Thank you, Laura, and thanks for having me today. My name is Brett Hagman. I'm a program director in the Division of Treatment and Recovery here at NIAAA, and I'm primarily involved with managing a lot of our recovery portfolio. So I am excited today to talk a bit more about understanding the new NIAAA definition of recovery from DSM-5 AOD and talk a little bit about the research and clinical implications. Now, I want to be honest, I hope this is the right presentation. If it's not, I do have my slides here, and I can read off of them, because the other presentation that I originally uploaded was not for prime time. So we'll see if we—I don't know if that's the proper one that's up, so we'll see. If not, I will just read. It's just easier that way. Okay, so this is just a little overview. I think, Laura, is this one of your slides that you put together here, I think? So what I'm going to do is just flip through this, because I already talk about this in my slides, so I'm going to just go quickly here. Okay, so this is my outline for today's talk. So what I'm going to first do is provide an overview of the NIAAA definition of recovery from DSM-5 AOD, and then I'm going to review a little bit of the clinical implications of our new NIAAA definition, and then what I'm going to do is talk about—actually, I have it here. I'm going to talk about predicting principles of health behavior change in what's called the construct of maintenance of behavior change in recovery from DSM-5 AOD. So this is definitely the former presentation, so we'll work a little bit with it, and then I'm probably just going to modify here. So first and foremost, why was the NIAAA interested in creating a definition of recovery from AOD? Well, we have a division of science with the term recovery, and yet we don't actually have an operational definition of recovery from an alcohol use disorder. More importantly, though, there's been a lot of attempts out there to define recovery, and so our review of prior definitions indicated some limitations, but not everybody may agree with this. But what we found was that—because what we were more interested in was a definition-specific alcohol. So most definitions don't distinguish between alcohol and other drug use. Typically, they require abstinence from both alcohol and substance use. More importantly also, most definitions don't actually incorporate remission from AOD. And also, what we're interested in also is acknowledging the importance of quality of life and well-being, and very few definitions really intersect the role of alcohol use in that process as well. We also need a definition, a common definition, which can be used for diverse stakeholders, for increased consistency in recovery measurement, and to simulate research to better operationalize recovery and related processes. So this is a bit of our process and the steps that we took to define recovery, and we were tasked by Dr. Koob and our division to do this. And so myself, Ray Litton, and Dan Falk were primarily involved in this process. And so what we first did is we just did a nice review of the literature to look more about recovery-based processes and trajectories. And then, of course, as I mentioned before, we also reviewed—we reviewed prior definitions of recovery and we identified some of the limitations, and then we conducted statistical analyses with an internal data team to kind of look at processes of remission and cessation of drinking and how they relate to improvements in functioning. And at that point, what we did is we tried to take a stab at just pulling together a working draft of a definition, and then we went out to our—we identified and then consulted with over 30 key recovery stakeholders. So recovery-focused researchers, clinicians, professionals also from recovery organizations. And so we jumped on the phone and we just received feedback. And you know, the feedback we took in, we hopefully had a scientific basis for it. And so the process was really more of a kind of continued evaluative process, and so really our definition is considered more not necessarily consensus, but it's more of a stakeholder feedback type definition. And so what we did at the end is our final definition was also—we received feedback from the NIAAA Council, and then we published the final definition in the American Journal of Psychiatry. So what I'm going to do now is I'm going to read the definition off of you. So this is our final definition, and then I'm just going to make a couple points about it, okay? So here we go. So this is our final definition. And we've had this—we've rolled this out for a while now. So we actually published the paper in 2022, so—and we, before that, had done some more work here in terms of promoting the definition as well. But here's the final definition. Recovery is a process of behavior change through which an individual pursues both remission from AUD and cessation from heavy drinking. An individual may be considered recovered if both remission from AUD and cessation from heavy drinking are achieved and maintained over time. For those experiencing alcohol-related functional impairment and other adverse consequences, recovery is often marked by the fulfillment of basic needs, enhancements in social support and spirituality, and improvements in physical and mental health, quality of life, and other dimensions of well-being, and that continued improvement in these domains may in turn promote sustained recovery. So just a couple points to make. First, you'll see we view recovery as a process of behavior change in which you're pursuing both remission and cessation from heavy drinking. Now, you may be considered recovered if you have achieved remission and cessation over time, and I'm going to intersect this idea in the next slide in what's called our duration qualifiers. And I'll—that makes more sense here in a minute. Okay. So this looks like it's a new slide now. Okay. So now my presentation is here. The next piece here is also this—the acknowledgment and the importance of quality of life and functioning and well-being. I mean, that was something very big from our stakeholders, the importance of acknowledging that. You know, there's a lot of stigmatization just focused on the behavior and remission, and there's a need to kind of focus more on the holistic kind of process there as well. Also in our definition—next slide, please, I can't, it's not working, okay—there are two key features of recovery in this model, and they're focused on the alcohol-related processes, right? So the considered outcomes, so remission from DSM-5 AUD, right? And that's defined by the DSM-5 criteria, which requires that the individual not meet any AUD criteria excluding craving. And then also our cessation from—why does this keep—cessation from heavy drinking. Cessation from heavy drinking is defined as drinking no more than 14 standard drinks per week or 4 drinks on a single day for men, and no more than 7 drinks per week or 3 drinks on a single day for women. So these are the lowest guidelines that we've had for a while. These are all also based—categorized based on duration qualifiers. So remember that term recovered? Well, initial recovery is up to 3 months, and if you've achieved both remission and cessation from heavy drinking, you can kind of move to the next phase. That's what we mean by recovered, so it's more of an outcome inside of these phases. But we also have early recovery, which is 3 months to 1 year, and so both of those are also based on their remission process. And then sustained recovery is 1 to 5 years, and then of course stable recovery is greater than 5 years. And a lot of that work comes from John Kelly's work looking at quality of life and functioning, which indicates that really around that 5-year point, you start to see some real improvements in those domains as well. So what I'm going to do now is talk just a little bit about some of our clinical implications of the new DSM-5—or our new recovery definition. I'm not a practicing clinician, but these are the things that I kind of thought about that I thought were important. But the important point that I want to make is that this is a research definition. That's why we developed it, but it does have clinical implications as well. So what we provide is a framework that can be broadly intersected for someone working in clinical practice, and like I said before, we identify really two key alcohol-related outcomes that should be assessed for in practice. And not only that, our definition does also indicate the need to think more about quality of life, also one's biocycle functioning and well-being in practice as well. And I think our definition is very useful because we start to now take a little bit more of a harm reduction approach. So working with somebody clinically has the potential to reduce maybe some stigmatization associated when working with somebody clinically who lapses. And more importantly, I think also it's kind of interesting too, I think it is important to kind of think about discussion about what does it mean to be recovered? So our definition does kind of provide some opportunity to start to think about what that means. And I don't have any answers for that yet, but it does provide some opportunity for that. I think though the most two important things here about our definition are related to the two key alcohol-related processes, which is more about assessment and measurement of them in clinical practice. One thing you know about drinking and measurement of drinking is we can standardize that pretty well. So we have a lot of reliable and valid measures now to be able to assess for alcohol use in clinical practice, right? The timeline follow-back, of course the Audit C. Quantity-frequency measures, which I'm actually kind of a fan of because they go over specific beverage types and review those. Also daily diary tracking, IVR daily reporting kind of measures. Not exactly sure those would be intersecting much in clinical practice because of the utility of those, but those are important as well. And then of course the Form 90. And these aren't just limited to these, but these are just some examples of what we have available to us. So we have a lot of reliable, valid measures out there. And then lastly, just the next implication for our, this is also the assessment for remission for DSM-5. So we have a number of measures that are available out there to do this, and I kind of bunched them into kind of structured clinical assessments and more sort of non-structured assessments. So