So, just to make sure everybody knows where they are, we're in the early lessons learned on the use of injectable long-acting buprenorphine in persons hospitalized with infections and opioid use disorder in a workshop. I'm just going to introduce myself, and I'm one of the co-chairs, Sandy Springer. I have full disclosure, am not a psychiatrist, but thank you for letting me be here. I'm an infectious disease physician, addiction medicine physician, and associate professor at the Yale School of Medicine in the section of infectious diseases. Is this working? Yes. Hi, I'm Frances Levin, and I have the honor to work with all the people on this panel in a multi-site that we're doing and you'll be hearing more about, and I'm at Columbia University and the New York State Psychiatric Institute and the co-director of a center that's called Chosen, which focuses on treatment of both substance use disorders with an emphasis on opiate use disorders. We're really glad people are here today, and hopefully we'll have lots of time for discussion, so I'll keep the trains running to make sure that we end with enough time at the end that we can all ask a lot of questions. Great, and we'll just introduce each speaker as they come up, and as Frances said, really what this workshop is about is actual real lessons that we've learned through conducting a currently ongoing multi-site trial of integrating infectious disease and opioid use disorder treatment using a long-acting form of buprenorphine, in this case, sublocade. So these are all of our, I don't know if Kathleen Brady's here, is she here? Oh, well, I think she's here, but she's also... She's in the meeting. Okay, so if she comes, we'll welcome her as well, but she's one of the PIs. So these are our disclosures, and the learning objectives are broad, but we hope through the discussion that we hope will come about from some of these presentations that we can kind of hone in on more of the details, but really to come away with understanding these coalescing epidemics of infectious diseases associated with the opioid use disorder epidemic that we're seeing everywhere, but in particular here in the hospital settings, and how we can do a better job of rapidly screening, diagnosing, and getting individuals on treatment while co-managing, in this case, concurrent infections, and also really talk about and learn how what we've learned through this process is how to really select forms of medication treatment for opioid use disorder in persons who are hospitalized, and you will hear in many cases with severe, life-threatening infections, and discussions about the low-dose transitioning to buprenorphine from full opioid agonists, and then on to long-acting buprenorphine. And then lastly, discussing how this collaborative effort through addiction psychiatry, addiction medicine, infectious disease, as well as hospitalists, has been really helpful in determining how to best serve our patients. So the first talk I'm just going to give here, and we're going to talk about really the epidemiology of these coalescing epidemics, which led to the design of this study, and then some of the preliminary data of the study. We cannot discuss primary outcomes or secondary outcomes yet because this is an ongoing trial, but we'll give you some discussion about how we're doing with acceptability and feasibility. So the specific objectives to this talk, again, really giving you, hopefully, coming away with this understanding of these epidemics, and maybe thinking about how one could, if you're an addiction psychiatrist, really thinking about infections and potential prevention, identifying diseases that you could potentially help that individual with, and how to identify opioid use disorder quickly, and getting people on to, in this case, long-acting buprenorphine. So you guys are all familiar with this. Our current opioid epidemic, starting with prescription opioids, then to heroin, mainly black tar heroin, and now really fueled by synthetic opioids and fentanyl, causing significant overdose deaths. I'll be remiss if I did not mention the stimulant epidemic as well, though we're focusing on the opioid use disorder epidemic, but as you're very familiar with, methamphetamine and cocaine continue to drive upwards of 40% of overdose deaths, and then combined with fentanyl and others are leading to significant deaths, to the point where we're having a straight trajectory without really a decrease seen. And as we know, through the COVID pandemic, unfortunately, we're now surpassed over 100,000 deaths, with a 30% increase just from 2020 to 2021. But in addition to the harms directly from opioid overdose deaths, where this is a point of this discussion here today, there's been an ongoing increase in other diseases, importantly, infections, such as endocarditis, septic arthritis, and osteomyelitis, skin and soft tissue abscesses occurring. This data is looking just from 2002 to 2012, so really before we saw the spike in the fentanyl epidemic, and showing about a 50% increase in hospital admissions from these infections associated directly with opioid misuse or dependence. In addition, we've had acute hepatitis C infections occurring across the country associated with directly opioid injection, and in particular with young adults, 18 to 29, 30 to 39, which has actually led to a change in our screening recommendations for hepatitis C in this country. And in addition to that, we've had several HIV epidemics occurring among people who use drugs directly, initially related in red, as you know, from the Scott County, Indiana outbreak related to injection of oxymorphone, a prescription opioid. But since then, in green, and this is not all of the cases, but multiple HIV epidemics occurring among people who are using drugs related to heroin, fentanyl, and in particular methamphetamine. So why is this happening? Traditionally, the treatment and prevention of substance use and infectious diseases has been siloed. And we really have, there are cases to show that if you can integrate care, if you can integrate screening and treatment, that you can improve care. And it's not just us saying that, it's also coming from the National Academy of Sciences of Engineering and Medicine, who put out a report, I was part of that group in January of 2020, making specific recommendations on how to improve integration. In addition, other people, including infectious disease doctors, have called for this new subspecialty within infectious disease to assess and treat addictions. And Dr. Nikhil Savel, who you'll see, an infectious disease doctor, has actually come up with a practical guideline on how infectious disease doctors can do a better job of screening and identifying opioid use disorder and treating it with co-occurring infections because of what he and others have seen in the hospital setting. And other national groups, like Infectious Disease Society of America, IDSA, HIVMA, have actually come out and called for specific, better ways to integrate care using, strengthening those collaborations that we already have, which we're going to be discussing. So that leads us to what we ended up doing. We wrote a grant way back when, preceding the pandemic, funded by the National Center for Advancing Translational Science. It's a multi-PI grant, multi-site trial called Project Commit, coordinating opioid use disorder treatment through medical management with infection treatment. There's an MPI project, so I'm one, Kathleen Brady, Ned Nunes, and Frances Levin, and then we have Alan Litwin and others, Prana Rath and Meredith Shad, who are co-investigators. So this particular study and what we're going to talk about and lessons learned that we've had through this ongoing trial is really where we were trying to assess a new model of care, so this IDLAB model, in which opioid use disorder is managed by infectious disease specialists and hospitalists, along with the concurrent management of their infections, and in this case, using long-acting buprenorphine or Sublocade, an FDA-approved medication treatment for opioid use disorder that can be administered every month, with a concurrent nurse care management model, and then with that, helping with discharge planning and following them onward. And particularly, the primary outcome was to assess whether an individual will be retained on a form of MLUD at 12 weeks, the end of the intervention period, and this is compared to treatment as usual, which in this case means whatever form of treatment, if that's what the individual wants, like buprenorphine, methadone, or extended release naltrexone for their opioid use disorder, as well as enhanced, where everybody gets overdose education, naloxone distribution, as well as education and treatment about safe injection procedures and discharge planning. Other outcomes that we're assessing are, of course, opioid outcomes, so abstinence, and importantly, infectious disease outcomes, so did they complete their antimicrobial recommendation treatment while they're hospitalized and then in the community, as well as could this intervention reduce rehospitalizations or reduce other emergency room presentations? So as I said, it's a multi-site trial recruiting individuals, adults, 18 and older, who are hospitalized with opioid use disorder, moderate to severe, by DSM-5, and have a concurrent or suspected infection, and that includes any infection, so it could be COVID-19, it could be bacteremia, endocarditis, could be hepatitis C, HIV, hepatitis B, and then they're randomized one-to-one to the long-acting buprenorphine arm, or the treatment-as-usual arm, in three sites, one Penn State in Hershey, Prisma Health Care in South Carolina, and then at Yale New Haven Hospital in Connecticut. And the goal is to get approximately 200 individuals, intervention period for three months or 12 weeks, so they can have three injections, and then a 24-week follow-up period. So the protocol paper is published and has more of the details and contemporary clinical trials, if you're interested. And I think one of the things you're going to hear about is we had to grapple with is how to identify patients who might have opioid use disorder in the hospital, and as we know, there's not a routine screening process at all. In fact, very few actually ask the questions about opioid use or opioid use disorder, so we had to create a very detailed evaluation to find patients, including, you'll hear later, ICD-10 codes, as well as laboratory evaluations. And then using a quick screener for non-clinicians or research assistants, others, to identify opioid use disorder, and then coordinate hospital teams to come together. So I won't go into all of this because Dr. Seville is going to discuss it a little bit more, and we can answer questions later about how we've done this, but it's been a very productive process, but really time-intensive. And this is one of the rapid screens we've used, Rapid Opioid Dependency Screen, followed by the mini to