I'm going to, I want to go ahead and push the agenda forward just because it's a lovely city worthwhile going out and seeing things tonight, worthwhile looking around and enjoying yourself for a moment. I'm going to start with a little clarification. There appears to have been a bit of confusion about reimbursement for percutaneous tibial nerve stimulation. I've gotten quite a bit of email in my box and a few texts. So let me try to very briefly clarify that. The CMS reimbursement policy is going to be, it's ever in motion. It's quite fluid and it can vary among the DMERCs. In general, everyone allows for 12 weekly sessions of PTNS. Halfway through that 12 weekly sessions, you need to document improvement. The current policies are at least 50% improvement. You've heard that number over and over, so that's not a foreign number. In my DMERC, they allow for nine monthly maintenance sessions. If you schedule them every other month, there's no policy against that. It says it can be generally every month, but it does allow for some flexibility there. And I searched through every DMERC I could find over the last 15 minutes and I found one that allows for 45 lifetime sessions, which would mean you could go up to two or three years and that's even better. I'd love that too. So if you have questions about PTNS, if I could ask you to seriously talk to me first and then I will get 25 more emails. So thank you very much. So let's talk about burning and stinging and lower urinary tract pain and recurring urinary tract infections. It's a tough area because it's something that unfortunately everyone loves to give away. The attending physicians that I worry would love to give that away to the APPs. Urogynecology often likes to give that to urology. Urology thinks of it as hot potato and they say, you know, don't you think the urogynecologists are really better at managing IC than we are? If it's a surgical question, there's no doubt who's better managing. You know, the surgeon says, I am. You know what I'm saying? But this is one of those hot potatoes that everyone gives back and forth. So we'll try to do that. I don't have any financial disclosures related to this one. But the objectives speak for themselves. So let's start out with a few definitions. I think we have to start here. Symptomatic urinary tract infection needs to be culture proven. If you want to have the highest level of evidence, it's perfectly okay to treat based on empiric evidence as you well know. And again, you can see the idea of what we're looking for symptomatic wise. It does vary slightly from guideline to guideline. Let's leave catheters out of the situation for right now. But it's generally such things as suprapubic pain and discomfort, dysuria, changes in urine character and color, no susceptive urgency, again, pain and stinging, frequent urination, hematuria can occur with that, and new or worsening incontinence. New incontinence would be generally an individual who probably already have OAB, but perhaps not. The recurring is going to be three or more culture proven urinary tract infections, symptomatic UTIs in a six-month period, or greater than three culture proven UTIs in a single year. So it's more than two a year would be probably the maximum we would consider to be, quote, epidemiologically within, shall we say, the mid-range. Asymptomatic bacteria, it should not intervene except for certain circumstances. The obstetricians are going to know exactly about how that relates to particularly third trimester of pregnancy. And I'm not going to tell the experts how to do their job. You tell me how to do that job. And then we're going to talk about the final big fat word on this is interstitial cystitis, painful bladder syndrome. And that's the one that's so difficult to deal with. It's the hot potato that everyone wants to give up. It's well as recurring urinary tract infections. I'm going to do my best to try to cover these issues. So let's start out with the myth of sterile urine. By the way, in case you're wondering about it, the big name on this slide is Linda Brubaker. If you don't know Linda Brubaker, you should know Linda Brubaker. She's, in my opinion, perhaps the most gifted researcher in her generation. And that's saying a heck of a lot. That's saying a heck of a lot. And among the amazing things that this woman has done over her career is she started to look at the urobiome. In other words, the normal colonization, the normal bacterial biome in urine. So there's no such thing as healthy urine. The idea that a certain proportion of women have asymptomatic bacteria is probably more of a reflection of our lab abilities, our laboratory examinations. And there's also some ongoing research that gives us an idea that the microbiota in normal women, number one, is age-related. It probably does evolve some during age. And we're coming up with some very broad ideas that certain predominant microbiota may be more prone to things like recurring UTI. So that's hardly the only answer. And so on and so forth. Again, these are correlations only. So what is painful bladder syndrome and IC? I have to call out a name here, too. This is a urology colleague. His name is Chris Payne. Anybody on the West Coast knows Chris Payne. Chris Payne has given this lecture multiple times, but I heard him once, perhaps one of the first times he gave it. And he basically divides interstitial cystitis up. And he says it's basically an umbrella term, which most of us would have agreed with. But he actually picks out the elements underneath that umbrella. It's a symptom syndrome. The characteristic symptoms are frequency, urgency, and cystitis-like, including no susceptive urgency. Again, pain-induced urgency, frequency. Most women will frequently urinate and achieve or experience transient relief only. A smaller group of those women will also have post-micturition pain. That's really the worst of both worlds. Hurts before IP and then, thank you, after IP. Payne argues for four phenotypes, classic interstitial cystitis. It will respond to intervescal lidocaine, myofascial subgroup, clear trigger with a sudden onset. These women, and I've seen these women over the years, they will say, I was perfectly fine and I woke up one morning with bladder pain and it was a sudden trigger. It can also be a traumatic trigger, such things as violence being visited upon these individuals. The idea of pudendal neuropathy, that's pain with prolonged sitting. Again, I don't see this as often, but they often will have normal bladder capacity and less severe LUTs. And finally, this idea of systemic pain. These individuals are going to have generalized pelvic pain. They may have fibromyalgia. They may have multiple allergies and hypersensitivities, chronic fatigue syndrome. Someone said, if you think it might be, would you give cetirizine? And that was an interesting question that was asked about that. And Payne would argue that in these individuals, that's probably something that you would use. But if you notice, the speaker said, that's not where I normally go first for IC. Why do you think one set of physicians and APPs are going one way, the other going the other way? And the answer is, we're all looking at this huge umbrella. And a lot of it's going to depend on the specific patients that we see. So then, it's what we call classic interstitial cystitis, a type of this. Is it one of those under there? Well, if you look at what we now think of as classic interstitial cystitis, and remember that we're coming from ignorance, really, with a lot of this diagnosis. But nevertheless, when you talk about things like Hunter's ulcerations, pictured at the top right of that slide, and you think about the fact that the patients who have classic interstitial cystitis, you look in with a cystoscope, and you don't just see those little ameliorations, those little dots where the bladder wall is hemorrhaging, just a wee drops and drops and drops. But you actually see a big old ulceration in there. They have very intense lower urinary tract symptoms. These are the women who have frequency 20 and 5 and 30 times a day. They have very, very severe characteristic widespread inflammation. It tends to occur later in life and not earlier in life. So