviewing.
Dr. Joshua Goldenberg:Okay. So they're maximizing the benefit, but they're not trying to juice the difference of the study, because even the placebo group got maximum potential placebo effects and motivational interviewing.
Dr. Adam Sadowski:Okay, gotcha, I'm with you now yeah, and so and so, to go back to your earlier point, what were the three groups in this trial? You had the e-cigarette group plus placebo, chantix, plus motivational interviewing e-cigarette, placebo, chantix and motivational interviewing. Okay, yep the chantix group had placebo e-cigarette. So that was an e-cigarette without any nicotine content but looked exactly like the actual e-cigarette with nicotine Plus. They got motivational interviewing and then, as we just said, placebo had placebo everything but real motivational interviewing.
Dr. Joshua Goldenberg:Yeah, so like double dummy we would sometimes call that plus motivational interviewing Okay, awesome, I like those, I like those groups Very nice.
Dr. Adam Sadowski:Yes, and the people who were using the e-cigarettes were allowed to to use it out of libidum, which I liked, because basically they said here is your e-cigarette supplies, do what you will with it. Right, because that's how, that's how people are doing it in in real life.
Dr. Joshua Goldenberg:No one's really like oh, you can only smoke two milliliters of liquid, well, and that's also kind of like an intervention in and of itself, right, like sort of like a taper or something like that.
Dr. Adam Sadowski:Yeah, yeah, yeah, and the study design was really cool. I liked it. It was an investigator-initiated, randomized, placebo-controlled, single-center clinical trial. So they're very clear here and I really liked how they reported this. So it's a randomized, placebo-controlled trial. We all know what that is Single-centered, meaning it was only done at one university, and then investigator-initiated, meaning basically these investigators all got together and were like, hey, we should do a trial on this. And they were like, yes, we agree, let's go do it. And it's independent of industry sponsorship, right, it's not an e-cig study, correct? Now, that being said, they did disclose and they were very clear about this that the trial was funded by grand um, which was, uh, which was a um, a grant, and with financial support from pfizer okay however, uh, the funding organization, ie pfizer, had no role in the design conduct, conduct of the study collection, management, analysis, interpretation of the data preparation, review, approval of the manuscript decision to submit.
Dr. Adam Sadowski:So basically they just gave them money and supplies and said, like here you go, like figure it out.
Dr. Joshua Goldenberg:So they so, just to clarify, they make Shantix, so they did have an incentive, but, like you said, they crossed their T's, dotted their I's.
Dr. Adam Sadowski:As far as their involvement, yeah, but also, even though they had an incentive, should the data show that Chantix was terrible and got blown out of the water, that was a risk that they were willing to take.
Dr. Joshua Goldenberg:Yeah, I'm cool with that.
Dr. Adam Sadowski:So for everyone who's kind of like, oh, industry sponsorship is bad, not really like read through the details, not these days.
Dr. Joshua Goldenberg:It's clean. These it's cleaner. These days. You have to be careful. I think supplement industry is still a bit of a mess, but oh, it's terrible.
Dr. Adam Sadowski:Yeah, yeah, um, but they're getting better and then the e-cigarettes were purchased, uh, with the grant.
Dr. Joshua Goldenberg:Okay, uh, so yeah, okay, so cool all right, I'm with you, keep on going so very low risk of bias there for anyone uh paying attention or interested well, let's talk about risk, about super fast.
Dr. Joshua Goldenberg:So, um, everybody was blinded, the only the design said it was good. But just, they did have a mention about masking, and I was just thinking about that. Like it seems, it would seem pretty obvious to me. I would imagine, if you're smoking an e-cigarette and you don't taste the nicotine right Like that, I feel like that would feel different and so everything.
Dr. Adam Sadowski:I thought everything was identical, so in flavor and everything.
Dr. Joshua Goldenberg:Yeah, but you're smoking. You're smoking non-nicotine. I mean it's going to be different. I mean it looks the same, but then you start smoking it. And. But then you start smoking it. And if you're used to nicotine, are you not going to notice that it doesn't taste like nicotine? I don't know, I just feel like.
