1-14-21_Springer_Yale Addiction Medicine Rounds

December 08, 2022

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00:33All right. I think we'll go
00:35ahead and get started just so
00:38we don't run too short on time.
00:40So welcome to our first addiction
00:44medicine rounds of 2021.
00:46We're all looking forward
00:48to a wonderful year.
00:52And did David and I did want to take
00:56a moment as many of you certainly
00:59in the the Yale circles and well
01:02outside the Yale circles circles
01:04know our dear friend and colleague
01:08Kathy Doctor Kathy Carroll passed
01:11away earlier this month and so.
01:14I just wanted to take a moment,
01:16have a moment of silence to think about
01:19her and all the work she has contributed,
01:22not just to our field,
01:24but so many of us have been touched
01:27personally and professionally by her.
01:30So I wanted to just take a moment
01:31of silence and then we will
01:33go ahead and get started.
02:07OK. So thank you.
02:09There is going to be a remembrance
02:13of Kathy next Wednesday through the
02:16division of addictions and so that
02:19has been circulated on the listserv.
02:21So if you'd like to join for that,
02:23that would be wonderful.
02:26We are extremely delighted to
02:28have Doctor Sandy Springer with us
02:31this morning or this afternoon.
02:33I don't even know what time it is.
02:34I apologize. Do any of us really?
02:37Um. I'm going to just do a couple
02:40housekeeping slides and then I will go
02:43ahead and introduce Doctor Springer.
02:44So Emma, I hope you have control of the
02:49slides because I don't believe I do,
02:50but I'm just a reminder to stay connected
02:53with the old program in addiction medicine.
02:56We have three main ways to do that.
02:57Our website,
02:59our list serve and Emma Bukaki
03:01can get you connected through that
03:03or through our Twitter accounts.
03:05We have our.
03:06Program in addiction medicine and
03:08certainly our Champ program Twitter
03:09account as well. Next slide.
03:13Our upcoming addiction medicine
03:15rounds will be our very own doctor,
03:19Lynn Phileine, speaking with us on using
03:21the power of play to tackle substance
03:24use in adolescence and that will take
03:26place on February 11th. Next slide.
03:31Just a reminder about our CME
03:35opportunities through this venue.
03:38So go ahead and text the number to
03:40that that you see here in the slide
03:43and Emma will also post it in the
03:46chat throughout the talk next slide.
03:52OK, so as I said, we're super excited
03:56to have Doctor Springer with us today.
03:59Doctor Springer is an associate professor
04:01of medicine in the Department of
04:03Internal Medicine section of Infectious
04:05Diseases at Yale School of Medicine,
04:08but also a faculty member in the
04:10program and Addiction medicine.
04:12She's board certified in internal medicine,
04:14infectious disease and addiction medicine.
04:17So, you know, spends most of
04:19her life taking board exams.
04:22She's the director of the Infectious
04:23Disease Clinic at the Newington site of
04:26the VA Connecticut Healthcare system,
04:27where she overseas the care
04:30of veterans living with HIV.
04:32She's had significant clinical and
04:35research experience with persons living
04:37with HIV disease and those with core
04:40comorbid substance use disorders.
04:43And her research has focused on
04:45evaluation and integration of
04:47substance use disorder and HIV
04:49treatments and in particular.
04:51Is focused on medication treatment
04:53for opioid use disorder and medication
04:55for alcohol use disorder to improve
04:58substance use and HIV treatment outcomes,
05:01especially among those
05:02released from prison and jail.
05:04And and we're really delighted
05:05she's here to talk with us today
05:08about her groundbreaking work on
05:10novel approaches to using long-term
05:12formulations of medication for the
05:14treatment of opioid use disorder.
05:16So without further ado, Sandy, go ahead.
05:21Thank you. And can I
05:23share my screen now? Yes,
05:25you should be able to.
05:31Great. So I've provided the slides
05:35that are there's for everyone,
05:38but I'm not going to talk about all of them.
05:40I just so just for time purposes.
05:44But again, I just wanted to say
05:46thank you for having me here to
05:49talk with you and I apologize I
05:51can't meet your meeting times all
05:54the time because I have other.
05:56Obligation.
05:56So, but I really value being a part
05:59of this really extraordinary group.
06:01So thank you.
06:05These are my disclosures for this talk.
06:11So we are all very familiar with this,
06:15this graph by now.
06:16I think I start out with my talks
06:19whenever I'm talking about the opiate
06:21epidemic to just kind of remind us about
06:24this latest opioid epidemic and how it
06:27started and then I proceed that way.
06:29But one thing I know is this group,
06:31I don't really have to explain this
06:33to you because you're in the thick of
06:35things and have been doing this work
06:37many of you even before me, but I just.
06:40A reminder that since the late
06:431990s when our prescription opioid
06:46epidemic started kicking off.
06:48Really substantially and then leading
06:50to a black tar heroin epidemic in
06:53orange and then as we know we're just
06:56it's overwhelming synthetic opioid
06:59epidemic since 2013 really that's just
07:02overwhelming us and back in 2017 I think
07:05it just was hitting like the public.
07:08We saw more press related to the
07:10opioid epidemic although it's been
07:11going on for a while and you know
07:13it's hard to remind people that
07:14yes we did have an opiate epidemic
07:16before that which is why I went into.
07:18HIV actually was causing new HIV infections,
07:23especially in Northeast but.
07:26Anyhow, it,
07:26it got a lot of public press and I
07:30think then there was some potential
07:33initial hope because the data that
07:37later came out showing data about
07:40overdose deaths in 2018 started
07:42showing they thought was a reduction.
07:44But many of us who do this work said,
07:46hey wait, you know,
07:47there's certain states where
07:48we're seeing a reduction,
07:49but other states we're seeing an increase,
07:51one of which here is in Connecticut where
07:54overdose state Rep deaths were not.
07:56Going down.
07:57But,
07:57you know,
07:58just overwhelming like over 450,000
08:01Americans have died from opiate
08:04overdose since 1999 up until that
08:07time point is just just astounding.
08:09And then sure enough,
08:11you know,
08:12one thing we knew when you looked
08:13at the data a little bit more was
08:15that in fact we were seeing this
08:17increase in synthetic opiate overdose
08:19deaths on either combined alone
08:21or combined with heroin and other
08:24opioids and of course stimulants.
08:26And then when the pandemic hit,
08:28one of many of us were concerned and
08:30started seeing increase overdose
08:32deaths in our site in our areas.
08:34And then as I saw you,
08:36you,
08:37you released this data to everyone
08:40in the Addiction medicine group.
08:42But the CDC reported that in fact,
08:45sure enough we had had substantial
08:47increases in overdose deaths across
08:49the country from 2019 up until
08:52May of 2020 where over 81,000
08:55individuals that we know of.
