Litfulo Lowdown: When to Wave Goodbye; Olumiant Showdown: Solo vs. Squad; Solar Shocker: More Sun Equals Less Death?

[ Silence ] [ Music ] >> Welcome to "Derms on Drugs." A new video podcast brought to you by Scholars in Medicine. "Derms on Drugs" is where cutting-edge dirt meets mediocre company. I'm Matt Zyras, nowadays a private practice dermatologist in Columbus, Ohio. And each week I'm joined by my residency buddies, Laura Ferris, who is now the chairwoman of dermatology at the University of North Carolina, and Tim Patton, who is faculty at the University of Pittsburgh, to use our 60 years of combined experience to discuss, debate, and dissect the hottest topics in dermatology. It's everything you need to know to be on the cutting edge of dermatology and it'll be the most fun you've ever had while actually learning something useful about dermatology. So tune in every Friday only at Scholars in Medicine. And with that said, we're going to jump into the first segment of our show. So as you may know, we break our show down into the big three, where we talk about our three favorite articles of the week, then we go into our deep dive, and I could not be more excited to have somebody on who is going to hopefully make you have thoughts that you have never had before about the topic of ultraviolet light and its health impact. And then we're going to talk about a few more articles after that. So let's go ahead and get into it, Laura. I believe you've got our first article today. So go ahead and jump in. All right. So I am going to be talking about a publication that was in JAD, sustained hair growth with continued writless, sitting in through week 48 for patients with alopecia area. So this is a post-talk analysis of the Allegro phase two, be three trials. So what did this show? So, you know, the first thing it showed was sort of what you might expect, which is that most people who are responders at week 24 still respond at week 48. So, you know, important to show, but I thought not the most interesting part of this study. I thought that the most interesting part was looking at what happens to people who are not responders at week 24. And if you continue them on drug, what happens at week 48? So they if we if we define non responder as patients who do not achieve a salt score of 20 or less. So salt score, meaning the, you know, extent of your hair loss. So if they didn't reach only 20% hair loss, those were considered non responders. So first of all, who were these people? So you're less likely to be a responder if you're male. If you've got more extensive AA at the start meeting, either you had a higher salt score, like maybe a salt 100, you had complete hair loss. Or if you had alopecia totalis or universalis, universalis, longer duration of disease, and also if you had more eyebrow and eyelash loss. And so, you know, what we can see is that basically a quarter to a third of non responders at week 24 actually did respond if you went out to week 48. And we also saw, you know, better eyebrow and eyelash regrowth to from week 24 out to week 48. So, you know, can you determine who these people are going to be? Should you just say anybody should just go to week 48? It turns out that if you really saw like almost no hair regrowth at week 24, you were going to miraculously see a great response at week 48. So, you know, in general, you're looking for those people who may have, you know, 40, 50% of regrowth, but they haven't reached that salt 20. So, those are the people. So, I thought this was helpful guidance. I think it's also helpful in terms of counseling patients. What do you guys think? So, I thought that it was super useful to know that if you've had nothing at six months, it's basically probably trying time to switch up and try a different agent or do something else. And the other thing that's just fascinating about alopecia are yada is what a strong correlation there is between severity of disease and duration of disease and response to therapy and how that's kind of different from other diseases and derm that I don't think of it as being. Oh, you've got 50% BSA of psoriasis. So, you're less likely to do well or you've had psoriasis since you were 30 and you didn't get it till you were 70. Like it's been interesting, but that that six month cutoff I found super useful. Yeah, except those curves were they were still going down right I mean we don't have any other options right. But it's a better situation. Well, it's so fun, but I think you know they're comfortable. Jack and him that are very close to the jack mecker whatever they are they're classifying or listening to. I think the patient was tolerating it and they you know they probably maybe have a little bit of peach fuzz. I think I would probably keep them on it right. I mean we've seen this with the jack inhibitors and alopecia are yada. It takes forever. I'm going to give you the two secrets iris hacks for alopecia are yada and these are relatively relatively literature based. There was one study of eight people with alopecia universalis and totalis who they started all eight on prednisone along with berry. Taper the prednisone over three months and all eight re grew and then maintained and then there's also some good data looking at 18 and a you using the month using clobatus all under a swim cap until you start to get regrowth. So now my because I didn't want to do either of those at the start, but now my spiel is if it's six months you're not getting better. I'll add three months of prednisone or I'll try the clobatus all under occlusion. Yes, sure that makes sense and I've gone under you know topical immunotherapy adding that to jacks that seems like because they're anti inflammatory maybe you would make that less effective. I don't know. All right, let's go on. If there's anything anyone to finish on that one. No, all right. Matt and let's go on or next one. All right, big three paper in the January jam a during my son of shawl at all titled combination of bear sitting in photo therapy and adults with active little ego randomized clinical trial. Study was conducted in four hospitals in France consisted of 49 patients with active non segmental bit of Lago that did seem to be important. The patients either had to have new or expanding patches of the Lago within six months. Okay. They also had that we've 5% bodice body surface area and the presence of hypokromic aspect or perifilicular like they really kind of selected these for like. Terror. These are active. Yeah, active active Vidal. 