This is Jennifer Burns. Welcome to tonight's webinar, Treatment of Overactive Bladder in Older Women. We're fortunate to have Leslie Rickey with us tonight. Dr. Leslie Rickey is an associate professor in the Department of Urology and Obstetric Gynecology and Reproductive Sciences at the Yale University School of Medicine. After completing her undergraduate degree at the University of North Carolina, Dr. Rickey earned her medical degree from Tulane University School of Medicine and an MPH from Tulane School of Public Health and Epidemiology. She completed her residency in urology and fellowship in female pelvic medicine and reconstructive surgery at Loyola University Medical Center, receiving subspecialty certification in 2013. Dr. Rickey was on the urology faculty at the University of Maryland School of Medicine from 2007 to 2013 before accepting her current position at Yale, where she's also the SPMRS Fellowship Director. Her clinical practice and research efforts are dedicated to the prevention and treatment of female pelvic floor disorders. Welcome, Dr. Rickey. And I am glad to be here. We are going to be talking about the treatment of overactive bladder in women, as Dr. Burns said, and there are also places, feel free to type in any questions that you have during the session, and we're happy to, Dr. Burns will be moderating that, we're happy to take whatever questions come up during the session. So, as everybody will know that's listening to this, we have many options for treatment of OAB in women, including first-line therapy that can include behavioral treatment and pelvic floor muscle training, as well as second-line therapy with pharmacotreatment, and then third-line therapy for refractory OAB. And we're gonna go over some of the epidemiology of overactive bladder, but there are some special considerations we need to make in older women. The segment of the older women in the U.S. is increasing, as are all older Americans, and this is leading to some unique considerations that we need to think about as we treat pelvic floor disorders in this population segment. So, in terms of the OAB epidemiology, until about 15 years ago, most of the studies were done in people presenting to the clinic, so people with clinical disease, and there was very little knowledge about the prevalence of pelvic floor disorders and incontinence and overactive bladder in general lower urinary tract symptoms in the community. There was a NOBLE study that was carried out in 2000, reported on in 2003, and it was found that about 17% of community-dwelling women report overactive bladder symptoms. In addition, women were more likely to have incontinence associated with their overactive bladder, sometimes referred to as OAB wet versus OAB dry. The EPI-LEP study was carried out in adults that were at least 40 years old, and in this group, 43% of women report OAB symptoms at least sometimes. So, this epidemiologic study incorporated a measure of severity and also some bothers. That gave us a little more information on the prevalence as well. And then finally, in both of these studies, the prevalence and severity of lower urinary tract symptoms in general increased with age, which is well-described. However, there's been some emerging data that other measures such as frailty may actually be more important than age alone. And I think most of us that see a fair amount of older women in clinic know that there is a great variety of health and wellness amongst women from 50 years old and up. And that can sometimes affect the treatment that you offer more so than age. So, what are some of the age-related changes in the lower urinary tract? What do we think happens that might increase the prevalence and the severity of these symptoms? So, there are neurologic changes that go on in the brain that has been shown that the sensation or of urge type signals, the threshold may be lowered as people get older. There is also some systemic changes. Atherosclerosis increases throughout the lifespan. And so, local atherosclerosis around the vasculature to the bladder can cause a local ischemia, which has been shown to increase overactive bladder symptoms. There's also the detrusor muscle. There are some changes in neurotransmitter release with a detrusor stretch that have been shown to correlate with a urinary urgency. The urethylium itself also secretes inflammatory mediators and these increases people age, which may change the bladder capacity. And finally, there is also the menopausal change in which there is decreased estrogen production and there are estrogen receptors throughout the lower urinary tract. And so, as part of the genitourinary symptoms of menopause, this also appears to affect sensation, urgency, capacity, and frequency. So, you put all these together and you get increase in the overactive bladder symptoms. There's also likely a cumulative effect of lifestyle impact over the lifespan. And this can include rates of urinary tract infections, childbirth, sexually transmitted infections, and other events that uniquely impact a female's bladder and lower urinary tract. So, this is the AUASUFU guideline on non-neurogenic overactive bladder in adults. And that is what we're going to be discussing today is the non-neurogenic overactive bladder. So, to summarize this slide, and this has been really helpful for me in my treatment of women with overactive bladder to both sort of target their treatment, find out where they are along this guideline, and I think organize their treatment more efficiently. But again, as people on this call will know, the first-line therapies, as we talked before, are mostly behavioral therapies, as well as pelvic floor muscle training. Then there are a whole bunch of medications, most of which are anti-muscarinics. There is one beta-3 agonist. And then third-line therapies, which include chemo denervation with Botox, as well as with neuromodulation, either with sacral neuromodulation or more peripheral tibial nerve stimulation. So, as we talked about, there are multiple impacts that one can cause the emergence of overactive bladder symptoms in older women, but can also impact our treatment decisions. And as I mentioned, frailty is one measure which is emerging as an important indicator of outcomes, not just with overactive bladder, but with many pelvic floor disorders and other comorbid conditions. And it's a combination of deficiencies in energy, problems with depression, slowed physical activity or less physical activity. So it's a composite reflection of someone's functional status. And that can include the functional impairment