structured clinical assessments, right, a little bit more of a gold standard, probably take a little bit more time intensive to do, such as the SCID, right, the Structured Clinical Interview for DSM Disorders. Also the AUD and Associated Disabilities Interview Schedule. And there's also been available now some briefer type measures that are non-structured assessments, such as the Brief DSM-5 AUD Assessment, as well as the Alcohol Symptoms Checklist for DSM-5. Those are done a little bit more quickly. They might be more easily intersected inside of clinical practice as well. So I've talked a little bit about the definition, reviewed that, talked a little bit about the clinical implications. Now I want to talk about a novel direction with our definition, and it's going to focus more on predicting principles of health behavior change in what's called the construct of maintenance of behavior change in recovery from DSM-5 AUD. And I have to admit, I didn't exactly intersect when we were developing, thinking about this, but I always had maintenance of change in mind in recovery, because it actually makes a lot of sense, right, because it contextualizes that as well. So this is pretty novel kind of thinking, so what you're going to see is more of my thought processes about this, and I'll explain that as I move forward here. But the first thing is, well, what is maintenance of behavior change? How do you define it? And there's lots of definitions that are kind of out there. I kind of settled on one by Kwasnik and colleagues, and it was defined as follows. It's the continuous performance of behavior following an initial intentional change at a level that significantly differs from the baseline performance in the intended direction. So what we're talking about here is remission and cessation of heavy drinking. So maintenance of change is also an important construct that's included in the phase and the process of behavior change. Over like 110 theories of behavior change, remember stages of change, right, has a whole maintenance phase in there. And in the process here in maintenance of behavior change also, it's focused more on avoiding temptations, higher situations that can lead to the return of a bad habit. And it focuses more on growth, building strengths, and quality of life. And I think defining maintenance of behavior change and kind of thinking about this construct is the implications for understanding relapse episodes, development of recovery continuing care interventions, and studying longitudinal recovery pathways. So what's important about our definition? What does it offer in terms of evaluating a maintenance of behavior change? Remember we have these outcomes. Well, you can also view them as maintenance of change thresholds to achieve, to be able to evaluate that process and to standardize that process. So in our definition, right, we have the following thresholds, right? Cessation of heavy drinking, abstinence, which is equally important in our definition, and then remission from DSM-5 AUD. But remember in our definition, it's sort of the combination of remission and cessation or remission and abstinence. And then of course, I also added in here, which is not a part of the definition, but also adherence to AUD medication. That's an also important thing to kind of think about in terms of predicting in this phase as well as adherence. And I also just want to mention that the OBSSR, the Office of Behavioral and Social Sciences Research at NIH, is really encouraging research on maintenance of change, maintenance of behavior change. So they've done a nice series of workshops recently on this process. So this is also why I've been very interested in intersecting this idea as well. So our definition provides, at least at some level, some of the standardization of the thresholds that you can evaluate in that phase. But what's most important is how do you predict and what are the mechanisms that underlie this process? And so what we're interested in is what is a mechanism of behavior change? A mechanism of behavior change can be defined as the processes by which behavior change occurs. So it's really focused on direct cause and effect relationships. It requires specific criteria that must be met, and I will review that in the next slide. But remember, mechanisms of behavior change are specified in theories of behavior and behavior change that can be seen to mediate intervention effects or processes of recovery. And the way I think of MOBC science, the way you've got to think about it, it's thought of more as like elevating mediators into a mechanism. So it's a process of science that takes time, takes a series of studies to do this kind of research. It's similar to sort of the process of identifying a biomarker, but it definitely has differences. So mechanism of behavior change is different than a biomarker, but they're kind of similar pursuits. So as I mentioned before, there are specific criteria for elevating a mediator into mechanism of behavior change. And so these are considered the CASN and NOT criteria. I'm pretty sure some of you probably have heard of them before. They're generally just pulled from tenets of causality as well and apply to evaluating mechanisms inside of treatments or outside in terms of understanding behavioral processes. So the criteria include things such as demonstrating strong association, specificity, gradient, experiment, temporal relation, consistency, plausibility, and coherence. And remember, like I said before, the process of kind of studying mechanism of behavior change is that you do a series of studies where you intersect some of the criteria along the way. And that's kind of the way I like to think about this kind of science. So where do we go to look at to predict maintenance of behavior change? Well, I'm going to suggest we start first with the broader kind of health behavior change science literature. A whole host of reasons why, you know, you can integrate, there's frameworks available that you can integrate so you don't have to just use one theory, you can use constructs from different theories. These behavior change science theories really focus more on common factors. And what I found a lot when we were studying treatments, there's a lot of support more for common factors than the etiological factors. It doesn't mean the etiological factors are not important, but you can really see a real demonstrated relationship with evaluating common factors. So what I'm going to do now is just sort of review some of those behavior change frameworks. So the first one here is one of my favorite studies by Kwasnika and colleagues. And what they did is just a nice qualitative review of approximately 110 behavior change science, 110 behavior change theories that included a maintenance of change phase construct. And so what they, through that process and through, you know, working with expert opinion and all of that, you know, they did a good, good work here to do this. They identified the following as important common theoretical constructs to intersect. And they're as follows, self-regulation, motives for drinking, physical, psychological and physical resources, which underlies that as coping and stress resilience and stress reactivity, habit formation, and environmental and social influences. So these are really seen as real important theoretical constructs to intersect. And the important thing to understand about these constructs is inside of them, you have all sorts of mechanisms that you can test. But that's not the only framework available to us. We also have what's called the theoretical domains framework. And this was developed by a collaboration of behavioral scientists and implementation researchers. And this identified specific behavior change theories relevant to implementation and group constructs from these theories into domains. So this is a lot of work with Susan Michie and colleagues. And so what they do is they provide 14 theoretical domains with each reflecting common broader health behavior change constructs. Right? So remember I said before that these processes focus more on common kind of mechanisms. So it cuts across other behaviors as well. And of course, these domains also kind of intersect what I just mentioned in the other slide, self-regulation, motivation, and those things as well. So each theoretical domain can be evaluated as potential recovery-related mediators that may be elevated mechanisms. But I think also utilizing this framework I think certainly has lots of implications for enhancing the development, translation, and implementation of recovery support services. One other framework that we have available to us is what's called the science of behavior change program at NIH. This was a science of behavior change was a common fund at NIH that used more of a systematic experimental precision medicine approach to improve our understanding of the underlying common mechanisms that would drive behavior change. The important point about the SOBC initiative, it's a basically occurs for 10 years and you do it for five years and then you renew it for another five years. And through all of this work, and then also it's a process that occurred across institutes as well, but they did lots of research that they funded that looked at these constructs across all sorts of different behaviors, HIV adherence, weight loss, also alcohol and other drug use as well. And so the focus that they were focused on was the constructs that they were interested in was the self-regulation, stress reactivity, stress resilience, interpersonal and social processes. What important point also about the science of behavior change initiative is they have this beautiful website that you can go to and you can intersect all the measures that are available there. You can also basically pick up where they left off in the research to think more how it applies to your, well in this case, alcohol use behavior and maintenance of change. But intersecting these inside of maintenance of change would be also a very unique opportunity here as well. And of course they overlap with all the other frameworks as well. What's also important here is the need to move beyond just some of the little stigmatization just focused on the behavior and remission and to start to also intersect the importance of wellbeing and quality of life, right? So our definition intersects the idea of enhancing fulfillment of basic needs, enhancements in social support and spirituality, improvements in physical, mental health, quality of life and other dimensions of