08:56Died of drug overdoses in that
08:58period of time, and in particular,
09:01again synthetic opioids,
09:02it was over a 38% increase
09:04in overdose deaths.
09:05And we know in Connecticut and there's
09:08many of you who've been working on this,
09:11we're seeing substantial rises in
09:13overdose deaths related to synthetic
09:15opiates where we have over 25% increase.
09:18In addition to the direct harms of overdose,
09:21deaths are over harms from opiate
09:23use I we just
09:24also are aware and again many of you
09:27also do the same work as there's also
09:30other consequences related to this,
09:32including infectious disease consequences.
09:35So we had made some strides and reduction
09:37in HIV incidence among people who reported
09:39injection drug use for many years.
09:42And then around 2015 sixteen we started
09:45seeing a stall in that and then in 2017.
09:50Started seeing new cases of
09:52eight incidents infections.
09:57In individuals who are reporting
09:59injection drugs use and as we're all
10:03familiar with since Scott County,
10:05Indiana when we had this first outbreak
10:07of HIV as well as hepatitis C and
10:09persons who are injecting oxymorphone,
10:12a prescription opioid, this is a no.
10:14I haven't updated this lately,
10:16but we have had substantial increases
10:18in new HIV epidemics across the
10:21country fueled by injection as
10:24well as unprotected or condom.
10:26Sexual intercourse and among individuals
10:28who are using drugs in particular heroin,
10:32fentanyl and a combination of
10:34methamphetamine and cocaine as well,
10:36one of which rate above us and
10:38in Lawrence Moe Massachusetts.
10:40And there was another outbreak
10:42in Boston last year.
10:43In addition to that,
10:45we know acute hepatitis C has
10:47increasing especially sadly among
10:50younger individuals with opioid
10:52use as well as stimulant use.
10:54And then this is just a summary slide.
10:56They don't have time to go into it,
10:58but you're well aware that even
11:00more commonly are other infections
11:02like bacterial and fungal infections
11:04associated with injection drug
11:06use that we see all the time.
11:08Unfortunately that have just just
11:10gone up substantially in hospital
11:13settings across the country,
11:15including endocarditis,
11:16osteons and other infectious complications.
11:20And then I there's other complications
11:23including increase in suicide and
11:26many other associated morbidity
11:29and mortality beyond just direct
11:33directly related to overdose tests.
11:35So you know and you guys are
11:38familiar with this,
11:39that's another nice thing
11:40about talking to this group.
11:41I don't have to go into all these details,
11:43but we have very effective treatments for
11:46opiate use disorder, all three methadone,
11:49buprenorphine extended release.
11:50Tracks down.
11:51This is just a summary slide.
11:53I love the fact that I don't
11:54need to talk to all of you about
11:56all this because you guys,
11:57you you are actually doing this.
11:59But you know there's differences in
12:02their activity differences and who can
12:05prescribe these medications differences
12:07and and and their formulations.
12:10And I think it's,
12:11it's really just quite astounding
12:13that we have these effective,
12:15effective treatments in this country.
12:17And you know, the bottom line, what do we do?
12:19What do we know? They're very effective.
12:21They reduce opioid use,
12:22they prevent overdose.
12:25They also can reduce transmission
12:28of bloodborne infections like
12:30hepatitis C and HIV and improve other
12:33psychosocial outcomes like unemployment.
12:35But the bottom line is, we all know,
12:38is that in addition to the problem.
12:40Getting people on treatment
12:41or initiating treatment and,
12:43you know,
12:43identifying individuals with Opus
12:45sorter and providing them the treatment.
12:47The big problem is once we get
12:49them on treatment,
12:50retention is poor across all forms
12:53of these traditional treatments.
12:55Roughly and I'm not going to go
12:57into it all but if you look at all
13:00medication treatment trials or and
13:02you also look at other data from.
13:04Large data sets of individuals who
13:07have been initiated on medication
13:08treatment for abuse disorder
13:10retention is around 50% at six
13:13months and much poorer and and and in
13:15other in certain subgroups as well.
13:18And then as we know when people stop
13:20treatment, relapse occurs quickly,
13:22can occur quickly and is associated
13:25with all of those direct harms.
13:27So there's really this high need for
13:30novel approaches to improving retention
13:33on treatment and some of which can include
13:37long acting formulations of medication.
13:40So as you know there's many other
13:42diseases in which we are looking at longer
13:46formulations of treatment including Prep,
13:48cabotegravir, relative marine
13:50ART for antiretroviral therapy,
13:52cabotegravir and roll pairing long acting
13:55medication formulations to improve adherence.
13:57So this is.
13:58Not a new idea so I I put
14:02together this table just to help,
14:05you know look just I like to do this
14:07but understand what are these long
14:10acting forms of medication treatment
14:13for opiate use disorder we have?
14:164 right now.
14:19Three of which are clinically
14:21available extended release naltrexone,
14:23FDA approved for opiate and
14:25alcohol use disorder.
14:27Umm you know it's an intramuscular injection,
14:30one fixed dose administered monthly.
14:33The major problems are that I'll
14:36well we know is you know you
14:38can't it's an opiate antagonist.
14:40So it is a difficult to administer
14:44in patients who are you can't
14:46administer in patients who are
14:47going through opioid withdrawal.
14:49Um, and also associated acute pain needs.
14:53And you have to be off of opiates for seven
14:55to 10 days before you can initiate it.
14:58But you don't need any special training
15:01and anyone could administer this,
15:03don't need an X waiver, etcetera.
15:04And then we have 3 formulations of
15:07these long acting forms of medication
15:10treatment for abuse disorder.
15:12One is an implant Probuphine,
15:15which is implanted.
15:16And I'll show you pictures you you're
15:19probably familiar with in the upper arm.
15:22It is, there are issues with it,
15:24right.
15:25So it's traditionally in the studies
15:28I'll show it has is is approved
15:31for individuals who are using
15:33low dose buprenorphine,
15:35so stable on 8 milligrams or
15:38lower of sublingual buprenorphine.
15:41And as we know,
15:42there's issues with that in terms of we
15:45would like patients to be on higher doses,
15:47typically around 16 milligrams.
15:51And there's issues you have
15:53to have live training.
15:54I went through this live training
15:55way back when where you have
15:57to actually show that you can,
15:59you know, provide,
16:00put the implant into the arm.
16:02I think what did we do it in in pig skin.
16:04I can't remember what it was.
16:06And then be able to take it out,
16:08take these four rods out so that
16:12live training.
16:12And REMS obviously risk evaluation
16:16mitigation strategies as as needed
16:19for this as well as the other
16:22formulations sublocade by indivior.
16:26Is an injectable medication that's
16:29subcutaneous administration in
16:30the abdomen and provides a nodule
16:33typically over every four weeks or
16:36every 28 days with plus or you know,
16:39plus maybe two more weeks.