that's unusual, right, for interstitial cystitis. It's associated with more intense pain, more urgency, very small bladder capacity, so on and so forth. And there's no evidence supporting PBS turning into ulcerative interstitial cystitis. But this interstitial cystitis, if you take definitive actions, you can actually relieve those symptoms somewhat dramatically. It's the only form of PBS, painful bladder syndrome, that this applies to. So when we talk about recurring UTIs versus interstitial cystitis versus painful bladder syndrome, you have recurring UTIs over here. You have ICPBS over here. We're beginning to make some distinctions. I think pain has the first categorization. It may not be the final categorization. And nevertheless, think about how many patients you see, what do they come in with, burning and stinging and frequent urination. So let's talk about each of these and try to break out some of the principles of management. So we're going to talk about the typical presentation here. It's a 35-year-old woman. She presents in consultation. The provisional diagnosis may be chronic UTI, OAB, dysfunctional voiding, burning, and stinging, right? So those get thrown around for this entire group of things. She's probably visited multiple providers before she came to see you. She's frustrated. She's angry. She may be tearful. She's likely been treated with antimicrobials for previous UTIs. And she says, you know, I was on a two-week course, and I finally got better three weeks later. So I guess I just don't respond well to antibiotics. No, we're mistreating her. You know, we're simply not addressing her issues. Her negative feelings are often driven by recurrence of these learning track symptoms, recurrence of learning track pain. The treatment either resolves it transiently, or they experience partial resolution over a period of weeks. And then it flares and comes and comes and goes. And one of the first things that I always say is, what you're experiencing is real. That seems like such a silly, obvious statement. And I often get a flood of tears and a statement like, you're the first person that says I'm not crazy. I actually don't believe that folks are going to say, honey, you're crazy. I'm saying that in a terrible way that it sounds, OK? But I do believe that many providers do give off that there's something not right about you rather than there's something not right about my diagnosis of your learning track condition. So it's something that I think that we need to be extremely aware of. So let's start with recurring UTIs. The good news about recurring UTIs is we can get some laboratory affirmation of what we're talking about. I'm going to be referring to some of the AUA guidelines. There are also SUFU guidelines. And the Canadian Urological Association also has some guidelines. And I'll be giving you a reference there. First off, what are the unresolved challenges? This is a qualitative study. The nurse practitioners in the audience are particularly sensitive to these because we get exposed to a lot of these in our nursing education. And it's a study of 26 women with recurring urinary tract infections. These were carefully, they were objectively diagnosed. They didn't just go on the internet and ask people to do that. They had had an average number of UTIs since diagnosis would be about five per year. Sorry about that typo. And here's what they say. There's too many points of care in the health system. No one owns my problem. I think that's very realistic. No one wants to be the recurrent, I'm sorry, I cannot name a single urological provider who says, I'm the recurring UTI specialist. Nobody claims that. I can think of an APP who says that either, which is pretty amazing. They want the recognition that this is not the same as having an occasional once a year, once every other year UTI. 52% of women will experience acute cystitis in their lifetime. And if I have a woman who says, oh, I had a UTI two years ago, and now I've got another UTI, you don't hear this level of frustration as when I've had four in the last year. And I keep getting treated, I keep getting treated, okay? They have suspicion that we're managing this based on guesswork. I don't know why it's a suspicion. I can tell you it's a certainty that we're doing this based on guesswork. But this is something that they find alarming, and I can understand why. You know, if I come into my provider and I have a diagnosis of, you know, bladder cancer, and I expect to have pretty rigid guidelines, you know what I'm saying, even if, I mean, I'm a urologic provider, even if I weren't a urologic provider, I would want to have rigid guidelines. With the current UTIs, we really don't have fabulous guidelines. You're going to see quite different approaches. And finally, they keep telling us to trust a self-diagnosis. Now that's a two-way street. It's a difficult thing to do. But certainly, there needs to be a balance between her getting quick access to care that's effective and suits her needs versus, I'm going to keep 500 fluoroquinolones in a great big bottle at home, and I'm just going to munch a few. You know, what we don't want to be is the chicken advertiser that says, throw the antibiotics at the car, and the lady's throwing, at the problem, and then the lady's throwing antibiotics that are injured because it doesn't work. I can see both sides of that. So the initial evaluation is going to focus on differential of recurring UTI from some of this, again, this PBS, painful bladder syndrome, non-neurologic causes of pain. You need to look at recurring episodes of hematuria with a suspicious eye towards urothelial or other urinary tract malignancies. And then finally, these inflammatory lesions. I see them a lot. I'm a highly biased practice, meaning that I'm seeing the referral, referral, referral. But there are these things like cystitis, cysta, you know, so on and so forth. And you just want to be aware that there may be inflammatory lesions that are going to be specifically addressed in order to provide her relief. Try to work with your care providers, your primary care providers, to begin to take urine cultures when a woman is now developing recurring urinary tract infections. Empiric treatment is exactly appropriate for a woman who comes in once or twice a year. If she's now had her third or her fourth UTI, say second or third in the last six months, four in the last year, it is time to start getting serial cultures so you get a sense of what it is that's going on. Is it E. coli every time? Is it serratia or something atypical and unexpected every time? Then we can start looking. Maybe it's a stone, you see, stone specialist, a urinary calculi specialist, looking at these sorts of things as compared to some other potential cause for this. Again, you want to begin to think about more culture-driven or sensitivity-driven courses of treatment. And finally, you want to repeat the study or obtain a catheterized specimen if you're getting lots of contamination with these urine cultures that you're running. Obtaining culture is definitely more than just an academic exercise. That's a big study there with over 48,000 women, and they found that obtaining a culture and using empiric-driven treatment, again, reduced risk of hospitalization, the need for escalating to intravenous or parenteral antibiotics. It does cause you to come in more. And then finally, culture aids in determining the clinical relevance of bacteria. There is an ongoing set of more quantitative urinalysis and culture, I'm going to call them related tools. One of the vendors here can talk to you about that. That is one vendor. There are other companies, but I will encourage you to begin to look at some of these quantitative things. These approaches are still kind of taking a little bit of a, the guidelines have not yet caught up with them, but there is ongoing research, and I think that you'll see some more with that. Focus history and physical examination, again, look at their main bladder management strategy. Are they spontaneously voiding? But do see, are they doing something like intermittent catheterization, in and out, indwelling catheterization? Some women will wear an indwelling catheter overnight. That's going