That's the pointer. All right, thank you for having me. And I'm very excited to actually be able to talk about some things we don't get to talk about very often, and some treatments that we don't always get to present at some of these meetings. I'm a pretty fast talker, and my coffee's kicking in, too. And I think we have the break after this. So hopefully, we'll get through this and have plenty of time for questions and maybe an early break. So we all know about GSM and the symptoms that go along with it, right? Urinary urgency and frequency are one of the big ones we see in urogynecology practices. But all of us, GYN and our urogynes, are seeing sexual pain, dryness, burning, irritation. Tightening and shortening is something we don't always talk about as much, but we definitely see it. And frequent UTIs, which I see a ton of. This affects, I would say, probably 80% of my patients. And it's something that we don't always address. Somebody comes in for overactive bladder or constipation, and we ignore this. And I'm going to be the advocate today for everybody to treat GSM more than you probably are. What's the pathophysiology? Why does estrogen deficiency lead to GSM? It's a thinning of the vaginal epithelium. We've all heard this many times. Cellular changes, reduced glycogen, diminished epithelial cell layering, reduced secretions. You get an alteration of the connective tissue structure, which then gives you the reduced elasticity leading to that tightening and shortening, which doesn't help the pain issues. So you can see in the pictures, the high estrogen environment before menopause with that thick superficial cell layering, which then decreases significantly after menopause. And in the histopathology sides, you can see that big difference as well. So I started asking myself, we don't sometimes think about it, what is something we treat all the time? Why do we get reduced vaginal secretions? Well, estrogen maintains hydration by stimulating mucous secreting cells in the epithelium. But it also, and this is something I actually didn't know until doing this study or think about, it increases glandular activity of the cervix and vestibular glands, which also contributes. It enhances blood flow, which as surgeons, we see all the time. How many patients do you operate on and say, oh, she must be premenopausal. I forgot. She has so much more blood during the surgery. We see it all the time. So that facilitates transudation of the cells and movement of fluid through the vaginal walls, which contributes to our natural lubrication. Declining estrogen leads to atrophy via those glandular tissues as well, decreasing secretion. And then there's the microbiome changes, which we've talked more and more about. The reduction in lactobacilli, which increases vaginal pH, predisposing to infections, including urinary infections. So what else happens? The lower urinary tract gets very involved. And this is one of the reasons I want you to think about treating it more. Don't just treat the OAB with a med or the SUI with a sling. Think about everything else that's going on in this patient. Because most of these women are postmenopausal that are seeing us or seeking treatment at that point. So estrogen deficiently thins and atrophies the urethelial epithelium as well, reducing its barrier effect. So hence, we get more infections due to that, not just the pH changes, but also to cause those recurring UTIs we all see. So that's one of the reasons estrogen treatment has shown to have over a 50% reduction in UTIs in these women, if you use it. We get decreased vascularization and collagen production in the bladder itself and the urethral tissues. So you get that urgency, the frequency, the stress incontinence. That's when all the OAB symptoms go up, right? Women who are menopausal or perimenopausal, those are our clientele. It also affects the neuromuscular control of the bladder. So it increases those OAB and detrusor overactivity symptoms as well as nocturia. So I have plenty of patients who get better for milder symptoms just with vaginal estrogen. It's amazing. These are some real life photos showing atrophy. You can see the pale, dry, shiny vulvar tissue, the pallor that starts to happen, the loss of the rugation inside the vagina. We've all seen this. But you've got to pay attention to it. Sometimes we go right by it with our speculum, right? You go just doing your basic exam and you ignore all these changes that are happening. And the patient doesn't always feel it at the beginning. That's one of the reasons this talk is called the silent shift, right? It's a little bit of a two-pronged sword here because silent, because at first it starts silently. The patients don't even realize it's happening until they start getting pain with sex, for instance. And that's why they start talking to you about it. But it's also a silent shift in treatment, which we'll talk about in a moment as far as what patients are starting to seek. So mainstay of treatment has been vaginal estrogen therapies for quite a long time. We've got so many different forms out there now between creams and tablets and rings, suppositories. You can get it compounded. And Estriol is a big one that gets compounded in Europe and utilized or made. Actually, they don't have to compound it. We are directly addressing the problem, right? We're directly addressing the low estrogen state of the vaginal