12 patients took placebo for 12 weeks 37 patients took Barry for milligrams for 12 weeks and then both groups got into narrow ban. Did they they have narrow been the first 12 weeks also. No. So first 12 weeks were just placebo or drug. Then at 12 weeks everybody started narrow band. Right. And they continue to take either placebo or the bear said. All right. So the figure. The figure two shows improvement in the mean vassie in both groups. It's better in the Barry. So mean of, you know, 44.8% improvement in the Vasi mean Vasi compared to 9.2 and the placebo. This was, you know, measured at weeks 30 week 36. And supplementary material. There were some clinical photos showing improvements and these were like obviously cherry picked by Eli Lilly. But you know, basically the person who got the placebo plus light her her. Her. Her. This was a face Vasi got worse. The other two had pretty decent responses. I thought it was interesting that the bottom picture you could see the effect that goggles have on eyelid repigmentation. You never occurred to me it was the goggles. I'm assuming that they didn't specifically I was looking for protocol has to be. Yeah. Figure three top three graphs, just different measures they had. Vasi 50, Vasi 75, face Vasi 90, all of which better in the Barry group. And then figure three D shows D L Q I which is about the same at 12 weeks. So that's kind of funny Barry and and placebo. They both had slight improvements. And then you started to see a little bit of separation. It looks like 24 36. It was a good separation. But the text says it was only statistically significant at week 24. Interestingly, the other quality of life measures didn't show any difference between the groups. And then I think the one of the big things they kind of brush by in the text because they're like adverse events was about the same. But one of the subjects in the Barry group had a pulmonary embolus. Okay. So my. Systemic Jacks taking on a little I go here in the US someday. So I just started doing the Ritlis it in a trial for this. It is slow so I'm not surprised nothing happened in the first 12 weeks in the Barry right that their quality of life didn't get any better. I was mostly shocked by how loud the narrow band UVB worked on its own. That 24 weeks. I was right weeks. So but but what you said of them selecting parry people with parifelicular people with some lucotricia. That makes more sense. Yes, that was their theory was Barry's gonna stop the active disease from progressing, then you hit them with a narrow band, that's going to allow the repigmentation and things like that that we usually see. Yeah, and it makes sense to put together something to stop the immune attack and then something else to stimulate the melanocytes. Ferris, where are your thoughts? Anything? Yeah, I thought it was interesting. I have not done obviously, well, maybe not obviously systemic jack inhibitors, Fervid, I've done topical. I have found that they work better if I do it together with either exomer or narrow bands. So it kind of supports that. I think to me, the question will be, when do we go to a systemic jack versus a topical? Yeah. Putting it together with UV, UVB makes sense. Just that of an interesting thought. It makes a lot of sense. I'm doing now for my primary treatment for facial bit of LIGO, Opsilura, and then I'm using topical Bimatoprost together with it, because you can get the little generic bottles of Bimatoprost Idrops, like really cheap, and so for three months, to stimulate your melanocytes with that in addition. Let's move on to our final big three article. This one, our first two, we're really looking at therapeutic interventions and how to use them most effectively. This one is totally different, and I'm so excited to go into this with our deep dive guest who is one of the authors and who's driving all this work. So a higher ultraviolet light exposure is associated with lower mortality. An analysis of data from the UK Biobank cohort study. Essentially, the biobank is, to my understanding, about 500,000 people that they've drawn blood, have genetic sequencing, if they need it, all of these health questionnaires, they know their social determinants of health. They are a very well categorized group, and it makes it incredibly powerful, because then you can really match people very well based on other potential confounders and hopefully rule them out. So that is what they did in the study. So they compared people, either people who said they used a sunbed, a sun went tanning, and then followed them over, I think it was about six years on average, and they also looked at the average UV radiation where you live based on sunlight. So using satellite data and that kind of stuff. And they showed a pretty dramatic reduction in all cause mortality with either tanning bed use or living in areas that have more sun. And it was kind of a linear relationship. There's tanning bed use. We didn't have data on how much they used the tanning beds, but with the sun UV we did. And there was a relatively linear relationship. The biggest effect is on cardiovascular disease. There's also a significant effect on cancer disease, on cancer deaths, and even on non cancer, non-CVD deaths. So on every marker, it improved overall survival. Now when we talk about skin cancer specific survival, the people who used the salarium or got more sun did get more melanoma, but they were they were no more likely to die from melanoma. And so the question becomes, do these advantages, so first, if these advantages in when I say if like to me, it is very well proven now. But if these are real, which I believe they are, if they outweigh the number of deaths from melanoma, it may turn out that it's a, there's this risk benefit where it's actually, we should be telling people get more UV, might increase your risk of skin cancer, but it's going to reduce your risk of dying from all that other stuff, even more than it increases your skin cancer risk. And you can't get it from vitamin D. So vitamin D doesn't help with any of this stuff. And that's one of the crucial parts. So before we have our guest on and kind of start going into this whole topic bigger, because there's a long body of literature on this that this is sort of the capstone of patent affairs, any initial thoughts on this. So I thought vitamin D is really more of like a