wellbeing. So I think now in studying this construct, this is a nice opportunity to really evaluate these pieces potentially as mediators, elevated mechanisms or even as potential moderators or as well as outcomes in our model. You don't have to have alcohol use as the outcome anymore. You can have quality of life or some sort of piece of that as well. What I also think is important with respect to setting quality of life and wellbeing is how they intersect with our focus on their duration qualifiers. You know, things such as our focus is like an early versus sustained recovery to see how these change over time in recovery. I also kind of see the duration qualifiers as sort of like maintenance of change phases as well. So again, intersecting these ideas move away a little bit from a focus on just alcohol use outcomes towards other quality of life outcomes as well. What's also important here is the study of intersecting the idea of what's called recovery capital. And this is a construct that's been on the literature for a while now. And this refers to all the internal and external resources with which a person can access and support of their recovery process. So it's really derived from a social ecological kind of framework and incorporates the importance of allocating resources and capacities to enable growth and development and recovery. And it focuses on capitalizing on an individual's strengths and wellbeing and recovery. So I think it's also really important to now intersect this construct and idea to understand how social capital predicts maintenance of change and also subsequent pathways to recovery as well. And then another piece of this as well is that what I've learned a lot in studying of recovery is that we intersect early recovery pretty well. Because we focus a lot on initiation of behavior change. And that's because we intersect it inside of the development and evaluation of behavioral treatment. And one of the limitations to that is just more the focus on individual factors. But we know from like a social ecological kind of framework that behavior change occurs at multiple steps here, not just at the individual level, but the social and community level as well. So it's important now to also intersect those ideas and look at the social and community factors as well. So I think it's going to be really important moving forward to intersect this idea of the social determinants of health, right, which are things such as education access, economic stability, social and community context, neighborhood and built environment, health care access and quality. And I'll just state one more thing about the social determinants is I've been kind of big on this over a while in my presentations and I've suggested that we should really be routinely collecting this in our treatment studies and recovery studies. So I'm going to end in something that I've been kind of thinking about. And it's to address some things that I see as a program director, which is that, you know, in a lot of our research and a lot of our scientists, they develop these beautiful behavior change models and theories, but they don't really have a lot of empirical support for them. So oftentimes they can kind of fall flat. And I've talked a lot with folks in the field about the need to start thinking more about developing a little bit more of a basic science approach to studying behavior change, particularly as it intersects this idea of maintenance of behavior change. So I'm kind of, in this process, I've been sort of thinking about what would that look like? Something kind of like, it occurs with like two phases. Phase one would be more just a collection of just a daily reporting of the mediator, an independent variable and an outcome. And you know, looking at it from an observational period for like 30 to 45 days. In assessment form daily, using something like interactive voice response technology or daily diary kind of collection. And the important point there is to look to see, are there associations? Do they exist? If so, move to the next phase, which would just intersect, the next phase would probably intersect this idea of like a micro-intervention and intersecting what's called micro-intervention science, where you would manipulate the level of the mediator, like the gradient, to see how impacts change. And if there is a relationship that's existing, then you can move to the fuller models that you have as well. So inside of this idea, this is what I'm thinking is, you know, there's just some things that come to mind is, you know, what is baseline maintenance of behavior change? How long do you have to be in this phase to predict it? You know, there's stages of change would say maybe like six months. We also could maybe intersect our duration qualifiers, but that's something that I'm kind of thinking about here as well. And then also, you know, what are the methods for monitoring assessment of our behavior? You know, as I said before, most likely what would intersect here is some sort of daily data collection kind of technology. More importantly also, which CASN and NOT criteria should be intersected? And then also, what statistical methods should we use for modeling our heterogeneity behavior? We have a lot of great techniques available out for now, such as dynamic systems modeling, growth curve modeling. And as I said before, what are some of the design considerations for this process for evaluating principles of behavior change? As I said before, that idea of maybe intersecting the idea of a micro-intervention and using what's more of a go-no-go kind of framework. The relationships exist, move forward. If they don't, you know, stop. So just some things that I've been kind of thinking about here. So I'm just gonna end up, and just as my brief recap, the NIAAA definition of recovery has both clinical and research implications. It's important to assess for cessation of heavy drinking, remission from DSM-5 AUD, and clinical practice as they are indicators of recovery status. Our definition does provide a unique opportunity to evaluate the processes of behavior change, especially maintenance of behavior change. As I said before, there are numerous behavior change frameworks. There's also ideological frameworks, and you're gonna see in my next presentation as well, that could easily intersect here as well. I'm just sort of sending more of a message of common mechanisms for today. But we have numerous frameworks that can identify specific mediators and moderators. And I think also taking a basic science approach to identify predictors of maintenance of change is also potentially cost-effective. And I think the study of maintenance of change really does potentially have implications for characterizing relapse episodes, developing novel maintenance of change interventions, as well as evaluating recovery pathways. Thank you, everybody. Thank you so much Brad as a clinician myself. I'm a clinical psychologist and still do a bit of work at our inpatient program I I always find it helpful to think about what are those behavioral constructs that are important in terms of maintaining recovery You know over the long term for folks struggling with AUD. Um, so now I am delighted to turn it over to Dr. Nancy Diaz Bernados, who is our deputy clinical director within our intramural research program and attending psychiatrist at our inpatient treatment unit And she's going to be talking about the addictions neuroclinical assessment and understanding functional domains in the treatment of AUD So as Laura said I'm on the intramural Research program and I work in at the clinical side So I work directly with patients and I'm presenting here some work we're doing to really understand I think we all know that Patients that have the same diagnosis You know are we we always complain in research about mixing apples and oranges and how hard it is to really? find treatments that work and processes that work for everyone and the addictions neuroclinical assessment, which is Bizarre to present it in front of Laura since this is really one of her, you know, she she started this project But the addiction neuroclinical assessment is an assessment to understand how our patients might actually be similar or different from each other and how we can improve our treatment and our assessment of these patients, so We and this also comes which is bizarre to present in front of dr. Kube and this comes from these three neuro these three domains functional domains That are part of the Kube and model of addiction so incentive salience negative emotionality and Executive functioning. So with these three domains, you know for years of research we have several Brain circuits that have been associated with these functions in these domains and we want to understand how Simple assessments that you can do in clinical practice might be able to show this function in these domains So we have at this point something that is not a simple assessment It's about four hours at this point, but we're trying to perfect it Hopefully to at some point present, you know Something similar to an audit at either three question or ten question assessment that will help us as a assess these domains and any dysfunction on them So we are hoping this will help us improve our Management of patients to understand where their dysfunction is and how to better treatment Some of this I don't think I really need to present to you. But you know, we we all know how You know I an example is you can have a patient who started drinking in their mid-thirties after they lost a child and You meet them in their mid-forties and they have been drinking for 10 years and they have a DSM diagnosis of severe alcohol use disorder But they say you can have exactly the same diagnosis the exactly the same criteria with a patient that started drinking at age 7 and has been drinking for 40 years and that Has a very different trajectory to their illness and you could say different genetics and you know, very different Risks and outcomes than the first patient that I mentioned Both have exactly the same number of criteria in the DSM Both have exactly the same treatment options and we're managing them exactly the same way But they might really that's where we have either non-compliance with treatment or you know Just failure to treat, you know, these patients because we are really treating very different patients Exactly the same way so we want to understand This heterogeneity and we want to manage these patients better Again, this is the DSM criteria Most of the patients I treat we