tissues. And it clearly increases vaginal epithelium thickness and elasticity. There's also systemic hormone therapy. It's making a big comeback, guys. If you're not doing it, learn about it. Because that is where things are headed right now every day. I see social media posts. I see hers, MD on TV, doing it, right? If you're not doing it, they are. And you're probably going to do it safer. But something to start thinking about. Because these women who present to you often have other menopausal symptoms, hot flashes, mood changes. They're not sleeping well. They're not eating well. Hot flashes, mood changes. They're not sleeping. They feel crazy, OK? Menopause makes people crazy sometimes. It really does. But if you treat it, maybe they don't have to deal with that anymore. But it's going to help the vagina. It's going to help the atrophy. So women who are often on HRT don't need the vaginal preparations. Maybe they do initially. You can do a combo. But they don't necessarily have to keep the vaginal preparations over time, which a lot of women hate, because they're messy, right? What goes up must come down. And no woman likes wearing pads after menopause, OK? No woman wants that. That's the one benefit of menopause is women don't have to wear pads, liners, or tampons. That is the only benefit, to be honest with you, because the rest is downside that we don't talk too much about. But we have lots of different varieties out there. For the vaginal estrogen therapies, one of the ones I actually like the best is the capsule, Imvexi. You've probably heard of it. Maybe you're not using it much. But women like it. You know why? Not as messy. It's a capsule. And it also has moisturizers in the capsule that start to work before the estrogen does. So it's kind of a nice combination. But use them to your delight, or whatever the patient benefits from, or sometimes what's covered, unfortunately, by their insurance carriers. Obviously, for systemic hormone therapy, we have to think about risk factors before initiation. We'll get to a slide a little bit about that. We have CIRM, so Selective Estrogen Receptor Modulators, like Osfina is really still the only one out there. Oral therapy now for dyspareunia. It also improves bone density. So if you have someone who has both issues, that's a nice option. But again, it's an oral formulation. And there certainly can be side effects with any oral medication that you have to think about. And then the other thing that we never really talk about in our society is testosterone therapy. We're going to spend a little bit of time on that. Not FDA approved, right? Although I'm going to tell you, systemic testosterone therapy has 35 randomized controlled trials and hundreds of non-randomized trials. But we say there's no data. Very interesting. There are testosterone receptors in the vagina, in the vestibule, in the vulva, in the bladder, in the ureothelial epithelium, in the urethra, and in the pelvic floor muscles. Testosterone preserves muscle mass. That's why men have more muscle mass. So interesting, right? When do women start seeing all these problems? Guess what's happening at that age, at that perimenopausal menopausal age? It's not just estrogen that starts decreasing. Testosterone actually starts decreasing around the age of 30. We don't talk about that in women. Why is that? We're going to talk about it today because Miles is letting me. So what happens with estrogen in vaginal tissue? We're going to restore the vaginal epithelium. We're going to thicken it. We're going to improve that elasticity that women can plan of with intercourse. We're going to increase vaginal secretions, improve collagen and vascularization. It actually stimulates fibroblast activity, increasing collagen deposition, promoting vascularization. The microbiome gets restored. We reduce infection risks. And then we also reduce those urinary symptoms, because we've got those receptors in the ureothelium. So I was interested, because I've been using estrogen products vaginally for a long time. But I'm going to say, I had never really pooled the data. So I was like, ah, let's see how many studies are out there. A lot. There's a lot of randomized controlled trials. So here's a bunch of big studies. Lots of women. All of them showing significant improvement clinically, as well as histopathologically. So we do have the data out there that it works. But does it work for everyone equally? How many people in here have used vaginal estrogen on women? And they come back, and they're just not doing great. They're like, it's OK. But it's just not working for me. Why is that? That's an actually great question. We don't know why, necessarily. Perhaps it's the more severe patients that come to you and didn't get treatment early enough. It doesn't always absorb. We can't always count on it to absorb equally in every patient. And we see that with topical treatments for anything in the body. We learn from other specialties sometimes that depending on the thickness of that tissue and what's happened over time, it becomes sometimes scar-like to you when you examine them, when they're really severe. Is that going to absorb the same way as a newly menopausal or perimenopausal patient absorbs? No. And you know why? You know why I can say this? Because when we get to some other things we're going to talk about with vaginal treatments that are not FDA-approved, but