Dr. Joshua Goldenberg:I've never smoked nicotine, so I don't know Well this is why I bring my deep knowledge base to this pod, these important matters. I feel like it would be obvious. And they do mention the potential risk of unmasking. So it was blinded. But you can always be unmasked, right if, like you just like, wait, this is, there's no way, this is nicotine or like we've talked about. If you you're blinded and then you start having lavender flavored burps, you're like there's no way, this isn't the lavender pills. But what they noted is that there was no difference in dropout rates and so they were kind of using that as a proxy, like if you, uh, if you felt like, okay, I was getting the placebo cigarette, maybe you would drop out more, right?
Dr. Joshua Goldenberg:so I don't know well that that was something that they brought up but they didn't seem too concerned about just because you know they they didn't see unequal dropout, I guess yeah, I feel like it's a bit of a reach too yeah, I'm, I'm all right with it, I'm totally right, and it's also more realistic, right, right, because I mean, this is designed to show efficacy, not effectiveness, but in real life, like you're going to know if you're having an e-cigarette without nicotine.
Introducer:Okay.
Dr. Joshua Goldenberg:Look, the thing is we don't do this for money. This is pro bono and, quite honestly, the mothership kind of ekes it out every month or so, right, so we do this because we care about this, we think it's important, we think that integrating evidence-based medicine and integrative medicine is essential and there just aren't other resources out there the moment. We find something that does it better, we'll probably drop it. We're busy folks, but right now this is what's out there. Unfortunately, that's it, and so we're going to keep on fighting that good fight. And if you believe in that, if you believe in intellectual honesty in the profession, in integrative medicine and being an integrative provider and bringing that into the integrative space, please help us, and you can help us by becoming a member on Dr Journal Club. If you're in need of continuing education credits, take our NANSEAC-approved courses. We have ethics courses, pharmacy courses, general courses. Interact with us on social media, listen to the podcast, rate our podcast, tell your friends.
Dr. Adam Sadowski:These are all ways that you can sort of help support the cause. And so, yeah, they randomized the participants with computer-generated randomization scheme. Everyone was one-to-one-to-one. And then participants, nurses making personal contact, people providing the motivational interviewing, and then the researchers assessing the outcomes and analyzing the data were all masked, meaning they were blinded. And then an external statistician from a different university did the uh randomization scheme.
Dr. Joshua Goldenberg:So super clean all good, very kosher, yeah, very clean what exactly do they do?
Dr. Adam Sadowski:each, each group went through 12-week intervention, which makes sense because chantix is uh prescribed for a 12-week course.
Dr. Joshua Goldenberg:Oh, okay, yeah, and then um in observation period of up to 52 weeks, so for a 12-week course.
Dr. Adam Sadowski:Oh, okay, yep. And then an observation period of up to 52 weeks, so for a year.
Dr. Joshua Goldenberg:Really nice, really nice.
Dr. Adam Sadowski:Yeah, and then the primary outcome was essentially assessed at the six-month mark and then the secondary outcome was assessed at the one-year mark. When it came to motivational interviewing, it was eight sessions of individualized counseling for 30 minutes.
Dr. Joshua Goldenberg:Seems reasonable to me. Yeah, and it's balanced across groups anyway.
Dr. Adam Sadowski:Yep. And then with that primary outcome, it was seven-day abstinence that was self-reported and confirmed via exhaled carbon monoxide levels of less than 10 parts per million. And then they basically did the same thing at the 52 week mark.
Dr. Joshua Goldenberg:Oh, and that helps us with unmasking. If it was unmasked and that influence? Well, let me think this through for a second. It's an objective outcome. So well, I guess it would be like if you're lying about, yeah, never mind, keep on going, we're still good, we're still good.
Dr. Adam Sadowski:Yeah, and then secondary outcomes were viewed as exploratory. So really it's mostly about the primary outcome at the six-month mark, not the 52-week mark.
Dr. Joshua Goldenberg:But it's nice that they have that follow-up yeah.
Dr. Adam Sadowski:Yep, and then everyone was randomized to the group they were assigned in. So the intention to treat protocol, which we love to see, and then that was really it from a method standpoint.