and the cognitive impairment. Additionally, comorbid conditions increase, which can affect your ability to treat overactive bladder and concomitantly our treatments can affect those other comorbid conditions, as well as the medications they're taking. And then, as we talked about also, the problems with estrogen deficiency, as well as decisions you have to make that go along with that particular person's goals and quality of life. We are in the business of improving quality of life. So we need to take that into consideration when we are balancing the risk benefit ratio of our treatments in each person. And that risk benefit ratio, I think, can become a little tighter as people get older and more important. So I'm just going to review pelvic floor muscle training. As we go through these different treatments for overactive bladder women, there are varying degrees of evidence for benefits or risk in older women, especially with our third line treatments and with some behavioral. However, this was a study that looked at 43 women. They had to be at least 65 years old and they either used or lived in kind of independent, older person's residential kind of neighborhoods or communities. And they participated in a six-week pelvic fitness class. This was a group fitness class. The mean age was 83 years. And some of them had stress incontinence and some people had overactive bladder with associated frequency. And about 83% did report symptom improvement demonstrating the usefulness of pelvic floor muscle training for overactive bladder. In addition, there was, this is an old study. This is, geez, about 20 years old now, but still, I think, significant. And this was a trial that compared pelvic floor muscle training to oxybutynin, to placebo. And they did actually show an, and this was also in older women, they showed an increased efficacy in women in the pelvic floor training group compared to drug. Now, this certainly could have been due to increased health provider contact, which we know increases overall satisfaction. However, I think you can argue that it's at least as effective as medication for some women. Roughly equivalent numbers reported 100% resolution of their leakage. And importantly, you can see that only 14% in the pelvic floor muscle training group desired another form of treatment compared to three quarters in the drug group. And I think this speaks to people increasingly wanting to use non-pharmacotherapy options, as well as likely side effects associated with anti-cholinergic medication or anti-muscarinic that may impact older women a little bit more with regards to dry mouth and constipation. So there has, everybody knows there was, there's been some mounting evidence about the effect of anti-cholinergic medication and the effect on cognitive function, particularly in older, all older adults. There are many drugs that have anti-cholinergic properties, not just the ones that we use. And so there is risk for a cumulative effect, not just over time, but also the number of medications that people are on. And so across studies, you know, one third to one half of older patients might take at least one anti-cholinergic medication. They are known to have cognitive adverse effects, including confusion and memory loss. What we don't know is the causal sort of mechanism versus just an association. And although most studies with anti-cholinergics, including bladder medications, have not been associated with dementia, and most of them have been associated with a decline in cognitive function and what's called mild cognitive impairment, those conditions in and of themselves are associated with an increased risk of dementia. So it's something we really need to pay attention to. So this, there's been some studies that have come out. I will say that the literature is a little complicated and reading through it is also hampered by the fact that we're not pharmacologists and we're not neurologists or neuropsychologists. So it's easy to say that anti-cholinergics affect cognitive function, but there's a variation in the way that cognitive function is defined and measured as well as the drugs that are used. So that is where I think, as I'll say, yeah, after reading through a lot of this literature, I think if we were gonna have a panel at Augs or at Sufu or something like that, we really need the help of our pharmacy and neuropsychiatric colleagues in understanding the nuances of this literature, but I'll do my best here. So there was a 2014 literature review. So this is a little while back and it looked at 46 studies all across the literature. Now there was significant heterogeneity, which they acknowledged as well as, again, in measures as well as follow-up. But 75% of the studies did report a significant decline in cognitive function. And the majority of these studies use a measure called the mini mental state exam, which is a 30 item inventory that scored from zero to 30 and higher scores are better, meaning no cognitive dysfunction and lower scores are associated with cognitive impairment. So about three quarters of the studies did report a significant decline in cognitive function. Four out of five reported no increased risk of delirium and there was no significant association with mortality. Now, remember I said before that up till very recently, the vast majority of the studies, and when I'm saying anticholinergic medication right now, I'm referring to the entire burden of anticholinergics and not just overactive bladder anticholinergics. So the JAMA study that came out this summer followed 284,000 patients. And these were from about 1,500 practices in England. And so these are people that, and so it's like a database where they can look at diagnoses and medications prescribed. So they took, all these patients were 55 years old and they did not have dementia, Parkinson's, any neurologic disease at enrollment. So the cases were those that were diagnosed with dementia during follow-up and the controls were matched five to one for age and sex and what they call calendar time, which is basically when these symptoms emerged. And the exposure was cumulative anticholinergic drug exposure prescribed between one and 11 years prior to diagnosis. And they did find an overall risk of dementia. And when they looked at the odds ratio for the bladder anti-muscarinic drugs, which included all of the drugs that we prescribed, the overall adjusted risk was 1.65 in age and sex matched controls for the development of dementia during follow-up. So clearly this is concerning. When I looked through this, I think 11 and a half percent of the cases were