they're out there, we see a difference. And we know it's because the thickness of that vaginal epithelium is different. In a severely menopausal woman, it's much different than a newly menopausal woman, right? We saw those histology slides. That doesn't happen overnight. It's a gradual process. So we can't expect the same thing to work for each patient the same way. So we're getting into non-hormonals a bit, but DHEA is one of the newer treatments that have been out there. There's some different formulations out there. One of the first ones was Enterosa. How does that one work? Well, it's converted into androgens and estrogens locally. It enhances, again, the epithelial thickness, collagen synthesis, and blood flow in a similar way, but it actually becomes androgens too. Did anybody think about that, right? So clinical benefits are all the same, but no systemic effects. No endometrial hyperplasia worries with this one. So that's something to consider, which makes it suitable for people that you're avoiding systemic estrogen therapy, or maybe they've had a history of hyperplasia. Looking at the data there, several randomized double blind studies looking at prasterone compared to estrogen cream and also to estradiol vaginal tablets. And it was at least as effective, if not slightly more, looking at that data. Now, we need more studies to say it's superior, but it's at least as effective based on those studies. So are there any risks, right? Every day I get asked by patients, or they take the script, they read the insert, as Miles had said, I'm not taking that. It's that increased breast cancer, or increased stroke, or whatever you hear. So what are the risks? Well, most of these huge studies show no increased risk of adverse health outcomes, including cancer recurrence or cardiovascular events. Some research suggests potential risks with some medications, which we'll talk about in a moment. So looking at one of the biggest systematic reviews that came out not long ago, a meta-analysis of eight studies concluded that estrogen use in the history of breast cancer, which is one of the ones that comes up the most, was not associated with an increased risk of cancer, recurrence, mortality, or overall mortality. Interestingly enough, it actually showed about a 40% decrease. So that was really interesting that nobody can quite understand. Selection biases are, of course, a problem in observational studies. And overall, when they look at the limitations of these studies, perhaps these were healthier patients because they're sexually active, seeking treatment. So there's always those aspects of studies we have to criticize a little bit. And certainly, we need larger randomized trials. But this was super promising. And nowadays, most of the oncologists are on board because all of these cancer patients, they're on tamoxifen, right? They're on other medications that are decreasing any estrogen they have in their bodies, even more so. And they're becoming miserable. After a couple of years on the tamoxifen, the vaginal dryness is real. And in these women, who especially are younger, they weren't expecting this. And they're more sexually active. So it was a Danish study that said, well, maybe there was a higher recurrence, actually, in women who were on aromatase inhibitors compared to those who are not. In breast cancer, just to recall, aromatase inhibitors are used in post-menopausal breast cancer survivors, typically, to decrease aromatization in the periphery to estrogen, and sometimes on high-risk stage 4 patients, whether they're pre- or post-menopausal, but who are usually also on an estrogen blocker. So then we go, well, why is that? Why did that recurrence risk go up? Perhaps it's because these were more severe patients. We're not sure. There aren't a lot of studies showing this. So it's something we have to keep in mind when prescribing it. And in cardiovascular events, the studies looking at those showed, over a million women, no significant increase with major cardiovascular events. So that's very promising. So in conclusion, it does not increase the risk of adverse outcomes. Certain combinations, perhaps, of aromatase inhibitors, we may want to consider that a relative risk as of now, but we need more studies. And it's essential to consult with our other health care providers and the patient and have a thorough discussion. And I know those discussions take more time than we want when we are dealing with atrophy, especially when we're dealing with five other problems. But just consider it part of your treatment plan when you're treating those other issues that we talked about, because it really, really helps. And a lack of it doesn't. So multimodal care, multimodal approach, is really where it's at. So let's talk about some non-hormonal therapies, because a lot of women want to know this. They're not interested no matter what you say, or maybe they need something in addition to that. Well, we certainly have vaginal lubricants and moisturizers galore. I mean, if you look at any shelf, and I every now and then like to go down my CVS aisle or my grocery store aisle and see what they have. Did you know, by the way, CVS sells sex toys? A whole section on sex toys. And I was blown away. I took a picture of it. I was like, this is amazing. Somebody probably thinks I'm a pervert and CVS taking pictures of sex toys. There's everything out there, guys. It's