16:41The FDA allows you to administer
16:44it after that.
16:46It has two doses,
16:48300 and 100 and the FDA package
16:52insert approved insert though
16:53says that you have to be on
16:55at least seven days of continuous.
16:57Sublingual buprenorphine of at least 8
17:00milligrams before you can administer it.
17:03And then the last one was Cam
17:062038 or brick Saudi from Braeburn,
17:08which can is provided in multiple doses
17:14that are equivalent to the sublingual
17:17buprenorphine dose in weekly and monthly
17:20formulations can be initiated as induction
17:22instead of sublingual buprenorphine,
17:25or you could switch you know
17:27from someone with sublingual.
17:28And can be administered in multiple areas,
17:31the upper arm, thigh, the buttock,
17:33the abdomen and it does
17:35not require refrigeration,
17:37unfortunately is not
17:38clinically available yet.
17:40They a letter as of last month,
17:43December of 2020 indicated there
17:45were production problems in one of
17:48their third party manufacturers.
17:50So the FDA has asked them to fix that
17:53and they're estimating earliest maybe
17:56six months from now could be available.
17:58But probably much longer than that.
18:03So limitations, these are just some basic
18:05things that we know through clinical trials
18:08as well as clinical experience that you know
18:11in terms of extended release naltrexone,
18:14I just mentioned a couple of limitations.
18:16So if you're seeing patients
18:18who are actively in withdrawal,
18:19it's one of the worst things to witness and
18:21you want to help them as much as possible.
18:23This is not a treatment you could administer.
18:27It's also been really difficult
18:29to get uptake in the community.
18:31A lot of providers don't feel
18:34comfortable with initiating treatment
18:35for opiate use disorder.
18:36It requires that abstinence period of seven
18:40days before administering the medication.
18:42In terms of buprenorphine,
18:44there's many advantages.
18:45It's the most widely available,
18:47except acceptable,
18:48accessible form of medication
18:50treatment for opiate use disorder.
18:53You can see it in primary care,
18:54you can see in a substance
18:56use disorder treatment.
18:56You can see in specialty clinics like
18:59infectious disease or HIV treatment where.
19:01I I was using it and as I said you can
19:06actively manage someone's acute opioid
19:08withdrawal in a matter of minutes to
19:11hours with providing buprenorphine
19:13reduces craving and reduces obviously
19:16relapsed opioid use and overdose.
19:19And it can be effectively used in
19:21patients to manage both their pain,
19:24underlying pain as well as their
19:26maintenance opiate use disorder treatment.
19:28So and again as I just pointed out
19:31there's multiple formulations.
19:32Now there's tablets, there's films,
19:34and we just went through the
19:36long acting formulations.
19:37One of the disadvantages could be
19:39and one of the reasons is having
19:40an X waiver and going through the
19:42training in order to prescribe and
19:44some of these REMS programs for
19:46these long acting formulations.
19:48So remember long acting buprenorphine,
19:51you can't just give a script
19:52to a patient and say,
19:53hey,
19:54go get your prescription and I'll see you.
19:56You actually have to administer
19:58it in the clinic and you have to
20:01have a pharmacy that has REMS.
20:03Certification in order to provide that.
20:06So there's some issues and
20:08obstacles that programs,
20:10especially rural programs,
20:11are going to have to think about.
20:13So why are we even interested in
20:15long acting formulations?
20:16I mentioned you know the issue with
20:18adherence and and other issues.
20:20You know potentially long acting
20:23formulations might be able to
20:26overcome some of those concerns
20:28about retaining on a daily sublingual
20:31tablet or film that patients face.
20:35So thereby an advantage would be you'd
20:38have you you know with a steady state
20:41potentially achieving with this.
20:43Long acting formulation of
20:44buprenorphine it you you,
20:46you don't have to worry about
20:49individuals missing their sublingual
20:51daily doses or the concerns about
20:54diversion that people have.
20:55You know,
20:57and thereby with this continuous use
21:00that's maintained in their system,
21:03you can wreak the benefits which
21:05is obviously what we want to see
21:08reductions and overdose and decreased
21:10HIV and hepatitis C transmission.
21:12And another area that I'm interested
21:13in and what we're interested in,
21:15I'll, I'll talk to you about is,
21:17you know, improved care of individuals
21:19who are coming from supervised
21:21settings like hospitals and criminal
21:23justice settings where there can
21:25be medication on board when they're
21:27discharged into the community that
21:29can help benefit both their underlying
21:32opiate use disorder as well as maybe
21:35other comorbid infectious diseases.
21:36So of these forms of long acting medication
21:39treatment for opiate use disorder,
21:41which have been compared to what
21:44we'd say the treatment of choice,
21:46I would say in the Community
21:48sublingual buprenorphine,
21:49three of them have been in clinical trials
21:51compared to sublingual view of norpine.
21:54They're listed here while the last
21:56sublocade has not been compared
21:58to sublingual buprenorphine.
22:00I'm not going to go into every
22:01all of the trials,
22:03I'm just going to mention a
22:05couple of the bigger ones.
22:06These are the two largest randomized
22:08control trials that have compared
22:10extended release naltrexone
22:12to sublingual buprenorphine.
22:14The first on the top the Tannum
22:17article Tanum study was in Norway,
22:20conducted in Norway, and the other,
22:22the bottom one here at what we
22:25know is X spot,
22:26was conducted in the United States.
22:29Josh Lee was the first author.
22:31Published in Lancet.
22:342017 and just for interest of time,
22:36I'm just going to talk about this
22:38the length the United States trial,
22:41the Norwegian trial,
22:42the slides are are there for you to look at.
22:48The bottom line was this was
22:49individuals and I think it's important
22:51to to to note that there were
22:53individuals with opiate use disorder,
22:54but they initiated either extended
22:57release naltrexone or sublingual
22:59buprenorphine in inpatient what we did
23:01to what is called detox which I hate.
23:03Term, but detox units,
23:05so inpatient units,
23:06so they weren't started in the community on
23:10these treatments and you know mainly white,
23:13mainly male.
23:16And the the their primary outcome
23:18was an interest in this time
23:20to relapse to opioid use.
23:22So they were powered for that detection.
23:25The graph on the left A is
23:28the one you've seen,
23:29you know we've seen this over
23:31and over again was the intention
23:33to treat outcome and there was
23:35superiority with the buprenorphine,
23:37sublingual muping orphine group
23:39having a longer time to relapse
23:42and the relapse definition is
23:44important to also look at.
23:46When I have underneath notes to
23:49to talk about that the graph
23:52on the the right graph B.
23:55Is what that was their per protocol
23:59analysis and the reason being one
24:01of the things they found is they
24:03had a harder time in and inducting
24:05or getting somebody to initiate
24:07extended release naltrexone,
24:09so a lower induction group for
24:12the extended release naltrexone.