confirm DSM-5. And this is just meant to show you in that published protocol paper, we've also developed a clinical safety sheet that you can use to identify individuals and having the ability to initiate long-acting buprenorphine. So when we submitted this abstract, we had roughly 113 consented, and now that's upwards of 120, and I won't go into all the details, but of the individuals who declined consent, it's important to know a significant majority had an idea of the form of medication treatment for opioid use disorder they would like rather than being randomized. And then there's also issues with self-discharges that we saw, as well as potentially not wanting to have sublocator being a research study. These are just the baseline characteristics of the first 107, and I just wanted to emphasize, again, these are all recruited in the hospital setting, and it could be anywhere from right when they admitted to having been in the hospital for some time. But importantly, almost 50% are identified as female, and about 40% have been homeless in the last 30 days, and about 56% are covered by insurance. I won't go into all the details, but just wanted to identify about 50% have a co-occurring DSM-5 stimulant use disorder, 20% with hazardous drinking based on the audit, and then in the 30 days prior to hospitalization, roughly about 11% had been on a form of MOUD. And although when we did the urine toxicology tests, they might not have been when they were admitted, it depended on when they were referred to us. I think it's important to note that of the baseline urine tox, almost 40% had fentanyl positivity. And then using the timeline follow-back in the last 30 days of self-reported substance use, again, the main drugs that were reported were fentanyl and methamphetamine. And this is just some other demographic data looking at the majority, about 23% were working. And then of the index infections, an individual could have more than one infection, and often do, but the number one infection we saw was bacteremia, almost 50%, and endocarditis, 23%. And I'm just going to show you, I can't tell you all the data, but importantly, at our intervention period of 12 weeks, we've had upwards of 80% retention in the study, and 73% or 74% at the 24-week follow-up. So the intervention's completed at 12 weeks, and at 24 weeks, we do a follow-up assessment. And it really shows you the potential acceptability of this intervention and assistance. And there's a lot of other things that go into this, including assistance with not just discharge planning to appointments, but transportation assistance, cell phone access that we can always talk about later during the workshop. And I last want to say about adverse events, we've had no serious adverse events related to the intervention, which I think is important. So any of you know the clinical trial that led to the FDA approval of Sublocade, most of these patients would not have been included. So several of these are really sick patients undergoing open-heart surgery for valvular replacements, septic brain emboli, other serious conditions. And so I think it's important to know that so far, there have not been any serious adverse events related to the intervention. There have been three deaths, one due to sepsis, one due to acute respiratory failure, and the other cause unknown, but not felt to be related to the intervention. So I'm just going to end here and say that as you hear about some of the other topics that have come up through this ongoing clinical trial, I hope you come away with understanding the importance of this integrated care model, and that we need to do a better job of screening and diagnosis and working together to treat these coalescing problems. And that I think the preliminary data so far is really striking in that there seems to be a high interest in acceptability and safety in this intervention. Thank you. Do you want to take maybe one question before we go? Want to just keep going and take a question? Okay, so we'll have lots of time at the end. I'm going to make this really brief, but I feel like I have to do some justice to all of these wonderful co-investigators. So Nick Saval is an infectious disease specialist whose clinical research focuses on the intersection between addiction and infectious disease. And just in short term, he was an assistant professor at Yale School of Medicine until just very recently. And he's now at Drexel University College of Medicine. I think one of the really nice things about this whole group, I would say, is really the working together of both infectious disease and psychiatry. And you don't often see that, and I think that's what makes this group unique. And it's really been, I've learned so much from all of you, and I think that it hopefully goes in both directions. So that's all I wanted to say. Okay, thank you, Dr. Levin, for the introduction. And I will elaborate on the identification of patients in COMMIT and their substance use characteristics. And then transition to discuss how the patients in the long-acting buprenorphine arm were inducted onto therapy, really in the context of their comorbid pain and medical complexity. So as Dr. Springer just described, we utilized an active electronic health record screening in addition to provider referrals to identify patients who may be eligible for the COMMIT study. And so the EPIC, or EPIC in particular, has a functionality that allows for reports to be created, which use inclusion-exclusion logic based on given parameters. And this is a screenshot here of the number of the EPIC reports that we had at the Yale site. We really used a number of them together. And the goal is to slice through the admitted population in different cuts to identify patients for whom certain diagnoses may be under-charted, uncharted at all, or undiagnosed. Afterwards, we had trained study staff who would chart review the patients more accurately to identify pre-eligibility. So some reports would identify patients more from a substance use lens. For example, all those who were admitted with an active buprenorphine order. And others may be more from an infectious disease lens. For example, those with positive blood cultures or a positive hepatitis C antibody. Typically, it would be a sign for patients who are identified on multiple lists that they would be high yield for study eligibility. So as of December 1st, we have 120 patients on trial. This graph here includes 107 participants from the late September data cutoff. And the graph here shows substance use diagnoses per the mini derived from DSM-5 criteria. This is limited to people who scored a severe use disorder per that assessment tool. And you'll see that almost every participant with the exception of two had their OUD assessed as severe and active by the time of enrollment, really showcasing the severity of their addiction. Concurrent stimulant use, as we've mentioned, is common, 47%. This graph here includes both cocaine and methamphetamine use for which we did see regional differences in use. And here you can see the urine toxicology at baseline. So this data is skewed by the fact that participants often were not enrolled into the trial immediately upon hospitalization. And so unfortunately, this does mean that drugs used recreationally may not still be present at time of testing. And then kind of conversely, inpatient prescribed medications, which are often started anew for withdrawal management prior to being in the trial, are apparent. And so this is reflected in about the 70% of patients for which urine buprenorphine positivity is shown. Especially since every patient who was already durably maintained on MOUD, such as buprenorphine, as an outpatient, typically was excluded from the trial. Despite those issues with urine tox testing, you'll see that almost 40% of the samples were positive for fentanyl, which is typically not used for analgesia in our institutions outside of the anesthesia and critical care spaces. The timeline follow back though provides a more granular viewpoint to participant substance use for which the baseline timeline includes the 30 days prior to hospitalization. And I'll just say the timeline follow back briefly is a measure validated originally for alcohol use to assess daily use patterns and amounts in a retrospective manner. Using trained study staff who use date recall techniques to improve response accuracy. And on the left, we have any substance use per type in the past month. And on the right, the mean days of reported use in a given month. And here you'll see much more prevalent opioid use with around 80% of persons using prior to enrollment. And over 15 days a month of use on average for heroin. The second most common reported opioid is fentanyl. Which of note, this is really reflecting intentional fentanyl use, because this is done through participant surveys, followed by pills and other opioids. Stimulant use now broken down here between cocaine and methamphetamine use, which was common in this cohort. So these slides kind of taken together show the pervasiveness of fentanyl, whether intentional or not, in the commit cohort. So much so that it persists in up to 40% of patients in urine screens, up to multiple days into their hospitalization. And fentanyl, as this crowd is very aware, poses unique challenges to substance use treatment for a variety of reasons. It is in large part due to its high affinity for fat tissues, which can then result in atypically prolonged pharmacokinetics, including reports of positive urine toxicology up to weeks from last known use. And this also can complicate induction with the partial agonist buprenorphine in particular. So the graph on the right here is from a study in the Journal of Addiction Medicine this past year. And these are patients with self-reported precipitated withdrawal symptoms after buprenorphine use in the fentanyl era. And the white bar graph in comparison is for those inducted with methadone. And you can see that bup use within 24 hours of fentanyl was associated with a five-fold increase in precipitated withdrawal. And less commonly, as you see going along on the x-axis, this phenomenon can persist for up to a week afterwards. So in our case, fentanyl, now ubiquitous in the community drug supply, it's just one example of a complicating factor to the question, really, what's the best strategy for MOUD induction, particularly at buprenorphine? And how does this impact eventually getting onto long-acting buprenorphine? So I wanted to discuss this with our first patient case here. And this will be in the context, really, of adding on some of the common complicating factors that we saw in our cohort, now with inpatient hospitalization and comorbid conditions. So briefly, I can read this out, and then we can discuss. This is one of the cases in our cohort, 35-year-old man with a past medical of severe OUD, intermittently adherent to high-dose methadone, benzo use disorder, also on prescribed benzos, chart