pretty amazing. So vaginal lubricants and moisturizers, first-line treatment, right? Any woman can use them. They can buy them over the counter. There's water-based, silicone-based, oil-based. Have any of us ever learned about any of those? Nope. Do you know the difference? Water-based, absorbed more quickly, doesn't last as long, no real risks. Silicone-based, slippery, lasts longer, can ruin silicone toys. Oil-based, how many patients are asking about coconut oil? A lot, right? A lot. Coconut oils, vitamin E oils, they can be useful. But coconut oils can decrease condom effectivity. So you want to make sure patients know that. In the vitamin E oils, some of the oils can actually trap bacteria. So you have to be careful there, especially in any patient who might be getting chronic infections. Maybe not a good one for them. But they're all temporary. Lubricants don't last more than really the day you use them. Moisturizers, on the other hand, usually last about three days. So those last a little bit longer. And there's plenty of vaginal moisturizers over the counter as well, one of which is hyaluronic acid nowadays. So you've probably seen a lot of commercials and docs on Instagram getting paid to promote Reverie. Reverie is a HA, but there's other ones out there. Hyaluronic acids are natural. You can use them every night at the beginning, and then every night thereafter, typically. And it'll improve hydration. All of our skin, all of our epithelium has HA in it. HA is what's in fillers, by the way. It's just cross-linked to last longer. But it improves vaginal hydration, elasticity, reduces dyspareunia and irritation clearly, and can enhance collagen synthesis to some degree, contributing to some tissue regeneration, whereas the lubricants do not. There's actually some studies comparing it to estrogen. So they are suggesting that it may be comparable to estrogen therapy, which I thought was pretty interesting. Interestingly enough, I would literally today, I saw a study that's about to be published in June in one of the sexual journals in Europe of one of our colleagues, Dr. Bechamel, who just did a study randomized on injecting HA into the vaginal and vestibular area. So stay tuned, guys. Unfortunately, it's all off-label, especially in the US, but people are doing these things, and it was consistently showing equivalence to estrogen. So very interesting stuff coming out on these things. So what alternatives are out there other than the ones we've talked about? And I'm sure all of your patients are asking and are doing some of these things, and maybe you're offering some of these things. Laser therapy and GSEM became quite popular in the last several years. And there's two different kinds of lasers out there, fractional CO2 and erbium. CO2 laser came out first, as you know, Mona Lisa. We've all heard that name. Love to know how they came up with that. But penetrates 600 to 800 microns, typically, into the vaginal epithelium. You're doing fractionated treatment here. What fractionated treatment means, you're not sloughing off the entire vagina, okay? You're creating microchannels of energy at once, keeping healthy islets of tissue in between, and then that decreases recovery time, side effects, et cetera, and risks versus sloughing it all off at once. Where do we slough it all off at once? You see the stars who get their faces done and they don't wanna be seen for four weeks, they stay in a Beverly Hills hotel, that's why. They look like zombies afterwards because they're taking that entire facial skin pretty much off and it's regenerating. Okay, so that's a more aggressive treatment on face that has a lot of good outcomes, but it's also a little higher risk, okay? More infections and risk of scarring and things. So very important when people do those things, they have to go to a skilled person. But that's why we're not doing that in the vagina, because it could potentially lead to probably more scar tissue. So CO2 laser goes a little deeper, so it requires fewer sessions, but can cause a little bit more discomfort and a little more risk of scarring. Erbium YAG laser penetrates a little less deep, 200, 400 microns or two to four millimeters, primarily targeting the superficial vaginal layers, okay? That's lasers are really treating more superficially. Erbium has more precise tissue ablation with less thermal spread and therefore less risk. So theoretically less risk of scar tissue and less downtime. So it may require a few more sessions, but generally face, body, vagina, okay? These lasers are all used in all these places now, less downtime and less risk. So both of them right now are actually same treatment protocols with three treatments a month apart and then usually require some sort of maintenance, okay? Because they're not permanently treating the issue, right? You're always still menopausal. So you have to keep that tissue regenerating. Both lasers are ablative, creating damage, essentially is what ablative means. They result in improved vaginal lubrication, elasticity, and vascularization. And there definitely are some studies backing this up and showing significant symptom improvement. So here's one little study on CO2 laser. This is the systematic review and meta-analysis. Looked at 14 studies with over 500 patients and showed significant reductions in all of the following GSM symptoms, dryness, dyspareunia, itching, burning, dysuria, and