biomarker review via exposure than the, you know, what is actually mediating the response. The salarium uses tough because somebody is used to sunbed ones versus, you know, has one in their basement like we see in the US. Those are two very different, you know, two very different exposures. You know, I think it's, I think it's interesting. I think it's also really hard. There's collinearity probably with using a tanning bed or being outside a lot or tanning and exercise and some other things. I think they control pretty well. Yeah. All of that stuff. I think they, I think it's hard to fully do it. It's hard to fully control for those things, but I, no, I agree. I think it's very interesting. A patent. I think it's interesting. And, you know, I started to think, all right, I totally completely buy into this. All right. How would I change my life? I wouldn't change anything. I mean, I'm not horrified of the sun. What about your patient? What are you going to tell your patients? I think that you risked stratify. And I think that, you know, it was kind of brought up in Australia, I think in January last year, January, February last year. They basically risk stratify their patients and they counsel them based on, you know, what type fits Patrick you are. It's a more reasonable counseling that I think makes more sense as opposed to just maybe saying what we tell our patients you need to protect yourself from the sun and UV. That's the most important thing. But I also do think that America is not England. There was another study out of Sweden. Like, we just aren't the same in terms of our sun exposure. So, right, is it relevant to people who live in North Dakota only or is it also relevant to people who live in Ohio and Pennsylvania and North Carolina? Right? That's the other question. Well, let's from there because we've got some interesting questions that I think we've got probably the best person in the world to answer them. So I want to induce Dr. Dr. Weller. So he's professor Richard Weller, dermatologist at the University of Edinburgh who has been doing this work for decades and I think every possible argument against it, he has heard repeatedly and I really can't wait to get into this. So Dr. Weller, the first thing that I really want you to start with is because we got to get people to buy this as possible. And so to start, explain the mechanism by which UV reduces cardiovascular morbidity and mortality and if vitamin D supplements help. And we're going to really stick to cardiovascular because I think that's got the best data. But let's start with that question. Can it just vitamin, just take your vitamin D pill and stay out of the sun? Yep, Matt, great. Thanks. I'm looking, it's great to be here. I spent two years in Pittsburgh doing research, which is actually where a lot of this started off. So it's great to be back with some Pittsburghers, it's nothing bit. So yeah, so mechanism, I think so, I suppose the first thing to say is vitamin D is being hugely overplayed. It's got some benefits, it prevents rickets. And there's all these, yeah, so there's all these observational studies. People with higher measured vitamin D levels are health yet in pretty much every way you can imagine. But correlation is not causation because we've now got the results of all the clinical trials, the biggest single one, of course, run an America, the vital study, the biggest of all run by NIH. And actually when you give people vitamin D, it doesn't do much. As you said, Laura, it's a biomarker for sunlight exposure, which prevents rickets in children and probably doesn't do very much. If you're going to believe randomized double blind placebo, can call clinical trials, which I think are a powerful tool that we should listen to. So if it's not the vitamin D, what could it be? And the mechanism I've really discovered is this nitric oxide release. So you know, it turns out that the skin contains large stores of nitric oxide. I was studying this down a blind alley in Pittsburgh. If you watch Ted Talks, I get a Ted Talk on this. And we found the skin contains large stores of nitric oxide, which have released, which have photo released by UV when it hits the skin. And then, well, so interesting. In our, in my original studies, we use UVA that was really to show this was a vitamin D independent effect, because vitamin D is made by UVB. And I wanted to show that there's a vitamin, this is a vitamin D in the benefit. So I use UVA lamps in my, my human studies. But I suspect UVB is actually as important if not more so. But we discovered it releases, I know, into the circulation, laser, I laid slowest blood pressure. And high blood pressure is the biggest killer in the world today. You know, it accounts for, it's 18% of all deaths in America are are directly related to high blood pressure. And we also showed then in later studies, we did an America that actually skin color really matters. So we looked at dialysis patients, mostly because they get that blood pressure measured three times a week, a week in, week out, year in, year out. And we took a data set by the Prisinius, who run most dialysis units in America. And they've got 350,000 patients on dialysis in 2000 different centers in America. And we could look at their blood pressure three times a week over three years in 2000 different centers. We could then look at effects of wavelength UVA and B. We could look at skin color really importantly. We could look at temperature. And what we showed was that more UV lower blood pressure, important, but that fall in blood pressure was much less marked in black Americans than white Americans. And of course skin color determines our response to UV. That's what it's about. Did you guys agree? We're able to rule out on that that temperature wasn't the issue because you hear that all the time. Yeah, we're blood, you're skitt to your skin when it's warm, so you get, but that didn't show the same. We did indeed. So looks about half the seasonal variation is due to temperature. But about half of it is independent of temperature. And that's really important. So it's not vitamin D, the clinical trials show that about half of it, about half of seasonal variation is temperature. But half of it is UV independent of the temperament. Laura, what's the first question you've got for Dr. Weller, Laura? You know, I can understand. I mean, I think that the data are interesting. There's a plausible mechanism for this. I