to be large in your neurogenic learning tract dysfunction, folks. Be sure and differentiate urgency with fear of leakage versus chronic nociceptive urgency. Okay, again, if it's chronic, the so-called chronic UTI, you may want to go down the PBS road. If it's urgency with fear of leakage, go down the overactive bladder road. Look for vaginal discharge or irritation, ask about menopausal status, post-coital UTIs, contraceptive methods, and of course, use of spermicides. Talk to them about previous abdominal pelvic procedures. You've already heard about pelvic organ or vaginal wall prolapse. I won't talk about that much, and of course, other pelvic pain syndromes. You're also going to hear a lovely talk tomorrow about pelvic pain syndromes. Don't do these all the time. Number one, upper urinary tract imaging, not every woman who has four UTIs in a year is going to benefit from an abdominal CT, though that appears to be where a lot of these women are guided. Cystoscopy, some people do cystoscopies a bit earlier than do other people. Don't do it as a routine. Think about it and think, is it justified in this sense? If you've got a woman who has recurring microscopic hematuria and you just have a suspicion, then do that cystoscopy. That's an excellent indication. If you do it second visit, just as a routine, consider the rationale for doing that. And I do urodynamics, but I will tell you that the chances of me giving you a urodynamically useful diagnosis that's going to impact your management of recurring UTIs is one in a hundred. About one in a hundred. I rarely give you anything. I can give you things like dysfunctional voiding. That will impact. I can give you things, rarely undetected neurogenic low urinary tract dysfunction, usually it leads to multiple sclerosis, tragically. That is extremely rare. So urodynamics is good, but it should be deep, deep, deep in your pocket. And I do that for a living. When you're talking about the principles when managing individual UTIs and recurrence, again, don't treat asymptomatic bacteria. If you're going to give a patient self-start therapy, be sure that she understands when to use it and how to avoid overuse. If she overuses it, then she's going to wind up with drug-resistant organisms. That's not going to help her, and it's not going to help you. Treat symptomatic UTI with first-line antimicrobials whenever possible. Trimethylamine sulfamethoxazole is a great one. Nitrofurantoin, Fosamicin. I've heard a few digs at Fosamicin. I still find Fosamicin to be, in some cases, a very useful drug. It's, as you know, it's a single dose. You mix it up with, I think it's 60 or 90 mLs, I'd have to look at the package. And then, you know, it can be drunk down. It can also be used in certain instances for suppression or prophylactic. And I think that my ID guys, my infectious disease colleagues at the University of Virginia, don't like us to use it because they're worried about some of the antibiotic stewardship things. But I think used correctly, it is a possibility. Limit duration of treatment to seven days. Extending treatment increases her risk of adverse side effects. It does not increase the efficacy of her treatment. The last thing I want to do is give her 10 adverse side effects, because you know what? She's going to start reporting. Same thing, I'd start reporting. If I were a patient, didn't know about hypersensitivity, allergies versus, they're going to say, sorry, I'm allergic to that drug. And if she's giving you 10 allergies because she's been over-treated and had a lot of adverse side effects, she's cut herself off from treatment options. You have to tread carefully to not cut yourself off from treatment options, so on and so forth. And finally, if the pathogen is resistant to oral drugs, treat with a culture directed. Always get culture if you're going to go to parenteral stuff. Parenteral antibiotics, as short a course as reasonable, no more than seven days. Update, there is a new antimicrobial for non-complex urinary tract infections. And I'm going to do my best with the words. This is what I call the word jumble antibiotic. Jepotitisin is a broad spectrum antimicrobial. It's going to be given, or it is being, the IND reads 750 milligrams twice daily. Sorry, I didn't get the twice daily down. It's a brand new slide for a five day course. It's the first in a new class of these, oh boy, here we go, triazine synthetholines. There we go. Topoisomerase inhibitors. So I'm going to call them TTIs. How does that sound? We're going to call them TTIs for a moment, because that's too big a word for me. And the idea is that the mechanism of action is going to sound familiar, but it is only just that. So what does it do? It inhibits two enzymes. Again, topoisomerase is three, which is also called gyrase or DNA gyrase if you look in the literature, and then topoisomerase four, which just gets called four. It was approved by the United States Food and Drug Administration March 25, 2025. The IND that I'm going to be talking about, and I'm going to just talk about the one IND, is non-complicated urinary tract infections in females, women, and girls, or whatever we're calling 12-year-olds these days, teens, adolescents, lovely people. Again, non-complicated UTI. There are a couple of pivotal trials, except for one recent trial in the UK. I don't think of any US trials that look at a true placebo for urinary tract infection because of its implications. So they compared it to an active comparator, and that was Nitroforantoin given 100 milligrams twice daily. That's the BID version of that particular drug. Again, gepatitisin was found to be non-inferior in the, quote, EGLE I trial. That's the official name of the trial. It was actually found to be statistically superior to Nitroforantoin in the EGLE II trial. They used the typical outcomes for this, symptomatic and microbiologic. I'm going to call it, in quote, sterilization of the urine, a resolution of the pathogenic. As with all the adverse side effects, diarrhea, when you combine EGLE I and EGLE II, 16% overall. When you combine that, nausea, 9% overall. Vovovaginitis, 1% overall. So that's pretty good. I'm going to go back to the mechanism of action and pick up a dangling participle that I forgot to tell you. And that is that if you look at this mechanism of action, it sounds like a quinolone, right? It sounds like a fluoroquinolone. It is not a fluoroquinolone. It is a unique. The fluoroquinolones do the same basic thing. They interfere with enzymes and unwrap, essentially, DNA synthesis, and the cell dies off. The bacterial cell dies off. But this is two particular ones, so it's a little bit more specific. And it is a similar but not. It is a unique and new class. Even though there has not been reports, I remind you, and even I looked at the package insert, which is what's quoted down there. The package insert says, we cannot tell you that C. diff-associated diarrhea or antibiotic-associated diarrhea is not going to be a potential outcome. We just don't have enough experience yet. So I would say that CDAD or ADD, whatever you want to call it, antibiotic-associated diarrhea, AAD, is going to be on the table. I will also tell you that this is not going to prove to be, and I'll just say this, and you can call me wrong. And if you prove me wrong, I'm going to be thrilled. But there's no way of looking at these data and say this is going to be the one antibiotic that's going to be resistant to resistance. You see what I'm saying? The bacteria will eventually, they're smart little buggers, whether we want to say that or not. They're already practicing, right? We're 30 minutes in, and they're two generations in. You see what I'm saying? So used badly, we're going to get resistance. I'm old enough to remember. Some of you may be, many of you may not be, but I remember when we were told, and it was thumped on in almost every major meeting, you need to be giving fluoroquinolones as first line for UTI treatment because there's such little resistance. It's such a great drug, and now we have five box warnings on that class of drugs. Five box warnings. So overuse, I'm going to just raise my hand up and say we've got to avoid it from the get-go because we are way behind in this