incontinence. And incontinence actually has a pretty high confidence interval there. So improvements were also observed in quality of life measures and sexual function indices. However, they note that their overall quality of evidence was low to very low, suggesting that, promising, but we need some more rigorous randomized control trials would be nice. But a definite option for women who don't want estrogen, can't have estrogen, et cetera. So women are seeking these other therapies out there. So it's good for you if you don't offer them to at least know what they're about and be able to discuss it with your patient as far as the risks and benefits. And generally the risks are pretty small. I do do some of the, plenty of these treatments do. So we really don't see issues. I have an Erbium laser myself. I have yet to ever see a complication from it, as long as you know how to use it correctly. So Erbium is what we're talking about next. Plenty of studies there as well. Prospective studies looking 24 months, three laser sessions a month apart. Significant improvement again, lasting in this study up to 12 months. Benefits may wane after about 12 to 18 months. So most of the time it's recommended to do a maintenance treatment at least once every year, year and a half. Another prospective study versus vaginal estriol. Now that's the one that's popularly used in Europe. That one looked at two years. So comparable symptom relief in each. So showing it was not inferior. And then another randomized trial compared to estriol. Again, significant improvement, comparable efficacy. So the studies and the literature that we do have are showing comparability. ERG-YAG laser is promising relief just as well as CO2 laser, but with good tolerability, slightly less risks. So let's talk a little bit about radiofrequency. So radiofrequency goes deeper. Lasers and radiofrequency are not equivalent. Radiofrequency uses controlled thermal energy, it's not a laser, to stimulate collagen remodeling. Now your patients are going to want to know how to stimulate collagen remodeling. Now your patients will call it a laser, they don't know the difference. But I always have a little talk with them just to kind of explain it a little bit more. And it also can improve tissue vascularity and elasticity. RF can improve the same symptoms just in a slightly different way. RF energy works by heat. Heating the vaginal mucosa and submucosa to 40 to 45 degrees can then induce neocollagenesis, elastogenesis and neovascularization. And this all also came from dermatology. Most of these treatments started with cosmetic therapies of face, skin, body texture. And radiofrequency is commonly used for tightening. So women who have loose skin, it's radiofrequency that treats that. Women who have loose vaginal tissue and complain of that, it's radiofrequency that works the best at that because it goes to the correct depth. So radiofrequency and heat are how these things work. And there's different devices out there. And I just put a few on there. Some are monopolar, some are bipolar. The difference being monopolar goes a bit deeper than bipolar. So depending on what you're treating, if you're just treating atrophy, probably doesn't matter which one you use. But if you're trying to treat a patient who also has vaginal laxity complaints, and maybe SUI, probably monopolar is a better option. So something to think about. Again, these treatments require, like the lasers, monthly treatment is usually recommended at the beginning every four to six weeks. And that's really to allow whatever breakdown of the collagen. Heat damages collagen, it actually breaks it down. And then it's the reparative process that the body undergoes that's building a stronger layer of tissue. So you've got to give it that time. And that's why you have that bridge of usually four to six weeks between any of these treatments. You have to let the regrowth occur, the healing to occur, and then you hit it again. So these are studies looking at radiofrequency procedures. Fairly small studies, so we do need some larger studies out there. But again, showing significant improvement in laxity, dryness, sexual satisfaction. So here's a bonus, okay? Requires, again, maintenance, depending on the patient at nine to 12 months based on some of these studies. And some people maybe even at six months. So the range of time that these things work does vary. Improvement in vaginal tightness and sexual function of the second. And then vaginal health index score, which is a histologic assessment as well as clinical assessment of vaginal improvement and GSM had also improved. So really all of these treatments are working by heat base. It's just different modalities of doing it. Do we do laser? Do we do radiofrequency? I have not found any head-to-head studies to see if one's better than the other, but that would be great if we could get that information. So obviously these studies are limited by sample size and none of them had follow-up after 12 months. And most of these procedures are only cleared for general soft tissue purposes. None of them are technically FDA approved for GSM or tightening per se. They're all general skin tightening or things like that. Well, there's also radiofrequency with microneedling. And so that's morpheus. That's kind of a newer approach. And again, came from face and body. Then got translated to vagina. So what's