prescribed bladder anti-muscarinic drugs compared to about eight and a half of the controls. So that 1.65 isn't all comers, that's adjusted. That's basically people that had bladder anti-muscarinic compared to those that had never been exposed to it was my interpretation of that. So they have a lot of data in there, but they did a lot of, they controlled for comorbid diseases, they controlled for taking other anticholinergic medications. So I'm sure there are nuances to this study that could be parsed out. And like I said, it would be helpful to have, I think a panel at one of our upcoming meetings where we did have some of our colleagues and other disciplines to help us understand some of the nuances a little bit better, but clearly concerning. So like I said, when we're talking about cognitive effects, what are the cognitive effects? And a lot of times this mini mental state exam is mentioned. So it's definitely worth kind of familiarizing yourself. And I think there are more people using this even in their clinical practice. So there was one two-year longitudinal study of adults who were at least 65 years. And overall amongst all of these adults, there was a 0.8 point decline in the mini mental state exam. And if you had taken an anticholinergic during this time, you had a 0.33 greater decline. So I said, well, what does this mean exactly? So basically in the folks that were exposed to anticholinergic, they had a 1.1 decline over two years compared to a 0.8 in these 13,000 people in the rest of the population. So I looked up, what is the minimal clinically important difference? You know, we have these for a lot of our measures in FPMRF. So what is the MCID for the mini mental state exam? And just as an hour field, you can see that this study was just published in 2019. So there is a debate in other fields as well about what really is meaningful decline. And they reported that a one to three point decline was clinically meaningful or clinically significant. So you could argue that most of the population fit into that, but there was definitely a little bit greater decline in people that were taking anticholinergic medication. And so then, you know, what are the drugs? And again, and most of these studies talk about anticholinergics in general, and they do mention bladder, anti-muscarinics, but it's hard to know out of all the drugs that folks took, how many of them were actually for the bladder. One thing that I will say in that JAMA study is that the most commonly prescribed drugs were oxybutynin and tolteridine and sulafenicin. All the other ones represented less than 1% of all medications prescribed. So there's been a few different kind of panels and scales that have been created where there have been drugs that have been designated to have strong anticholinergic properties. And the ones that are pretty consistently included in that group are oxybutynin, darafenicin, and tolteridine. And clinically, however, even in this large systematic review that's often used to rate these medications, there is significant heterogeneity noted. So for instance, who or what determines what is clinically relevant anticholinergic activity of a certain drug? And this is affected by variation in the criteria used to create some of these scales. There was another study that looked at five anticholinergic scales that were basically trying to rate the clinically relevant activity with regards to cognitive function, and there was only low to moderate concordance between those five scales. And so you have to wonder a little bit how do differences in anticholinergic burden measurement affect the validity of these studies? And again, not discounting the pretty large body of evidence that there is a link, but it's a little bit hard to pick through given some of this heterogeneity. And in addition, there could be an indication bias. So do patients that require anticholinergic medicine have a greater risk for cognitive impairment in the first place? Or in other words, does the OAD population have more predisposing central nervous system disorders that could make them more vulnerable to anticholinergics? And I think this is important because we know that risk is not the same in every person. So I think we need to have a little bit, we need to have some better tools and predictors to let us know who can safely take some of these medications and who we should really be avoiding them in. So exposure to any anticholinergic medication is also associated with older age, lower socioeconomic class, former smoking and more health conditions overall. It's also been shown that patients with overactive bladder have more systemic symptoms, including neurologic, psychologic, cardiopulmonary and musculoskeletal disease. And also patients with OAD are more likely to have central nervous system and cardiovascular comorbidities, 45% versus 29% in people without OAD, along with overall chronic disease scores and comorbidities as measured by the Charleston Comorbidity Index. So they may as a group represent a more vulnerable population overall that are more vulnerable to the effects of anticholinergics. However, we also know that this, there can be benefits of overactive bladder treatment in reducing burden of disease. So how do we balance this? Because like I said, right now, it sounds like all risk, risk, risk, and why would anybody take these medications? However, I think we have to consider the benefits. And OAD has significant associated morbidity. It's associated with higher anxiety and depression. Nocturia, getting three or more times at night is associated with increased risk of incident fall within three years. In people that have urgency urinary incontinence, at least once weekly, they have a significantly increased risk of falls and fracture, which we know can be devastating in the older population. And then also elderly patients treated for overactive bladder report overall better health-related quality of life and less activity impairment. So again, when we think of, these are already people that have other comorbid conditions like obesity and diabetes and cardiovascular disease. If you compound that with anxiety and depression and being less active, it's probably gonna have an overall impact on a wellness. So not just the lower urinary tract, but overall health and wellness. And morbidity. So in terms of overactive bladder medications and cognitive impairment, why is there cognitive impairment? Well, there's muscarinic receptors in the brain and the majority are M1 receptors, whereas the majority that affect detrusor activity and the cholinergic effect is