history of PTSD, anxiety, and depression, admitted with bilateral upper extremity cellulitis in the setting of injection drug use. Got started on IV antibiotics. Restarted on his high-dose, 150 milligrams of methadone. Underwent bilateral INDs of these abscesses. At this point, is on both standing and, as needed, oxycodone for pain. He was interested in the trial, enrolled, and randomized to the LAB arm. So how would you all induct this patient onto buprenorphine? Feel free. Yes. Keep him on his methadone for now, micro-induction. OK. Or do you keep the ER on, so the opioids can't get any more? I don't know. I think it's just too much. Yeah. Sure, yeah. And just to repeat, the suggestion here is really to do a low dose or micro-induction, liberally keep on full agonist opioids as needed for pain control. They probably have to go after a dose. Would anybody do anything differently? Whoops. Matt Stose from Milwaukee. I would probably keep him on the full. I mean, you keep him on the methadone and the pain control and slowly walk him up a buprenorphine. And then once the buprenorphine was high enough, I would stop that. But I would be careful not to stop the methadone or pain meds until they were comfortable that the pain was managed and he was recovering. So I'd be careful to time it right. That's great. Thanks. And would anybody want to taper down the methadone dose? We got one vote over here. OK. You want to comment, Dr. Vaughn? I think I was thinking that. I don't know. I think I would have tried to lower it before, just to get the process started. Sounds like a lot of a full agonist. And so these were the conversations. That was great. These are really the conversations we would often have in our group and our weekly meetings for the commit cohort to discuss clinically how we would recommend and assist for the clinical teams how to proceed with the inductions. And as the group mentioned, there are a number of issues here that can make a standard cessation-based induction onto buprenorphine challenging. So the patient's on both standing and as-needed opioids for analgesia. So in this setting, that makes sense in the setting of their known opioid tolerance and recent debridement. So it would be hard-pressed to stop these. And then similarly, stopping all opioids for the pain and for the methadone and awaiting at least mild opioid withdrawal is challenging, really due to suboptimal pain control and now having the patient withdraw. And then lastly, for his substance use history reported using IV heroin and fentanyl use. And this was in addition to smoked crack cocaine use. There is this theoretical risk of precipitated withdrawal as well, even if everything is done right in a classical induction. And as you had alluded to, this could be a perfect situation for microdosing or low-dose transitions, which are often used synonymously. Sometimes the term low-dose transitions are used in some circles to avoid confusion with the other use of microdosing in substance use context. I have a question. Yeah. I should have asked. Here, Rick. Rick. This person's in the hospital, right? They are, yes. Seems to me you could switch him over to a shorter-acting opioid to decrease the chances of the interaction with the buprenorphine and the methadone. Because if he was changed over to a short-acting equivalent pain dose opioid, oxycodone, or whatever you chose, for a week, you would then have the ability to stop that wait for withdrawal and immediately give him an injection. Or you could start with PO and then give him the injection. That's a great point, yeah. And I think one thing that we can talk about in our discussion afterwards are the variety of strategies that exist out there. And I think that's a good segue to discussing this. And I think some of these concepts will really be familiar to the group. But this schematic here was created by Sean Cohen and others at Yale. It's a helpful analogy of the car on the highway, which is full opioid agonism, is akin to our car going well above the speed limit. And our goal is to bring the speed down, as it were, by inducting onto the partial agonist buprenorphine. So we see in figure A to start, this demonstrates really a sudden rapid decrease in speed. So imagine going from 120 miles an hour to 60 miles an hour, which would be analogous to bup-induced precipitator withdrawal. And as the group knows, since bup has high receptor affinity and low receptor activity, these full agonist opioids are then rapidly displaced. And the effect is both noticeable and uncomfortable, both in the car and for the patient. So then moving on to figure B, which represents a more classical cessation-based induction strategy, in that the full agonists are held on the scope of hours to days. And you can imagine at some point gradually slowing down until you're going 30 miles an hour on the highway. And this represents mild opioid withdrawal, at which point standard low doses, somewhere between 2 to 4 milligrams of sublingual bup, are initiated. And then in figure C, we have our low-dose strategy. And if the goal is to really avoid any perceptible changes in speed, we do that by very gradually decreasing the speed over the course of days. And from the receptor standpoint, these very low doses of buprenorphine, so under 1 milligram in dose, will still displace full agonist opioids and provide less receptor activity. But this is really going to be subclinical for the patient when the doses are low. And there are a number of ways that these low-dose transitions can be operationalized. So one predominant strategy used is known as the modified Bernese method. So we have two figures here, which in its original publication lasts seven days. And it utilizes a starting dose of 225 milligrams of bucobuprenorphine, which will convert out to around 0.5 milligrams of sublingual buprenorphine. And that 225-microgram dose is assembled using a combination of the 75 and 150 film dosing, a trade named Belbuca. And then that's gradually increased day by day into the sublingual dosing. Also bring your attention to what's happening with the full agonist, which is nothing. And that's in that the modified Bernese really calls for no concurrent adjustment. And by the last day, it's fully discontinued since all the opioid receptors at that point are going to be fully occupied by the buprenorphine. So we can now see the advantages of such a strategy in the context of the patients in the commit cohort. So full agonist opioids can be continued during the induction, in particular for analgesia. No requirement for the patients to undergo opiate withdrawal. And then the risk of precipitated withdrawal really is going to be theoretically lower given the smaller intro doses of bup. So there have been seven patients thus far in our trial who have been assigned to the LAB arm, whose bup induction met criteria for a low dose microdose strategy. The induction strategy in the trial for those randomized to LAB was at the discretion of the clinical hospital teams with the input and guidance provided by study staff. And this was also together with the shared decision making of the patient. You'll see here the age ranged from 29 to 67 years old. There is a mean age of 40 years. Everybody in this cohort had severe OUD. You can see once again that severe stimulant use disorder was common. And all patients were admitted for serious and at times life-threatening infections. These included, as you'll see here, bloodstream infections, endocarditis, septic arthritis. Four out of seven of them required surgeries. And some of these are major surgeries like open heart surgery. And then so four out of these were not on MOUD prior to the hospitalization. For the ones that were, there was one who had intermittent adherence in the community to buprenaloxone. There was one who was started on methadone the week prior to admission with a desire to switch to bup. And then one on methadone with the intention of switching off at time of admission. And the majority of the patients had methadone as a component of their full agonist regimen by the time of study enrollment. And that was because three of these were initiated onto methadone on admission, typically for acute opioid withdrawal management in the context of acute pain, upcoming surgery, or sepsis. And we do note that initiating bup in these situations could have been reasonable. But this was often prior to participants enrolling in the trial. Comorbid pain was also really common. The assessment used in this trial was the PEG, or Pain, Enjoyment, and Life in General Activity Scale, which is a 0 to 10 rating scale with three questions, including past week pain. And also, there is a single question added. We termed it the modified PEG to assess pain at the time of assessment. And the scores were pretty high. So average pain in the past week at 8.2, and then average pain at time of questioning of 5.7. And so you can see here we have the details for each patient's induction per day. And the x-axis here is time. So on the bottom to orient you, you'll see a legend and kind of a small circle that's scored into quarters on the bottom left. And each of those quarters is equivalent to 225 micrograms of buccal buprenorphine. Moving on, we have the rectangle with each quarter being equivalent. I think it's cut off a little bit there to 2 milligrams of sublingual bup co-formulated with naloxone. The star represents our long-acting buprenorphine with the intro 300 milligram dose, in this case, sublocade. And then you can see the two rectangles here, one of which represents what's going on with the full agonist opioids, and the other with what's going on with the methadone. And there's a few things I want to highlight here. So one is you'll see case one and two are really pretty similar to what we had described in the past few slides with the modified Bernese method. They really hew pretty closely to that. But as we gain more experience in the trial and time moved on, you'll see that there were some aspects where modifications were able to be made. And I'll note that there's a number of low-dose transitions that have been published in the literature, and some of which that happen more quickly than seven days, sometimes as short as one to three days, depending on the clinical necessity. And also, shortening the induction period was, across the board, a major goal for both the patients and for the clinical primary teams. So we had good tolerability with bup dosing strategies that were a bit more rapid in the first few days, which shaved off some days from the overall induction. Next, unfortunately, there's limited real estate on this slide, but I'll tell you that the low-dose transition portion of the induction really was tolerated remarkably well by all patients. Only one experienced withdrawal that required amendment of the regimen. And you'll see in case one, day five and day six have the same dosing. And this was because their standing methadone actually erroneously fell