Hello, and welcome to the panel on midurethral slings, pursuing evidence-based practice in the world of litigation and regulation and innovation, as we heard upstairs. I'd like to welcome our illustrious panel. Professor Duckett from Kent in England. Professor Duckett is chairman of the British Society of Urogynecology at the moment and very involved in the discussions in Great Britain. Bernadette Brown from Australia, who's involved in the Queensland Pelvic Mesh Service, where patients with problems due to mesh are referred. Dr. Charlie Reardon, Professor Reardon from Providence, Rhode Island, past president of this society, past president of the Society of Gynecologic Surgeons, also very involved in these things. My name is Karl Tamasino. I'm from Austria, and I was involved in TBT registries from way back. Just to set the context and the historical background, it started more or less with this article by a Swedish group describing an ambulatory surgical procedure. And this was a very small study, just over 50 patients. It was not randomized. They did not have long-term follow-up, but it really took off. We jumped on this, and the rest is history. It became known as the TBT operation. Evidence. We wanted, back in the day, to do a randomized trial of the TBT versus the birch-culpal suspension, which was the standard at the time, and we were unable to. We got it through ethics committee, but nobody wanted to randomize patients. Patients didn't want to participate, and physicians did not want to participate. So as a plan B, we set up a registry to try to collect data, and we found some interesting things and some unexpected things. Interestingly, the randomized study came out in the British Medical Journal, 2002. Interestingly, in the country where tapes are now banned, they were the first, Dr. Ward, Dr. Hilton, to put out a big randomized study showing the effectiveness of this procedure. But here, again, the randomized data were years behind the marketing data and the real world situation. Also around the early 2000s, a French urologist, Dr. Delorme, came out with the trans-opterator approach, and again, this is a classic. It's 40 patients, and if you see down here, one of the complications, sepsis. So there are indications here that this is not a totally benign procedure. Again, we set up a registry, and we found that, for example, that some of the tapes that were used were associated with a high rate of infection, inflammation, and sepsis. And it's worth remembering with the mesh debate today that a lot of the tapes that we now consider midurethral tapes are pretty safe, but there are a number of products that were out there that are gone now, and some of them were not safe, such as the IVS, the protogen optape ureotapes that caused high rates of infection, inflammation, and sepsis. The situation in the German-speaking countries today is that both transvaginal mesh and the midurethral slings are widely available. The big-time discussions that have taken place in England and Australia and the United States and the legal problems have not really hit the German-speaking countries, so they're pretty still widely available. With that, I would like to hand over to Professor Duckett, who will talk about the status of midurethral slings in Great Britain. Thank you very much, and good morning. So, yeah, I'm Jonathan Duckett. I'm currently the chair of the British Society of Urogynecology in the UK, and I've been involved with the mesh debacle for the last six or seven years in various different guises. What I'm going to do this morning is just go through a sort of brief version of what's been happening in the UK, although I can go on for hours about it, as can my wife and children, and they're not doctors. So it all started on the 10th of July last year, when we found that we were no longer allowed to use the TVT-type procedures. There'd been a certain amount of patient group pressure over probably five or six years before that. The patient groups were very good at mobilising electronic communications and mobilising their numbers. They had contact with our Members of Parliament, and an all-party parliamentary group was set up to look at this issue. The all-party parliamentary group then decided that this should be looked at in more detail, and another group was set up under Baroness Cumberlege to look in detail at TVTs. She'd been working for a relatively short time on this, so about four or five weeks before the 10th of July. She'd seen us as specialist societies for one hour, so she had a very rudimentary grasp of all things MeSH, but she'd listened to the groups of patients, and she decided to take this at that stage to the Secretary of State for Health and Chief Medical Officer. The Chief Medical Officer phoned her mate, the President of the Royal College of Obstetrics and Gynaecology, who then phoned me. I was watching the football, actually. I think England were actually winning, unusually. I stopped watching the football, and I gave what I would hope would be a coherent set of reasons as to why TVTs shouldn't be banned. It was the Monday afterwards this was. We explained that the amount of data that was available, and that patients deserved a choice, and that we may be pushed to doing operations which were