24:14So they wanted to see,
24:15well let's just look at that subgroup
24:17of individuals who actually got the
24:19treatment in both groups and then
24:20see what happened to the primary
24:22outcome and this is where they did
24:24not see a statistically significant.
24:26Difference in the individuals who
24:28were were able to start treatment.
24:30So something there's a lot of
24:31things we could talk
24:32about this trial,
24:33but just you know that's the main one
24:37when we look at the Probuphine trial.
24:40So this is just showing you how you
24:42administer it and then don't forget
24:44you got to take it out in six months too.
24:46So it's X planting it here and
24:48then putting it in the other arm.
24:50There was one trial comparing
24:53it to sublingual buprenorphine.
24:55And the bottom line is they were
24:57looking at as typical of these studies
25:00looking at opioid abstinence and
25:03in particular they looked at urine
25:05toxicology screens as well as self
25:08report through the timeline follow back.
25:11And the bottom line was the group that
25:14received the implant of buprenorphine
25:15or had a higher percentage who did
25:19not use opioids compared to the
25:22sublingual buprenorphine group.
25:24The sublocade,
25:24it has not been compared to buprenorphine,
25:27just want to point that out.
25:28But this is how you would inject it.
25:29It's in the abdomen.
25:30It creates a nodule.
25:32It's important to tell patients
25:34that you're going to have a nodule.
25:36And so they're not nervous about that.
25:39This is just the main study that
25:42was published again not compared
25:44to sublingual buprenorphine just
25:46compared different dosages and
25:49compared it to placebo looking at
25:51again urine and self reported illicit
25:54opioid use and 500 individuals and.
25:58Bottom line,
25:59they found superiority over
26:00placebo and that and so that
26:03one's been available since 2018.
26:06The latest one is brick Saudi or Cam 2O38.
26:10As I mentioned,
26:12it's not yet clinically available,
26:13but it has been FDA approved
26:16for clinical use.
26:17This is the comparative,
26:18this is the one large random,
26:20there's two,
26:21but random one,
26:21I was going to talk about randomized
26:24trial to sublingual buprenorphine.
26:26This was carried out in outpatient settings.
26:29Of individuals with opiate use
26:32disorder and it compared their
26:34monthly injection to a sublingual
26:36buprenorphine and they allowed a
26:39nice higher flexible dosing up
26:41to 32 milligrams of sublingual
26:44buprenorphine comparison group.
26:45And again their primary outcome
26:48was looking at the proportion of
26:51negative opioid urine toxicology
26:54screens and they found superiority of
26:56the the Cam to a monthly injection.
26:59Cam 2038 over the sublingual
27:03buprenorphine group in terms of
27:06negative proportion of opiate
27:08urine tests at 24 weeks.
27:10They also what they call responders,
27:12this is where they combine the
27:16self reported opioid use.
27:18Also had superiority 37 to 31%.
27:21So have any of these long acting
27:24formulations been compared to each other?
27:26No, not yet.
27:27So we haven't seen like an extended
27:30release naltrexone study you know
27:32out coming out or hasn't been,
27:35there's not been any data yet out
27:37to comparing it to say any of
27:39these long acting formulations
27:40of buprenorphine or one of them
27:42better than the other it's.
27:43Um, so this is gets into there.
27:46There's a lot of reasons to think
27:48about when you look at these
27:49clinical trials right.
27:50They're always done in individuals
27:52who are considered healthy.
27:53So anyone with you know comorbid
27:57endocarditis was was ruled
27:59that you know was like
28:02excluded from the study
28:04individuals who might have?
28:07Had other comorbid medical conditions
28:10were excluded from these studies.
28:12So one thing we don't really know
28:15is you know what is the real world
28:17like kind of effectiveness of these
28:20intervent of these medications and
28:22could they benefit some of the more
28:25vulnerable populations that we know
28:28have higher morbidity and mortality.
28:32So I was just going to present three active.
28:37Uh, clinical trials that were
28:40conducting that are focused on
28:42these three populations here.
28:43And I'm not just saying that
28:44this is the only group.
28:45Obviously there's many others and I have,
28:47you know, I know many other ideas,
28:49but and I know you guys are also
28:51interested in doing research
28:53similarly with these products,
28:55some of these products.
28:56So talking about people coming from prison,
28:58in jail.
28:58So this is an area I actually started
29:00out with when I was on an ID fellow and
29:03became fascinated from an HIV perspective.
29:05And I think one thing we have to remember.
29:09Is this population is has a higher
29:13prevalence rate of substance use
29:15disorders than in the community and in
29:19particular opiate use disorder is common.
29:22Very few in the criminal justice
29:24system are offered medication
29:25treatment for opiate use disorder,
29:28and the majority go through what
29:30we call force detox or ABS.
29:32You know, no,
29:33no treatment while they're
29:35in prisons and jails.
29:37And yet,
29:38regardless of how long
29:40they've been incarcerated,
29:41the number one cause of death for
29:44individuals as they're being released
29:46to the community from jails or prisons
29:48is overdose death and so relapse.
29:51As quickly, this says in one year,
29:54there's other data shows occurs
29:56quickly within date, you know,
29:58hours to days after release.
30:01And in addition to the overdose
30:04mortality population I've worked
30:06with and those living with HIV
30:08interferes with their ability to
30:10adhere to antiretroviral therapy,
30:12etcetera.
30:12So it's a population we should
30:16really be focusing on.
30:18And this was an early study did a
30:20long time ago when I was a fellow
30:22right after it was started right
30:24after the FDA approved Pupin Orphine
30:27to be used by primary care doctors.
30:29And this was for individuals coming out
30:32of prison in jail with HIV and just,
30:34you know looking at would they accept it.
30:37And yes one thing was it reduced craving
30:40and it was highly there's high satisfaction.
30:43Well that was flipped I should have said,
30:46but anyways the cravings on the top.
30:48Where the excuse me,
30:50the satisfactions on the top
30:51and the cravings on the bottom
30:54and it reduced opioid use.
30:55In addition,
30:56there was a subsequent study that
30:58showed that buprenorphine is associated
31:00with improved viral suppression.
31:02Josh Lee and Chuck O'Brien in
31:04the group also looked at extended
31:06release now truck zone for criminal
31:08justice individuals and these
31:10were on community supervision,
31:11so not in prison,
31:13in jail comparing it to treatment as usual
31:16for people with abuse disorder and they.
31:18And their primary outcome
31:20was time to relapse again,
31:21and they found a statistically
31:24significant benefit.
31:26I've also conducted with my our
31:28group extended release no truck zone
31:30trials and people with opioid use
31:32disorder coming out of prison and jail
31:34and there was high acceptability.