off and had to be restarted later in the day with clonidine, at which point the patient clinically did very well, and we were able to proceed. And then lastly, I'll have you focus on the time period around the LAB dosing. So the average time between the start of the induction and the LAB dose was 7.5 days. It was as short as six days, you'll see here. And then the average time between the last methadone dose and LAB was 3.2 days. I think the natural question that arises out of this is, did anybody experience precipitated withdrawal with the LAB dosing? And the answer to that is no. So we had Cal scoring performed for all patients both before LAB dosing and then in 30-minute intervals up to two hours on the day of, and then daily for seven days until time of discharge. And you'll see the max score here was four immediately prior in patient six. Otherwise, no scoring greater than three, really showing high tolerability of the LAB post-microdose. So I'll sum up by saying that in our trial-based experience, we observed a number of patients for whom low-dose buprenorphine inductions were felt clinically necessary in the context of concurrent medical fragility and pain. And in our limited case series here, we showed good tolerability, both of the transition and then the subsequent LAB dosing without any precipitated withdrawal. And we see this as just an additional tool in the toolbox of addiction medicine providers, including hospitalists and ID docs, to facilitate depot MOUD dosing successfully. And then I'll end there for further discussion. Thank you. And I just want to say that discussion that Nick led, he has published. Well, it's in the press right now at Journal of Addiction Medicine as of last week. So those details will be coming out soon. All right. We'll probably take more questions at the end. Did you want to introduce the next speaker? OK. You're doing a very good job. So the next speakers are Elaine Litwin and also Michelle Strong. Michelle, I think I just got your description. I know you're a nurse practitioner. Where are you located? In Greenville. In Greenville. Greenville with Elaine. So you can expound a little bit more afterwards. And I just want to also introduce Elaine, who is the Chair of Academics and Research and Professor of Medicine at Prisma Health, University of South Carolina School of Medicine, as well as Clemson University School of Health Research, where he leads the Center for Addiction Research. And I think they're going to split their talk. And thank you very much. All right. Well, thanks so much for inviting us to this great opportunity. It's been a really exciting study, fun to do, and really one of the best teams because of that interdisciplinary nature that Fran was talking about earlier. So long title here, but essentially, we're going to be talking about shared decision-making between addiction psychiatry, medicine, infectious diseases, and surgery, as well as some other team members. OK, these are our disclosures. And the learning objectives, basically, we're going to be able to understand approaches to shared decision-making in the following areas, choosing appropriate meds for opioid use disorder, timing of buprenorphine initiation and modified low-dose protocols, which Nick already reviewed, managing self-discharges in the context of social determinants of health, and complex pain management and medication decisions, and surgical decisions, as well. Long case here, but our patients are complicated. And I think there's a lot of important points here. So AD is a 38-year-old woman with a past medical history significant for opioid amphetamine use disorders and paravertebral retropharyngeal abscess complicated by cervical osteomyelitis requiring two spinal fusion surgeries with hardware. And that happened prior to coming to our health system, but now hospitalized with MRSA bacteremia. During the hospital, she received vancomycin for two weeks and oral rifampin, which is an adjunctive medication. Patient came to our hospital instead of the other hospital where she'd gotten the previous surgeries, because an outside surgeon declined to see her due to an unpaid medical bill of more than $300K related to these surgeries. Again, we're a non-Medicaid expansion state. A posterior paravertebral fluid was drained. And AD was noted to have loose hardware requiring future surgical intervention. The initial treatment plan was six weeks of IV antibiotics, vancomycin. However, the patient verbalized the need to discharge early as she was the primary caregiver of her partner's children. Infectious diseases had a secondary treatment plan, which involved two dalbovansin infusions, one in the hospital prior to discharge, followed by a second infusion to be given outpatient. A patient continues to report severe 10 out of 10 pain was discharged on hydromorphone, four milligrams every six hours, was unwilling or unable to start buprenorphine inpatient due to severe pain. And the reality of what she was, of her existence is that she lived with a partner in rural South Carolina, more than an hour away with very poor access to transportation. She did come to the buprenorphine program driven by her partner, was started on outpatient low-dose buprenorphine induction while continuing the hydromorphone. Patient was eager to have neck surgery due to this debilitating pain and her inability to extend her neck. After several months, she'd separated from her partner, became homeless, was unable to drive to our pharmacy, returned to injection use, and was lost to follow-up. She also never got her second dalbovansin infusion or injection. So part two, six months later, and this is very common where patients will come back and forth into our health system and other health systems, she was readmitted to our hospital after return of C-spine osteomyelitis in the setting of daily injection opioid use. She completed, this time, eight weeks of IV antibiotics. There was a lot of trust that had been built. And after shared decision-making and advocacy, which we'll hear more about involving addiction nurse practitioner, orthopedics, and patient, the loose hardwood was surgically removed. She was enrolled in the commit trial randomized to the treatment as usual arm. And after engaging in shared decision-making, initiated buprenorphine in the hospital through a low-dose induction protocol to allow for assurance of appropriate pain management post-surgery. She stayed this time, was discharged after a two-month hospitalization. She went to live with her mother, who also was still using methamphetamine. Addiction medicine physician, myself, manages her long-term infection in consultation with her ID doc. And the goal is lifelong suppressive bactrim, because she still has hardware, despite the removal of the other hardware. She makes her monthly addiction virtual visits, is inherent with both buprenorphine and antibiotics. And she hasn't used opioids for six months. Her pain has markedly improved. She can extend her neck. And she, most importantly, has a positive outlook on life. So I'm just going to say a little bit, obviously, for this audience. I think we all understand the medical shared decision-making. But it's been really nice to use Ned's guide from the CTN SWIFT to help kind of have these conversations. We kind of modified to really, it's a little different. I used to work in New York. And in South Carolina, there really wasn't as much kind of preconceived notions around which medications and not great access to any of them. So really kind of talking about the medical pros and cons of the different options. But I think what's equally important is shared decision-making. I'm going to turn it over to you, Michelle, as kind of the realities of the social determinants of health when we're making these decisions. So I don't know if you want to tackle that. Everybody's sleeping? You there? Yeah. As Francis introduced, my name is Michelle Strong. I'm a nurse practitioner. I'm certified in addiction medicine. Work on this incredible team. But I get to come at this from a little bit of a different perspective. So shared decision-making, to me, it's not about me. It's not what I want or what I think is best. Some of this for our patients, because of their such limited access in where we live and on the fact that we are not an expansion state, it's not always the first line choice. It's not always the best choice. It's what fits best for them. With this patient specifically that Dr. Lewin was discussing, methadone would have been great. It would have been great to help manage her pain. She couldn't get there. There was no option for her. So part of this conversation that we have in these patients is not only about the medication, but it's about who they are as people, where they come from, what their home life looks like, and what their access is. I think those are probably the most important conversations that we end up having with our patients as we start to help them make medical decisions. I view my job on this team as a guide. I am not the do-all, be-all, end-all. It is my goal to help guide the patients to the right option for them. We have read the literature. We have done the understanding. But it also needs to fit into their life and lifestyle. If this patient had been started on methadone, she would have fallen off immediately because she had no access to get to the clinic. So conversations with her looked a lot about understanding what her home life was, what her access was, finding a treatment option for her that was going to be a little bit more flexible and then finding a clinic that allowed virtual visits as well. What some of this shared decision making looks like from our perspective has to do with timing of buprenorphine injection, has to do with alternatives to treatment. So this patient was offered dalbovansin from an infectious disease standpoint because we heard that she had to go home to help care for her partner's children. Our team works very hard to find out this information immediately so we can work to reduce those self-discharges or those surprise self-discharges from these patients so we can have a better understanding of what the barriers to care that we are going to face with them are. Most of them will tell us, hey, I have to go. I know that I could die. I understand that, but I have to leave. This isn't a choice for me. A lot of that doesn't really have to do with substance use. Some of it does. But if we do our jobs and management withdrawal and ask the right questions right away, very much of that is limited and it more has to do with home life and some of the other components that impact care for our patients. So working to anticipate and managing those self-discharges is really, really important to our team. We work a lot with infectious disease and hospitalist management to talk through these cases. If there is going to be sudden self-discharge, what does that look like? What does that look like from prescribing antibiotics? Even