M3. So in general, if you want a greater M3 to M1 receptor selectivity, also molecular size ionization and lipofacility of the drug affects crossing into the blood-brain barrier. So that's one of the reasons why you hear a lot about Trospium or Sanctura, that it does not cross the blood-brain barrier. And then some of the other drugs that have less cognitive impairment, even though they do cross the blood-brain barrier, their other characteristics make it less likely to affect cognitive function. However, age affects the blood-brain barrier as does comorbid disease and stress. So you can think of the blood-brain barrier as getting a bit more leaky. So some of the medications that we think don't cross may cross. And so again, this is creating a phenotype of older age plus comorbid disease plus some stress that there's probably a more vulnerable population that we don't understand very well yet. Most of the OAD medication studies are secondary analyses of phase three trials that don't have a whole lot of people over 75 years. They didn't necessarily incorporate measures to look at cognitive and functional or cognitive impairment or status with fine granularity. And then a lot of the follow-up is short. So they may not have shown a difference but maybe it was only four weeks or 12 weeks and you need a little bit longer. That being said, there are definitely some of the anticholinergic studies out there that even 30, 60, 90 days showed an impact on cognitive function. And I would say, argue that within our OAD kind of specialty specific literature there are some studies that go out that far that don't show that same impact. So I'm gonna go over some of the evidence that we have. So darafenicin, this was something that did actually employ cognitive measures at baseline in three weeks. So these are subjects that were 60 years or older that were randomized to darafenicin, oxybutynin extended release or placebo. Cognitive measures were at baseline in three weeks and oxybutynin, which does show a repeated impact as you see through these studies did show some memory impairment. Interestingly, there were no differences in self-reported memory of the participants, which sort of speaks to, I think, the need for us as prescribers of these medications to be a little proactive about utilizing some kind of measure in follow-up that can detect early changes. Because there is pretty good evidence that at least case-by-case basis that when the medications are discontinued that whatever may have been the impact can resolve. I will say overall, though, there's not a whole lot of evidence about whether or not cognitive impairment reverses after certain kinds of medications over a certain amount of time. Tolteridine looked at their studies that they had, like they looked at the safety and efficacy of Tolteridine and they divided their cohorts into greater or less than 65 years. The average age in these two cohorts was 74 years old versus 51 years old. There was similar and significant improvement in both. So we want to pay attention not just to side effects, but also the efficacy in older populations. There were no CNS visual cardiac safety concerns noted and the dizziness insomnolence in both was about 3%. Again, this one was not designed to look at CNS specifically but it was an ad hoc analysis of their existing databases. The strengths are that there's a lot of participants in these studies, but again, lacking specific cognitive measures and looking more for side effects. This was an interesting study that was looking at Fezoteridine and this specifically enrolled adults who were at least 65 years old and designated as the vulnerable elderly. So these are the folks I think we really struggle with in our clinics. So there's a vulnerable elderly score that looks for dysfunction in five different areas and a score of at least three indicates a four time increased risk of death or deterioration over two years. So pretty significant. And so these to be in this study, you had to have a VES score of at least three. So, and then they were randomized to Fezoteridine or placebo. About 65% of all of these people reported an improvement in the PPBC, which is the patient perception of bladder condition and their improvement was measured as a two point decrease in the PPBC, which is shown to be associated with significant improvement in incontinence episodes as well. Overall in the patients on treatment, there was a 72% satisfaction versus only about half in the placebo group, which we see commonly in placebo controlled trials. When they looked at specific cognitive impairment, there were two patients with subjective memory impairment after increasing to the eight milligrams, which resolved when they went back down to four. And then there was another patient who was withdrawn due to mild confusion after four weeks on the four milligram dose. And again, went back to this resolved after coming off the medication. So this was, I think a well done trial that really rigorously categorized and followed people and really asked specifically about these cognitive function. And I think at least over 12 weeks showed that, remember that the end point is at 12 weeks, it showed that there was no difference in fesiterity in our placebo, which is 90 days, which has definitely been a primary use in some of the cognitive impairment studies. However, when you're looking at longer term cognitive function and dementia, maybe 12 weeks isn't enough, but I think it's long enough to see some markers, but we do need longer term follow-up data. There was also a senior study that looked at solafenicin, and this was a little smaller study, but they took patients that were at least 75 years old that had mild cognitive impairment diagnosed by a physician. And they were also randomized to three drugs for three weeks. This was a crossover study, so they'd wash out for two weeks and then cross over into another. And again, while there was no change in solafenicin, oxybutynin was associated with decreases in attention measures, and this is just even over a small three-week period. This was a study with Liz Geller out of UNC. So she had done some work with trospium that when she looked at just a cohort study, looked like there may be some cognitive effects of trospium. However, so she did a randomized trial, and so these weren't necessarily all elderly. They had to be at least 50 years. Cognitive impairment and depression were screened out using validated measures, and then cognitive measures were taken at baseline one week and four weeks. And while there was significant difference in efficacy