Dr. Joshua Goldenberg:I really like the way that this study was conducted and reported. Yeah, one thing I wanted to add which makes it even better is so it's one thing to say like intention to treat principle like what does that mean for the people that actually are missing outcome? Like intention to treat principle like what does that mean for the people that actually are missing outcome? So for losses to follow up, they assume they kept on smoking, which is great. So they basically had a worst case assumption about missing outcome data or loss to follow up, which is a very conservative way to do it, as opposed to multiple imputation or coming up with all sorts of different sensitivity analyses, which is what we usually do. They actually just assumed the worst and if they were missing the outcome, they just as missing the fallout. They just assumed they were still smoking. So very good. So any difference that you would see would be a conservative difference there, yep.
Dr. Adam Sadowski:Okay, do you want to jump over to what the baseline, like demographics were of the trial?
Dr. Joshua Goldenberg:Yeah, let's do some baseline stuff briefly and then let's jump into the results. So, baseline we've got a pretty even split between male and female, more female than male.
Dr. Adam Sadowski:Nominally yeah, nominally more female than male, which I thought was really interesting, surprising, right.
Dr. Joshua Goldenberg:You would think the opposite, or maybe not, I don't know. By about 10%. Yeah, 55% versus 45%, mm-hmm mm-hmm.
Dr. Adam Sadowski:Yep right, you don't. You would think the opposite, or maybe not. I don't know by about 10.
Dr. Joshua Goldenberg:Yeah, 55 versus 45 yep, so um, mostly female, but not like crazy skew. Average age about 50 years of age. Average bmi 26, 27, 28, so you know overweight. And average years of smoking 3334 years of smoking. So balance, that's a lot, that's a lot.
Dr. Adam Sadowski:That's a really hard group to to then get smoking. Cessation with.
Dr. Joshua Goldenberg:That's right, 30. Yeah, let's just take a second there. That's three decades of smoking. That's a strong addiction and, like you pointed out earlier, they've tried multiple times to quit. They've even been involved in clinical trials to quit before and failed. So they're very motivated. They're showing up again to quit.
Dr. Adam Sadowski:Yep. And then about 64% have smoked at least half a pack, so 11 to 20 cigarettes per day. And then about a third, 30% or so, smoked even more than the pack, so about a pack and a half, 21 to 30 cigarettes. And then you have some who are smoking even more than that, and that was about four to five percent of people smoked at least 30 cigarettes per day yeah, okay, good, so that's our population.
Dr. Joshua Goldenberg:Um, like you said, a said only maybe concerned with homogeny because it's all from Finland, but still it's a really good trial and I like the population, it seems very appropriate for primary care. Good, okay, I think the only other thing I want to mention about that was the use of what they call snus. That's like snuff, that's like chewing tobacco. Okay, okay, that's what I thought. I had to Google it because I was like, is that different than the little pouches? So it is the little pouches, and I think that's so relevant because essentially, like, they have this objective marker of carbon dioxide level, but if you're getting your nicotine another way, you could basically be making up for it, and your nicotine another way, you could basically be making up for it, and, and it would appear as if you had quit, when still you're just as addicted to nicotine. So I thought it was great that they were so cautious about that and it did not seem to influence results one way or another.
Dr. Adam Sadowski:Yeah, and the Gen Zers love to use what's called Zyn pouches Z-Y-N.
Dr. Joshua Goldenberg:Oh, is that a? Thing?
Dr. Adam Sadowski:It's, it's just nicotine pouches. They seem to be pretty addictive, yeah.
Dr. Joshua Goldenberg:So that's a thing that's so interesting. I was like Josh, you're so out of touch, I know, doesn't it cause like holes in your gums or something like that? I just remember. Anyway, the whole thing's not good. Don't start smoking, okay. So let's, can we talk about results? Can we jump into results yet? Yeah, okay, cool. So here we go.
Dr. Joshua Goldenberg:So the main outcome here. So we're talking about confirmed abstinence at six months. So the e-cigarette group we have so this is like true nicotine e-cigarettes with placebo, shantix and the motivational interviewing 40.4% were abstinent at six months. That's remarkable. I would think 40% of this tough population is abstinent at six months. That's outstanding.