if they are not first or second or third line, is there an option that we can give for a take-home regimen and hope that we can build that relationship with these patients that they will come back? So this patient was one that I saw on her first admission. We had a great rapport, great relationship. She worked well with our team. Unfortunately, we weren't able to enroll her in the study at that point in time. She came back to Prisma Health because of our team. She came back because she knew the level of care that she was getting, knew the level of care from our social workers, from our research coordinators, and wanted to come back to a place where she was heard, listened to, and felt that there was value in the conversation that was being had as part of the medical team with her, not for her. So when this patient came back the second time around, hardware reinfected, full-blown needs surgical intervention. Orthopedic surgery called me and asked me, why should this patient have surgery? She's relapsed multiple times. She continues to be non-compliant to medication, non-adherent to therapies. Why should we touch her? Why should we go to surgery? And it was one of the easiest conversations I've ever had with orthopedics because there's no other option for her. We've never given her another chance to step into something different. We've never given her a chance to live a different life. This patient, she was nearly six feet tall, neck was fully fixed downward, could not raise her head. She used to tell me that when she would cook dinner at the stove because she was so tall, her spice cabinet was above her, and in order to see what she needed, she would have to step back, raise her eyes because she could not lift her neck, grab it, and step back forward. So her quality of life was completely diminished by previous surgeries that she had had and previous complications that went untreated. She continued to return to use and go back to substance use to self-manage for pain because there was no other option for her. She was an incredibly talented artist, previous tattooist, who just ended up in a situation that she could not seem to get herself out of, and by not doing surgery and not advocating for her to have another chance, we are just going to continue to perpetuate that cycle. So when we had that conversation, that was an incredible opportunity to impart some knowledge to other colleagues who may have not looked at it in the same perspective, and they did, and they went in, and they did surgery, and they couldn't believe what her hardware looked like and why it was actually compressing her to not allow her any motion at all. Just really quickly to some basic points related to the timing of when you have an injectable sublucate, basically 48 hours of blood cultures being negative, 48 hours of being afebrile. Dalbovans is a really interesting option that needs to be studied more because it's a glycopeptide long-acting medication that interferes with the cell wall, and it can be given evidence-based for soft tissue infections one time, and infusion can stick around for two weeks, but it's been used, and we've had a case report out of our health system for more serious infections, bacteremia, osteomyelitis, endocarditis, and two injections a week apart can have levels of up to eight weeks. And then just the concept of a lot of times we're still fighting this idea that if people leave self-discharge, they don't get anything, and are hospitalists and so forth, and so we really have to work with changing that culture and even preventing that self-discharge by working with the patients so we don't have to do a sudden discharge even though they're telling us they're going to leave, and we pray they don't. Really quickly, just finishing up with this case, GZ was a 38-year-old male with severe OUD, actually intranasal fentanyl use, admitted after an MVA motor vehicle accident, actually ejected out of the car, found to have traumatic brain injury, subarachnoid hemorrhage, orthopedic polytrauma, facial skull bone, left femur, pelvis, multiple vertebral body rib fractures, followed by multiple surgery groups, neurosurgery, orthopedics, plastics. Addiction medicine was consulted by pain four days after admission due to patient's uncontrollable pain, and they found out about his daily intranasal fentanyl use for seven years prior. Patient expressed readiness to quit, interest in starting buprenorphine, remarkably looked pretty well, although in terrible pain. He was starting on low-dose buprenorphine while still maintaining his hydromorphone PCA. He was eventually weaned to oral oxycodone 15 every four hours, but had persistent and uncontrolled pain. Pain management was reconsulted for further assistance, was transitioned back to PO-hydromorphone every four hours, even every three hours, got some Ketorolac IV, was able to increase his bupe to 24 milligrams, taken three times daily, and then was finally able to participate with his inpatient physical therapy and discharged a rehab program and was able to go home. But complex in terms of going back and forth with addiction. And so, I don't know if you want to, you want me to just, yeah, so just, we already kind of went over, but sometimes the Bernice method is great, and we all know it, but it wasn't really studied in inpatient settings with complex patients that are very dynamic. And so, again, it needs to be studied further, but we do think it's very important to facilitate the patient's locus of control and self-efficacy, and people are pretty powerless just sitting back there. They can't even move. They can't even get to the bathroom. And so, being able to give some control if we need to do some of the things that Nick was doing I think is quite useful. And finally, it's quite a song and dance of working together with the services. It's not all kind of perfect, you know, depending on the day, and sometimes we have to consult people back, but we got to try to all work together, and we do it more times than not to figure out a plan. And finally, there's other members of the interdisciplinary team for shared decision making that are quite helpful. So, social workers, we have peer recovery coaches, people with lived experience, co-management with the emergency department, you know, obviously the advocacy that we have to do with CT surgery for valves. We've gone a long way in our health system to be able to do valve surgery. But again, there's still need for evidence. Guidelines differ, and it's unclear exactly what the best options sometimes are. And you know, obviously, hospital medicine, screening for other common infectious diseases, and we can even initiate antiviral treatments for HIV, for hepatitis C, in some cases hepatitis B, you know, really kind of not waiting for the discharge, treating when we get it if appropriate, and linking to care to continue the treatment. So, I'm going to turn it over to Ned, and appreciate that. And I'll just briefly introduce him. He's the professor of psychiatry at CUMC and New York State Psychiatric Institute, the co-director of the Chosen Center at Columbia, and he's the MPI of the Greater New York Node of the CTN, and we've worked many years together, Ned. Yes, yes. Many, many years. Well, thanks everybody for coming. I just want to make a few comments, and then I have a few questions for the group, and hopefully stimulate some discussion with the audience. I was thinking about this talk, and I recalled that I first met Sandy Springer at a meeting that had to do with planning a VA cooperative study, so this was, Sandy was collaborating with our own Izmini Patrakis at Yale, putting together a large multi-site trial in the VA comparing sublingual to injection buprenorphine, and we were chatting over coffee. Remember how you used to chat over coffee before the pandemic? We were chatting over coffee, and Sandy said to me, you know, we see the same patients. We're treating the same patients, and, you know, it was a very salient moment for me that we should really get together and collaborate and see what we could accomplish by collaborating. And among things I've been involved in, I've kind of stumbled into helping out the addiction medicine field, which has been developing a lot over the last decade, really, and, you know, there's now thousands of physicians taking, who have taken the addiction medicine board exam, and if nothing else, these are non-psychiatrist physicians, mostly internist family physicians, and if nothing else, expressed a real interest in taking care of these patients. And so a couple things strike me. One is that, yeah, we see the same patients. We actually like working with these patients, and I think these patients are used to being treated not so well in the medical system, right? They're treated with quite a bit of stigma, and so I think that the kind of interest and energy put into the patients that you hear from Nick and Michelle and Alan is really salient. You know, these patients are often viewed as being uncooperative, and yet, as was pointed out, they have complicated lives, and they've got to go, and they've got to go for good reasons, actually. It's not, you know, it's not just that they're uncooperative. So we've had some discussions on the research team about, one of the things that strikes me, actually, about the findings is the high follow-up rate. What's the follow-up rate at 24 weeks after these patients enter the study? At 24 weeks, it's been about 74 percent, and at the intervention period, about 80 percent. Yeah, which is really pretty remarkable follow-up, and I think it speaks to the tenacious interest of the research teams in keeping track of these patients, visiting them at home and so forth to follow up with them. And so we've talked a little bit about what could we learn from the research effort that could be applied in clinical care, and vice versa, what could we learn from clinical care that would inform the research process in the future? So I'd love to hear more comments about that from the panel or thoughts from the audience. A couple of other points, you know, you look at the demographics of these populations, 40 percent homeless, mostly unemployed, unmarried, real severe social determinants. And also, it's a largely Caucasian population. The reason for that is it's largely rural, and one of the imperatives from the funding agency when this grant was written was to study rural populations. So I'd love to hear more from the panel about the implications of that. How many folks in the audience practice in urban or suburban settings? Yeah. And how many practice in rural settings or close to rural settings? Yeah. So I think most of us are sort of urban-based, and so I think it would be really interesting to hear more about the rural dimension. Greenville is in a rural area, right, and, you know, Yale and New Haven we talked about. It's urban, but there are surrounding areas that are rural, and Penn State is in Hershey, Pennsylvania, in