with trospium, there was no difference in these cognitive measures at four weeks. She did notice a difference based, the only predictor of change in cognitive function was age, whether you're on trospium or placebo. I'm not sure why at four weeks, even on placebo, you would see a difference in cognitive function. However, that was really the only predictor of change. So it was age, but not what treatment group you were in. And then even though mirabegran, as we know, is a beta agonist and not an anticholinergic, I think with this medication, there are some concerns sometimes about the cardiovascular effects. I think we still don't understand this very well, and who is at risk for having blood pressure type issues. This, again, was a secondary pooled analysis of three randomized controlled trials and one year safety endpoints. They noted that 35% of their participants were 65 years old or older, and seven to 12% were over 75 years old. They did note that about two thirds of these patients were taking antihypertensive medications, which is common in this age group. There was a reduction in incontinence episodes in all patients. The most common AEs across all groups, not just mirabegran was, sorry, this was in the treatment groups. And for these RCTs that are carried out in Europe, they have to have another active comparator. So all of these studies, it's not just the medication that you're looking at versus control. There has to be another medication in there. So this trial had both mirabegran and tolteridine and placebo. So at 12 weeks and one year, hypertension was actually similar or higher in the tolteridine group, and pretty equal numbers of patients in the placebo, mirabegran 25 and 50, and the tolteridine group had to deceive their medication for this reason. So I think just like with the cognitive impairment, there may be a smaller, more vulnerable group who is at risk, maybe for cardiovascular effects, but I have to say, I haven't seen it very often in my patients. I've seen it a few times, and it's always hard to know how much of it may be due to medication versus variation in their blood pressure, or just the natural history of their disease or their antihypertensive medication effects. But I do avoid it in people that, of course, have uncontrolled high blood pressure as is recommended. And if somebody's on a bunch of like several different blood pressure medications and their blood pressure still looks sort of like, not terrible, but not great, I'm a little leery there too, although I have to say I don't have a, that's not really an evidence-based treatment decision. And then I just wanted to, you know, when we talk about pharmacotherapy, I just wanted to end with a few words on estrogen for overactive bladder. Symptoms of urinary urgency frequency fall under genitourinary symptoms of menopause. I think exogenous estrogen in post-menopausal women can have beneficial urothelial, myogenic, and neuromodulatory effects in the lower urinary tract. And while systemic estrogen can be, has been shown to be associated with increases in stress incontinence, vaginal estrogen has been associated with improvements in frequency and urgency and nocturia, not necessarily incontinence in my experience or in the studies, and you don't see the same improvement with systemic or oral estrogen, really it's just the vaginal estrogen. And there was a study in 2011 that compared oxybutynin immediate release five milligrams BID to vaginal estrogen and showed similar improvements in frequency, which of course, with associated decreased side effects. Again, these side effects are really bothersome and may actually be more frequent in older women. So just to kind of summarize my take on the pharmacotherapy in older women, I think we need to consider frailty as well as baseline cognitive impairment. And after kind of, I knew this literature, but after doing a little bit of a deeper dive into it, I think I am going to encourage my group to start incorporating some of these measures into a baseline, if you're gonna put somebody on an anti-muscarinic. We also have to look at their overall anti-cholinergic burden. There's some medications that have anti-cholinergic properties that to be quite honest, I didn't know they had anti-cholinergic properties, you know, and so I think we need to either have a nurse or somebody reviewing their list for some of these medications that have high anti-cholinergic burden as identified on some of these scales, because it looks like some of this risk can be cumulative. I think we need to proactively monitor for cognitive adverse effects and, you know, certainly efficacy we pay attention to, but it may be worth, you know, maybe in the first one month and then three months and then at a year or something, monitor, you know, administer some of these, some of these measures of cognitive impairment. Of course, as I showed with one of those other studies, there is a known decline, not in all older people, but there's sort of an average decline if you look at a whole community of people, whether they're taking anti-cholinergic or not. So we also, I don't think have, we really don't have any guidelines stating what we should or shouldn't be doing. And in addition, I don't think we have a lot of good expertise about what would be a stopping point. You know, like if the mini mental went down from 27 to 23, that's pretty impressive, I'd probably stop it. But if it went from 27 to 26 or 25, you know, when would you withdraw somebody from a medication? And I think we do need help from our psychiatric and pharmacology colleagues to interpret these nuances of anti-cholinergic burden and risk, because just, we have to be careful about treatment, but completely withholding treatment is not the right answer either, because that's gonna have a significant impact, not just on the quality of life, but I think comorbid conditions in our older patients that have overactive bladder. I've been talking for a little bit, I'm gonna stop for just a second and just see if Jennifer has any questions that she wants to pose or anything that anybody's typed out or any questions that she has. Hi, yeah, nothing from the audience yet, but how have you changed your practice? I feel like a lot of times our specialty is damage control with some of these things. And so when you get patients referred to, who are either on medications or when you're initiating medications for the first time, how has your conversation changed since this information came out? Yeah, that's a great question. And I literally had a patient this week or maybe it was last Friday