little skirmish we're running with pathogens, and we're losing badly, as you well know. So there it is. I'm rather excited about that. We want to talk to them about fluid intake. In almost every study that's ever been done, the women were taught because they saw good research nurses increase those fluids. And you know what happened when they were taught to increase the fluids? The UTI rates went down in both the placebo groups and in the treatment groups. I'm referring to things like cranberry and a lot of the supplements, as well as some of the other trials. Again, I would say using either the US Food and Science Board, which is 30 milligrams per kilogram for 24 hours or half an ounce per pound per day, or you can go with the IOM, which I find a little bit easier, which is roughly about 1,500 to 2,200 mLs in women. I would remind you that that does not count for the 20% boost they get from their food. And then it's slightly lower in adults. I would also remind you that this is for persons with moderate activity in moderate climates. This is for the office worker, for the, we used to say, white collar worker. It is not for the woman who's out working construction in Tempe, Arizona. So it has to be modified based on individualized needs. Hygienic measures are often recommended. The supporting evidence is pretty weak or absent. It's hard to really study in any great way. But hand hygiene always, there's just no way not to do that. In terms of bath water, taking baths, the addition of perfumes and chemicals to the bath water appears to have a more irritating effect. So there's some weak evidence that probably it's going to slightly increase the rate of urethritis, possibly urinary tract infections. What about these dietary supplements and these types of things we can use to prevent recurrences of urinary tract infections? The best is probably cranberry. There still are mixed outcomes. There's the most recent one that I could find was from 2025. It's from the American Journal of Clinical Nutrition. It was an RCT done in about 150 women. And they used a, quote, whole cranberry powder capsule. And they found that it reduced UTI risk by pretty much 52%, with a risk ratio of 0.48. As you see, the intervals did not cross the one. So it is a statistically significant and clinically relevant outcome. So I can also quote you things that were not as positive. I'm a little bit pro-cranberry because I worked with Betsy Foxman. And she had a very nice trial where she showed some benefit to this as well. At worst, you're going to do no harm. The tragedy with this is that with many of these supplements, the more expensive the supplement, the more likely it is to be effective because it has higher amounts of active ingredient in it. In this case, paranthocyanins are why the cranberry is effective in preventing UTIs in some women. Sexual activity is a well-established risk factor. Again, this is just basically a kind of guideline sort of interventions, less frequent intercourse, limiting partners, hand washing, voiding within 30 minutes of particularly when intercourse is part of intimate actions, and also switching birth control methods. Again, I just remind you that there's always a lot of interplay between these factors. So I can't tease out the magnitude of each of these problems. But these are things that can be safely recommended to women, particularly those who are sexually active of childbearing age and so on and so forth. Patient-initiated antibiotic treatment, I still think it's extremely effective in women with good education who are self-starters and self-managers. If they have an internal loss control, I will take care of my health. I'm responsible for my health. That's a woman who's going to be good for this treatment. If she says, you know, she puts her hand up to her forehead and she says, doctor, it's the worst case I've ever had in my life. Nothing helps. What are you going to do about me? She may not be as good a candidate. She may turn into a good candidate. But that external loss control, it's going to be more of a difficulty getting her to buy into that treatment. Unfortunately, the outcomes of these trials have not been great. You have to balance it against the overuse of antimicrobials. You also have to balance it against shopping. I've had patients who come to me and they say, I have recurring urinary tract infections. I do not want cefalexin. I want cefireme or whatever version of it they want. I do not want ciprofloxacin. I want levofloxacin, and I want that first, and I want that only. That is my antibiotic. I love that antibiotic. It's my baby. Those types of relationships aren't doing us any good, because the drug is only as good as its effect in a certain urinary tract infection. And I think that we unwittingly, and I'm talking about the big health care, not the urogynecology, not the urology, but the big, big, big health care, do drive that when the primary care provider says, OK, if you'll let me go to my next patient, I'll prescribe whatever you want. And that's a difficult thing, but I also have sympathy for them over that. Again, you want to counsel your patients regarding the risk, benefits, and alternatives. You can also consider prescribing antibiotic prophylaxis. It is effective over the first six months. There's no doubt about it. Every research trial that we've looked at shows it's effective over the first six months. I've given you a, essentially, systematic review of 28 trials. Again, if you look at that, it's the relative risk is going to be 0.26. That's quite a bit below above 1, so that means it's reducing that risk. The Cochrane review, again, they had a relative risk of 0.21. Remember, anything below zero means it's a good protective factor. Now then, it comes at a price. The first line, antimicrobials in these trials tend to be nitrofurantoin, trimethylmethoxazole, a single strength. And some will be trimethoprim only, and others will be a cephalosporin only, often a cephalexin because it's a first generation, economic available drug that can be given for prolonged periods of time. Again, recurring UTI in women. Administers a lower dose of empirically selected antimicrobial. First line are gonna be most commonly, you have to look at the pregnancy category on these. Fosamicin every 10 days is a category A, so it is a safe in that, and it's been reported good outcomes. I just don't see it used in clinical practice. Some of you are shaking your head. I expect that your ID people are like mine. They say, no, no, no, please don't use that. No, no, no, don't use that. So I don't know where else to go with that. Again, here's the thing. Typical duration, six months or less. Do not leave your patients willy nilly or let your patients be left willy nilly on a suppressive antimicrobial for years, for more than six months. Here's the risk of adverse risk of side effects. Again, if you look at the Cochran Review, again, it goes up to about 1.58. For any side effects in one of the other ones was 1.78. And what are these risks? They're not nothing. Increased risk for ED visits for UTI and sepsis. Increased risk of multi-drug resistant organisms, and of course, an increased risk of C. diff associated diarrhea. Couple of specifics, nitrofurantoin, pulmonary fibrosis, hepatotoxicity, exacerbation or creation of new peripheral neuropathies. They are uncommon, but they do happen. And I have patient after patient that I've seen over the years, particularly neurogenic learning track dysfunction women who will have some of those things. Trimephthalate, sulfamethoxazole, hyperkalemian patients with CKD, bad adverse effects if they're taking ACE inhibitors or ARBs, hypersensitivity with adverse skin reactions. They are rare, but you do see that occasionally, and they can happen months and months after she starts. It's obviously extremely rare, almost unheard of, but there is a tiny, tiny one in a million risk, I suppose, of Stevens-Johnson or some sort of more severe reaction. All the drugs are gonna increase the likelihood very significantly of multidrug-resistant organisms. You wind up playing, unfortunately, that means that she's gonna be playing for higher stakes with more antibiotic-exposed and sophisticated drugs. What about