in the inpatient pro in the intramural program We have an inpatient unit where we treat patients with alcohol use disorder that are treatment seeking so they want to stop their use and I would say Ninety nine percent of my patients have more than nine criteria. So I treat mostly severe AOD patients We also have an outpatient program where we treat our controls. These are Non-treatment seeking patients. So there might be patients with an AOD But we also have people that never drank and we do the same type of assessments in every patient So we want to understand how different levels of alcohol use might affect people through these assessments Talking about these three domains that we're assessing with the addiction clinical addiction or clinical assessment incentive salience is How our patients might find cues and might find Alcohol as something that is a motivating factor or a stress relief factor or a you know anger relieving factor and how Alcohol, you know, it's Really a trigger for them, you know, most of my patients when they're in the unit, they promise us They will never drink again. They know how bad it is. They're done with alcohol They don't want to ever see it again But once they have alcohol in front of them, it's very hard for them to really stay away from that drink We we did before covered Patients in the inpatient unit would go out for you know watching a movie. They are inpatients for 28 days So we'll take them for like a movie night and for them. It was a big and difficult process because they will walk past You know the bar on their way to them the theater and all they could see around them was alcohol When they're sitting in the inpatient unit, you know, if they turn on the TV all they can see around them is alcohol and It is hard for them to just walk away, you know, they all hate alcoholism they all hate alcohol, but When it is in front of them They don't have much of a saying they really want that drink So that's the incentives incentive salience part The negative emotionality domain is and and dr. Coop has been talking for a few years about hyper catifia this negative emotional state that comes with alcohol withdrawal and that comes with You know alcohol use disorders where patients are really? Not drinking for pleasure. They're not drinking because they like alcohol. They're not drinking because they again like What alcohol does to them they're drinking to relieve all of the negative Consequences of withdrawal, you know, they are anxious are depressed They cannot sleep they are in pain and they really need that drink to relieve that anxiety depression insomnia and everything else so this negative emotionality has some progression for some of us is After a bad day at work, you really want a drink to relieve your stress or you know to kind of compensate yourself for a stressful day but again for some patients, it's really Their response to to alcohol withdrawal and their risk ponds to you know just coping with their emotions and with where they are which after chronic alcohol use Puts them almost constantly in this negative emotionality state that they're trying to relieve and with executive function We all know that At some point patients with alcohol use disorder kind of lose their capacity To stop to control their use they might know the consequences They you know have been warned at work that they're gonna lose their job Their partners have told them that they are gonna leave them but they really have very little control at some point in their illness and We want to kind of understand where this control happens and how this might change through treatment So we want to understand how a patient that knows it's gonna lose their job still drinks or how a patient that knows they Know have cirrhosis and need a liver transplant and have some sobriety Requirements for that liver transplant how that patient is still drinking And how this executive function how that this control or not of their drinking how this works This is what I was telling you about major brain circuits, this is one of my favorite papers in addiction It's the New England on 2016 from Kovan Bulkow and It shows how these three domains that I just explained are related to different brain circuits And how as you progress in your alcohol use from someone that drinks Occasionally to someone that drinks compulsively How these affects brain circuits and how this really changes the way your brain functions? We've been talking for a long time about alcohol use disorder being a brain disease, and I've been also discussing With some of my colleagues how of course alcohol affects every organ in your body, so it's not just a brain disease It's you know it really affects everything in their body, but they control part and the part that really will You know I'm a psychiatrist, so I'm very biased, but the brain is what runs this illness You know it's it's brain circuits that run this illness. No one is drinking to you know Manage their liver needs they're drinking to manage their brain needs So Again, this is kind of the cycle that I was mentioning As someone continues to drink their symptoms worsen over time and kind of their need for alcohol grows so the Treatment becomes more difficult and their needs for Help, and you know a very comprehensive program around them Changed dramatically. This is what I was telling you that we end up treating Apples and oranges We have patients that might have dysfunction of every domain We have patients that might have only a dysfunction in one of these domains But we're treating everyone with you know three drugs maybe five But three FDA approved drugs, so we're treating them exactly the same even when exactly the same even when you know someone might be an ADHD patient that really has no impulse control or a Bipolar patient that when they are manic You know just completely loses their control as opposed to someone that is Treating self managing their depression or self managing their PTSD and kind of treating their negative emotionality or someone that Again Really has a different response to alcohol and in the incentive salience You know we all know that there's people that just don't like alcohol Don't respond well to alcohol and never drink much Versus patients that you know what my patients will tell me is at age seven when they tried that Drink that they stole from their parents their anxiety was relieved immediately. They just loved it You know it changed their life and after that they were looking forward to that next drink You know for the rest of their lives So their incentive salience is very different than the incentive salience of that 30-something year old woman that lost her kid and is drinking to relieve her depression from her loss So we are trying to understand how these patients differ and how these patients are similar and how This would down the road hopefully Give us more adequate Management of these patients you know we don't need to treat every patient with naltrexone Which works on the incentive salience side if they don't have an incentive salient dysfunction We have a battery of tests as I said at this point it takes about four hours But we're you know trying to really collect from this battery of tests What are the key predictors of any dysfunction in these domains to create a much Abbreviated battery that all of you as clinicians could use in your outpatient practice when you're doing an initial assessment With negative emotionality we are of course looking at anhedonia depression resilience attachment anxiety insomnia insomnia personality characteristics with incentive salience we're looking at how people respond to alcohol and Alcohol sensitivity risk of compulsive drinking and cravings with executive functioning. We're looking at you know memory response inhibition mental flexibility So impulsivity of course so we are assessing different domains in these patients And through those domains we actually have data that show that dysfunction in these domains and i'm sorry This is just my table um, but we have These numbers sadly are what covid did to us so We really want everyone treatment seeking patients and non-treatment seeking patients But during covid in our inpatient program, we could only bring treatment seeking patients So my table shows 200 aud patients and only 19 non-aud patients We are now Post covid and really working to increase our non-aud sample But from this group we could really show a significant difference When you someone has a dysfunction in these domains And i'm sorry i'm going when someone has a dysfunction in these domains We could pretty much diagnose them with aud just by having this dysfunction. So it was very predictive of a diagnosis um and You know incredibly sensitive incredibly specific for aud diagnosis just having a dysfunction in any of these three domains Incentive salience is probably the most and negative emotionality kind of marriage But they are the most predictive of an alcohol use disorder in these patients Um, and this is kind of the research the analytical approach so we are Looking at the sample we're testing and validating our hypothesis looking at predictors and outcomes And we want to understand who as a predictor has an alcohol use disorder I'm, sorry as an outcome has a alcohol use disorder And also we're looking at family history to look at both genetic and environmental factors um on the incentive salience Alcohol motivation the drive to consume alcohol. What are the what what are the reasons why someone would drink or not? And alcohol sensitivity as I was telling you it's very different the patient that drinks half a glass of wine and falls asleep to the patient that drinks, you know a Glass of beer and immediately has a relief of anxiety depression Tension and just loves it. So on the incentive salience alcohol sensitivity um and alcohol motivation are Very good predictors of developing an alcohol of having a diagnosis or an alcohol use disorder diagnosis On the negative emotionality. There's these three different domains Internalizing externalizing and resilience. So in internalizing negative thoughts directed directed inwards Externalizing which is the negative behaviors that are toward the environment And resilience which of course is a protective factors. These three domains are incredibly predictive again of an alcohol use disorder and in the Far, i'm sorry in the far I want to say to your right you can see the the Domain, so of course depression anxiety negative affect alexithymia anger hostility physical aggression under resilience and positive affect