guess my question is, how much does it take? So patients always say, oh, they're always worried about making vitamin D, which I think we can say. That's actually not what you need to worry about. But it's like, what's the dose response here? And how can you get to it? Yeah, look, so the answer is we don't know because we haven't done the experience. What I would say is that in Northern Europe, the seasonal variation in blood pressure, so the difference to winters this dog, blood pressure and some of this dog, blood pressure, is about six millimeters of mercury. Now, so if you were experiencing summer levels of sunshine instead of winters levels of sunshine, that would lay your blood pressure by six millimeters of mercury. Well, what does that mean? Well, that means a reduction in your risks of death from cardiovascular disease of 23%. That is huge because cardiovascular disease is the biggest killer in North America, Europe, and the world, more. And this is huge. And so we have this-- there's currently mid-winter here in Britain. We are having our usual winter bed crisis. When I was a young doctor, every winter you have a bed crisis, I have to say the modern NHS, we have a bed crisis 12 months a year, but it used to be a seasonal thing. And it progressed. It progressed. We love it. And we know that people in the sickle and winter hip-pop crates described this two and a half thousand years ago. There's a kind of culture as an internal medicine doctor in Britain that you don't take holidays in winter because it's bad form because everyone's bloody busy. And if you're on vacation, you're dumping your colleagues in it. It's an unstated rule. It's just how the world is. And so nobody thinks about it. Why is everyone sick or in winter? Hypocrites observed it, didn't explain it. And it looks like for cardiovascular disease, a big part of it is sunshine. All right. I got to ask this because I followed this literature pretty carefully, Laura. So there was that Korean study that people getting narrow-band UVB from Vidaligo got a 30% reduction roughly in cardiovascular ribidium or 10. And that made me think, well, it looks like getting two minutes of narrow-band UVB two or three times a week is probably enough. If you were to use this interventionally, if somebody was to be like, hey, Dr. Weller, we think there's a $1 trillion business in America. People all love to be tan. We can't get them out of those damn tanning beds anyways. Let's make narrow-band UVB tanning beds. How often do you think people should go in to get most of the benefit? Yeah, really interesting. And I know that study very well. I reviewed that for the JID. So it was sent to the J-- can I not say this? I reviewed it in a year's back when it came out. And it was submitted to the JID. And I have to say it was really poorly amolized when they first did it. They had looked at people who had-- so they compared people that got their Vidaligo treat with narrow-band UVB phototherapy versus people who had it treated with topical steroids. And they took it from the health data in career. And the great thing about Vidaligo-- if you're looking at psoriasis, they've got so many bloody comorbidities. I mean, sorry, addicts are unhealthy people. So you can't do it there because the comorbid is kill it. But Vidaligo, you don't really have comorbidities. It's a very clean population group. You're just treating them with UVB. And their initial analysis-- they looked at people that got a bit of UVB, then a bit more, then a bit more-- and looked at lifespan. But the problem is what's called a mortal time bias. You have to live a long time to get lots of UVB. So you know, it's-- you reverse the argument. And the other of you and I went, maybe me, you can't analyze it like this. Go into case control. Look at people that have lots versus steroids and just do that. And they-- and a couple of iterations. And you know, we were all lined up. The paper got better and better every time. I have been earmarked to write an editorial on it. And the JIT, we were all lined up. The paper was great. And the authors, for one of the sending it back, they didn't want it. And they sent it to a lower ranked journal. I would look up the journal yourself. And what I would say to anybody out there writing papers, is the reviewers are often on your side if they're saying something. If they're saying something. When I don't like a lot of people-- When the random is, they want to make it better. And that paper's a damn good paper. I-- I say it because I think-- Yeah. I've been the other reviewer. And so-- So-- Wait, let's finish this. So twice a week, you think that's enough? So look, so I don't-- the answer is I don't know. What I would say is, don't get. But it's interesting. So we use UVB to treat inflammatory skin disease. You know, psoracist, bit of x-ray. It's a great treatment for inflammatory skin disease. My strong suspicion, also based on work I'm doing at the moment, is that actually, it may well be a systemic anti-inflammatory treatment. And actually, probably far more important than just an inflammatory skin disease treatment. So yeah, I think-- Yeah, we're talking about that little IGO study. And wasn't it fascinating when you can buy and debarry with the phototherapy, then you get the benefit? And I mean, it's-- So yeah, I think lots of-- All right, thanks. Question, just about the level of exposure. So I like the vitamin D as a biomarker of UV exposure. Interestingly, I think it was end-hist, but it was like from one of the health interview studies, they were-- they also labs. They looked in-- people's reported sunscreen use and shade-seeking behavior did not correlate with their vitamin D levels. So I guess one question is, can you still get beneficial exposure while still using some kind of shade-seeking, like, and some kind of sunscreen level that would prevent a reduced your risk of skin cancer specifically? Yeah, look, don't get sunburn is the important message. I have to say, we've done some unpublished work where we showed that the fact of 50, SBF 50 sunscreen blocks end-oh release. And that is more of a concern to me. I mean, that's a concern to me. The truth is we know that patients don't put enough sunscreen on. So the SBF 50 is a theoretical lab test. There's no relation to the SBF when it's applied. So I think sunscreen can be better than it is, I suppose. All right, Patten. What do you-- so Kim is often our biggest skeptic of