postmenopausal women? I will tell you that in our practice, we use this very frequently. And my colleagues, I live literally next door to the urogynecology department at University of Virginia, and they use it pretty liberally as well. We do tend to have, at least within university agreement about this, that intravaginal estrogen will give the postmenopausal woman a vaginal vault that is more resilient or more resistant to the typical coliform E. coli and all the nasty cousins that go along with that particular one, urinary tract infection. Again, retrospective view, a little over, well, almost 6,000, between 5,000 and 6,000 women. And the idea is that, again, it reduces the UTIs by 50% in the first year following initiation of treatment. And I've given you some other positive ones there. So I think that it is something that you should seriously consider. I have no evidence at all related to oral agents, so I'm strictly talking about intravaginal, exactly what you would be doing in your normal practice for these individuals. I think the antiseptics are worth taking a look at. Usually it's gonna be something like methanamine that's gonna be administered a gram twice daily. It's excreted pretty exclusively in the urine. It converts hexamine to formaldehyde. It drops a urinary pH, and that has an antiseptic activity. Okay, again, how big an effect is it? The Cochrane Review is a little bit older. It's only 13 studies. It's just over 2,000 women. Poor rating on that, but basically they said it was more effective than placebo. D-mannose, mannose, monosaccharides, no evidence supporting their utility. At worst, you're gonna do no harm. I'm not gonna ever criticize you. If you're using that, keep using it because you're going to do no harm. Even if you get your women to drink more fluids as part of some of these supplements, you're already doing good, and we have evidence to support that much. Physical therapy is well-established for women with pelvic floor muscle dysfunction. We've already heard about high-tone pelvic dysfunction. It's routine care. Physical therapy is useful in a very tiny subgroup of women with recurring UTI, and that are those who have some other dysfunction avoiding. The idea that we should routinely send women with recurring UTIs to physical therapy, I don't have any evidence to support that or suggest that that's economically viable. Plus, I have a tiny workforce. In my area of the world, I don't have a lot of pelvic floor PT specialists. They are diamonds to me, absolute diamonds, wonderful clinicians and very scarce clinicians, and I'm not sure that I'm really willing, you know, if we flooded them with our PTs, we'd never get a poor woman with dysfunction avoiding or ICU who desperately needs them now into their offices as they'd be so flooded with this other larger group. So again, if there is evidence of pelvic floor muscle dysfunction, get them into PT immediately. Those are probably those who are gonna benefit the most. Wow, a lot about recurring UTIs. Let's talk about interstitial cystitis and painful bladder syndrome in some more detail. First thing, again, the history is, I've sort of talked about before, but it's pain and pressure. It needs to have lasted more than six weeks. There's no instrument I can recommend to you, but here's what you need to do when that patient walks in. Take a deep breath, sit down, and let her tell her story. It's not, it's painful to hear because, not because I don't wanna hear her, but because it's a painful story. She's gonna be talking about being ignored, Being subtly or explicitly told she's an irritable patient with an irritable bladder. She's going to get negative comments. She may have a partner who is extremely unsupportive. I hear that all the time. He and I no longer have relationships. She and I no longer have relationships because he or she does not understand what I am going through and we are now isolated from one another. So now she has less support. You see what I'm saying? Now she's two steps away. Allow her to tell her story. The simple things that I say back to her your pain is real, your symptoms are real, I hear you. And just like I said before I get amazing responses to that. It is simplistic as all get out. Give her, I do gently bring the story to an end but give them at least five or maybe even ten minutes to tell that story. Gosh that's hard to do but it is so useful with your new patient. Abdominal examination is going to be for masses. Tenderness, hernia, pelvic floor muscle tone. They're going to be you know when you if you do a vaginal exam I don't need to tell this group to be gentle. If it was a group of gentlemen I would say for God's sakes be so so gentle. But you know you're not going to have rubber bands that are normal right? We say rubber bands are normal we say that you know no tone at all. They're going to be piano strings and you can just touch that and her whole pelvic may light up, her whole pelvis may light up. So you're going to have high tone and discomfort. Okay so palpate very very gently when you do that. Again she may have trigger points. We talked about suburethral diverticula you know like that there may be trigger points and you may have an individual who does have an untreated or unrecognized suburethral diverticulum and if it's like the one that I showed you earlier this morning on with the x-ray that can be cause a lot of irritative warning symptoms. It can cause a lot of pain and pressure and dysuria and post void pain. The woman that I showed you I didn't get into her case deeply but that's exactly what she had. She was diagnosed with interstitial cystitis PBS and she literally traded worsening exacerbation of her incontinence because of the location of suburethral diverticulum. The surgeon did a great job none do with that for that and she said my life is so much better I can deal with this leakage I couldn't deal with that pain. So just think about that from an individual thing and of course prolapse and then assessment for obviously an infection. You're going to do your analysis they're going to have had buckets of your analyses they're going to have all kinds of that stuff you generally don't have to go very far with that. Do a do a bladder diary it's well worthwhile. Do a evaluate her learning track symptoms. I think that your dynamic testing is only useful when she has other dysfunctional voiding goes along with the chest frequency urgency and it's no susceptive induced urgency. You do not need to do your dynamics to prove that. I've made too many women cry with your dynamics to even get a little bit of fluid in there because it's simply an uncomfortable examination. Any more than I'm you know really want to go back to the potassium sensitivity testing days again many of you won't even remember that but that was a no no fun thing as well. Obviously cystoscopy the big thing about cystoscopy is she has very intense pain and very intense symptoms. She may need cystoscopy under twilight or under anesthesia to rule out classic Hunter's ulcerations. Why am I so anxious that she have that because if she has classic Hunter's ulcerations we have a lesion. We have a protocol and we can give her often up to about 90%. We can give her very significant relief. So that's important I think. And again you also want to you do want to look for undiagnosed cancers and other things like that and she may have benign stuff the inflammatory myofibroblastic tumors they're pretty rare but again cystitis cystis cystitis glandularis. Again lesions that we can go after and give some interim relief from her symptoms. We're going to do a lot for you. We're going to give you a lot of interventions and we may not know exactly which one is going to make you better. Help us to understand how these treatments affect you. Okay you're going to do behavior and pharmacologic treatments. You're going you may do or a plus or minus intravascular. I've already heard a mention today of intravascular therapy for individuals in her cystitis. They are it is effective some people use a lot same people use it less. They may have trigger point injections. The idea is that this multimodal treatment approach is necessary in order to get a good hold on her pain and a related learning