Dr. Joshua Goldenberg:The Shantix group was 43.8, so a little bit higher, also outstanding. And the placebo group was 19.7. So one in five people on just well, it's say just placebo. Remember they had motivational interviewing as well. 20% of them essentially quit, which is amazing at six months. And then you had double that essentially with the e-cigs with nicotine or the shantix, which is pretty cool. There was a statistically significant difference, clearly, with those numbers, between the Shantix, which is pretty cool. There was a statistically significant difference clearly with those numbers between the E-SIGs versus placebo and the Shantix versus placebo, but not between Shantix and E-SIGs. The difference was too close. So we can't say statistically that even though Shantix nominally had a higher abstinence rate, that may just kind of be random error when compared to e-cigs, but both seem to be very effective versus placebo or motivational interviewing alone.
Dr. Adam Sadowski:Yeah, you might even argue that this is a negative trial for Pfizer.
Dr. Joshua Goldenberg:Why.
Dr. Adam Sadowski:In the sense that, you know, e-cigarettes may be as effective as Chantix.
Dr. Joshua Goldenberg:Oh, that's true. Yeah, so not only better but right. Maybe statistically the same as e-cigs. That's right, but definitely reinforces this idea that it doubles the response rate versus placebo. Yeah, good point, okay.
Dr. Adam Sadowski:But it's really important because I mean it's important clinically, because now it's like, hey, here's a fourth option that we can consider.
Dr. Joshua Goldenberg:Yes, yeah, that's right, that's right. Love that. Okay, what else did I want to say? I think that's it for the six-month outcome. Should we talk about the one year?
Dr. Adam Sadowski:Yeah, let's talk about the one year which remember was a secondary outcome and viewed as exploratory and it was a little bit upsetting. Yeah, 50% reduction, like a I don't know 30% reduction in the number of people from the six-month mark who were abstinent at 52. So remember, confirmed abstinence was biological, in addition to self-report. And at the 52-week mark we have 28% in the nicotine electronic cigarette group versus 38% in the Chantix, versus 20% in the placebo. So placebo basically went unchanged. The Chantix group dropped off from 44% to 38%, rounding up, and then the nicotine group dropped off from 40% to 28%, yeah, so, so Chantix did a little bit better.
Dr. Joshua Goldenberg:Yeah, and was statistically significant still at one year, whereas e-cigs were not.
Introducer:Yeah.
Dr. Joshua Goldenberg:Barely Interesting one year, whereas e-cigs were not, yeah, barely interesting. Um, so we have the at six months. They're about equivalent, both double the placebo response and at one year. Uh, we see that, yeah, the shantix has held most of the benefits, still statistically significant, whereas the e-cigs have dropped no longer statistically significant when compared to placebo I love how they reported the absolute um change in the difference too.
Dr. Adam Sadowski:Uh, within on the bottom of table two. Yeah, so yeah at at the um at the self-reported and confirmed abstinence. When you look at the confidence intervals for the e-cigarettes, it went from negative one to 18%. So so no difference there. And then for the Chantix group it was 8.4, let's say 8%. Let's round up 8% to 28% was the 95% confidence interval there. So that remains statistically significant. And then placebo was also minus 1% to 20%. So across that threshold of no significance.
Dr. Joshua Goldenberg:Yes, and the other interesting thing, just about the snuff or zing or zang or whatever you call it even when you look at that at one year, the results are analogous where it's barely not statistically significant with e-cigs, still statistically significant for shantix, and then the difference between the two is not statistically significant at the one year mark. Now, remember, it's the six month mark. E-cigs are still doing well, but yeah, they kind of lose there. Um, e-cigs are still doing well, but yeah, they kind of lose their. It's interesting that the e-cigs would lose their benefits, some of their benefits, at one year, whereas shantix would not, because if it's just a 12 week, were they taking shantix all the way through or just for those 12 weeks?