anything. But maybe we got you already, Patten. What do you got? No, I am maybe skeptical on both sides. I think that the shield yourself from the sun, things like that, I think that's a bit much. I did, in reading your papers and some of the references that you had mentioned, I wound up chasing down this one paper, American Journal of Epidemiology 2013. And it was prospective study of UV radiation exposure and mortality risk in the United States, where they actually-- I mean, they set their definition of how they were defining who got more UV versus less. But the patients who seem to get more UV, by the way that they determined it, actually had worse cardiovascular mortality. What was your comment on that? Did they not really look at what UV exposure? Yeah, look, so that's the only paper I should have really heard the papers on sun exposure. That is the only one I could find. We found the one article in the world ever. It is. and basically. What they found was that people in Louisiana die more than people in New Jersey because they compared I think six states. But what was interesting was the mortality was not cancer, the big cause of mortality was respiratory disease. Now if we're saying that cancer's UV's great danger is melanoma, that's what we expect. Not at all. The big killer was your far more likely to die of respiratory disease in Louisiana than you are in, you know, Ohio, Pennsylvania, and I, that we're new England states. And actually the deaths from cancer, no increase in deaths from cancer and women are generally increased in men, but it was liver cancer. So, you know, so it's an observational study, full of all the problems you have with observational studies. However, America's different. You know, you guys live a way lot further south than we do. New England is the same latitude as the Mediterranean coast of France, the Cote de Zure. Florida is the same latitude as the Sahara desert. So, you know, you guys live in a different UV environment to us. White skin is very, is not, you know, skin color, white skin in Europe and in China has evolved as an adaptation to the lack of sunlight there. It is not the skin color adapted to an American environment, in the south of America. So, you know, maybe there is a difference there, but the data is not nearly as good as our biobank data. You mentioned the biobank study we did. I mean, I was actually one of the subjects, half a million subjects. The assessment of the start took three hours and they took three years for the assessment group to move around Britain, recruiting these 500,000 people, a mass, hundreds of questions in the questionnaire, all sorts of measurements. And of course, it's then linked in, we have a universal health service here. Everybody's records go into the same health service, same death outcomes, same health outcomes, same cancer outcomes. We have incredibly robust data here for the population studies in Britain and in Scandinavia because we have these universal health services. And we adjusted that very carefully for the confounders, that the sunbed use, we didn't call it sunbed use, we call them sun seekers because we were looking at sunbed users as a behavioral marker because we know that behaviorally people that use sunbeds seek the sun more, they sunbed more, they exposed more of their, you know, more of their skin to the sun. So that would really be wanting behavioral marker for sunbed exposure, rather than, and as I always say to journalists, I am not saying sunbeds make you live longer. This is an observational study, you need an interventional study to give causation. I am saying that sun seekers live longer. So there is something about being a sunseed cup. So what do you tell, so patient normal patient comes in, you know, they've got, you know, six moles to look a little funny, but nothing terrible. They've got maybe an A.K. or two, but haven't had skin cancer yet. So normal to low risk patient, what I would do here, what you tell them. And then let's take a cardiac transplant patient who's had, you know, nine squames and two melanomas. Did you, did you, what, yeah, what do you tell them? They're completely different people. So your bog stand and grit, don't get burnt, jets on shine, you know, we have what's really interesting is this whole evolution rating. How, what's fascinating is that white pale skin has independently evolved in humans who move to low light areas. So the genetic variance leaving the pale skin in China, there's about 20, 20, 25 genes affecting skin pigmentation, but it's three or four big ones. So, so independently, Kittel G predominantly white skins of old and people who move to China. And independently, white skin has evolved and people who move to Europe. Padom like SLC 45 A2. The point is humans who move to low light environments repeatedly and independently evolve pale skin to make up for the lack of sunshine. Because what skin color does is it determines your risk of sunshine. So as a day Adamson shows beautifully in America, if you've got dark skin in America, you have no risk of UV and due skin cancer. I've been working in Ethiopia on and off for the last 14, 15 years. My colleagues there, and I've spent about nine months there, I suppose. We see no UV induced melanoma, no UV induced SCCs, sure we see April melanoma, sure we see marginous arse as those are not UV ones. So you have no risk of UV induced skin cancers if you've got that skin. But the big things that killed black Americans are the blood pressure ones. Blood pressure is higher with its stroke, with its heart disease. That is what kills black Americans. And you need far more UV to get that healthy fall and blood pressure if you've got dark skin. And we are putting out this one size fits all message and it's wrong. Do you like the Australian, like the new guidelines they put out last year or do you think either they do? Yeah, I think they're a bit cautious. I mean I know them all well. I'm Rachel Neal who's the first author to come in today with me in August. And so I know those guidelines. So they've said they've said some let's got health benefits. We need to think about that. And they've said skin color absolutely determines your response to you. I used to work in Australia as well. I did internal medicine there 30 years ago and a bit of work for flying doctor service. Again, Aboriginal Australians, the original Australians, but maybe you'll be in the skin cancer. They've been there for 