track symptoms. If they don't work move on to something else. A little bit more Franklin Roosevelt and a little bit more stay the course. I don't I can't think of a president that said that but I'm sure somebody said that. Don't stay the course. Don't say you have to have six months to see if it's really effective. If she tells you after months it's ineffective try something different. Try a different combination. Interdisciplinary care is often indicated. We frequently will consult with our pain management colleagues particularly some of these PBS variants that are more systemic and we'll respond to that. If she's got classic interstitial cystitis we're probably going to use less of them. Okay just depends on what it is. If you again if you suspect ulcerative cystitis with the cyst with the cystoscopy again I'm going to show you some of the cases that I'm talking about. Multiple case series 106 procedures 60 patients 45 percent required repeat full duration 13 required repeat treatment within 12 months and 57 required retreat treatment within 48 months. However the initial relief in these patients was actually comparatively bright. You can use triamcinolone injections so again there's a few things that that can be used mostly there's going to be off-label. You're going to hear me say off-label all afternoon now because I'm into the IC territory. Educate her about normal lorning tract function the chronic nature of interstitial cystitis and PBS. Talk to her about symptom flare. She needs to understand what a flare means. She's understand what she can start doing about it immediately. Okay again it's a sudden rise in pressure and pain. It's a sudden exacerbation of her lorning tract symptoms. 61% of IC patients they say that they have flares that last for a couple of hours an hour to a day. 76% reported long time flares that lasted for at least a day and up to weeks. Almost everyone's going to have flares. Emotional distress acts as a trigger if she is emotionally distressed or traumatized and I'm including physical trauma to this other types of trauma to this. A departure of a spouse, a divorce from a spouse, a death in the family. All the things that occur that would that do distress any normal human being those can be triggers. Other possible triggers birth control pill changes the climacteric cigarette smoking and vaping have also been shown to be potential trigger flares and can lead to some positive health things like smoking cessation. Here's the problem with it I'm not trying to go through this table but look at the idea about these flares when they actually try to pin them down. It's such a huge list you know for one woman it may be spicy foods for another woman it may be she may have also grown up with spicy foods and find that that doesn't make a difference. Caffeine is a traditional flare sort of a thing if she over packs in caffeine so on and so on and so forth. I'm just trying to show you the number of things but when a woman tells you this is a trigger and this causes a flare I encourage you to listen to her and help her to strategize ways to avoid that. If it's spicy foods and you can do something like again you know giving her explaining to her that she may need to take a rapid-acting prophylaxis before when she goes out to eat and cannot prepare and supervise her meal preparation. Techniques to relieve that again yoga, meditation, mindfulness, deep breathing, and interacting with a pet. The latter is my preferred but you know I'll let my patients choose mindfulness I can't do I'm too type A but anyway you can decide the ones that might be dead. Removal from stressful situations they talk about taking a walk in nature taking time to be alone. A good old sitz bath there's something wrong with a lovely old sitz bath. Get in some nice warm water and you know get a candle on the side read a little book you know what I'm saying but don't put additives in the water that's often triggering. Again psychologists, qualified counselor, massage therapist, supportive group therapy online or the community let them go online and encourage them to do that. So what do you do within 30 minutes of the symptom flare this is a general strategies. Sit down using a heating pad to encourage pelvic floor they're literally sit with a heating pad on the low setting please at their pelvis to try to encourage flow. Drink water don't pour it down but drink small amounts or sips don't force fluids okay tell them that they need to have straw colored urine this is a classic British advice but it can be very good advice. Increase urinary pH using one of the following 345 milligrams of calcium glycerol phosphate I'm not supposed to be giving you brand names but you all know what I'm talking about. It's got a pre and there's a relief in there somewhere so you get the idea and you know or they can simply take a gram of calcium carbonate a half a teaspoon of baking soda dissolved in water. You know some of women who say look look look I went I looked at that bottle that stuff and that's expensive you know I got children I got a budget here and a half a teaspoon of baking soda will give a broadly similar effect with them. Okay and again if it lasts for more than hours if it's day you know when they get a day or more than a day into it then then they need to call you. Tell them to call you and let's talk about what we're going to do about this symptom flare and there's many other things that you can do. In terms of analgesics it's a little bit difficult but I will tell you with the analgesics we generally try to avoid opioids because they're simply not effective for this group. There's some women who have very very very severe flares and sometimes we will use a very short-term opioid that will help with that. In general over-the-counter analgesics are helpful to some women and other women say they have no helpful at all. Perfect floor physical therapies in my opinion essentially first-line therapy. I was on the American Urological Association interstitial cystitis guideline. By the way they wouldn't let me be on the urodynamics guideline even though I think I have more expertise in that because I was not a physician but they did let me be on the IC because you know nurses help with pain so I was like okay I'll take what I can get and I was very proud. Diane Newman and I were both and we were both very proud to be on it and I know I found that a little bit amusing myself I must admit but anyway and to be honest we had to actually have a long talk because when we looked at the treatment we basically said we're just going to give this whole group of patients up to the PTs because they have the best data of anybody in town. So I'll let I don't know how many PTs are here this year but I'll let that sink in. We literally didn't know what to do because you guys had the best data in town so congratulations my PT colleagues. Well done as a group and and what I'm going to say to you is PT ought to be first-line therapy. I very rarely see a woman who walks in with painful bladder syndrome that doesn't have high tone pelvic dysfunction. I think it's a part and parcel with that and if you can get her and help her and give her keys to relieve that high tone pelvic dysfunction then she's going to get a level not the only level but a level of relief from that alone. Qualified PTs too and most of the PTs in my community they very honestly put up their hands I say oh I don't I treat sports injuries I have no idea about any of that. So you you have to identify the APTA does have us on their site a national list it's not comprehensive that's my only objection that's not the APTA's fault. If you if you know colleagues that aren't on that list get themselves on the list any kind of marketing that you can do we're going to be running to your door as fast as we can possibly get there. Analgesics again it's sparse evidence again all use the same thing you do with all chronic diseases documentation of rights and responsibilities of the woman and yourself a paying contract single source for these things so that we're not you know multi multi prescribing low threshold for referral to pain management. They know how to handle this thing they're good at the patient contracts they're good at keeping