come in and she is like, I think she was like 60 years old, maybe 65, 60 or 65, very healthy. She had had not urgency incontinence, but urgency frequency. And someone had started her on oxybutynin, extended release, five milligrams. Now, whether that was their choice or whether it was insurance driven, I'm not sure. She had been on it for a few months and she was really happy on it. It really had significantly improved her symptoms. She had no side effects. By side effects, I mean, mostly like the constipation, dry mouth, no overt cognitive delirium or anything like that. But again, how often do we really see that? And her gynecologist had talked to her about, I think probably because of the JAMA study about coming off of it or trying a different medication. And I talked to her about it and she really didn't want to. I'm also a little leery about quoting specific numbers like two times risk of that, or until we have a little bit more information about the risk. And she definitely did not fall into the frail category. But that JAMA study, I really wish we had somebody who could really kind of give us the dirt on it. You know, like, okay, what does this mean for us clinically so that you don't freak out patients? Because like I said, completely withdrawing treatment, I don't think is the right answer. So, but I do think, so my counseling has changed a little bit. And even though I haven't incorporated this yet, I really feel like we need to administer a short measure and then be proactive about following up on that. So if something is changing that's subtle, the patients I don't think notice it necessarily. It has to be pretty significant. I don't know the data behind that, but based on some of these studies, it has to be pretty significant decline for even their partners to notice it. Yeah, that's such a great idea. One of the participants had a question about informed consent for anticholinergics and experience with insurance denials. And if you've been able to get anything covered by insurances by sort of including this information. I have not tried yet, but I think there was a thread going around on, it might've been the program director that I'm not sure, but it was one of the OGS kind of listservs. And I think it's something that insurance companies are really gonna be held to the gun for a little bit, especially with oxybutynin. I'm not saying the other medications are perfect, but most of the data, even if the other ones didn't show one, and oxybutynin is also one of the most commonly prescribed. You know, that JAMA study was out of England. It wasn't the US, but I believe it was tolterite and oxybutynin were the two most frequently prescribed. So I think it could be used for leverage as needed. But again, I think, like you said, we don't just wanna be reactionary and damage control. I think we need to educate ourselves a little bit and not throw out everything. But, you know, it makes a compelling case too for, you know, you could just say, well, why not just do mirabedron? Why just not do, that doesn't have any anti-cholinergic activity, but I think you also don't just wanna have one treatment that everybody, for everybody, you know, you wanna have some options also. Yeah, definitely. So I think there's a lot about predictor and risk that we don't do a good job. I mean, just look at overactive bladder in general, there's like a pretty wide heterogeneity and everybody has the same guidelines to guide them. So, all right, I will move on a little bit. So I'm gonna start talking about third line therapies. I will warn you, there is not a whole lot here, but this study right here, actually, I'm gonna start with PTNS, sorry. With PTNS, there's really very little study on differences in older people. I think it's something that could be offered to older people a little bit more. I don't know if that's been shown, but because there really are no downsides other than somebody being able to come to the sessions, you know, the time burden, but in one retrospective cohort study, they weren't looking just for older people, but their average age happened to be 74 years old, which was about 10 years older than the RCT by Ken Peters that showed its efficacy. And they did have a quarter reporting at least 75% improvement and 60% reporting 50% improvement. So not bad considering that we right now are usually held by insurance companies to only use this when somebody has failed medications. The only predictor of improvement was the number of sessions they attended, which I know seems like a little bit like common sense, but kind of their degree of severity and their age did not predict improvement. It was just the number of sessions attended. The other thing I've been thinking about, and there's not a lot around this, but a lot of older people also have edema or they have peripheral neuropathy and that could affect PTNS outcomes. I did see one of the original studies where they did exclude people with edema. So that's just something to think about that might, along with transportation issues and that sort of thing might limit the PTNS uptake in older people. However, I think there's more studies coming along where they're looking at implantables where this could be a home therapy versus having coming into an office. And I think that would be very compelling for older people. So one of the most like interesting studies I came across, which really just across all of the OAD literature was a study that specifically enrolled frail elderly versus elderly versus non-elderly. So elderly was more than greater than or equal to 65. Non-elderly was less than 65. And then 61 were considered the frail elderly. So they had to meet, remember I said there's like five different areas where you get rated in with regards to functional and cognitive function. And so the frail elderly met about three plus criteria. They also just happened to mention about 40% of this population used canes or walkers and they had a higher comorbidity than the other group. So it looks like they really did make a concerted effort to get the people that walk into your office where you go, jeez, I don't know if I wanna subject this person to a third line therapy. So, and again, their success was defined as a reduction in two points on the patient perceived bladder condition. They did a hundred units injection. Now they did show, if you wanna look at the table at the bottom, similar success rates across all three groups at three and six months. We know that the success and the efficacy declined with time. It was sort of interesting that at 12 months it declined more in the