Dr. Adam Sadowski:just for those 12 weeks is my understanding interesting, very interesting now, perhaps this is where the the, the bench scientists come out from their gremlin hole and start talking to me about. This is why mechanism of action matters. It's because perhaps there's something here that would explain that, perhaps, but again, I don't care.
Dr. Joshua Goldenberg:Oh, man Beautiful. I thought it was a very clear study.
Dr. Adam Sadowski:I don't think Wait, we're not done, we're not done, yeah Well what else was there to talk about?
Dr. Joshua Goldenberg:Side effects? Adverse effects? Yes, no adverse effects, no adverse effects. I guess that's something to talk about. Some people died, not many. Oh my God.
Dr. Adam Sadowski:Oh, dear listener, when, when you receive, when we see josh in in the uh lawsuit and they say they say, dr goldenberg, you have killed some patients, and dr goldenberg's response will be yeah, but not many it's all about the absolute effects here it's not statistically significant. Your honor yeah yeah, your honor. It was a non-statistically significant increased number of participants who died under mike air well, that's essentially what happened here.
Dr. Adam Sadowski:Um, we see a couple people die, each group, yeah four people died in total two in the isa group, two in the placebo. Neither were related to intervention. There were really no significant side effects. Uh, for all of these, with the exception of chantix, had nausea. That was statistically significant and that was basically it.
Dr. Joshua Goldenberg:Well, so one other thing. I didn't catch this before. Look at the part. So we're in table three listeners Adverse events leading to discontinuation of a study treatment. The Shantix group was double the amount in the e-cig or placebo. That's interesting.
Dr. Adam Sadowski:But they also had higher success success rates overall, which was also interesting which is also interesting. So you're explaining that bench scientist so you're.
Dr. Joshua Goldenberg:You're more likely to get side effects significant enough that you would stop your treatment if you're taking shantix, but overall you are still more likely to benefit, particularly at one year and just as likely at six months. Interesting, Okay. So we might expect higher side effect rates with the shantix. That's useful information. Whereas the e-cig. I mean I'm not surprised that the e-cig is the same as placebo. I mean, they've been smoking cigarettes and now they're just smoking electronic cigarettes. Like I would be surprised if there was much of a difference. I mean, maybe you get shocked by this e-cigarette.
Dr. Adam Sadowski:I don't know if that's a thing, but, um, probably not well, there was, there were e-valley concerns, um, uh, so I forget what e-valley totally stands for, but it's like e-valley yeah, it's like e-cigarette vaping associated lung injury, something like that. Oh, um these were early concerns back when e-cigarettes firsting associated lung injury, something like that. Oh um, these were early concerns back when e-cigarettes first came to market and a lot of it had to do with with people tampering with um, the combustible oh and so a lot of people were getting like into like icu admits for um pretty severe pulmonary injury from the e-cigarette tampering.
Dr. Joshua Goldenberg:Okay, so that would be a good thing to look here. We're not seeing an increase with these. Okay, beautiful, what else? Anything else you want to talk about?
Dr. Adam Sadowski:I thought discussion was interesting. I kind of agreed with them that they showed that they said not only was Chantix helpful but so was the e-cigarettes at six months. And then they just kind of talked about the lack of evidence that kind of exists looking at e-cigarettes and whatnot, but that kind of they're off to a good start with this. You know what's available right now and the direction that the research is heading in.
Dr. Joshua Goldenberg:Yeah, you know it's interesting in actually looking at the data versus what they said. I'm actually more impressed with Shantix the second time through here because of the one year mark. But it's funny because, like, apparently Pfizer gave them a bunch of funding but you don't get that sense from reading their article. They just make them seem like they're equivalent, which is interesting. So clearly they didn't have an overly impressive influence on the on the authors, if anything. It seems the opposite. They kind of downplay the Shantix benefits. Interesting, okay, cool, I like it.
Dr. Joshua Goldenberg:Now, just to reinforce the big debate, I think, is what is the population that you're giving e-cigs to right? Like if you're giving it, like you said in that first study you were talking about, where people that had no initial interest and they're young and now they're going to start smoking, whatever, it's not good compared to nothing. But if they're like hardcore smokers for 30 years and have tried everything to quit, like yeah, it's kind of an obvious no-brainer, so it really does matter. Like it seems like these this debate gets at least a couple years ago it was like a big debate like is are these e-cig things brilliant or harmful?