up with their patients and I love that. Finasal pyridine again you can take it up to three times daily it does relieve burning and alleviates the dysuria. We don't know the mechanism of vaccine Alan Wien a world-famous urologist once took it and chewed it he said he had orange teeth for weeks he had thought he was going to go to the dentist and get him referred he said but he did feel numbness in his mouth for a couple of hours afterwards so it does something and again just counsel your patient I know that's I can I can't make that up true story but anyway counsel your patients regarding that pumpkin orange color that deep deep dark some of them are a little fearful that that might be hematuria so do let them know that that's not hematuria that is a deepish burnt orange sort of a color that they'll often get. Again I just want to remind you that if your patient is taking finasal pyridine for more than a month they will have an increasing creep in terms of a hemolytic anemia it does carry that risk with long-term use so don't put her on that and just say yeah because it's over-the-counter and say yeah go take that to you you know just take that freely watch your blood counts and just counts her about that that it's meant for short-term it's sort of like the ibuprofen I call it a bladders it's meant for short-term exacerbations and short-term relief don't use it chronically pentosan polysulfate is the only FDA medication approved for oral use there are medic other medications approved for use in IC it's the only oral medication it's it's a little bit difficult it only has grade B evidence in the guidelines which is not fabulous you think it'd be great a since as an FDA approved medication nevertheless there were statistically significant results but the magnitude of the results were weak subsequent clinical research has been very mixed we don't know about the mechanism of action you can get the little dump truck and get the drug rep to tell you about that it you know makes the gag layer better blah blah blah it it may restore the glycosaminoglycan layer the urethane and we just don't have enough to say that that the adverse side effects are not insignificant they include nausea hair loss particularly attractive for women who really don't want that for me it's just part of life diarrhea here's the new one there is a box warning related to retinal maculopathy and that's a real one it's not a typical effect and I'm not saying stop all your patients that is way beyond my pay grade but I'm telling you that it is a new box warning and you need to talk to your patients about the potential for changes in vision and these is significant and by the way seventy point nine percent of those cases reported women there's more men are going to be taking but nevertheless amitriptyline is off label I'm back off label again there's a single RCT that reported the efficacy of amitriptyline it was 25 milligrams titrated up to a hundred milligrams is tolerated how do you know your patients at the top of the dose they'll tell you that they suddenly feels like Benadryl they're suddenly sleepy all the time that's the most common effect that I get it appeared to be superior to placebo at four months again what is the onset of action for if I go back a slide and only I can go back a slide so I won't but anyway the onset of action for penicillin is going to be six months so these are not for exacerbations or flares this is for long-term relief sedation drowsiness and nausea is the biggest one that's seen with amitriptyline nor tryptoline I do not have trials on it's the same drug class I have no idea if it's better or worse it might be better in individual patients intravascular therapy can be quite effective it's put in it can be used for flares it does give a more direct one the oldest one is DMS or dimethyl sulfoxide that is it's been used in veterinary for in humans as far as I go for generations it rapidly penetrates the skin and the urethelium not a lot does that it's instilled and left in for 15 to 20 minutes and again it is it is indicated for that heparin or synthetic glycosaminoglycan it can be mixed lidocaine can be put in there and what you're going to see is a lot of cocktails DMS o plus some you know heparin plus some lidocaine heparin plus lidocaine so on and so on and so forth the adverse side effects generally are due to the root of administration transient discomfort when it's instilled and DMS o cause a detectable taste and detectable garlic old odor that can persist for up to 72 hours she's going to smell like she's just eaten a very garlicky dish and that has nothing to do what she had for lunch or breakfast or any other meal in her day it has to do with a drug adverse effect so if she tells you she's about to leave your office and go out for a job interview hold back for a few minutes and talk to her about that potential adverse effect and I say that only because I've had women who did that and say he looked at me funny or she looked at me funny and I thought Jesus gray you could have done a better job with that patient so don't make the gray mistake again avoid these ineffective treatments long-term antimicrobials we pretty much moved on from that but I still see that done intervascular BCG was proved did not prove to be helpful for these patients high-pressure or longer-duration hydrodistension they used to put literally they would put them under anesthesia and blow that bladder up and really hydrodistended it wind up being more long-term harmful the bladder than helpful long-term glucocorticoid these are not effective interventions for interstitial cystitis or painful bladder syndrome I've tried to talk to you this afternoon about the part of that and I'm going to call it what what we call it among ourselves the wastebasket of ignorance that we have when it comes to burning and stinging recurring UTIs interstitial cystitis painful bladder syndrome it's the hot potato please please please my APP colleagues hold the potato let it cool off and help these patients you'll get more hugs and you can possibly imagine what are your questions thank you I wanted to I actually have given a full nine minutes for questions just in case because I want you to be able to get up and say gray you're wrong and that's okay if you do yes ma'am I'll repeat the question if you can't get to a mic I got all of it, but do you recommend doing what now? The last, the last phrase. How long, how long do they treat and, okay, got it. So the question is, correct me if I'm wrong, self-start antibiotic therapy, how long do they treat it? Do you just wait till the symptoms go away? We would teach ours to do a five-day course, a regular routine five-day course. I don't know of evidence that contradicts that. That is more routine based on guidance for empiric or culture-driven. Yes, yes. Okay, I have two questions that are kind of unrelated. One is about trigger point injections. I'm trying to get into learning how to do those. Do you know of any educational training? Education for trigger point injections, I know of nothing. I would go to my, are you a PT, DPT? No, I'm a nurse practitioner. Go to your DPT colleagues, all your PT colleagues. Sorry, I just call them DPTs because that's what they're coming out now, and I love that. So go to your PT colleagues. They're gonna be much more sophisticated with that education than I. And then my other one was about, I've seen a lot of new research on low-dose naltrexone use in patients who have severe IC that not a lot of other treatments have worked on. Do you know much about that, or what are your thoughts? So far, inconclusive evidence to determine efficacy. I can tell you of at least 17 alternative treatments like that, I would take it with a large grain of salt, but don't throw it away. One day, we're gonna find one. We keep searching, desperately. Thank you. You bet. Maybe here because she was standing, and then I'm gonna come right back over. Is that okay, is that fair? Thank you. Yes, ma'am. Do you have your patients that are on methenamine take vitamin C at the same time? That's an excellent question, and I've heard that question before. So the idea, if you take vitamin C, it would boost the acidic nature of the urine. Some people