60,000 years. They have a skin adapted to a the user environment. But the message is for white Europeans who arrive there when we couldn't send convicts to the Americas, we ship them off to Australia when you guys left. And we have this, I have to say in Britain we have this, and of course they've got this you know slitslapsed lot the whole UV. That is for white Europeans in a real high UV environment. So why was a an internal medicine, like a kind of middle grade doctor in Cairns in Queensland 30 years ago? And in Cairns midwinter June, the UV index in the middle of the day is seven correct for a bad man in mid summer that UV index is 14. So in Britain in Scotland we copy the Australian sunlight slitslapsed lot guidance. If you're out, you know, elementary, you know, put on sunscreen. So last year, the UV index in Scotland, Tim, how many weeks do you think the UV index hit seven in Scotland last year just three weeks? I'm going to say eight weeks. Okay, well Laura any idea, you maybe you don't know Scotland, how can you be in that sense? Okay, so it was the 24th of June, five minutes, just after lunch. Just after lunch. And yeah. And yeah. Wow. So I was close. And the year before the year before it was 10 minutes, the year before it was 10 minutes. So and yet we copy the Australian slitslapsed that. It's madness. It is madness. Yeah. Well Dr. Rell, I wouldn't thank you. So this has been so much fun and so hopefully enlightening for lots of our colleagues to at least start to think about this and think about, you know, baking your melanoma patient feel like they should never go outside again. Because that's often what we end up making them making these patients feel like. So I really enjoyed really enjoyed the discussion today and I want to invite you to stay around while we move on to our trivia section. So the rules that Dr. Patton has set, we have to let him finish the question. And then as soon as he finishes the question, you just can shout out whatever, whatever, if you think you know the answer shouted out, we got to let him finish. All right. You guys ready? These are UV related trivia. All right. In what year did Hawaii's sunscreen ban targeting oxybenzo and octanoxy officially take effect? 2018. 2018. 2020. Recently 2020 is my guess. I'm going to go with 2019 then. It was 2021. 2018 was when the law was passed, but they gave everybody two years and Matt, you were just in Hawaii are there swap teams at the airport and on the beach, confiscating, sunscreens and stuff? I saw a lot of shady looking characters, but I wasn't sure what day that's probably it. There's a whole black market, I'm sure, right? All right. Number two, which form of cutaneous tuberculosis did Neel's Rhyberg-Finson success? successfully treat with concentrated light radiation leading to his Nobel Prize in 1903. Millions of people. Million. Right. It was Lupus. Gareth. How would you treat? Those patients are on death. It was Lupus. With the bruncus. With the bruncus. You just get it in there and pour the UV in. Yeah, that was how Trump was going to fight COVID, I think. That's a beach. It's going to work. Hey, there's paid. I'm not going to. It's a long dive, but there is very good evidence that you view substantially reduces your risk of COVID death. And then after well as better man of that work. No, I was watching another interview with Dr. Weller where he went over that data. Pretty interesting. Yeah. Okay, yes, it was Lupus, Volgares. We used to, Derms used to win Nobel prizes and now we sell $300 skin care lines. All right. Number three. Which popular sunscreen brand was created by World War II airman Benjamin Green who added coconut oil and cocoa butter to red veterinary petroleum. Copper. So. It was copper tone. That was a little bit of a time. I think I know our men. I'm taking it. I'm taking it. I got. It was the week was the transatlantic link. I was at first. I really was. I was. I'm giving you the best. I'm trading like on a trading floor. You want your computer to the next. It's a mill if I can lead. All right. Well, Dr. Weller, thank you so much. This has been so much fun and I'm certainly expecting we'll be having you on again in the future as this story continues to develop because it's it is fun to talk about. Well, thank you. I really enjoyed it. I hope to see you guys at the ad. Yes. That's you. All right. Well, let's. Let's move on. Stop. To the little three. So these are three more articles that we thought were important or three more topics, but not quite as important as the big three. I'm going to start us off. And really, I'm going to do three very three articles that are all very quick. So number one was that if you got a immune checkpoint inhibitor induced rash and then you got do pill a map, your survival was better. Then if you didn't get an immune checkpoint inhibitor rash or if you got one, but did not get to pill a map. The main takeaway from the article that the authors had was to put them have works well for immune checkpoint inhibitor rashes without making prognosis worse. My takeaway is it makes prognosis better by stimulating your I.L. for system, but that's a pretty big jump. Second one was about the cardio metabolic safety of do pill a map. So this was a large database study in which they compared people on Dupy for AD to people on method tricks eight for AD and people on Dupy for AD to people on cyclosporium with AD. And the main takeaway was that the cardiovascular risks were a little bit lower for the people on Dupy. The main important thing here is I've always been a little concerned that blocking I.L. 13 might increase cardiovascular risk because we know that coronary plaque macrophages are inhibited by I.L. 13. So maybe blocking it increased cardiovascular risk. This seemed to not show that. And so there were a few that were even statistically significantly decreased, but I you know they were I don't think it was multiplicity control and all that. But then the third one was do pill a map and neuropsychiatric outcomes and little kids. And it's kind of exactly what you would think. All psychiatric once you go on Dupy your risk of getting any psychiatric disorder as a child is cut by almost 50% specifically neurodevelopment on behavioral disorders mood disorders anxiety disorders sleep disorders learning disabilities were actually cut the most. And then for negative controls to make sure it wasn't just some weird you're getting more care or something