the middle of rural Pennsylvania. So that concludes my comments, and I might first throw out that question about rural-urban. What thoughts do you have about treating these kinds of patients in a rural setting? Okay. Yeah. So, I mean, I've worked for most of my career in New York City in the Bronx, and so really obviously huge urban area, and then moving to Greenville. It's a city. It's 60,000 people, and Katchemarian's large, but we draw a lot of rural patients, and we have a large health system, the largest in South Carolina, so 12 hospitals. We've actually recruited, yeah, up to 17 now, and recruited from eight of these places, and so a lot of the folks are coming into rural, small, 80-bed hospitals, 60, but there's not a lot they can do. They get then transferred to, you know, our setting, which was kind of rural-urban. And similar social determinants of health in terms of, you know, housing issues and so forth, but it's much more dramatic because there's no subway, right? There's no, in fact, Uber doesn't even go to these communities, right? There's no one there, and the taxi cabs, even though there might be a few taxi cabs, they don't even want to pick up certain people. They know them, and they're like, I'm not going to pick up that person, so there's really nothing there. There's not broadband access in a lot of places, so even to do televisits, it's really hard. There's criteria in South Carolina that are pretty strict, where you can't do it. For a short time during the pandemic, we could do an initial tele-visit for buprenorphine, but that lasted probably a year, and we can't do a tele-visit initially. You have to do it in person, and then you can do follow-up tele, but that becomes prohibitive. You have to drive, you know, somewhere. So we're starting mobile programs and so forth, but there's a lot of food insecurity, a lot of intergenerational drug use, so three generations using together things that you might have seen in Scott County. Michelle, what else do you want to add to that? Our public transportation is almost nothing, so patient options to get to one of our clinics or another clinic, even if they are in a more urban setting, is almost zero, and there's just not a lot. There are not a lot of programs available. The choices are very limited, and when it comes to patients who are homeless, not working, or have some sort of financial insecurities, the majority of the times they can't pay. Either way, even if we can get them somewhere, the options for them to come up with $250 or $300 out of pocket for some sort of intake is almost nothing. There are programs in the area that do support that, and we try to send the majority of our patients to those, but there are still limitations that come with them, and those programs fill up very, very quickly. So it does add a layer of complexity when trying to work with patients, offer treatment options, and find something that's going to be sustainable for them to make offers that I can't promise to keep. I'm in the inpatient setting, and I can't show up at their house to drive them to their appointments. So it's very challenging to offer that without looking at that lens of what is going to work for them. And just really quickly to add on here, even in the city, the buses don't work like in New York City, right? So it might take two hours. If they have someone with terrible heart, like EFs, like 15%, they're rushing up to get there. You know, they miss the bus because the connections don't work, and they miss their appointment. People walking 10 miles to come see me. And the recovery homes, a lot of homeless folks, they live in encampments behind in big roads where they can go panhandle. They live in tents. And the recovery homes don't allow medications for opioid use disorder. And we have our first question. John. Hi. You should all be congratulated. This sounds like it's going really well. I mean, for such a difficult-to-treat population to have this level of engagement says something very favorable about the research and clinical staff working with them. So I think you should feel good about that. Whatever the end results are, so far, this sounds like it's going very nicely. So congratulations. You know, I've been hearing about the trial from Francis secondhand. So it's nice to see it formally presented. She probably can anticipate what I'm going to say, which is, you know, I have two types of discussions with people about fentanyl. You know, one is that it's impossible. The patients don't want buprenorphine anymore. It's so complicated. We have to come up with all these new ways to treat people. And the other conversations I have with people are analyzing data sets and say, we don't see any difference in induction success, right? And so, like, you know, you can at the same, like, hour of, like, talking to people who you're speaking to really get these different pictures of this is like a crisis. We don't know what to do anymore. And other people saying, I don't know what everybody's talking about. It looks the same. So I think both things are true in that it is different, but I don't know if it's as different as we think it is. And one, the bias I always have, and, you know, I think this is very interesting work, and it's a very particular population, and they're stuck in the hospital. But I'm always worried every day that goes by that the person doesn't get the shot is just another day for something to go wrong or them to leave or something. And so, you know, my question would be, what about doing it much sooner? And, you know, I don't have as much, I really have very little experience with transitions from methadone. I think I'm not really, this is probably, I'm overstating, you know, how easy it would be. But fentanyl is not that really different pharmacologically from methadone when it's accumulated in the person's fat. You're basically, fentanyl becomes like methadone when you're using it regularly because it stays in the person's system for a prolonged period of time. And our experience is giving the shot very soon is actually okay. And people tolerate it. And what I would say is, why not give it the first day? What do you think would happen? Yeah, no, this is such a great point. And it was interesting, you know, even putting together our case series and publishing it and trying to find the published literature evidence base for, you know, higher incidence of precipitated withdrawal. It's really scant, you know? So it's really something that you're hearing a lot kind of on wards from patients. We see this disconnect. So yeah, you know, I think from our clinical experience, we really saw good success even bringing down that time period of the induction from seven down to six to five. And I would really think that we could continue to see that. One thing that I think Frances will say here too is, you know, the experience of people talking about really giving the shot and kind of pushing through on that day. You know, the hospital is a controlled environment. We can support people with, you know, non-agonist based withdrawal medications as much as possible. And I think that's totally possible and kind of part and parcel with the shared decision making where some patients may say, hey, this is what I want to do. I'm happy to do it. Give me all the meds I need. Yeah. Yeah? Yeah. And just to be clear, Frances and John, you've developed a one day, right? Yeah. Same day. Huh? Same day. Okay. Right? Yeah, no, we're totally supportive of doing as quickly as possible. I think some of these patients though, because they were like, somehow we're undergoing open heart surgery and we're on, like we couldn't, we couldn't do that quickly. Maybe not the best one to experiment with. Right. But I think one of the important points is that every, it's individualized, right? And we, there's not one size fits all and like you were giving a demonstration of those who could safely get on to low dose transitions and then we've had others that we could go ramp up. You know, they had one dose of sublingual buprenorphine and could give them a sublocate. But I think I, we completely agree with you and it's actually been, you know, seeing this data that there really wasn't any evidence of precipitated withdrawal, even in these like high, high level opioid agonists and that one could potentially push it forward. So I think. The shot itself is like almost like a drip. I mean, it's a very grand, you know, and I, I would even advocate for not doing the pre-medication with any sublingual because I think that's actually causes most of the problems. Thanks. Yes. Hey everybody. Thanks so much for the talk. My name's John. I'm a medical student. Super exciting to hear about your work with this population. I started to do some work with patients admitted to the hospital with serious infections. And one thing that I've heard from them is that when they come to the hospital, those were able to engage with treatment and they have these wraparound services where they're seeing all different types of providers. Sometimes they're able to reconnect with family. It's this real, you know, important moment for them and an opportunity for change. But then when they kind of transition out of that very acute setting, like wondering how to kind of keep that momentum going from being in the hospital, being cared for every single day to then, you know, the outpatient setting, which is very different. And I'm wondering how your experience has been with the long acting injectables kind of facilitating that momentum or other ways that you've been able to keep that momentum for patients. Yeah. Excellent question. So there's a lot that, you know, when you do a clinical trial and you have a presentation, you can't put it all in here. But one of the benefits of this is this, we have for all participants, regardless of which arm they're randomized to, everybody gets this nurse care management model where every day while they're in the hospital, they're evaluated, their other needs are assessed. And then discharge planning, and it includes afterwards, not just a weekly medical management call. It's like, how are you doing? What is it that you need? Other needs assessments that are done, which we know are not happening in the hospital. And as an HIV provider, infectious disease doctor, where there's a lot of other, you know, seeing this forever, and one of the reasons why I love, you know, taking care of substance use disorders is there's not a lot of that, you know, early on needs assessment that's being done with assertive evaluation and how to address those needs. So sure, we can't give everybody a home, right, which I would love to do. And we know that improves substance use reduction and substance use and other things. But there are other things we can do. Transportation, absolutely critical. And you know, just communication, having ability to communicate, so cell phone. But yeah, so other things that we, I think, you know, all of that will come