more dangerous and higher risk and would cause more problems. I think all of this really fell on deaf ears, so it was a sort of a done deal almost at that stage. So the pause came into effect. It's really a ban, although it is called a pause. There are ways that you could be able to use TVTs in the UK at the moment, but they're quite difficult, so you're only allowed to use them in cancer patients or if there's no other alternative, and of course there is always usually other alternatives. So for practical purposes, we're not allowed to use midurethral synthetic slings currently at the moment. Before this, we were already not using prolapse meshes, so we were not allowed to use them so nicely. Our regulatory body had ruled that meshes for prolapse inserted vaginally could only be used within the research context, which is obviously quite different to other places within the world as well. So this was more specifically looking at TVT-type tapes. So there were two parts to the ban or the pause. One was a restriction of use, and this related to TVT-type retropubic and trans-obturator and mini-slings as well. There was also a high vigilance restriction as well, which aimed to capture other operations that were being performed. So there was more rigorous governance regarding fascial slings, culper suspension, periurethral injections, and also mesh inserted abdominally for sake of culper pexing. So this was for NHS and private hospitals, so you couldn't actually go to your private hospital and get it done. I live in Kent, and we've had a few thoughts we might send our patients over the channel before the 31st of October and get their TVTs done in France. I'm sure the clever ones may well do that. But there were specific things that people had to do to be able to actually continue to provide the other operations, so the fascial slings, culper suspensions, and periurethrals. So I wrote a letter that was going to be signed by my medical director, my boss, and it went through various steps that you had to say that you could do. So you've been appropriately trained, maintained your skills, and were appropriately following up your patients and using a database. So all of us had to go through these fairly rigorous ways of maintaining our practice and just being able to provide any other continence procedures as well. So there's now a set of criteria for how we can reverse the pause. And there's a similar set of criteria that people have to fulfil. So you need to have been appropriately trained. That's quite difficult for some of our surgeons. I'm the old and bold who learned culper suspension and fascial slings, but anyone a bit younger than me in the TVT era would probably never have seen these operations rather than actually been trained in them. So the British Society of Urogynecology has set up a training scheme which involves mentorship and also there's a cadaver workshop and things so that people can have a governance process to say to their medical director and say, look, I've been retrained at this or I'm competent at doing these operations. But the numbers are still quite low. So last year, or at the height of TVT, we inserted about 14,000 TVTs a year. It was sort of gradually falling down to around 10,000. It seems now that around 6,000 periuretals are being performed. There's approximately 600 culper suspensions each year since the ban and also around 400 fascial slings, although the culper suspensions and fascial slings are going up as well. There are bits here we have difficulty delivering. We're setting up a registry which all people will be obliged to put their cases on. It's interesting, although we're one nation, we have different health set-ups in Scotland, the devolved countries, Scotland, Northern Ireland and Wales, and linking all those together is quite a challenge. Administrators don't really care about this and they have a very different sort of time scale that they want to deliver or reverse this. We sit in meetings getting quite frustrating and they'll say, oh, next month, or oh, in six months' time, and all this sort of thing. We kind of feel our patients are maybe suffering and having bigger and more complicated operations or operations aren't suitable. Some trusts are just not doing any confidence work at all. We find that the patients are just left there leaking while nothing as much has been happening. So that was where we were with the registry, although there does seem to be some progress. The initial Cumberlege report was due out on the 31st of March this year. That was then put back and is now probably going to be Christmas. The rate limiting factor I thought was going to be the introduction of the NICE guideline, but that came out in April. So the registry is holding us back, and also the accreditation of specialist centres, although that's currently happening. So there will be seven centres in England which will be designated for treating complications of mesh, so mesh removal centres. I know the specifications have been written for those, and the call has gone out for those centres to be set up. So we'll hopefully have a cunning plan to get there. These were other, there were the six initial requirements for the reverse of the pause, and then these were also put on the back as well. So