like that. They showed that accidental injury was not affected by the pillow map use. And they showed that conjunctivitis increased with the pillow map use. So just a bunch of data that three different articles all looking at either ancillary benefits or lacks of harm with Dupy. I don't know is there anything super interesting that you guys want to comment on that. I guess we don't have a deal on disclosure portion of this podcast. I could pay a lot of money. Because I can be I'm just. Do you not. Do you not give enough talks for Dupy like you're this is a big lot of anything. I'm sure yeah. All right. It may be that people with bad immunotherapy rashes are more likely to get Dupy and the more cutaneous amine related adverse events more severe associated with better. Yeah. And I'm not out there. It also may be that Dupy saves. All right. I'll go on to the next. All right. All right. Okay. So this is a little bit of follow up to sort of what do you do with patients on biologics. Do you switch between classes? Do you stay within the class? Last week we talked about a paper. You know, looking at people who moved from one aisle 23 inhibitor to another showing that they, you know, in general had a pretty good response. So this was a J J E a D V. NAMM and this is out of soul and comparative analysis of switching basically between aisle 23 a and aisle 17. So this wasn't a huge study. There were basically and they compared them to, you know, patients who were starting naive. And so, you know, most people most common biologic was about half a patient's were on risen kids, you know, about a third on gazelle, you know, in about 17 18% on exek his mad. Most people they just were, you know, not switching. And then basically like 21 switched intra class and then 22 switched into a class. And so what you can see here is that basically the patients who switched clapped switched between classes were more likely to reach a Pazzy 90 or Pazzy 100 response than the patients who switched to another drug within their within their same class. So, you know, I think it sort of it's it's it's it's it doesn't just it doesn't detract from what we saw before. I also still think you have pretty good darn good Pazzy responses, even if you stay on an aisle 23. But some data that if you really are looking for improvement, you're more likely to get it when you switch mechanisms. And I know they were small numbers did I owe 23 to I owe 17 work just as well as I owe 17 to I owe 23. That's a good question. I think they didn't see that they dissected it out like that enough to be able to tell. But basically, I read that and saw better. And the takeaway that I now have is intra class switching can work, but it's a higher probability that inter class switching is going to work. That is correct. I think we talked last week like we like I owe 23s and so somebody was failing his and kids you have would you switch him up to the other. Trimphia, dammit patent used the great name. And I think we all kind of said back then probably stick with trimphia because we like the 23s. Does it would this change anything or would you kind of have that conversation with the patient like look, there's data that suggests you really want to get that really, really good Pazzy score. Let's switch you over to 17. I would say and again, like nobody had less than a Pazzy 75 response. Okay, so these weren't like bad non responders. I would still go to one more aisle 23. If that didn't work, I go to an aisle 17. If they're on an aisle 17, I'd say let's go to an aisle 23 just because I like the efficacy safety. We still heart aisle 23s. Yeah, heart. They just say they're just safer. Exactly. All right. Nothing, nothing. You don't do any drug talks. I forget up here. You are. Okay. Well, I wouldn't go that far, but I mean, that's my little three paper was from 2024 jam a Derm. No, 2025. Yeah, Gunter Adal titled see reactive protein in response to Adaluma patients with hydrod and nitose upper T the post hoc analysis of two randomized control trials. So they looked at the data from the pioneer one and pioneer two. That compared Adaluma lab versus placebo and patients with moderates is a very chest and they wanted to see if CRP levels were associated with responses. And they put all the data and table two, which was a totally confusing table. I feel bad. I called Ferris on Saturday. I'm like, I don't. I literally don't understand these numbers. They're all over the place. The point being. Just like Residue, you don't understand to call Ferris. Exactly. Elevate overall elevated CRP associated with lower odds. Odds ratio of clinical response. Adaluma. Meb had a higher odds ratio of clinical response compared to placebo in both CRP high and normal CRP patients. And the higher the CRP, the reduced odds ratio of clinical response. I don't know what to take away from this paper. I didn't think it was terribly useful. I mean, if you had higher. And more so you're continuously these you had higher CRP. So basically worst disease is gonna be Well less responsive to Adelim and Mab. I don't think that's a huge surprise I don't know if this helps us manage these patients at home. Yeah, I was hoping it was gonna be something like if there's CRPs This high then you should use it, but no, it was basically more of the higher their CRP the worst their disease like that would yeah, it's a marker of bad disease and high CRP patients just aren't as likely to respond, but it's still better to put them on Adelim and Mab than placebo It's not like they're non-responders to the drug. They just have worst disease. That's our directory Yeah, right and you kind of you know that from you know, you're heavier patients You're like this this may not work. We might have to bump up the dose or try and go to influx a map, which is weight-based dosing And the more severe disease you're kind of like in I don't know if how well Adelim and Mab's gonna work So it was almost like a reflection of the patients that you know are gonna be harder to treat But that doesn't stop you from from treat. No. Yeah, all right We're gonna jump on to our next segment the baby three. These are all three supposed to be quick hitters My first one was looking at pre-gablin Versus gabapentin for itch and here's what was interesting They work the same for itch improvement. Maybe Maybe that gabapentin was a little bit even better for each improvement According to the 5d paritis scale, but for dlQi It