frail elderly compared to the other two groups. I'm not sure how really clinically significant that is given that most people need a reinjection at six to nine months. However, the side effects were, as you might expect, but this actually showed it, but the urinary retention was higher in the frail elderly. And they usually instituted catheterization if the PBR was greater than 250 mLs and they were symptomatic or having emptying symptoms. And you can see here, and this is what I think is so interesting that again, there's a difference between the frail elderly and the elderly and the non-elderly in the rates of urinary retention. And then in addition, the recovery period of spontaneous FOID was also longer. So it took three and a half months in the frail elderly versus one month in the elderly and only half a month in the under 65 years. So this I think is really like helpful information. I think we need more studies like this that separate out, you know, the super fit, you know, 70 year old walking into your office, you know, versus someone who doesn't look so hot, who you're a little worried about, not the treatment efficacy necessarily, but subjecting them to some of the risks. There was no difference in UTI, by the way, in this group. So another Botox study, this was another good one. This was a secondary analysis of Rosetta which if you will remember was carried out by the Pelvic Floor Disorders Network and randomized women with refractory incontinence to Botox or to sacred neuromodulation. So this was actually a planned secondary analysis. It wasn't an ad hoc one. It was one that they planned to do. So they had 191 women that were less than 65 years old and 173 that were greater than or equal to. Now the outcomes were looked at at six months, which I know is relatively short term, but that was one of their primary outcomes. So when they looked across all of the treatments, the reduction in mean daily incontinence episodes was similar. However, in the Botox group, the younger women were over three times more likely to report a 75% or greater improvement in their incontinence compared to the older group. So although overall reduction in mean daily incontinence episodes was similar, it looks like the younger group did better with regards to reduction in incontinence episodes. However, the quality of life overall measures were similar amongst all these groups. In both the sacred neuromodulation and the Botox, there was a greater reduction in the OAB questionnaire short form if they were less than 65 years old. So other things that predicted less improvement were degenerative disc disease and higher baseline severity. Also, just to speak to the UTI side effects, because we might worry about this a little bit more in older women, any UTI was a little bit higher if they were older than 65 years old, 43% versus the 30% that we commonly think of. But when they looked at recurrent UTI, there was no difference. There was also in this study, no differences in need for a catheterization or sacred neuromodulation revision. And as I move into the sacred neuromodulation revision, sorry, the sacred neuromodulation outcomes, this no difference in need for revision or reoperation in sacred neuromodulation has been borne out in some other studies. So I will say that most of the, a lot of the sacred neuromodulation literature are retrospective reviews. This is just a compilation of about three different studies. The progression to stage, the progression overall to stage two is similar when they look at women older than 70 years old, no difference in revision or explantation. And in one study at a mean of 48 months and those that had successful progression to stage two, about 65% reported continued improvement, which was greater than 50% reduction in their symptoms. And in a secondary analysis of a prospective cohort study, they stratified patients into three groups, less than 40, 40 to 64 and 65 or older. The implant rates, meaning people progressing from stage one to stage two were similar. The explant rates were similar also. They only had about 50% of their patients with one year follow-up, but the improvements in bladder diary measures, OAB, bother surveys and health related quality of life was similar. So I think when we think about, again, I apologize, there's not a whole lot of data. I kind of come from the literature and that's what I could find. So I think when it comes to refractory overactive bladder in older women, one of the things, and I found a patient preference study for what women would choose, between Botox and sacro neuromodulation and PTNS, but I haven't seen this in older women. There is this sense though, that they need to be able to manage the technology for sacro neuromodulation. But I don't know that that's actually been looked at, that they're less able to study, I mean, to manage the technology. I know I have a partner that would ask patients if they had a cell phone and if they didn't, and that was one of his criteria, or if they could manage a remote control for the TV. But I think some of these things, I think are a little bit of biases we have that we project on, and I'm not sure how true all of this is. I think you definitely need to consider the need and ability for CIC after Botox. I think you would be surprised at how many older women can actually learn CIC is needed. So I don't think you can just look at somebody that's ambulatory and discount it, but it is something that you need to think about, because especially the frail elderly, they're at increased risk for needing to do it at all in that one study, and it lasted for longer. So two weeks, not so burdensome, three and a half months is gonna be a real drag, and we really don't wanna leave somebody with a catheter. Like I said, we don't have a whole lot of papers that describe some of the risk factors that may affect the percutaneous tibial nerve stimulation, but some of these things like peripheral neuropathy and edema are, I think, gonna be more common in older women, so something to take into account. But this is an area where I think we really need more work. And just to wrap up, so we need some more time, some other time for questions. I think in conclusion, we know there are good treatment options for overactive bladder and urgency incontinence that are really important for our patients. I think we need to pay more attention to cognitive status in aging patient populations, and I think whether you pick an age or a frailty index or something, it sort of needs to be applied across the board, because I don't know that we have a good ability to look