and extroversion Are kind of protective factors for these patients? And finally with executive functioning we have Several areas of executive function that can really predict A diagnosis and diagnosis of an alcohol use disorder and how these patients will eventually function So as I was mentioning earlier impulsivity um rumination Interoception working memory and inhibitory control are kind of key domains on how these patients might work and how What are the risks for a relapse or for you know sobriety once they're trying to seek sobriety When we put the full model together they And there's a lot of correlation between all of these domains As I said, I have a sample that is on the severe end So these are mainly audie patients and these are mainly patients that have More than nine criteria on the dsm. I would say every patient here has more than nine criteria on the dsm So they're on the severe spectrum and they're really on the severe end of the spectrum So once there's a dysfunction in one domain, you will see a dysfunction in almost all of them um And these are kind of the difference between the alcohol use disorder patients and the non-alcohol use disorder patients where You can see resilience and you can see Executive control and incentive salience kind of Functioning a little bit better on these groups Um These are the factors that I was just mentioning and how they differ between alcohol use disorder patients and non Alcohol use disorder patients so you can see there's a significant difference between the groups you can see how patients with an alcohol use disorder really have very different motivations for drinking they have their internalizing behavior is significantly different between Aud patients and non-aud patients and the same with impulsivity, which I think we all know clinically Um, this is what I was telling you about how good we are at diagnosing Patients just looking at these domains We have very good Curves for motivation and sensitivity on the incentive salience just an incentive salience dysfunction It's you know, incredibly effective at looking at an alcohol use disorder Negative emotionality also does really well Executive function doesn't do as well as you can see But impulsivity is the one area on executive function. That is very interesting Um, and I think that's essentially my talk Thank you so much nancy as as uh nancy mentioned I um 10 years ago. I think gosh I started working on the addictions neuroclinical assessment very closely with Dr. Koob and dr David goldman our clinical director and so it's just so exciting for me to see kind of where we are now, since I've moved on and don't work closely with this project. It's just really exciting to see, I think, the clinical relevance of the addictions neuroclinical assessment. So I'm going to give the final talk, wrap up. We will have, I'm gonna try and leave a good 20, 25 minutes for questions at the end, and we'll have all of our speakers come up. I will have to duck out to catch a plane, so if you have any questions for me afterwards, feel free to get in touch with me later on, and I'll be happy to talk. So I'm gonna be presenting on our newest resource that we developed at NIAAA, that we call the Healthcare Professionals Core Resource on Alcohol. And the HPCR, or core resource, as we call it, really came about at the urging of Dr. Koob, who said, I want us to have something that is essentially a primer on what every healthcare professional needs to know about alcohol. So we designed this website, and you'll see some of the screenshots and content as I talk. So we designed this website with primary care practitioners in mind. That's sort of the audience that we wrote it for. But really, this is for every healthcare professional, and we offer free continuing medical education and CEC credits to physicians, nurse practitioners, psychologists, pharmacists, RNs. And so it's something that we hope will be both robust and succinct for all clinicians. This is just an overview of my talk. We published the HPCR back in 2022, again, to address those gaps in alcohol-related knowledge among healthcare professionals. It's organized in topics that are foundational. We have information on medical complications and comorbid psychiatric disorders. The topics themselves are complemented by additional content and links to evidence-based resources. And then again, you'll see this is a theme. We offer free CME credits. And also, I want to note that the core resource is a living document. This is something that we're updating periodically. It's not that we published it once and that's it. That's all we need to know about alcohol. We are actually currently starting that process to see what new evidence is worth being included in the HPCR. And we'll be making those edits in 2024, 2025. So again, this is, you can see sort of what the original or what the initial landing page looks like. It's what every healthcare professional needs to know about alcohol. It includes 14 concise, practical, user-friendly articles. We wrote these with busy clinicians in mind. We know that you don't have a lot of time. And so we really wanted to kind of maximize our bang for our buck. And then again, the free CEs, CMEs. And so that's the URL that you can go to. Again, overview of my talk. I'm gonna start off by talking a bit about how we think that the core can help practicing healthcare professionals. I'll talk about its organization and give an overview of those 14 topics. And then talk a bit about our content development process. So how can we help healthcare, practicing healthcare professionals? So again, this resource was designed to address common barriers to optimum alcohol-related healthcare. It provides knowledge to fill in common gaps in training, including information about the neuroscience of addiction, evidence-based treatment, and then those varied paths to recovery, as Brett spoke about earlier. We provide information about quick, validated alcohol screening and assessment tools. There's clarity about what constitutes heavy drinking, AUD severity levels, and also recovery. And then finally, we have practical steps that clinicians can take to reduce stigma surrounding alcohol-related problems. So this is our general organization framework. We have knowledge, foundational knowledge. We have clinical impacts. And then we have strategies, concrete strategies that people can use. So here, you just see a little bit of the overview. I'll talk more in depth about each of these topics. But for foundational knowledge, we have a topic on what we're calling the basics. Very simple, what is a standard drink? You'll see I have a slide on that in a sec. Information like that. Risk factors, really thinking about what are those genetic and environmental factors that create this varied vulnerability to harm from alcohol. We have a topic on the neuroscience of addiction that focuses on the brain in addiction and also in recovery. We thought that that was really important to convey to clinicians. And I actually, in my clinical practice, have found it very helpful to discuss with my patients. When they report cognitive-related decline, concerns related to their drinking, we talk about the fact that with sustained remission, they can hopefully expect some improvement in those symptoms. And many of them have said to me directly, I'm really glad to hear this. This is really a relief that my brain could get better. The last foundational topic is one that we really insisted on being in there on stigma. Stigma is just one of those pervasive barriers to optimal clinical care. I don't think it gets enough attention, but it is something that we really wanted to highlight. Looking at our section on alcohol's clinical impacts, we have topics on medical complications, alcohol medication interactions, mental health issues, looking at common comorbidities, and then a whole specific topic on alcohol use disorder itself. So how do we look at risks, diagnosis to recovery? Again, looking at those strategies, we have topics sort of along the SBIRT continuum. So we have a full topic on screening and assessment that, again, provides those reliable, well-validated brief clinical tools. We have a topic on how to conduct a brief intervention, how to recommend evidence-based treatment, making referrals, and then supporting recovery. And then last but not least, and this topic was not in our original grouping, but it came about as we were developing the core, and we said, you know, we really need something that will provide information for healthcare professionals on how they can actually take these manageable steps. So we're giving you all this information about this is what we want you to do, but how can you really do it? So this is just, you know, very simple, not easy, but simple kind of concrete steps that healthcare professionals can take to promote change in their practice. This is just some of the supporting content that we have, you know, for folks who want to take a deeper dive. We have a lot of information about, you know, different specialties, different areas of practice that are relevant. Again, those free CMEs, additional links for patient care, and then, of course, a section on our contributors that I'll be showing you. And here's just more, like, you know, an example of, you know, we have further information about primary care for adults, adolescent primary care, cancer care, chronic pain, et cetera. You see it's a really comprehensive resource. And we also have information for healthcare systems, looking at the US Preventive Services Task Force recommendations, thinking about implementation, quality improvement, and reimbursement. So moving on to these 14 topics, this is the structure of each of these, and we wanted to keep it the same, again, just for practicality, for simplicity's sake. So we start off with an outline. There are key takeaways, like, if you only need to know three, four, five things from this article, what are those? We put those front and center because we wanted to really highlight them. Then there's the main content section, additional resources, references. Every single one of these topics is extensively supported by peer-reviewed research. We went over every reference with a fine-tooth comb to make sure that all of the statements that we're providing in the core resource are accurate and they're evidence-based. And then, again, the link to the CME CE credit for every topic. So starting off with knowledge, and I mentioned that we have a topic on the basics, really how much alcohol is too much. And you