out in the final, we'll describe all of that in the final outcome paper, but that's going on, so everybody's getting that in addition. But long-acting buprenorphine, similar to what we've done, or like others of us, like I've done trials in people who are being released from prison and jail with extended release naltrexone or other forms, long-acting forms could be really beneficial for this population as they're being discharged into the community, have the safety net, and sure, you might not get everything fixed, right? But you have opportunity, you have time to actually work on those things. Other interventions like I'm working on are providing the care, like bringing the care to them through mobile health interventions or having a navigator, a patient peer navigator who can help facilitate that. And I think all of those, we really need to think about how we can do that clinically and how we can do that administratively, and from a research standpoint, all of those types of interventions need to be evaluated in cost-effectiveness, et cetera. And there are going to be differences, right? Rural versus urban settings and others. Thank you. Thanks. Rick? Hello. You know, I always have to say something, right? So a couple of things. Half your group is using methamphetamine, probably injecting, or they may be smoking. It is interesting, you know, the study in San Francisco showed that people that switched over from heroin to fentanyl, most of them stopped, well, half of them virtually stopped injecting and a bunch of them injected less, at least for the heroin part of things. But now, unfortunately, some smoke both methamphetamine and fentanyl. So paradoxically, fentanyl, as it replaces all the heroin market, a whole lot of patients that I've seen don't inject anymore. So you've got an increase in overdose deaths. You've got a decrease in infections, which is sort of interesting. But you didn't give us any data on what was going on with those 50% of methamphetamine users, which isn't really affected by whether you give them long-acting bupe or tuna fish. So that's one thing I wonder about. Second thing is you didn't give us changes in pain management. You showed us that a lot of those people had pain management in the 10 ratings or 8.2. How well did that do on injectable buprenorphine? I mean, most of us have had people with multi-pain problems and opioid dependency, and we have been on high dose several times a day bup. But you didn't give us ratings on either methamphetamine or on how pain management was happening. And by the way, you and I talked a lot back in the days of injectable naltrexone for ultra-severe alcoholic people in downtown, and we published that. Yeah, I remember. Yeah, so just the first question, so everybody had met criteria for moderate to severe opioid use disorder, and in addition, the high degree of costimulant use disorder. So in terms of all the secondary, we can't give you the data by treatment arm of the pain co-management and how the costimulant, because we're still ongoing trial, but we are tracking that and their pain, and also how if they're injecting versus if they're using oral forms of treatment, and then which forms of substances that we're using. So that data will all be there, but the pain, co-management of pain is a significant factor that we are following, and it may very well affect our outcome data. There is, as you know, published data, one from our group that showed that retention on MOUD was improved if the person had pain. So this idea of, and it was methadone and buprenorphine treatment. So I don't know, there's other things that we'll find out, but Alan can probably talk about that this is an ongoing issue of comorbid pain management, and we are keeping track of that in this database, and so hopefully our trial will be done next year, and we can present that. Go ahead. Yeah, I don't know how much, I think those are great points, most of all. I think I'm looking forward to the data, right? It's a big challenge doing both inpatient and outpatient work because of the co-occurring stimulant use disorders, but people do stay engaged, although they're continuing to use often. We do use interventions like RESET and RESET-O, but it is incredibly, incredibly challenging, and so I think we need more interventions, but do you have a follow-up to that? Yeah, just one comment. I work in a level one trauma center in downtown Seattle, and believe it or not, across the Rocky Mountains, all the way from where you guys are, we also have the same patient. Oh, yeah, yeah. But anyway, the way we've chosen to try to intervene with that with our level one trauma center is our biggest opioid use program at the University of Washington, or at least in the trauma center, is in primary care internal medicine. So half the doctors, numerous doctors, are addiction medicine doctors, and we have an opioid use consult service in addition to an alcohol intervention consult service in addition to our psych consult service, and the opioid use one is composed of medicine people, addiction psychiatry people, a chemical dependency counselor who's really good at both recovery and harm reduction type therapy, and a social worker who does all the linkage stuff, and these people roam around all together, and different people have different levels of stuff, but there's a lot of follow-up. Most of the follow-up actually happens through the primary care medicine group, and we also have a lot of peripherals all around the greater Puget Sound area, besides in Seattle, but that model, you know, the thing you showed earlier that is really interesting, you know, everybody talks about overdose deaths. Nobody's talking about how expensive infections and those kind of things related to both meth and opioid, and how ultra-expensive it is, and that we really need to create these teams in hospitals where they're seen to engage, so it's not just deaths, it's this immense pile of money that needs intervention. Yeah, no, absolutely, those are great comments, and I just want to, another thing you had mentioned the first I forgot to address is that I think it's often that we think of infections associated just with injection drug use, but there are also infections that we're seeing that are occurring even without injection drug use, so as we're seeing the turn, we're seeing this as well in Connecticut, now there's less injection use, but more oral use, pressed fentanyl pills, infections can still occur in terms of whether it be an intranasal use, so hepatitis C, acute HIV, they're through more sexual encounters because of the disinhibition from the substance use and other infections, but yeah, no, all of your points in the multi-team collaborative model, what you guys are doing sounds awesome, and we need more of that, and I see there's more questions, so I'll keep going, or you keep going. Thank you for the great presentation, my name is Kapila Murambige, I'm an addiction psychiatrist at the UT Southwestern University of Texas Southwestern campus, so I had the privilege of working with some, like, infectious disease on a program called OPAT, I'm sure you are familiar with that, so that's where, you know, we have outpatient antibiotic treatment where people are given, like, put a pick line, and they sometimes would be sent home for six weeks worth of antibiotics, or even less than that, it spreads through to a maximum of about six weeks, I think, so I had the privilege of working with them as an addiction psychiatrist because we have this major problem in that the OPAT exclusion criteria would be that if they have any substance abuse at all, they will not be taken out, like, you know, they will not be allowed to be on the OPAT program itself, so what I did was I collaborated with Dr. Bhavan and a few people you might know from there, and we chose the low and, like, a low severity substance use population using the NIDA tool, and we started sending them off on the pick line, and we had good success with that, now we want to expand it a little more and go to the moderate and the severe categories where we will be able to, so it's a bit complicated in Texas because of black tar heroin, and you might know that it causes venous sclerosis, and anybody who gets a pick line values it much more than how it might be in the East Coast, maybe. So my question specifically is that we were considering to go to the next stage, maybe using either Vivitrol or Sublocade. Now, Sublocade is not on formula yet, Vivitrol we have gotten on the formulary, so I am going to work on the formulary and get the Sublocade. Do you have any views on the pros and cons of either one of those? Like, I'm sure you have worked on the Sublocade, but do you have any ideas about Vivitrol, the comparison of which way I should go? Yeah, no, that's a great question. I think that's the kind of situation that I think folks that do inpatient consult work, these are very much the same patients we're seeing because these are all people with serious infectious diseases, and, you know, this putting in a pick line and deciding their disposition is this dilemma, you know, because all of a sudden they have vascular access that's even easier. On the contrary, they already had vascular access, they can get any, you know, so it's this interesting thing where, you know, there's a dearth of data here. We were looking at our own OPAT outcomes at Yale and retrospective that we're working on now, and there's an assessment tool by folks over at UAB looking at this exact question, and I think assist people who are on, you know, consult liaison, you know, how do we answer this question, and they did a similar thing where they created a mild, moderate, and severe assessment tool to decide who may be safe to go home with a pick line, and I think that's probably the biggest takeaway. I think when you do that patient-by-patient risk assessment, you're going to find people who have been on methadone for 30 years, and if they do use, it's nasal, and I think those people really are well served by being able to go home and do their IV antibiotics. In terms of what the MOUD should be, I, you know, I think, you know, in a way it's two separate questions. I think if they're adherent to it and they have high desire and acceptability to be on sublingual, and that may mitigate their risk, that could be the answer. That being said, you know, I mean, I think my vote would always be for a full agonist if you can. We just got sublocate on the inpatient formulary. Sure, yes, you're right, buprenorphine, as opposed to Vivitrol, but we just got sublocate on the formulary at Yale, so it is, you know, these things are possible, and I think advocating for those pushes really can just kind of increase the options that you have for treatment. Yeah, I advocate for the sublocate also in a way because it, you know, actually works on the receptor system in a way that it will kind of help the psychiatric symptomatology a little bit better, I would say, compared