routinely have their patients take vitamin C. First off, let me get rid of the stone issue. If it's a stone issue, then they're gonna be making stones, and that's gonna be a special group that you're not gonna put on either drug, okay? So let's get rid of that issue right away. The answer is that vitamin C causes an extremely transient reduction in pH. At worst, you're probably doing no harm. I also remind you that there is a small body, a very weak correlating evidence that taking high doses of things like vitamin C may increase overall cancer risk. That is very weak. You're gonna need to look at the British literature for that and I'm so ignorant about it, I can't even quote you a study right now. But there is some epidemiologic data looking at that. Just bear that in the back of your mind. I do not think there's anything wrong with taking vitamin C as a supplement until the British data becomes strong enough that I feel like that high-dose vitamin C is truly something you don't wanna be prescribing. And then I just have a second question. Do you have patients avoid any foods or drinks when they're on methamphetamine? I have patients that come to me and say, oh, the pamphlet says I can't drink milk or even citrus foods. What's your take on that? You might wanna avoid them right when you're taking it, but there's no 24-hour things. Once it gets into the tummy and down, they're okay. Yes, thank you. Yes, ma'am. I just have two things. First question was we talked about the benefits of cranberry with recurrent UTIs, but curious on if you have an IC patient or PBS patient, are you avoiding cranberry in those patients? Almost always, almost always. I would never actively encourage taking it. And if they were using it for recurring UTIs and we had no documented history, it's one of the things that I would put in the elimination diet. A lot of them come to us with that. Me as well. Yeah, they'll come on it. And then when we eliminate it, it seems to have a modifying effect, but small. The other question I had was with IV antibiotic therapy, you said no more than seven days. Is that in reference to even complicated UTIs? It does not refer to sepsis and highly complex UTIs. It's for febrile UTIs or others that we can treat in the community. If you did have one that was- If they came in septic, then they're not gonna be treated by the likes of me. They're gonna go to the ED. They're gonna go through my intensivist and they're gonna do as long an antibiotic treatment in the ID folks as long as they wish. I don't even have an opinion other than they handle that. You know, when COVID first happened, they made me trained to be an intensivist. And I said, let me tell you something. If it's above the waistline, much less a respiratory diaphragm and I'm treating it, COVID's gonna be mighty dang bad because I do not do treatment above the waistline. If it's sepsis, I let somebody who knows how to do it, do it. Yes, ma'am. I had two questions as well. One was about recurrent UTIs. I've been hearing a lot of data about the MV140, the vaccine. I don't know if you've heard at all about that or what your thoughts are on that. You know, I wanted to put a vaccine thing in here and I decided I wouldn't. Sorry. No, to be perfectly frank, it was a topical thing because I was afraid that maybe Mr. K would have his little spies in here and, you know, throw me out of medicine or healthcare practice. I'm exaggerating, of course. Needless to say, so let me start you out. There are several, there's more than just one, but that's an excellent one. There are several vaccinations for various strains of E. coli that tend to be fimbriae positive and really cause UTIs. They are, several are commercially available. In Germany is one example where it's kind of easy to get stuff commercially available. None are commercially available in the United States market. I will tell you that I think in the short term, I think that, I don't think anybody's gonna try to be bringing anything to market in the next couple weeks, to say the very least, but I think it's a highly potential and a highly likely to be effective treatment alternative, not the be all end all. Some of my women just have different and unpredictable things in their urine, but many of my women have E. coli, coli, coli, coli, you know, that type of thing. And I think for them, it could be very effective. And then my other question is about painful bladder syndrome. A couple years ago, probably in like five years ago, there was a thought process that it was histamine related potentially. And so low dose antihistamines. Antihistamines can be used. I didn't go into it in detail. The effects on those trials have been modest. And that does not distinguish them. That does not make them, but it is not FDA approved. And I do not have adequate evidence to really be enthusiastically recommending that to you. That doesn't mean that it may not work in some of your patients. And I'm not telling you not to do it. I'm not gonna tell you not to do anything that I know is not actively harmful. Okay, thank you. You bet. Go over here and then I'm gonna come back, ma'am. Yes. I have a question about use of methenamine long-term. I usually try and limit it with my patients to about six months. Some of them feel very strongly about being on it for longer than that because it's kind of changed their life completely. What risks are there for long-term use of methenamine for these types of patients? Long-term use of what drug? Methenamine. Oh, methenamine. No, that did not apply to methenamine. That applied to the antibiotics only. Methenamine is an antiseptic. Great, but are there risks with methenamine long-term? None that I, I may not know, but I'm not aware of any long-term risks such as there are with nitrofurantoin. Big fan of the drug, but again, when you look at those long-term effects, those are not insufficient. I mean, I used to, look, I've treated spinal cord injury patients all my life because there were two women back here who said, we need one of them neuro-neurologists. I'm gonna tell you right now, they don't call me the urodynamosaurus for nothing. Yeah, they're laughing when they're saying, oh, that guy was listening to our conversation. I was, because it was good conversation, by the way. But the moral story is the neuro-neurologist is very rare in practice these days. They're giving it up to other titles. So the big thing that I can say is I know of no long-term adverse effect with methanamine. Thank you. You bet. Yes, ma'am. I'm sorry if you already said this and I missed it, but when you were talking about that brand new antibiotic that came out, is it administered IV or oral? Oh, thank you very much. I'm sorry I didn't make that clear. It is not, I'm sure they may develop or they may have in the pipeline a parenteral version. I don't see why they wouldn't. But it was developed. That's why it's good for non-complicated. You don't wanna come in for shots for non-complicated. Do you know if it's available in pharmacies right now? My understanding, and please, if anybody knows more about this drug than I do, my understanding is late, second half of 2025. Ma'am, educate us. Fantastic. So were there any major points that I missed that you would like to bring out? So 750 twice daily, so 1,500 over the day, okay. Oh, my apologies, three grams a day, 15, oh, okay, that was my mistake. Thank you for correcting that. Oh, I did have Eagle one and two. And to be perfectly frank, I actually got that off of a site that had your name up at the top of it. I'm not saying it was your site. I'm just saying it was a site that had your pill and your little logo up top of it. So I'm sure it wasn't yours. Just to let you know, you might wanna go searching. It's kind of fun. So it's Eagle two and Eagle three. I knew it had an IND for gonorrhea, but I didn't wanna talk about that because it's not an STI thing. So two and three, thank you. I'll correct my slide. Thank you for that education. Oh, thank you both.

urological issues

percutaneous tibial nerve stimulation

urinary tract infections

painful bladder syndrome

interstitial cystitis

hot-potato syndrome

urine cultures

antibiotic resistance

multidisciplinary approach

gefditapin

patient education