Dr. Adam Sadowski:and horrible and it really depends on the population, I think is the take-home context. Yeah, context matters a lot context matters.
Dr. Joshua Goldenberg:Yeah, yep, yep, yep. So if you're in finland and you've been smoking for 30 years and you've tried a bunch of other stuff, you might try e-cigs or shantix and you might double your chance of abstinence, which is super cool. All right, I like that little study it was. It was not that little, it's about 500 people, 150 in each group. Um, nice job, adam. Thanks for recommending that one.
Dr. Adam Sadowski:Any last minute words of wisdom to our listeners, sir well, yeah, although it was a small study, given Small study, 500 people Relative to other studies that are large, right, it was a long-term. It was relatively long-term a year.
Dr. Joshua Goldenberg:Yeah, year outcomes.
Dr. Adam Sadowski:Very well conducted.
Dr. Joshua Goldenberg:Yep Agreed.
Dr. Adam Sadowski:Seems like we've now got two high-level evidence papers.
Introducer:Mm-hmm.
Dr. Adam Sadowski:Do we need another study?
Dr. Joshua Goldenberg:I mean, I don't think so.
Dr. Adam Sadowski:If we did it, you know, if we repeated it in, let's say, a different patient population, even if it was like a homogenous patient population. Let's say, like in Australia, right. Or let's say we did another one in the States.
Introducer:Mm-hmm.
Dr. Adam Sadowski:And we get the same results, would you? Would you be like, hey, I think we're done here, or would you want to continue beating this like crazy, like a vitamin d trial?
Dr. Joshua Goldenberg:I mean I don't even know that they needed this one. So they had high level evidence for what they had high certainty evidence that nicotine containing e-cigarettes are associated with an improved smoking abstinence. So I mean they already had before this was even done. There was high level grade evidence that you're going to increase your abstinence with e-cigarettes compared to nicotine replacement therapy. So so the debate is okay. Well, what about compared to Shantix, which is not nicotine replacement? But I guess, like for the point of, should you try e-cigs? They already have that data. Like grade high by definition, literally means that any future study is extremely unlikely to change the overall result.
Dr. Adam Sadowski:And it's really cool. It's cool to see that confirmed here.
Dr. Joshua Goldenberg:Yeah.
Dr. Adam Sadowski:Hey, yeah.
Dr. Joshua Goldenberg:That's true, I think that's cool.
Dr. Adam Sadowski:Yeah that's the idea, because you, you read about that. Yeah, that's the idea of like, hey, if it's high level of evidence, really nothing should change. But you always wonder, but I haven't seen. Yeah, you always wonder and like I haven't yeah I haven't really seen like, okay, like they say it's high level, but we're gonna do another trial and then confirming that like I just haven't stumbled upon it, whereas this was like, hey, there's high level of evidence, we're going to repeat it. And yeah, we found the same thing.
Dr. Joshua Goldenberg:Yeah, it is interesting, like when they were setting up the rationale in the introduction. You know, when you already have high level evidence of something, it's like, well, what's your rationale? And their spin was in the like having this additional arm for shantix. But yeah, as far as actual e-cigs, yeah, it's already there. And to your point like I think we don't see that a lot because a in theory, you shouldn't be running extra trials and wasting resources if you already know it's high level evidence. But also very few things are high level evidence right, Like we've done some papers like that. I can't remember what the percentage is, but it's in the low single digits, isn't it? Like things that are effective and high level evidence in medicine.
Dr. Adam Sadowski:Probably. We're probably like 4% best.
Dr. Joshua Goldenberg:Yeah right, it was something. I remember that somewhere between four and seven, I can't remember, but like absurdly low. And so this is one of those rare things where e-cigs apparently are in that fancy group of high level evidence and efficacious. So I am impressed, but don't start if you're a little kid who has no interest in starting to smoke, only if you're finished and have 30 years of smoking. E-cigs and viagra, well, what's the what's the evidence on viagra?