we have new patient decision aids and information, so the specialist commissioning has gone through, and the registry is hopefully moving in the right direction as well. So I kind of say I hope so, in England, that the ban will be reversed. I'm less confident in Scotland. I think they may get stuck with a ban that they have difficulty reversing. We're in a slightly odd situation now that we have a NICE guideline which says we can use TVT-type operations, but we then have a non-scientific quongo saying we shouldn't be using them. And they both come under the Department of Health, so it is quite odd that the two are arguing possibly from different ways. So I'm quite hopeful that our government can't just say we're going to ignore clinical evidence, NICE guidelines, which is how the whole NHS works. So hopefully at some stage we will be able to apply those NICE guidelines and we'll get the ban reversed. Thank you very much. Good morning. I'd like to thank the organising committee for asking me to speak today. My relevant disclosures, I received a Trouble scholarship a couple of years ago through Coloplast. I'm going to discuss where we are with mid-urethral slings in Australia, briefly touch on multidisciplinary services for major complications, because if we talk about evidence for mid-urethral slings, we really should be looking at evidence for putting them in, but also when we're actually taking them out. And then the pursuit of evidence, where can we get this from? I think this quote from A Tale of Two Cities captures really well where we are with mesh at the moment. I don't believe that any clinician ever got out of bed in the morning and thought, let's see how many women I can hurt today. I think everybody really came from a place of truly believing at the time that they were doing the right thing for their patients. But now we're all sort of feeling like we're very fast heading somewhere and it's not heaven. Just very briefly, Australia consists of six states and two self-governing territories. There's a portion of our funding that comes from a federal level, but then each state has also got some responsibility for healthcare. Medicare is our universal healthcare system that covers our public hospital services. And then we've got the TGA, which is the Therapeutic Goods Administration, which is the equivalent of the FDA. And these are really the key role players in where meteorosal slings are today. The TGA, the government through the Senate inquiry, the Australian Commission for Safety and Quality in Healthcare, the consumers, which similar to the UK, have been very vocal in this whole journey, and the law firms. And then as clinicians, we've... I mean, in a lot of other countries, we have very much come out of this whole debacle looking like the perpetrators. And so clinician involvement has been mostly through the Senate inquiry with the submissions that have been made through various societies and bodies and individual clinicians, and also through the Australian Commission. And I really believe it is the work of these specialists that's really taken a place behind the curtains very much, that has meant that we still have meteorosal slings available in Australia. Otherwise, we would probably have gone the same route as the UK. A brief timeline. So the first meteorosal sling was placed on the Register of Therapeutic Goods in 1998. The TGA only received their first adverse event report in 2006. In 2010, they conducted their first review of mesh products, following on from the FDA notification in 2008. In 2012, the Mesh Down Under Facebook group was conceptualised in New Zealand, and following on from that, the Australian Pelvic Mesh Support Group came to fruition. In 2014, they held a second TGA review of mesh products, and by the end of 2015, there were only 12 adverse events related to all meshes reported to the TGA. And then things started to speed up really quickly. So at the end of October, the Australian Pelvic Mesh Support Group met with one of our senators, Darren Hinch, and I just realised I spelled his name incorrectly, so I'm sorry about that. And really, he brought that to the government, and he was the first and they launched a Senate inquiry into mesh products in February 2017. The J&J class action trial from Shine Lawyers kicked off in July 2017. In November 2017, all vaginally placed prolapse meshes and single incision slings were removed from the Register, and by the end of January 2018, we had 327 adverse events reported to the TGA. The Senate inquiry finished their public hearings at the end of 2017, and then their report was handed down in March 2018. And the big thing that we're all waiting, really holding our breath for, is the outcome of the J&J class action suit. That was heard in front of a single judge rather than a jury, and I think that is going to be one of the big predictors of what's going to happen in the next few years. The report that was handed down from the Senate inquiry came up with 13 recommendations, and considering the way it could have gone, these have all been quite reasonable. They've asked for mandatory reporting of mesh complications by medical professionals, and this needs to be coordinated through the government. They've asked that patients get little