31:36This was looking at viral suppression,
31:38the primary outcome and the people
31:41who received extended release mail
31:43checks done had a higher likelihood
31:45of achieving viral suppression
31:46compared to placebo and I won't go in
31:49and a secondary outcome was looking
31:51at time to use and although there
31:53was no statistically significant.
31:56Difference in the left hand graph
31:58between the two groups of intention,
32:00you know if you received extended release,
32:03no checks on placebo,
32:05those who received at least three
32:07or more injections.
32:08So retention on treatment did
32:10have a longer time to use.
32:15So what we're interested in is,
32:18is there any difference in potentially
32:21extended release naltrexone
32:22to potentially a longer acting
32:25formulation of buprenorphine and in
32:27helping this group of individuals
32:29and retaining tree on treatment?
32:31And so we have an ongoing trial
32:34funded by Nida.
32:35It's one of the J coin on healing awards.
32:38Josh Lee is a contact Pi and then
32:40there's a whole host, there's,
32:43I'm one of the other five Pi.
32:47And across NYU,
32:49Dartmouth and friends in Oregon
32:51Health Science University and
32:54our really our primary outcome is
32:55just to compare as the first time
32:58compare extended release naltrexone
32:59to a long acting formulation of
33:02buprenorphine for specifically
33:03people coming out of prison and jail
33:07or criminal justice involvement.
33:10On retention and treatment after release,
33:14we're also following other
33:16important outcomes like overdose,
33:19other substance use,
33:20we're doing HIV and hepatitis C testing,
33:24especially in our Connecticut Group
33:26and quality of life and other things.
33:30And you know,
33:30I I think I've emphasized why it's
33:32important because obviously there's
33:34population it's really in high need,
33:36but we don't really know what
33:38which ones better.
33:39And if you think about the XBOT trial,
33:41which was not in criminal
33:43justice populations,
33:44it compared extended release
33:45naltrexone to sublingual buprenorphine.
33:47You know one of the things we
33:49always talked about is well,
33:50what if somebody wasn't taking their
33:52sibling will be anopheline or what happens.
33:53So you know really having a comparator
33:56that's just administered in the same
33:58way and maybe reducing the concern.
34:00Our adherence to it.
34:04Daily treatment,
34:05which would help reduce some of that.
34:09Potential confounding?
34:11So we this is a this study is
34:14going to be is probably one of the
34:17largest trials comparing it's going
34:19to recruit over 1000 individuals
34:21across six states.
34:23Connecticut is one of the states as
34:25I said there's a randomized control
34:27trial arm where we're comparing
34:28a long acting buprenorphine to
34:30long acting naltrexone.
34:31But we're also recruiting this
34:33population called treatment as
34:35usual where they're individuals
34:37who may not be interested in the
34:39randomized control trial or you know.
34:41Interested in being on methadone
34:44or sublingual buprenorphine just
34:46to compare as an extra group
34:48so there's an additional group
34:50that will be following.
34:52And they're going to have intervention
34:55for 24 weeks with another 52 week long
34:59term outcome and this is where we are.
35:03You know, obviously we're
35:04mainly in the East Coast,
35:06but we also have Oregon here and
35:09so Liz Waddell is the Pi out there.
35:12For Connecticut,
35:13we're partnering with the DOC obviously,
35:16and Connecticut,
35:17but also C HCI or community clinics
35:20and we're focusing for the most
35:22part in the New London area.
35:24We also are taking participants
35:26in the Hartford and New Haven
35:28area and we have developed.
35:30One great thing about J coin
35:33is that you had to have like
35:35partnerships with your community
35:37and justice and they're actually
35:39actively involved with the research.
35:42And they are actually going to
35:44be in the community clinics be
35:48giving the medication.
35:50So it's very different than these
35:52like detailed randomized control
35:53trials where you're you're actually
35:55get you know the researchers
35:57giving the medication in this
35:59setting it's the community partner.
36:01So they'll be really rich data
36:03to assess the effectiveness.
36:05So we're really focusing on
36:07individuals are coming out of prison
36:09and jail with abuse sort of we're
36:11also accepting participants who.
36:12Might be in the community with
36:14a criminal justice history in
36:15the past six months,
36:17because this is predominantly
36:18spurred on by COVID-19.
36:20Because of many of our other sites
36:22that are not allowing individuals
36:25and now and then we're going to
36:28compare these treatments as I said
36:30for six months and the medication
36:32was provided in kind from the
36:34medical pharmaceutical companies.
36:36So if they can actually receive
36:39the medication,
36:40if they are randomized to
36:42those two treatment conditions.
36:44In addition,
36:45everybody gets opiate overdose education,
36:49there's loxone distribution and.
36:50For the Connecticut site,
36:52we also have peer navigators who
36:55are working with individuals
36:56to link them to appointment.
36:58We're actively enrolling.
36:59As of last week, Woohoo,
37:01we had art,
37:02the first participant for the
37:04whole 6 state was in Connecticut
37:06and we have another one coming up.
37:08So this is our project coordinator, Elise.
37:12She's on the call.
37:14And if you have anybody who's
37:16in the community,
37:17I know you might not be in
37:18the prison and jail system.
37:19But if anyone has a criminal
37:21justice exposed exposure in the
37:23past history in the past six months
37:24and is interested in medication
37:26treatment for abuse disorder,
37:28don't forget to call us.
37:29Because they get a lot of
37:31other resources as well.
37:33In addition to medication treatment,
37:35veterans, so the other population,
37:38I'm also a VA provider as you know and.
37:45You know, it's pretty quite amazing.
37:48A lot that I've learned.
37:50But veterans,
37:51as many of you might be aware or not,
37:55have two times the rate of
37:56overdose deaths then in the
37:58United States general population.
37:59Opioids are a major drug that
38:02is is involved with that,
38:04Umm,
38:04and among our Operation Enduring
38:07Freedom and Operation Iraqi Freedom,
38:10Veterans comorbid mental health and
38:12other substance use problems are
38:15very. Very high and but. You know,
38:20I don't have a lot of time to go into this.
38:22One of the problems is, is there, isn't it?
38:24Well, the good thing is there's an
38:26initiative within the Veterans Healthcare
38:28system to get people on buprenorphine
38:30who have opiate use disorder.
38:32That's a win win.
38:34But when we looked at this data earlier,
38:36we found that similar to
38:38what we see in the Community,
38:41that patients who start buprenorphine have
38:44a hard time staying on buprenorphine.
38:49And follow up and this is data from.
38:53This is fiscal year sixteen, 2016,
38:55but of individuals who are started on
38:58buprenorphine veterans who are started
39:00on buprenorphine only 35% were were
39:02still on buprenorphine at one year out.
39:04So you know again that issue that
39:06I've talked about is retention.