can see here some of the topics that are included in there. This is possibly my favorite graphic on the website. What counts as a drink? What is a standard drink? I mean, I think we all know that there's a lot of misunderstanding about what that is, and so we wanted to make it very clear, visually, what a standard drink is. And so you'll see here we have along the top the amounts of different beverages, for example, 12 ounces of regular beer, not 16, 12, at roughly 5% alcohol. And so then along the bottom of each of the different glasses, we note what the alcohol by volume percentage is. So this is something that, again, we really wanted to make it very clear that we want there to be a shared understanding between patient and healthcare professional about what constitutes a standard drink. So moving on to our second topic, risk factors. Again, this is on that varied vulnerability to alcohol-related harm. We think about what the risks are for different age groups of individuals. What are risks for alcohol consumption and development of AUD by gender? And then also, importantly, what are the risks of prenatal alcohol exposure? Moving on to our neuroscience topic, again, the brain in addiction and in recovery. And this is just a little piece of what the content is. There's obviously a lot more at the website, so I just wanted to kind of give a brief overview. But we have information about the dual reinforcement properties of alcohol and that it activates the brain's reward processing system that mediates pleasure while reducing the activity of the brain systems that mediate negative emotional states such as stress, anxiety, and emotional pain. However, as we know, with repeated and heavy use of alcohol that leads to the development of addiction, the system is sort of flipped. And again, the way that I talk about it when I'm working with patients is that there's this shift in drinking motivation from positive reinforcement to negative reinforcement, but also really an increased activation or up-regulation of the brain's stress systems. So instead of initially kind of that high reward, low stress, the balance then shifts with the development of addiction and the consumption of heavy alcohol. Stigma, again, can't talk enough about this, but we have information on how might the effects of stigma show up in patients. So what are some of those signs to be looking for? What underlies stigma for patients with AUD? What are some of those societal and individual level contributors? And then how clinicians might inadvertently contribute to a patient's sense of stigma and what can be done to address that. So moving on to our impact section. Again, we have, this is probably our longest topic. It's very comprehensive. As you saw in Dr. Koob's talk, alcohol affects every system in the body. It affects over 200 health conditions. And so this had to be a very comprehensive article. So again, that's one of our clear takeaways that the whole body is impacted by alcohol use. It's not just liver. It's not just pancreas. It's the brain, the gut, the lungs, cardiovascular system, immune system. And then we also include information about how alcohol consumption can impact things like managing hypertension, atrial fibrillation, diabetes, lung infection. And we also really wanted to highlight the fact that many people, including patients, are unaware that their alcohol use may be contributing to their medical problems. They may not know that it's causing problems with sleep. They may not know that it's, this is the reason why they just can't get their hypertension under control or their diabetes is just so persistently difficult to manage. That alcohol use may well be a contributor to those complications. Again, I mentioned we have a topic on alcohol medication interactions. And that includes sections on the types of alcohol medication interactions that we see, how healthcare professionals can check for alcohol and medication interactions. And then we provide some concrete examples of the common medications known to interact negatively with alcohol. A topic on mental health issues, alcohol use disorder and common co-occurring conditions. Some of the takeaways here, we know that the severity of both the AUD and the co-occurring mental health disorder or disorders determines the appropriate level of care. So there's a range of treatment setting, but also focus of treatment. And whether we wanna really emphasize, say for example, depression or anxiety versus alcohol use or both. And we also know critically that the likelihood of recovery from both conditions is higher if both the AUD and the co-occurring mental health disorder treatment. It's not either or, this has to be a both thing. Oh, sorry. And then our topic on alcohol use disorder. Again, this is a comprehensive section on what alcohol use disorder is, what are the diagnoses, what are the symptoms, and then what puts people at risk for developing AUD and a bit of information there about recovery as well. So now moving on to a more practical section, our strategies. So screening and assessment. Again, we know that healthcare professionals are very pressed for time, to put it mildly. So we highlight here the two brief assessments, screening assessments that are recommended by the U.S. Preventive Services Task Force. This is the recommendation for adults. And it's the Audit C, which is three questions, very brief, and then even briefer, the NIAAA single alcohol screening question. And so this question for women is, how many times in the past year have you had four or more drinks in a day? For men, the question is, how many times in the past year have you had five or more drinks in a day? And this single question has shown pretty remarkable sensitivity and specificity in terms of identifying people at risk for AUD. And it's also something that can be woven in very easily into a verbal clinical interview. We are also really excited in the core resource to include this new assessment tool. This was developed by some of our grantees at Kaiser Permanente Washington that it's a form, as you can see, that lists all of the AUD diagnostic criteria in patient-friendly language. And this, you know, hopefully isn't something that is too confusing for people. And this is something that patients can fill out either on a tablet or on paper, you know, prior to an appointment. It allows identification of the AUD diagnosis, including levels of severity. And it was designed to provide openers for motivational interviewing and for further questions in follow-up. So that a clinician, you know, once they've provided this to the patient and they've read through, you know, they can say to them, you know, tell me more about, you know, you said that, you know, you've at times drunk more than you intended to or over a longer period of time. Tell me more about that, right? So again, these very practical ways to really ground the clinical discussion. We have a full topic on conducting a brief intervention, building motivation to change. That includes sections on how we can help patients develop a change plan, set goals with them. And also for patients who are diagnosed with AUD, really providing that added support that they might need by linking them up with specialty care, possibly including prescriptions of FDA-approved medications to treat AUD. And then recommending evidence-based treatment. You all know these, but you know, we, again, we wanted to make it very clear to our healthcare professionals. There's a wide variety of evidence-based treatment options out there. It's not solely Alcoholics Anonymous or a quote-unquote rehab, as many people think. You know, there's a wide range of behavioral health approaches that are supported with good evidence. And then there's also our three FDA-approved medications for treating AUD, camprosate, naltrexone, and disulfiram. So we also have a topic on making referrals. So how do we connect people with care that meets their specific needs, right? We've heard a lot about patients with severe AUD, but surveys, including the National Survey on Drug Use and Health, suggest that most people with AUD, approximately 60%, actually have more mild AUD. So, you know, for them, they're gonna need a different kind of treatment approach. So we can talk through, you know, what are those treatment approaches for the individual? And really emphasize that these different treatment options, you know, may be more acceptable to patients than, again, one that requires them to go to an inpatient treatment program for 28 days, which is a difficult thing to do for many people. And then supporting recovery. Brett gave a really great depiction of our new recovery definition, which, even though it is a research definition, does have those clinical implications. So we present that in this topic. We talk about the odds for recovery. And that's something also clinically that I found very helpful with people. Like, yeah, there's a good chance that you can recover, you know, that it's not always going to be like this. So that's important information to convey. And then also we discuss what that change process for AUD recovery looks like. You know, there are different trajectories, you know, including folks who stop drinking, and then that's it, they remain abstinent, to people who may have kind of a bumpier first six months, first year before settling into a more abstinent pattern, and then people who, you know, may, again, experience more difficulty sustaining abstinence. We also include information on specific strategies that can help patients prevent return to heavy drinking or recover from a return to heavy drinking, so that it doesn't end up being a long-term return. And specifically talking about managing stress, and then helping patients recognize the cycle of drinking in negative mood, which a lot of people don't, you know, necessarily know, may not think of, but when it's discussed with them in a clinical setting, they often are able to realize, oh, yeah, you know, even people who may not have AUD, right, they may be drinking heavily, or maybe they have very mild, they have two symptoms, you know, but they're not aware of how drinking can affect their irritability and anxiety. Again, how healthcare professionals can support recovery, negotiating recovery goals with patients, again, recommending that evidence-based treatment with continuing care. So, you know, for most people, this isn't gonna be something that is wrapped up in six weeks. How are you going to support yourself? What is the continuing care that's gonna be beneficial in