cards that they can keep in their wallets, essentially, for all implantable devices, and that should also include information on where they can seek help if they have complications. They've asked for a registry of all high-risk implantable devices. They've recommended that our coding, essentially, finishes up their consultations, because prior to all of this happening, we only had one code for vaginal repairs, and it didn't actually distinguish between native tissue repairs and mesh repairs. They've asked for a post-marketing monitoring scheme. They have asked the Australian Commission to produce guidelines and information sheets for patients, as well as clinicians, on informed consent, and they've also asked that transvaginal mesh should still be available in the form of midurethral slings, but only with fully informed consent and as a last resort. The Commission's resources should be utilised by members, and that's where our professional societies have been asked to disperse this information to their members. They've also proposed credentialing for practitioners, both in public and private hospitals, and they've put that responsibility on the state or territory governments. It hasn't come through, but that was one of the recommendations. And they've also asked for increased governance for using transvaginal mesh procedures, including adequate training, that it occurs in the setting of multidisciplinary care teams, that the outcomes and the complications are being monitored. Everybody should keep an audit of their own procedures and outcomes, and also the Committee has asked that we retrospectively try and audit the mesh procedures that were done. Prevention of industry incentives, and then they have recommended that specialist units be set up for the management of mesh complications, because one of the big concerns of the Australian Pelvic Mesh Support Group was that they didn't feel that we had adequate treatment options available for mesh complications in Australia. These are the patient information leaflets that the Commission has put together, and it also includes a list of recommended questions to ask your practitioner, but really they are just basic things that we would, or we should really be including in our informed consent process anyway. The practitioner credentialing that's been proposed, so they have divided practitioners up into new practitioners, so that would be a newly-followed person completing their training. They have to be a board-certified gynaecologist or a urologist with specific supervised training and documentation of that training, and not just of actually doing the operations, but also where they were involved in patient selection, procedure outcomes, and monitoring of complications. An independent practitioner would be somebody who has been doing these procedures for a number of years. They have to still fulfill the initial criteria, but also have documented evidence of their outcomes for two years prior to application for credentialing, and they have to show that they maintain their annual CPD and the treatment of stress incontinence. For maintenance of skills, they have recommended at least 10 stress incontinence procedures annually, and these outcomes need to be tracked prospectively and submitted to independent clinical audit, and the reported outcomes have to be over a minimum of six months post-operatively. So this has led to the fruition of the Queensland Pelvic Mesh Service. In January 2018, we were asked to submit business cases for our hospitals to offer these services. The Gold Coast University Hospital was elected, along with one other hospital that subsequently withdrew. We went through a 15-month preparation phase, where we had a steering committee that included clinicians, administrative people, as well as three consumer representatives. It is a statewide service. Now, Queensland is about 1.8 million square kilometres, which is two and a half times the size of Texas, with a population of about five million people, which is about a fifth that of Texas. And we also had to consider travel and accommodation subsidies for patients that live rurally or far away from the Gold Coast. The middle column shows the full-time equivalents that we asked for in the business case, and then the other side column shows what we've ended up with. Interestingly though, the two that we've really significantly underestimated was the psychologist and the social worker. And so from the get-go, really, we had to improve the psychologist's FTE from 0.5 to 1, and she is already functioning at her full capacity. And the social worker, we've had to increase just with what we've had available to 0.6. But there is actually scope for having two full-time social workers working within this clinic. I think part of that is the fact that so many people are quite some distance away from the Gold Coast, so there is quite a lot of subsidies and travel and accommodation and things to arrange. This is a pathway that the patients follow. So we do require a GP referral to the service. We try and get the operative notes where we can. Our clinical nurse specialists phone all the new referrals to try and triage them. They complete patient questionnaires. Then they are discussed in an MDT meeting to decide the most