39:08So as you guys all know as mini patriarcas.
39:13Is you're should all be very familiar
39:16with our expertise and and treatment
39:18of addictions as well as comorbid
39:21psychiatric disorders at the VA she and
39:23I are study chairs of a A VA cooperative
39:27studies program that's actually going
39:30to be comparing 2 formulations,
39:33the two formulations of of of buprenorphine
39:36and veterans with opioid use disorder.
39:38So we're 900 veterans and across 20 sites.
39:43Nationally,
39:44we're actively recruiting individuals
39:45who have opiate use disorder who
39:48are seeking medication treatment
39:50for opiate use disorder.
39:51And then we're randomizing them
39:53one to one to receive either the
39:56monthly injectable buprenorphine or
39:59daily sublingual buprenorphine.
40:00And this is a 12 month study,
40:03so they're followed,
40:05it's data is and follow up is is
40:10occurring every two weeks for 12 months.
40:14So it and with the nice thing
40:15about the VA data system too is if
40:17they're still in the study we can
40:19also we can continue to do passive
40:21follow up within the VA record for
40:23the duration of the study as well.
40:26But what is also interesting about
40:28this group what we decided to do is
40:30to two Co primary outcomes which
40:32is unusual and one is which treat
40:35looking at the retention on treatment.
40:37So again we don't know if a long
40:41acting formulation of of treatment
40:43for abuse disorder.
40:44Is better at retaining individuals
40:46than a daily sublingual buprenorphine.
40:48We assume it is, but we don't know.
40:51So that's one.
40:52And then the second is abstinence
40:54from opioids,
40:55which is going to be a combined urine
40:58toxicology and self report method.
41:00And then we're as you can see,
41:01we're looking at a whole host of
41:04secondary outcomes including overdose pain,
41:07HIV,
41:07hepatitis C and cost effectiveness as well.
41:11This is our site,
41:12so the red ones.
41:14Are those that are site that among
41:16the 20 sites and in yellow are our
41:19backup sites if something happens
41:21to one of those 20 sites.
41:23So we're quite excited about this group.
41:26It's kind of been amazing.
41:29These are our study questions.
41:30As I said,
41:31we're going to compare these two
41:33formulations to see if they're we're
41:35actually looking at superiority if
41:37one is better than the other and retaining
41:39veterans and medication treatment
41:40for opioid use disorder and opiate
41:42abstinence and then of course secondary.
41:44Looking at a lot of these other outcomes,
41:47is 1 better than the other in?
41:49Reduction in overdose,
41:51improvement in, reduction in?
41:54HIV and hepatitis C, etc.
41:57So there's lots of here and I just
41:59want to make this point about
42:02these two Co primary endpoints.
42:04Again, you know,
42:05having been in clinical research for a while,
42:07it's rare to see two primary endpoints,
42:10but we felt that this was really important.
42:14And uh, this is how we defined those
42:17outcomes and this took a lot of decisions
42:20in terms of the urine positivity.
42:22This was kind of we wanted to do
42:23just as many and I really wanted
42:25to look at self report opioid use.
42:27But the VA,
42:30CSP Coordinating Center wanted
42:32us to to ensure that we had urine
42:35positivity in that Co primary endpoint.
42:37So that will be combined.
42:40You know, again,
42:41I think I've said this a number of times,
42:43it's important to compare these.
42:44Active treatments.
42:45What's really cool about this is
42:47this is a real world comparative
42:49effectiveness trial.
42:50There's no placebo in enrolled where
42:53we're actively enrolling people
42:54and we're going to be assessing and
42:56seeing like what is the uptake,
42:58what are the problems.
43:00This potentially could have a high impact.
43:04And this is a really huge group
43:06that needs to be evaluated.
43:07We found out that this is the first study.
43:10Conducted of medication treatments
43:12for opioid use disorder and veterans.
43:15That's the first,
43:16first one which is mind boggling
43:19to me given the high comorbidity
43:21in this population.
43:22So this study is actively enrolling
43:25since before Thanksgiving of
43:26last year across these sites.
43:28West Haven actually is a clinical site.
43:31So the LSI for that is getting gehen yune.
43:36Lucy Gu is one of our national study
43:39coordinators and she works with
43:40this meaning and I. Over at the VA.
43:42So if you have any questions or if
43:44you're come calling in from another
43:46state and wondering if your VA is involved,
43:48you know you can contact her,
43:50of course me or his meeting.
43:52And then the last group which I've
43:54already talked to talked with you
43:56guys about before is hospitalized
43:58patients with opiate use disorder.
44:00So I'm an infectious disease doctor.
44:01This has been you know in addition
44:04to HIV comorbid other infections
44:06with opiate use disorder is a major
44:09interest of mine and what we see.
44:11But I don't think I have to remind
44:13you that we're,
44:14we we do see a lot of these infections
44:17and that infectious disease management
44:19can be undermined by undiagnosed.
44:22Untreated opiate use disorder.
44:23So if patients are going through
44:25active withdrawal or craving,
44:27that's the first thing that is going to be.
44:32You know, on their mind,
44:33and it's hard to treat any other
44:36medical Cohen condition,
44:37especially an infectious disease.
44:40Unfortunately,
44:40many individuals are not diagnosed
44:42when they're in the
44:44hospital setting.
44:45And they can leave before their medical,
44:47medical treatment is completed or can
44:50have readmissions and discharge back
44:52to home without medication treatment.
44:54Phobia disorder obviously leads to,
44:56can lead to overdose.
44:58So it's really important to
45:00consider how we can improve that.
45:03So this is another third trial that we have,
45:06this one funded by Ncats National Center
45:09for Advancing Translational Science.
45:11It's called project commit.
45:12You might have seen Flyers in the
45:14hospital or you see my emails.
45:15Going out you know refer, refer, refer.
45:17This is a multiple Pi project as well.
45:21Just a bottom line.
45:24I've collaboration with other
45:26experts in the field.
45:27It's just been one of the most
45:29wonderful things I've been involved
45:30with and all these trials I've
45:32shown you are a testament to that.
45:34This is working with Kathleen Brady at
45:36Medical University of South Carolina,
45:38Ned Nunez and Columbia and Francis Levin
45:40who you probably know Alan Litwin,
45:43Prisma, Prana Roth and Meredith.
45:45Data on Penn State Hershey.
45:48And our our main aim is to see can
45:50you combine infectious disease
45:52and opiate use disorder treatment
45:55using a long acting formulation of
45:58buprenorphine like I've been talking
46:00about to improve the likelihood.
46:03The primary outcome is to improve the
46:06likelihood that it'll help patients
46:08enroll or or can continue on a form of
46:12medication treatment when they're discharged.
46:15Obviously we're looking at
46:16opiate use outcomes and.
46:18Also infectious disease outcomes as well.