terms of supporting long-term recovery? And then our final topic is on promoting practice change. So what are those manageable steps that healthcare professionals can take towards providing better care for their patients? So these include things like reducing stigma, conducting screening and brief interventions, and then prescribing those FDA-approved medications for AUD. So, very briefly, and then we'll shift over to questions, I wanna let you know how the content was developed. We had 70 contributors to the core resource, including many practicing healthcare professionals and researchers. Each article had between four and 10 external reviewers per article, and also NIAAA staff, including Dr. Koob. Every single comment that we received was discussed. We had a team, including myself, Dr. Ray Litton, Maureen Gardner, we had an expert contractor working with us, science editor. We had, as you can imagine, hundreds of responses, hundreds of comments, and we resolved all of these in real-time editing. And again, we designed this with busy clinicians in mind. All of the content is clear, it's concise, and it's cohesive. Here is a list of all the folks. I am not gonna read every single person's name, but I think this slide just really shows the breadth of expertise and really generosity of time in terms of developing this resource. We had a lot of support, both within and outside of NIAAA, and we're very grateful for that. This is some of the sample feedback from our reviewers. We wanted them to provide feedback that was honest, and most of them really mentioned what a good resource they found it to be. Critically, I've said that this is a primer for every practicing healthcare professional, and it is, but it is also designated as an American College of Academic Addiction Medicine recommended educational activity, and it's a recognized activity for certification of diplomas by the American Board of Addiction Medicine. Even though this was designed for use by non-specialists, it's robust enough for specialist certification. I think that tells you the balance that we struck here. Thank you. There's my email address. Now I would like to call our presenters up for questions and answers. Thank you. As I said, I unfortunately need to leave. If you have questions for me about the core resource or the NIAAA Treatment Navigator, which I didn't get to in this session, there's my contact information. I'm happy to talk, and I will turn it over. So I guess you're welcome to start. Thank you, and thank you all, including Dr. Cuoco. Thank you. Dave Conde, Philwaco, Washington. We have a cleanup company whose slogan is, as if it never happened. I tell my patients, I'm not that company. I can't give them an as if it never happened brain. In light of all we know about the persistence and craftiness of this disease, it was jarring to hear the word recovered rather than the word recovery or remission. And I'm wondering why you chose that word recovered to describe the recovery process or a stage in the recovery process. To me, it seems jarring, and I really want to hear why you did it, because I'm sure you did it thoughtfully. The term recovered really serves as more of an outcome inside the duration qualifiers. So since we developed the research definition of recovery, what we wanted to understand is how people move across those phases. So it was the pursuit of those two key alcohol outcomes. So that's really what it's focused on, is the outcome inside of the qualifiers, to move to the next phase. So you consider recovered inside of that. But you're thinking more clinically about the term recovered. And I'm just saying that we throw that word out there, so it's something to kind of think about and what that means. But I think a lot of people acknowledge still that recovery is more of that process. And so clearly our definition focuses on both in that way. And so we have gotten, I have had criticism based upon that term recovered, because some people think it's kind of stigma related to that, but you know. Respectfully suggest that a more appropriate term might be sustained remission, which would parallel what the cancer specialists use when we see no external or detectable manifestations. But still, surveillance and healthy behaviors remain extremely important. Thank you. Hi there. Darren Hullab from just west of Toronto in Canada. Thanks for the wonderful session today. Just curious, you might have heard of the Canadian Center on Substance Use and Addictions safe drinking guidelines that were released about a year ago. A lot of press up in Canada anyway, and quite a bit of controversy. They were recommending no amount of drinking is safe and a maximum amount of consumption of two standard drinks per week. Thoughts and reflections on that? Because it's inconsistent with the United States and most other countries. So there is a committee in the U.S. Department of Agriculture that sets the guidelines. I emphasize these are guidelines. And currently in the U.S. it's two drinks a day for males and one drink a day for females. They are right now gathering together to revisit the guidelines. And so they will probably ask us for some of our input and we'll provide what we know. But that's how the process works in the United States. I am personally, and I think many of my fellows here at NIAAA are very interested to see how that's working in Canada. So stay tuned. I'm sure people are doing studies there. If they're not, we'll probably initiate a few and see how you did do in Canada. So great question. I think most people are failing. And if I can add, how I see this is similar than with tobacco. I agree with no amount of alcohol is really safe at the end, and I think we just need to do more education about it. So, you know, every country will have their guidelines, but with my patients I'm not necessarily asking everyone to be completely abstinent, as we discussed, because culturally it might be difficult. But hopefully culture will move as it moves with tobacco, and it will be less acceptable to drink and to drink as much as it is acceptable now. Yeah, I mean, obviously we tried Prohibition, Nancy, and it didn't work. By the way, there's a great documentary on Prohibition by Burns, so I highly recommend it if you want to see how it did and did not work. Hello, I'm Ellen Edens from Yale School of Medicine in Connecticut. So with any bag of potato chips, I can find out what counts as a serving and how many servings are in that container or bag. What are the current consumer protection advocacy efforts that NIAAA is involved in or aware of to improve labeling of alcoholic beverages so that we can all become more informed consumers? That is not our domain. I'm afraid that belongs to—I wish Trish was here, but there—Laura, do you know? Oh, Laura had to go. I can go over there, and I feel lonely over here. Anyway, there is another government agency that sets those kind of policies. We don't set policy. What we can do is, you know, I know the World Health Organization. I believe the World Health Organization is interested in getting calories of alcohol or the grams of alcohol on every beverage. So there are organizations out there working on this, one of which is the World Health Organization. But we don't set guidelines. Thank you. I'll come over and join my friend. I feel like I'm in the middle of nowhere. Hi. I had two questions. One is around the term recovered again, because it said something over time, but maybe I missed it. What time are we talking about? go from in-recovery to recovered, and what happens if someone who is recovered then returns to drinking? Are they no longer recovered, still recovered? What? Well, it's a good question. So again, I kind of want to bring up the idea that the term recovered is really related to those qualifiers, and it's about having an outcome to achieve to just move forward. But we still recognize the important point that recovery is a process, and that's really an individual kind of thing, too, for folks to think about. But so in the duration qualifiers, we have early recovery, like up to three months. And then next one is, is there's, I keep forgetting the name, what's the second phase? It's from three months to one year, and then from one to five years, and then five years plus. So is recovered five years plus? I mean, that's long-term recovery, and that's the point what we learned where a lot of changes happen there with respect to quality of life and functioning. It takes a while to see those changes over time. So I mean, yeah. You've got to remember, we developed this definition for research purposes. We have no clue what facilitates recovery in the real world. And so these are arbitrary designations that we came up with that are very similar to what you see if you look at Steve Stahl's description of recovery in depression or an anxiety disorder. And so we're going to be using these as ways that individuals who are doing study on recovery can find out, was it the cognitive behavioral therapy that worked, or was it the yoga that they went to, or was it the mindfulness that was combined with the cognitive behavioral therapy, or was it some other element of mechanisms of behavior change like Brett was talking about that we find this golden nugget that is a key to every individual who recovers. So that's the purpose of this. You know, in your clinical practice, you can use it or not use it. Obviously, somebody who presents in your clinical practice with five DUIs or four DUIs, you're not going to be going to a harm reduction approach. It's going to be abstinence probably as a recommendation for that patient, as Nancy pointed out. Nancy, you may want to comment on this too. I think the part of this definition that I really like is I have patients that are so sober, but they are still very harmed by their illness. And this definition, as it was mentioned, includes other aspects of their functioning, of their quality of life, other dimensions of them as a human being, and how these dimensions will change over time for some patients, and I think that's what Dr. Covey is asking me to discuss, for some patients, cutting down their drinking. So if we look at college-age AUD patients, you know, the highest proportion of AUD patients in the U.S. is college-age people, but they eventually learn to stop binging, and that's all they need. You know, they can continue to drink, but they stop binging, and that's all they need to recover. The patients I treat are patients that, as I said, are at the severe spectrum and have been drinking for years, and