appropriate clinicians to see them at their first visit. They have their reviews. They have any imaging or examinations. And then we have a further MDT discussion to collectively decide on the best recommended treatment course. Once they've completed their treatment, there is another MDT meeting before they exit the service. And this is just a quick overview. So we opened our doors officially on the 15th of April this year. To date, we've had a total of 114 referrals. There were four referrals that were rejected because they were ventropixie meshes or hernia meshes. Our urogynecology specialists have had a total of 159 occasions of service. The social worker, you can see is functioning at her complete capacity. The psychologist is at her capacity. Where the numbers are lower, she's had a week or two of leave in that time. Our physiotherapist was on leave in June. That's why she didn't see any patients. And our urogynecology CNCs are also seeing a number of patients through these clinics. When the Senate inquiry came about, one of the big things that became glaringly obvious is that we didn't actually know exactly how many women had had vaginal mesh procedures over that 10-year period of time. The closest numbers that we could get came from industry, but they could only tell us how many products they had supplied to hospitals. They couldn't tell us how many had actually been used. We haven't had any databases or registries to verify these numbers, and this is despite a number of our senior CU members campaigning for ways that we can monitor these procedures since the mid-2000s. We have got the AXA database, which is based on the BSAC database, but it is a voluntary database, and it is also subscription-based. And 14 out of 108 registered centres contribute 90% of the data, so that wasn't a very reliable place to get the numbers. In April this year, the Australian government committed $2.3 million to establishing a pelvic floor registry. This is very much in its infancy. It will be in line with the breast device registry as well as the bariatric surgery registry that is currently running in Australia. It would mainly be for monitoring of urogynecological meshes, but the question has been asked on whether non-mesh procedures need to be included so that we can have a denominator, but there are still multiple phases that this needs to pass through before it will eventually be rolled out countrywide. And currently we are really just trying to establish the scope of the registry. As we all know, a well-designed registry requires that the practitioners can actually engage into it. It should facilitate routine audit for all of us, as well as clinical review, and ideally it should also satisfy the Commission's proposed requirements for credentialing. I'm not going to spend too much time on the evidence that we have for using TVT midurethral slings. We all know the European Commission, the Scottish Review, the NICE guidelines that was just recently updated. They've all agreed that there is certainly a place for midurethral slings in the treatment of stress incontinence. We also know that overall the rate of removal is low. We know the information that we have and the limitations of that evidence for complete excision, partial excision, thigh dissection. The questions that we need to answer is, what is the true incidence of pain after midurethral slings? And if we're asking that question, we should also be asking, how many women get pain after colposuspensions and after autologous fascial slings? We should figure out if there are any pre-existing pain conditions that make them more likely to develop pain after slings. Are there medical conditions or surgical factors that include the risk of pain? We need adequate screening tools to try and identify these women before we operate on them. And we need to decide what is the most appropriate way to treat these complications and have the evidence to back that up. And this is where we need international collaboration. Through specialist multidisciplinary clinics like ours, we can get prospectively defined and agreed upon outcome measures that we can share amongst ourselves internationally, because we need data, and we need lots of it, and we need it quickly. We need to evaluate the treatments of our surgical outcomes, our allied health interventions, as well as our pain management strategies. So where are we with midurethral slings in Australia? Well, this chart really says it all. From 2015 to 2018, a third fewer patients have had midurethral slings for stress incontinence, and it hasn't shown up in a significant increase in other treatment options. So there are a significant number of women out there who are troubled with stress incontinence who are not coming forward to have treatment. And when it comes to evidence, I hope that in the future the patients will rely on prospective evidence-based research from well-designed medical studies rather than the evidence base that they find on their social media posts. And we need to be aware of unintended outcomes. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. 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Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you.

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