the difference? Well, microneedling clearly creates micro injuries into the vaginal tissue, which is stimulating deeper collagen remodeling and allowing that radiofrequency to be delivered in a slightly deeper fashion. So when combined with radiofrequency, not only does it do tissue heating, but it drives that tissue heating deeper and does perhaps a bit more for tightening. So a study on fractional RF microneedling with GSM, again, showing improvements in all of our markers, vaginal elasticity, lubrication, symptom relief, improved collagen density has been shown and vaginal architecture. So these are all beneficial treatments for women because they're not hormonal. They're minimally invasive and done in your office. Now this one needs numbing. Okay, microneedling doesn't feel good. I've tried it. I've done all these because I like to tell my patients what they feel like, okay? Appropriate numbing, it's fine. Takes a while, gotta numb for 30 to 60 minutes, okay? But it can provide an option for women who can't take estrogen therapy, who want alternatives. And in those women where your estrogen's not absorbing, this guys, because now I'm improving the tissue and now that estrogen absorbs better. So I'm a big believer in multimodality treatment for these women. It doesn't mean they can't use those other therapies that are FDA approved, okay? It can help the absorption. So now those things can work. And when you do microneedling or injury, thermal injury to tissue and those microchannels, think of it like aerating your lawn and then fertilizing it. It works better, right? Why do we aerate lawns? Because it absorbs into the soil better, right? Same thing happens here. So with the microneedling, it gives a more precise heat delivery. The pins are coated that are delivered and you have different depths, usually one to three millimeters. And the coating is a safety coating that insulates the epidermis so you don't get spread and it doesn't slough off, okay? And it creates those microchannels, which again can give potential for biologics as well. So PRP, I apply it at the end of my treatment. Exosomes are a new thing out there. They're the signaling messengers from cell to cell, which may even be better than PRP. Stay tuned. There's a lot going on in the regenerative medicine world, which unfortunately we don't bring to our conferences. I have to go to other conferences to learn about, but I'm bringing it to you a little bit today to think about and start reading and learning about. These things penetrate and enhance neovascularization and mucosal thickening and are the multimodal approach that I'm talking about, especially in the women who will not do estrogen. So what are our limitations? We don't have long-term efficacy and safety data. I can give you my anecdotal experience that I'm not seeing a problem with it. I don't expect to see a problem three years later, okay? But we do need more studies and stay tuned to what's happening there and watch our patients. So this is a study by Karam in the Journal of Sexual Medicine this year. Multi-centered prospective study case series of women with GSM confirmed by the VHIS. They received three treatments, four weeks apart, and followed up at six months. 71 women were enrolled, and they were also looking at pain scores with each treatment as well as the quality questionnaires, the UDI-6 for urinary distress, female sexual function index as well. So low pain scores, so they must have numbed appropriately. They definitely saw an improvement in the VHIS score from baseline to three months as one of their objective measures, and that was sustained at six months, which is nice to see. Significant improvements in the urinary distress inventory and the sexual function index between baseline and six months. No adverse events were reported. So this suggests that RF ablation of the vaginal canal using the RF microneedling device is a safe and effective treatment for GSM, but also seeing subjective improvements in urinary incontinence and sexual function, okay? So who doesn't want that benefit? Stay tuned. There will be newer studies done currently looking at increasing the depth of those pens, not currently available, but that is ongoing. So what's another emerging treatment? So this is brand new. I just learned about this, and it's called VITA-AV. It's a non-hormonal disposable device. Works totally different than the lasers in RF. So this stimulates the body's natural healing process by a negative pressure treatment, a vacuum, okay? It's basically a vacuum device with little microchannels creating slight microtrauma, right, what's the underlying theme here? Microtrauma, just a different way of doing it. So this one's a quick therapy that doesn't require any numbing. Five-minute therapy, and you can see in the pictures there the little microchannels. This is magnified, but you can see what it looks like afterwards, after the treatment. First human trials showed 10 out of 12 had improvement in their most bothersome symptoms, eight out of 12 improvement in the VHI, the Vaginal Health Index, and 12 out of 12 patients rated it good or very good. Comfort was a 12 out of 12, so very low pain procedure. Approval process is undergoing right now for the FDA and in Europe.

genitourinary syndrome of menopause

vaginal estrogen therapies

non-hormonal treatments

DHEA

emerging therapies

VITA-AV device

multimodal approach