I cannot tell them that cutting down their drinking works because every time they have a glass of wine, they end up drinking a gallon of vodka. So they don't have much control once they start, and if I tell them that cutting down is an option, you know, they tried it for 30 years and it never worked. So again, with AUD, we have a mix of apples and oranges, as I was trying to discuss earlier, and for some patients, cutting down works. For some patients, abstinence is needed. And I think we need, as clinicians, to make that distinction with each individual patient in front of us. Thank you. Hi, George. Jim Halikis from Naples, Florida. A glaring omission, I think, in your research attempt is family, the penumbra of the family promotes or retards recovery, relapse, and needs to be studied in some way. And I think that should be part of, and also part of the, what Dr. Quirk. So I didn't present this here, but on this sample that I'm discussing on the addiction neuroclinical assessment, we have genetics on this patient, we have epigenetics, and we have family histories on this patient. And we have really interesting data on how the genetics might carry a risk for the illness. There's no question that these are genetic. No, I understand. I'm describing the family that the person lives with. During treatment. During treatment, pre-treatment, post-treatment. I understand. Yes. It's completely different. Yes. We understand the genetics of the disease. So I was just going to say, we developed a framework which you can intersect important questions. So intersecting family and understanding family involvement in those pieces are important. Absolutely. So, you know, the important part of the definition is just recognizing it doesn't, it's not going to cover every construct, right? You know, and that certainly didn't come up a lot with our stakeholder feedbacks, but I certainly recognize the importance of family involvement in those pieces. Certainly encouraging research to do that is absolutely important. I mean, you raise a really important point that will be in our strategic plan, which is that, you know, addressing family issues is another part of the recovery process. We totally agree with you. We have like research going on with folks like Alan on and those things as well. So. Yeah, go ahead. Hi, Priscilla Jones, third year med student from Oregon. I'm kind of short, sorry. So especially during COVID and after COVID, we've seen a lot more young people with heavy drinking use. And at least in some circles, it seems like not drinking heavily is almost more stigmatized than the opposite. So I'm wondering if you have any recommendations about what we can do to address the heavy drinking culture, especially in young people without coming off, you know, chastising or paternalizing. So the question I understand is how can we help younger patients that are drinking a lot after COVID? How can we help them without promoting complete abstinence or, you know, not chastising them for their drinking? Going back to what I was discussing earlier, it's very interesting to see how younger groups are not smoking tobacco as much. They might be vaping and using marijuana, but they have enough education about tobacco to think that it's not a good habit and not something they want to get into. I think we need to move into education about alcohol and health consequences to help them understand that it's not a good practice and it's not healthy and it's something that they need to modify. I think most people, and I know that most adolescents and young adults are invincible and can just get away with anything. But I think if we give them enough education, they'll understand that it's something that it's better to move away from or to be careful with. So I think we need to move into more education early about some of these aspects. And it worked with tobacco, so I'm hoping it will work with alcohol eventually. Your question is why we are embracing some of these new movements with mocktails and dry bars. One of the things we emphasize is that no one should ever host a party without providing a non-alcohol containing beverage at the party. We need to not only reduce the stigma of alcohol use disorder, but we need to reduce the stigma of not drinking. And so that's another area that we're focusing on. But it is a real challenge, and there's some hope that young people who are involved in a healthy lifestyle now are reconsidering their relationship with alcohol. Hi, Karen Drexler from Emory University and Medical Director of AAAP. I would like to thank the whole panel. Thank you so much for an amazing presentation. And also for your comprehensive research approach to understanding the whole continuum of alcohol through severe alcohol use disorder, and promulgating this idea that it is a continuum and a multidimensional, multifactorial continuum. So I have a question about if you have any results yet to tell us about predictors of success from the first couple of weeks or months of recovery. I remember at one of these meetings several years ago when Roger Weiss was presenting about the POTS study, a little kind of side takeaway was folks who weren't doing well in that medical management model, who couldn't achieve abstinence from opioids in the first two weeks, really weren't going to achieve abstinence from opioids with longer exposure to the same intervention. So it was really time to start diving into why it wasn't working, adding other interventions to support. Do you have anything like that about alcohol at this point? We have a couple of studies underway. Laura had to leave, but one that she's been guiding is with Kaiser Permanente in Northern California, and they've actually adopted alcohol as the fifth vital sign and have been doing extensive screening and brief intervention, hopefully referral to treatment. Those data should be coming in soon. So we do have a number, but in some sense this falls into our health services domain, and that's Laura's charge, and that's why we hired her to guide that branch. And so stay tuned is what I guess I would say. I don't know whether you... That's for me the key question, and what I wish to have an answer at some point, I don't have it yet. So I don't have at this point a clear kind of factor, question, biomarker that will tell me who will relapse and who will not, or at the clinical side, sadly, if you ask my own clinical intuition, if you want to call it, I'm not good at predicting who will relapse and who will not. There's patients that I'm completely sure will relapse, and five years later they're sober, and there's patients that I am completely sure will never drink again, and they are drinking on their way home from the hospital. So I don't have at this point a good answer, but that's what I'm looking for. That's one of the things that I want to know and that we're trying to find with some of this kind of deep phenotyping that we're doing. Thank you. I think the key to behavior change and maintenance of behavior change is reaching an inflection point, or a point of realization where the patient says, you know, that life doesn't work for me, it's not an option. And I think you've got to keep that in mind for a maintenance of behavior change. No, I concur. I mean, I think, but I mean, again, it's kind of characterizing that phase, right? And what does that mean? What does that look like? And I agree, there's potentially a point with which, you know, you start to understand what that means. What were you going to say? Yeah, and I have to say on my practice, it's so difficult. You know, I treat severe AUD patients every day, and I have patients that are on a transplant list, and, you know, they come into the unit, as I said, they promise me they will never drink again, and they're drinking 10 minutes after discharge. And I do believe they are at that inflection point that you refer. I am sure when they're leaving that they will never drink again, because they really hit bottom if you want, even though it's not the best term, I think. But I'm not, I haven't found that inflection, a predictable inflection point, the way that you describe it. I cannot, in my practice, really use it as much as I would want. I just really want my patients to know there's a very high risk for the severe AUD patients of relapse, and that they need a lot of support. They need recreational, kind of restructuring their mind about how they have fun, because they always have fun with alcohol, vocational rehab, because many of my patients are working in areas where daily drinking is allowed. So going back to these type of jobs, being a barman, or working in the service industry might not be ideal. So there's a lot of things that need to be in place for these patients to do well, and it's very hard to help them at times when they are at the severe end of the spectrum. We are close to ending here. So real quick question, and then we're going to have to wrap it up. Larissa Lukiano, Mayo Clinic, Addiction Psychiatry. Question for Dr. Koops. Question about possibilities of what would you consider as biomarkers of recovery, if any. A biomarker of recovery? I don't think we have a real biomarker of recovery. I mean, the closest probably is PETH, which we're hoping could be made easier to get samples. It's a blood, it's a phosphoethyl, what's the, I don't remember the enzyme. So basically you're talking about toxicology screens. I was wondering if there's anything other than toxicology screens, such as like corticotriphin releasing factor, or anything that related to your work on a stress system that is implicated in negative effect. Well, I think this is what we're planning on looking for. We do know from what Nancy said that these internalization actually predicts, let me take a step back. Katie Witkiewicz has just recently published a paper showing that individuals who express the negative emotionality domain, which the one I call hyperkatifeia, actually are more likely to relapse and less likely to show recovery. So that's the only study I'm aware of so far that's actually taken the three domains and applied them to recovery. Look up the studies of Katie Witkiewicz, but there are about now six studies published in the literature on utilizing these domains, showing that they're validated and what predictive validity they have. But we're on our way, is what I'd like to say. We're out of time, folks. We've got to wrap up. I know they've got to get up to the next. Let's thank our NIAAA panel for a wonderful presentation.

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