at somebody if it's very obvious we can, but sometimes mild cognitive impairment is very, very easy to miss. I think, like I said, we could use better predictors of third line treatments in older women, and overall, since my research is focused in prevention, just a plug for prevention research, given the burden of disease and some of these difficult treatment decisions and sometimes having no good option at all, I think that prevention research is critical across the life course of women. So I am going to wrap up there and just ask Jennifer for some other questions that might pop up. Thank you so much for your presentation, Dr. Ricci. We do have a few minutes for questions. You can submit them on the left-hand side of the window, and we have a couple coming in. The first is for patients who are Medicare, challenging with OAB treatments, high risk for being frail, and oftentimes have a very severe disease burden with adult diapers and flooding. So if you have a patient that's in this category and really severe, you have concerns about starting anticholinergic, perhaps Medicare won't cover myrbetrics. Do you ever get them from first line to third line kind of skipping over medications in the meantime? So I think that's a great question. And we have these guidelines with first and second and third line therapy, and I think they make sense certainly from a risk benefit, from a risk standpoint, and also the fact that some people do very well with first and second line therapies and don't need to go on to third line. But we, there's what the ABC trial, there is probably, there's only a very few studies that compare third line therapies to medication as sort of in like treatment naive patients. And I think quite honestly, that we should have the ability to be able to take somebody to third line more quickly if some of the easy stuff doesn't work. And, you know, because the insurance companies can't kind of incorporate this sort of risk stratification so that we can appropriately prescribe meds the way we want to. I think that that should be an option. Have I had success in doing it? I can't say that I can recall a time where this was a specific kind of scenario that I had to leap right over. You know, we might try some of the anticholinergic medications, but I think it's a valid scenario. And I think it's a valid thing to argue for. And I would be fine with doing it from a safety standpoint if it made sense for the patient. Yeah, agree. So for patients that are looking at third line therapy, you have elderly patients. The question was, is it not realistic to expect them to be able to manage CIC? What if they or their family could, could be feeling comfortable with like a long-term catheter? Would you say Botox is contraindicated if they could not manage CIC? For me, that is a little bit of a no-go. I mean, if they have family members that are willing to do CIC or there's somebody already doing it, I think that's one thing. I have been in situations before where partners have said that they will not mind doing the catheterization if the retention occurs. And when that does happen, some of the partners are fine with it. Like they're like, I have no problem doing this. I said I would and I would and others are quite unhappy with it. I don't love the idea of an indwelling catheter because then you really have increased risks of bacteria and bladder stones and infections. And in addition, I mean, if that was, you could argue that clearly putting a catheter into somebody with urgent continence or their urgency frequency is not a good treatment to control their symptoms. You could argue that, so it's not something that I would wanna go into knowing that that might be something that we end up with. Maybe if they had the Botox injections and it's working, then they have less chance of leaking around the catheter, which they might do in an untreated situation. But again, I just think the long-term catheter has its own set of side effects. And so that situation, I don't know where the risk benefit ratio falls out. I think it's something to think about, but it's certainly not something I wanna commit somebody to. It might happen every now and then, but I wouldn't want that to be my plan going into it. Do you incorporate CIC teaching as part of your pre-op, either workup or counseling, or do you wait and see, do you just ask the patient? Yep, I would feel comfortable. No, I wouldn't feel comfortable. Do you have to actually- You know what? Yeah, I tend to have them learn it. I've talked to other people that don't feel the need to do that, and I don't think there's a right or wrong answer. I think in the vast majority of people that we're treating for this, so idiopathic, non-neurogenic, not frail elderly, people with run-of-the-mill urgency incontinence, I think the rates of retention that require a catheter, I mean, a catheterization are fairly low, but I think it's a different conversation than you're having with an older person. So I don't know, and I don't actually know if there are data about what, I'm sure there's something about what people's different practices are with regards to that. You don't wanna scare people, but I think it's something important that for some people, it is an absolute deal breaker for them. Even people that are totally capable of doing it, I have some women that are like, no way, I'm not gonna do it. I said, but you're wearing like briefs right now, and you could not be, and they still, they're really reluctant to consider the idea of catheterization. And sometimes there's some older people that I look at that I think, geez, I'm gonna be surprised if they can learn how to cath, and they are. So I think it's something that you should give people the chance to at least explore. And I try to diminish the risk of that, but it's something they sort of have to wrap their heads around as a slight possibility. I agree, yeah. Does anybody else have any other questions for Dr. Ricci today? All right, thank you so much. On behalf of the August Education Committee, I'd like to thank Dr. Ricci and everyone for joining us today. Our next webinar is entitled Obstetric Anal Sphincter Injuries and Rectovaginal Fistula Repair. What is the best approach for repair? It'll be presented by Dr. Christina Luquigo, and that's gonna be on September 11th. All right, thanks everybody for joining. I appreciate it. And thanks, Jennifer, for hosting. Yeah, thank you.

overactive bladder

older women

treatment options

behavioral therapy

pharmacotherapy

pelvic floor disorders

OAB symptoms

cognitive impairment

individualizing treatment