really looked like Gabapentin was better and that was primarily because pre-gablin caused more dizziness and it's a real issue with these drugs Pre-gablin and gabapentin I rarely use any of them anymore because there's now data That they increase the risk of hip fractures and elderly patients because of falls So I use mrtazapine almost all the time. I rarely use gabapentin because of dizziness and feeling like a zombie Anything different anything else you guys would take from that just that it kind of confirmed for me lots of dizziness and that kind of side effect with these drugs I never use pre-gablin So I mean rarely gabapentin some mrtaz I agree mrtazapine It also makes people more hungry so they put on late, but that's right which is often good for old people patten I use gabapentin all the time Do you ever use mrtazapine? I have But it's usually in patients that fail gabapentin and I've not had Great results with it. It's much easier to use in gabapentin 15 milligrams Probably a habit thing The hip fracture thing is definitely something I'm gonna think about more. Yeah, all right. It's going to it's going to our next one Let's see here. I think this is fairies Yeah risk this is risk of different sub types of psoriasis following an episode of guttate psoriasis This is creed in et al from lubec and so this was a trinetics database study Basically follow patients who who were diagnosed never had a psoriasis diagnosis diagnosed with guttate psoriasis between 2003 and 23 and then looked at their lifetime risk of developing psoriasis Turns out that about a 12.5 percent lifetime risk of getting plaque psoriasis 7.7 for psoriasis And then around 2.9 for like gpp public planter pusillosis nail or rithroidermic Most of that risk seems to be in the first one or one to five or zero to five years after their Guttate diagnosis. So previous estimates were like 25 percent This was lower, but this is probably more rigorous and less biased than previous studies So you useful thing to be able to say to people 80 percent chance There's gonna be one time thing and go away 20 percent chance that it's gonna come you're gonna get something like this back I really only like it most a 12.5 percent chance. So Patten, what do you what do you do when you see guttate psoriasis shot a catalog some of moxasillin what do you know method tricks aid What do you if they got a bad guttate that you need to do something with? I'll see if they can come in and get the lightbox topical tack I don't know maybe I'd give him a sample of binzalex right that's gonna be a one-time shot. They'll be clear Do you give me do you give me moxas spares to do you empirically give people moxasillin? I don't If I mean if they have a you know strap That's yeah, yeah, I don't I you know I try I agree if they they can do narrow band. I like narrow band I'll try to kind of hit them with like method tricks aid even sometimes just a sling we can do for a you know Three to six months and then try to take them off So okay, do you guys check do you send them to urgent care somewhere to get a strap test? No No, okay, interesting. All right. Let's let's finish it up. So Patton what's our last one? Yeah, you know what I didn't write down the journal and the the author I think it was in Durham's Yeah, let me see here it was comparison of affectionate between steroids. There are gloves during mose updated systemic review and metanalysis just Sardo et al journal of coutaneous medicine and surgery Thank you. Thank you. So metanalysis for studies about three thousand most cases with non sterile gloves infection rate was two percent About 7500 most cases with sterile gloves infection rate was 3.1 Essentially no difference and non sterile gloves are 10 times cheaper So I am taking this data to my chair and I'll take a cut of how much money we save and I will be rich beyond my wildest dream I think it was did you say that the opposite non sterile 3.1 sterile right so no it was a lower Infection with the non sterile gloves it was a higher rate. Okay. Yeah, it was you know statistically insignificant Yeah, technically it was 2% versus 3.1 Yeah, so the only thing I would say when I see these is mose is almost all in the head neck It's really rare to get infections, you know, is it different if you're looking at the lower leg? I learned that Ferris essentially puts her people in like a bubble like bubble boy He's like you will not get infected stay in your bubble for two weeks Don't touch your kids stay away from your pets Okay, for a month off work LMFA I mean you know, yeah, I you probably don't need to do the sterile gloves But I think it's a good point that Ferris brings off the mose on the head neck They they don't get infected lower leg trunk. I mean the feed. I don't I don't think those infections come from the gloves right? I mean I know you're right. I think they're from Using my takeaways using sterile gloves for the stuff that we do actually probably doesn't make sense and it is expensive Yeah, I could say it's like two bucks a surgery. Peri sterile gloves is like two 25 pair of non sterile gloves is like a quarter They're not even a quarter a pair of non sterile gloves is like three cents. What do I talk about 10 times cheaper? Yeah All right, so We want to thank everybody for joining us today So it was a really fun episode next week. We are going to have on dr. Yakka But this in from Denmark so we're continuing our Very hoitty toyty tour of people doing cool stuff in Europe. I will be in that mouth Europeans last week You're lucky. You still have an audience So I'm and I have to admit something so I will actually openly admit in Exima so I believe in my heart of hearts that I'm the smartest person in the world when it comes to Exima I know that's not true, but I still believe it It's gack of this and is smarter than I am knows more than I am I literally if we're gonna be talking about a hand eximen particular. I cannot wait To hear what he's got to say. I think it's gonna be some really cool stuff But so I would again thank everybody for joining us today uh, you know, terms on drugs. Well, thank you and if you got questions comments or ideas for topics Should we cover on the show shoot us an email a questions at termsandrugs.com And I hope you learned a few things. I hope you laughed a few times and mostly I hope to play into joining us next week Until then I'm Matt Cyrus I'm Tim Patton And on more affairs and we are terms on drugs