46:21So this study has been actively
46:23enrolling since last year.
46:25It's very kind of a small
46:26clinical trial in my opinion.
46:28It's only about 200 individuals
46:30across these three sites.
46:32In addition,
46:33they're randomized to long acting
46:36buprenorphine or treatment as usual.
46:38So that's whatever is going
46:41on in that hospital.
46:42Some could be rent,
46:43some could be getting
46:45sublingual buprenorphine,
46:45some could be getting methadone, nothing.
46:48But in addition,
46:49we provide what's called enhanced treatment.
46:52As usual, everybody,
46:53regardless of their randomized group,
46:55gets education about their substance use,
46:58opiate use disorder,
46:59medication treatment for abuse disorder,
47:01overdose education, naloxone,
47:04linkage and medication management.
47:08And linkage to in the community
47:11to their treatment to continue.
47:14So this nurse care managed
47:17model occurs across the groups.
47:19This is a 12 week intervention
47:22trial medication was donated and
47:24kind by the drug company so they do
47:28if they get randomized long acting
47:30buprenorphine they can receive it
47:32and Yale New Haven Hospital which
47:35is where we are at both campuses
47:37at Yale New Haven.
47:38Hospital medication is controlled
47:40by the Investigational Drug Service.
47:42There's an epic order and it just
47:45comes up to the floor and is
47:47administered in the hospital and
47:49then continued in the community.
47:52So this is where we are, you know,
47:54just to show I like graphs, like maps.
47:58And our inclusion is just you
48:00know you get have one of these
48:03infections pneumonia bacteremia,
48:04osteo and have opiate use disorder
48:07and and interested in treatment.
48:10Her willingness to participate
48:11in a trial I should say
48:13how it's working either there's a
48:15direct referral addiction medicine has
48:17thank you has referred to us could
48:19be infectious disease hospitalists or
48:21it could be we can do epic screening.
48:26And then while they're in the hospital,
48:28you know we can approach them,
48:30ask them if they're interested and
48:32then go through the screening process.
48:33And then we have an Ind with the
48:35FDA to do more rapid induction than
48:38what the FDA is approved for this.
48:40We're using sublocade.
48:42So we can initiate sublocade within
48:45one to three days after induction it
48:48occurs in the hospital and then we if
48:51they get randomized to that group and
48:54then continued for three months with.
48:56As I mentioned the other aspects of that
49:01opiate overdose education etcetera.
49:02So we're actively enrolling the project
49:05coordinator is Victor he's on the
49:07call you guys know Nick Savelle he's
49:09an ID attending former ID to fellow
49:11fellow he's a medical director you
49:12know you can text us call US e-mail US,
49:17Epic inbox us whatever you want.
49:20So just let us know and we have already
49:23enrolled I forget five people at Yale and.
49:26Five at Prisma and Penn State just
49:29came on board a couple months ago.
49:32So you know, I'm just,
49:33you know and I don't have to tell you
49:35enough about how the opiate epidemic
49:37is is worsening and it's causing a
49:39lot of significant direct morbidity
49:41and mortality and also associated
49:43with these infectious diseases there.
49:45We have these long acting formulations
49:48of medication treatment for opiate
49:51use disorder that are available.
49:53We just don't know how well you know.
49:56What what their effectiveness will be
49:59in real these what I call real world
50:02settings and we really need these kind of.
50:05These types of studies to to see you
50:07know are more vulnerable populations if
50:10they're effective in retaining people
50:12and reducing these negative harms.
50:14This is the VA brave group.
50:17I like always showing his media me
50:19next to each other she knows that and
50:22this is our in Stride Group which is
50:26our our team and we have a wonderful
50:28group of research assistants, clinicians,
50:32project coordinators everybody.
50:34Victors over here.
50:36He's the project coordinator who's
50:38on the call.
50:39Louise Barbara Yolanda, research assistants.
50:41Esther Nick, you know,
50:43Steve is a physician assistant and
50:45Esther W Wagner is a nurse who's been
50:48administering the sublocade to patients
50:50who are here at Young Haven Hospital.
50:53So you might have seen her on the floor too.
50:55So thank you.
50:56I'll end there.
51:00Yeah, we we missed the,
51:03the applause not being in person.
51:06Awesome. Thank you so much.
51:08What a wonderful overview
51:10of some tremendous work.
51:13So I I just want to.
51:15Acknowledge that our our reach is growing.
51:19We've there are people on the
51:21call from all over the country,
51:23which is extremely exciting.
51:24It is a COVID silver lining to
51:27be able to have all these folks
51:29be able to join us virtually.
51:31So there is a question in the chat,
51:33one was about the slides being available.
51:36We will follow up with you on that Sandy.
51:39Dr Hakimi, are you still on the line?
51:41Did you want to ask your question live?
51:47Hi, I am. It was answered nobody.
51:49There was no comparison. OK, all right.
51:53OK. Yeah. The question was about
51:55the dose equivalents of supplicate
51:56and suppling will be Bernardine,
51:58but you had answered that.
52:02Lots of lots of great works in
52:05the chat any any other questions
52:07people feel free to unmute yourself.
52:10We do have a a good 5-7
52:12minutes to answer questions
52:14and I just wanted to say that if you
52:17have any questions about how it's
52:19being done like we are administering
52:20sublocade to into patient in with you
52:23know patients want it even with active
52:25endocarditis septic pulmonary emboli.
52:28You know and all the and we're
52:30following up for the commit patient
52:32the people coming out of the hospital
52:34this came up on another call.
52:36We do do active follow up with them
52:39they're being called weekly and so
52:42it's not just it's there's other
52:45you know other things that are
52:48happening help help these individuals.
52:51Elise who's in over here is a
52:54project coordinator for the criminal
52:57justice study and.
52:59Uh, working actively with
53:00individuals as they're coming out,
53:02we're focusing on the women's prison
53:05in jail and in Connecticut, so.
53:09They it's been interesting starting up.
53:12So if you have any like questions about that,
53:15they're all on the call about
53:17anything you might want to know about
53:19the logistics of how to do this.
53:23I have a quick question about.
53:24This is Steve Holt from Yale.
53:25I have a question about.
53:28In terms of the logistics of
53:31buprenorphine sublingual versus
53:33buprenorphine extended release,
53:34do you do you foresee a time where the
53:37FDA may allow providers to give XR
53:41buprenorphine without a waiver because
53:43in many ways it's less dangerous.
53:46I mean to be clear,
53:47I don't think sublingual bupe is dangerous,
53:49but I'm just making the point
53:50that they may see it as,
53:52I mean it's just an injection.
53:53You have to make sure it's
53:54not on opioids and that's it.
53:55You don't have to worry about the
53:57complexities of induction and all that jazz.
53:58Just to make it even more broadly available.
54:03Great question. I think one of
54:04the things that's going to come.