Dr. Adam Sadowski:it's high level the number needed to treat is like two is it so?
Dr. Joshua Goldenberg:yeah, okay, that's interesting and it's uh, and the evidence level is high.
Dr. Adam Sadowski:It works for yeah okay, interesting, all right I I'm assuming, I I'm pretty sure it is you're assuming I'm assuming they have a good, they have a good lobby apparently.
Dr. Joshua Goldenberg:Um, it's interesting. I, I, I would love to see a list of the stuff, of the interventions that are high level and efficacious. At high level, efficacious and a large effect size, like here we we double the, the response rate, right, like I would love. That's got to be a rarefied list. It's like it's like three items cigarettes and viagra. What's the third? I wonder what the semaglutide glp1 oh it would?
Dr. Adam Sadowski:it would probably be suboxone am I is?
Dr. Joshua Goldenberg:is the evidence? Is the level of evidence high for suboxone?
Dr. Adam Sadowski:don't quote me on that, I don't. I I'm going to assume. Yes, I know the number needed to treat is very low with suboxone oh, that's interesting but it's likely high level of evidence. Huh, very curious. I'm assuming. Don't quote me, it's not medical advice, don't? I don't know.
Dr. Joshua Goldenberg:I'm telling you outwardly I do not know if you're a listener, and, oh, you know what. There's another one. Um, mark's always talking about it. It's probiotics for Ulcerative colitis, some, no, not even for some pediatric oh my God, necrotizing something or other. I think that has high level evidence. Mark's always like it's one of the few things that has high level evidence, and it's true. Okay, so we got Viagra, probiotics in that one pediatric population and e-cigs. And then, listeners, if you've got any others, please send it our way.
Dr. Joshua Goldenberg:That would be cool to kind of make a list and maybe do a series of papers where we talk about the things that actually work, since we're always fetching about the things that don't work and how most things don't. So it might be a nice little tweak. Yeah, little tweak. Yeah, our two episode series, things that work in medicine. We've already covered them, right? Yeah, all right. Well, uh, we're not jaded, okay. Well, talk to you later listeners. Thank you, adam, good paper at the end of all my complaining. Um, it was a good paper and it was interesting to know that we have high level evidence for that. So cool man. Yeah, step back into primary care and never.
Dr. Adam Sadowski:The world is your oyster.
Dr. Joshua Goldenberg:All right, talk to y'all later. Bye, if you enjoy this podcast, chances are that one of your colleagues and friends probably would as well. Please do us a favor and let them know about the podcast and, if you have a little bit of extra time, even just a few seconds, if you could rate us and review us on Apple Podcast or any other distributor. It would be greatly appreciated. It would mean a lot to us and help get the word out to other people that would really enjoy our content. Thank you, hey y'all. This is Josh.
Dr. Joshua Goldenberg:You know we talked about some really interesting stuff today. I think one of the things we're going to do that's relevant. There is a course we have on Dr Journal Club called the EBM Boot Camp. That's really meant for clinicians, to sort of help them understand how to critically evaluate the literature, etc, etc. Some of the things that we've been talking about today. Go ahead and check out the show notes link. We're going to link to it directly. I think it might be of interest.
Dr. Joshua Goldenberg:Don't forget to follow us on social and interact with us on social media at Dr Journal ClubClub DRJournalClub on Twitter. We're on Facebook, we're on LinkedIn, etc. Etc. So please reach out to us. We always love to talk to our fans and our listeners. If you have any specific questions you'd like to ask us about research, evidence, being a clinician, etc. Don't hesitate to ask. And then, of course, if you have any topics that you'd like us to cover on the pod, please let us know as well. And, of course, if you have any topics that you'd like us to cover on the pod, please let us know as well.
Introducer:Thank you for listening to the Doctor Journal Club podcast, the show that goes under the hood of evidence-based integrative medicine. We review recent research articles, interview evidence-based medicine thought leaders and discuss the challenges and opportunities of integrating evidence-based and integrative medicine. Be sure to visit www. d wwwdoctorjournalclubcom to learn more.