to the naltrexone. So most of these patients will have comorbid psychiatric issues as well, so we are looking at that very carefully and we want to choose. Second part of the question, if you don't mind, is how to manage the pain, which I think you answered. So if most of these patients will have deep-seated infections, a lot of pain issues, you have any insights on that, like how to co-manage the pain while they're on sublocate? Yeah, I think the quick answer is, unfortunately, we don't know yet. There's no published data on sublocate and pain control, and when we enroll people into the trial, we let them know that. We're not sure if this is going to have similar analgesic effects as sublingual, you know, oftentimes people will do TID dosing. So, you know, stay tuned. That's going to be one of the things that's going to be an interesting secondary analysis for us as well. Thank you so much. Hi, Chris Blazes from OHSU. So I use sublocate all the time. I think it's an amazing medication, but I have one concern, and I'm hoping the panel can convince me it's a misguided concern, and that's the dosing is so high. The serum levels of even the low dose of the sublocate is actually much higher than even 16 or 24 milligrams, and that dose, like, and norepinephrine itself, the primary metabolite, is actually a full agonist opiate that does not have a sealing effect on its respiratory suppression. So in sick people who might be on other medications or might go out and use alcohol, I don't know, I have concerns about these people. What do you guys think about that? That's my question? I actually don't have the mic here. Yeah. So actually, I've looked at the pharmacokinetics that's published in the package insert, and I guess the area under the curve is higher with the injection, but the day-to-day spikes with the daily buprenorphine, I think the daily sublingual gets higher spikes. I'm interested in what you say. I haven't worried so much about the dosing. In fact, clinically, we hear some patients who say, you know, the sublocate's not enough. It's not covering me. And the other thing I think we've learned, and we haven't looked at this with sublocate yet, but we've looked at this a lot with naltrexone is that these long-acting injections, there's a lot of individual variation in the blood levels you get. So with Vivitrol, for example, a substantial proportion of patients have got virtually no naltrexone left by 21 days, and some even less than that. Others are okay. So you know, you look at the package insert, and you see this blood level curve that's the average, but actually there's a lot of individual variation within that average. So I would guess that, you know, even when you get 300 milligrams of sublocate, some patients may experience that as a pretty high dose and get side effects. Others may feel underdosed, and it's a function of that the depot isn't releasing at the same rate or with the same efficiency in all the patients. So I think you have to kind of follow your nose. It's an interesting point about the norbuprenorphine being a full agonist. I actually haven't thought about that much, and I don't know if anybody else in the panel or in the group has thought about it. But what I like about, you know, you give 24 milligrams sublingual or a 300 milligram shot, you've locked up most of the receptors. And so with a high affinity agent, so at least if someone takes other opiates, they're just going to bounce off. Yes, if they take a lot of alcohol or sedatives, they can overdose, and you know, we know that. So anyway, thank you. Those are really interesting points. But we shouldn't, but I think that also brings up a comment that we can't withhold treatment for opioid use disorder, but we have to, those with alcohol and benzodiazepines, we have to like, you know, also focus on, careful with that. But good question. Sorry. Hi, everybody. My name is Eric. I'm one of the clinical fellows over at Columbia. So I'm just finishing an inpatient consultation that is on rotation, and I've encountered a bunch of cases with this intersection. And one of the most challenging situations in my experience is when they have like, for instance, infective endocarditis, and recommended treatment is six weeks of IV antibiotics. And on a systems issue, even if the patient's on board with medications for opioid use disorder, and there is a plan for the antibiotics, there's nowhere to send these people because all these acute rehab facilities, for whatever reason, they won't accept them, whether it's stigma or outright discrimination. But I've called them and I've asked them, why are you not accepting this patient? It's like, oh, the medical director, either cancer or won'ts. It's like, well, what happens if we send them with buprenorphine in their own supply? They still won't touch them. And so I was just curious what your experience is with this and how we can address these systems issues. Have you tried to sell sublocate to any of them? No, because we don't have sublocate in New York Presbyterian on primary. Yeah. Yeah. And this is a national issue. And I will say, I think this is part of the theoretical advantage of depot medications. You know, one half of this has been the trial and the other half has been the kind of real world creation of policies to try to make the trial happen, which has been good because it really kind of has blended into QI for a lot of our sites. So, yeah, you know, I think it was Massachusetts that actually had an ADA-based lawsuit against skilled nursing facilities saying that it violated patient rights, that they wouldn't be able to have disposition to certain places. I'll say, practically speaking, I've worked, you know, I was in New Haven. Now I'm in Philly. One of the first things I learn are which of the skilled nursing facilities that accept people on MLUD. Those things make a market for themselves. They do. And, you know, and unfortunately, sometimes their care, you know, may not be as good. But, you know, making that phone call has been really interesting because those connections are made. And I think that's part of the de-siloing of all of this is, you know, you meet the ID folks, you know, at Columbia. You make those calls and connections. And we've seen kind of small but measurable progress in things like that when you kind of go across the parking lot and talk to folks. So it's tough. We've seen it. But we've seen some progress too. Eric, do you think if they were on supplicate they'd be any more willing to take people or is it just a total stigma against somebody with an opiate use disorder? I wonder if how much of it really is stigma. You know, part of it, I think we may run into problems if considering that it's still an agonist in some capacity. I think that perhaps there might be a more palatable for some of these facilities if it's naltrexone, for instance, because it's not an agonist. But it's confusing because I ask them, like, if the patient's on like a benzodiazepine, would you do that? It controls substance. And they're able to do that. It's just like the medications for opioid use disorder, which to me speaks to the stigma associated with the substance use disorder. Yeah. Yes. Hi, my name's Allison Smith and I'm an addiction psychiatrist at the Medical University of South Carolina and really appreciate all the work and everything you guys are doing. I got like a small state grant to fund some addiction services into our existing psych CL, so peer recovery, case coordinator, and then sublingual bupe and Narcan because our hospital also wouldn't fund any sublingual bupe for unfunded patients. And I'm kind of running into the sustainability issue. So I'm just curious, it sounds like all of you guys at these institutions have got a lot of buy-in and supplicate on formulary, which is very impressive, of just like how to, any big measures that you are able to take to get the hospital to buy in. In my experience, sometimes you prolong length of stay so that it's kind of hard to measure what is cost effective or improved quality because it's not always cheaper. A patient center discharge is the cheapest discharge for the hospital, unfortunately. So I'm just curious, kind of, any, I know it's kind of maybe a long question, but just any measures that have been, you know, across the board, a good point to like make an argument to just hospital administration. Yeah, when you take good care of the patients, they stay in the hospital longer and... Yes, exactly. Yeah, it costs more, yeah. Yeah, those are all good questions and since you guys are both at Medical University of South Carolina, I'll let you, or you're at Greenville, but you're a partner. But I'll say two things. Yeah, I do this, it's the same thing with the criminal justice system. So, you know, what is cost effective and all that. But one thing, I can't speak for the group that, all of Yale, but showing that there's less emergency room readmissions or less admissions, they like to hear that, right? And then it might not be, it might be a shorter stay or it might be a longer stay, but taking into consideration what their underlying other medical illnesses are, so that's important to know. Like if they're post-surgery from a valve replacement, did they come back or did they have a reinfection or not? So keeping track of those types of data points are really critical. Back to Rick's point, every case of osteo or endocarditis you prevent, it's a lot of money. Yeah, yeah. So I know we're over time, but basically just draw, we don't, you know, collect our own data. We're doing it, but I think we can draw the literature and kind of pick and choose. It becomes a little bit of like arguing a case, you know, and then developing business plans. So that's what we do for our outpatient. They're never going to be great, but you can start to kind of figure, you know, some billing, you know, billable stuff. We're learning that social workers, if they're providing counseling, actually can bill. And so we built some pro formas that way. We can talk more offline, you know, about some of those strategies, but it's a battle, especially now with the climate of health systems that are all losing money now. And shutting rural hospitals down, too. Yeah, we've gone over our time, but come on up front. I want to make a plug, too. Petition the DEA as well, because right now the only way you can get sublocated is in a REM certified program in the clinic. And through research, we can actually bring the medication to people wherever they are under an IND. We can go to a prison. We can go to a jail. We can go to the community. We can to, you know, mobile health unit. And so, you know, we need more of that. Sorry. Bye. Thank you.

injectable long-acting buprenorphine

hospitalized patients

infections

opioid use disorder

Project Commit

Sandra Springer

Frances Levin

infectious diseases

addiction psychiatry

shared decision-making

social determinants of health

integrated care

substance use disorders