54:06So my bottom line is I.
54:08I personally have been on the
54:10record to say that I do hope that
54:13buprenorphine is able to be present.
54:15You know that we can won't have the
54:19waiver to but I don't know about this.
54:24I think one of the biggest
54:26challenges we're seeing like for say.
54:28Long acting buprenorphine are challenges
54:30where you know you have to have this
54:33R.E.M certified pharmacy it it has
54:35to be given to the clinician they
54:37have to administer it in the in the
54:40clinic and you know thinking about
54:42challenges in rural situations as
54:44well as you know patients I see in
54:47Connecticut you know where we don't
54:49have the best public transportation
54:51system is you know it's it,
54:53it is quite challenging so I
54:56I can't speak to do it.
54:58Think that they're going to relinquish that.
55:01I mean, so far, historically,
55:04probably not anytime soon,
55:06but I don't know that.
55:08You never know, things might change.
55:13I just highlighted in the in the notes,
55:15I think obviously if somebody's hospitalized
55:18then a dated Nate waiver is not
55:19required and so provision of that
55:22medication by folks in the hospital
55:24prior to discharge is already allowed.
55:28And the same thing at least
55:29for the bricks Audi product
55:31where you can start de Novo,
55:33you could do that in the Ed as well
55:35without requiring an A data waiver so.
55:38There are. That's a good point about
55:40and even sublingual buprenorphine and
55:42methadone for treatment of opiate.
55:44So it can be started in the hospital
55:47too and I think a lot of people don't
55:50know that, so it's good to know.
55:53That I'm worried about exactly.
55:57The same for every, you know,
55:58I think that's one of the biggest issues is,
56:01well, there's two huge issues is we're
56:03not getting enough people on medication
56:06treatment for opiate use disorder.
56:08And then, you know,
56:09that retention aspect is of those we start,
56:13you know, there's a huge,
56:14huge problem with keeping people
56:17on treatment and giving injections.
56:19I think 1 interesting group
56:22is a pharmacy pharmacist.
56:25I'm a big proponent for pharmacists.
56:27Being involved with with providing treatment,
56:30they do vaccines you know other
56:33things and then the other one would
56:36be you know maybe someday if they
56:39relinquish control over you know
56:42medication treatment is you know
56:44obviously utilizing you know provide
56:47going out into the community with
56:49like a a nurse care model to provide
56:52treatment where needed instead of
56:55individuals coming to the clinic.
56:58So things like that,
57:00mobile health units,
57:01you know providing treatment where
57:03and you can get it to the patient.
57:08There's another question in the chat I'll,
57:11I'll go ahead and read it
57:12from Kellen Russoniello.
57:14Are there data or current research
57:16on overdose risk for people who start
57:19but then fall out of XRL texone
57:22treatment given reduction of tolerance?
57:26Well, I can say that there's data to
57:29for the extended release naltrexone
57:31studies that have been completed,
57:34there has not been found to be an
57:37increase in overdose deaths related
57:39to those who are in treatment
57:41in terms of those who fall out.
57:43So do not retain an extended
57:47release naltrexone.
57:48There is overdose,
57:49of course that that happens in terms
57:52of is it greater than an individual
57:55who ceases or does not retain.
57:57Sublingual buprenorphine or does not.
58:00You know, it doesn't it doesn't
58:02stay in treatment or does not
58:04receive their medication.
58:05I, you know, I I don't think
58:08there's enough data to say that yet.
58:10But you know anyone who doesn't
58:12stay on their treatment, yes,
58:13there's an increased risk of of of overdose.
58:18Doctor Springer,
58:19our our vanzee in Virginia.
58:21Thank you for a very good talk.
58:23I have no experience with the SUBLOCADE,
58:26but can you tell me how you handle
58:28situations like somebody's on supplicate?
58:31They have some.
58:33Terrible pain, acute pain problems,
58:37massive injuries,
58:38multiple fractures,
58:38and how do you how do you deal
58:41with that kind of situation?
58:43Yeah. So I I have not had a situation
58:46where they've had that yet or we
58:50haven't experienced that yet.
58:52However, we have had patients who have
58:57come back in and required say surgery for.
59:03Whatever underlying infection,
59:04osteo or what have you and that that need
59:10so the buprenorphine can be maintained.
59:14While it's you know it's an can be as
59:16a polarized partial opioid agonist,
59:19I think working out acute pain.
59:23You know, there are ways in which you
59:26can work with the anesthesia team.
59:30To provide additional pain treatment,
59:32one individual I know we had Nick Savelle,
59:35Dr Saval who was involved talked
59:38directly with a the anesthesiologist
59:41and they were going to amputate
59:44or clean out part of a foot osteo.
59:47They did a direct nerve block for
59:49that patient and while the patient
59:51was maintained on sublocade.
59:52So I think those are good questions
59:55and good treat.
59:56Good.
59:58In addition,
59:59you know just that that idea of
01:00:01management of acute and chronic pain
01:00:04conditions in individuals who are on
01:00:06long acting buprenorphine treatment is
01:00:09a is a really good clinical question
01:00:12and and we need more more on that.
01:00:18Great. It is 3:00 o'clock.
01:00:21So I just want to be mindful of folks time,
01:00:23Umm and you know there is some some
01:00:27discussion in the chat about difficulty
01:00:30actually getting supplicated and and
01:00:33other injectable formulations out at
01:00:36different clinical clinical sites.
01:00:37So we do have folks who are doing it
01:00:40effectively and in outpatient settings
01:00:41and it would be great to to link up with
01:00:44some of those and and learn from them.
01:00:46And then Caroline asked about.
01:00:48Is it possible to administer in
01:00:50people's homes as long as it's
01:00:52being done so I think, I think.
01:00:53In addition to all the work that you
01:00:55highlighted that needs to be done,
01:00:57there's going to be lots of models
01:00:59of care that need to be studied,
01:01:00absolutely.
01:01:02Yeah, you can't unfortunately go
01:01:04take sublocade to someone's house.
01:01:05But what we found out it being part
01:01:08of this research study because the
01:01:10medications and the investigational
01:01:13drug service are research team can go
01:01:16to short term rehabs and administer the
01:01:20medication and to other facilities.
01:01:21But from practical clinical purposes it's
01:01:24true you so far the way it's regulated
01:01:26you couldn't couldn't do that which is.
01:01:28Is an obstacle.
01:01:32All right. Lots of work to be done,
01:01:33but thank you for sharing with us this
01:01:36tremendous body of work and hopefully
01:01:39you'll have some folks that can,
01:01:41can refer patients to you at least in
01:01:43in our local area. Thank you again.
01:01:46We'll see everyone on the 11th
01:01:49to hear Doctor Failey's talk.
01:01:51Take care. Have a great day, everyone.