ChatGPT-4: Alcohol use disorder responses.

BACKGROUND AND AIMS: Alcohol use disorder (AUD) is characterized by low levels of engagement with effective treatments. Enhancing awareness of AUD treatments and how to navigate the treatment system is crucial. Many individuals use online sources (e.g. search engines) for answers to health-related questions; web-based results include a mix of high- and low-quality information. Artificial intelligence may improve access to quality health information by providing concise, high-quality responses to complex health-related questions. This study evaluated the quality of ChatGPT-4 responses to AUD-related queries. METHOD: A comprehensive list of 64 AUD-related questions was developed through a combination of Google Trends analysis and expert consultation. ChatGPT-4 was prompted with each question, followed by a request to provide 3-5 peer-reviewed scientific citations supporting each response. Responses were evaluated for whether they were evidence-based, provided a referral and provided supporting documentation. RESULTS: ChatGPT-4 responded to all AUD-related queries, with 92.2% (59/64) of responses being fully evidence-based. Although only 12.5% (8/64) of responses included referrals to external resources, all responses (100%; 5/5) to location-specific ('near me') queries directed individuals to appropriate resources like the NIAAA Treatment Navigator. Most (85.9%; 55/64) responses to the follow-up question provided supporting documentation. CONCLUSIONS: ChatGPT-4 responds to alcohol use disorder-related questions with evidence-based information and supporting documentation. ChatGPT-4 could be promoted as a reasonable resource for those looking online for alcohol use disorder-related information.

Improving Social Recovery Capital Research To Enhance Clinical Utility: A Proposed Agenda.

Social recovery capital (SRC) is the combination of social resources that can be used to initiate and sustain addiction recovery through friends, family, and peers. Broadly, understanding one's SRC allows us to get a sense of where one has social support for recovery and where there may be social barriers to their recovery process. SRC is often a vital component of many people's recovery journey, yet our understanding of how best to use this concept in research and practice remains underdeveloped. To improve understanding of the role of social recovery capital and strategies to measure and increase it, we present a roadmap involving a five-pronged research agenda to: (1) Refine the measurement of social recovery capital; (2) Model the complexity of social recovery capital empirically; (3) Integrate personality science with social recovery capital research; (4) Optimize evidence-based behavior change techniques of social recovery capital; and (5) Incorporate an intersectional framework when examining or applying social recovery capital. Overall, this five-pronged research agenda seeks to enhance the clinical utility of SRC research to maximize the impact of SRC on one's recovery.

Visualizing the Influence of Social Networks on Recovery: A Mixed-Methods Social Identity Mapping Study with Recovering Adolescents.

Background: Social recovery capital (SRC) refers to resources and supports gained through relationships and is vital to adolescent addiction recovery. Much is known about how substance use relates to social networks, but little is known about how other dimensions of social networks influence recovery (e.g., network size/exposure, degree of conflict). Methods: This mixed-methods study sampled 28 adolescents who received treatment for alcohol and other drug (AOD) use disorder (14-19 yrs.: 71% male; M = 17.32 yrs., SD = 1.33; White 82%): 20 were recovery high school (RHS) students. Adolescents completed a social identity map for addiction recovery (SIM-AR), survey, and interview. Qualitative data were content analyzed and the data from the SIM-AR were quantified. Results: On average, participants reported belonging to five distinct groups within their network (Range, 2-9; SD = 1.63; M = 27.89 people, SD = 20.09). Of their social network connections, 51% drank alcohol and 46% used other substances, on average. Larger networks involved more conflict (r = 0.57). Participants were more likely to spend more time with groups that had greater proportions of non-substance-using members. These linkages were stronger for RHS than for non-RHS students. Qualitative analyses revealed that youth reported their recovery-oriented groups as supportive, but some reported that their substance-using friends also supported their recovery. Discussion: SIM-AR was a useful measurement tool, and, through qualitative interviews, we identified unique aspects of youths' social networks important for further examination. Research with recovering youth should examine SRC-related elements within their networks including relationship quality, belonging, and conflict, alongside the substance use behaviors of network members.

Diagnostic discrimination of social network indicators in alcohol use disorder: Initial examination using high-resolution and brief assessments.

OBJECTIVE: Social network analysis (SNA) characterizes the structure and composition of a person's social relationships. Network features have been associated with alcohol consumption in observational studies, primarily of university undergraduates. No studies have investigated whether indicators from a person's social network can accurately identify the presence of alcohol use disorder (AUD), offering an indirect strategy for identifying AUD. METHOD: Two cross-sectional case-control designs examined the clinical utility of social network indicators for identifying individuals with AUD (cases) versus demographically matched drinkers without AUD (controls). Study 1 (N = 174) used high-resolution egocentric SNA assessment, whereas Study 2 (N = 189) used a brief assessment. RESULTS: In Study 1, significant differences between AUD+ participants and controls were present for network alcohol severity (i.e., heavy drinking days; d = 1.23) and frequency (d = 0.35), but not network structural features. Network alcohol severity exhibited very good classification of AUD+ individuals versus controls (area under the curve [AUC] = 0.80), whereas network frequency did not (AUC = 0.61). In Study 2, significant differences were present for network alcohol severity (d = 1.02), quantity (d = 0.74), and frequency (d = 0.43), and severity exhibited good differentiation (AUC = 0.76). CONCLUSIONS: Social network indicators of alcohol involvement robustly differentiated AUD+ individuals from matched controls, and the brief assessment performed almost as well as the high-resolution assessment. These findings provide proof-of-concept for severity-related SNA indicators as promising novel clinical assessments for AUD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The UK National Recovery Survey: nationally representative survey of people overcoming a drug or alcohol problem.

BACKGROUND: Alcohol or drug (AOD) problems are a significant health burden in the UK population, and understanding pathways to remission is important. AIMS: To determine the UK population prevalence of overcoming an AOD problem and the prevalence and correlates of 'assisted' pathways to problem resolution. METHOD: Stage 1: a screening question was administered in a national telephone survey to provide (a) an estimate of the UK prevalence of AOD problem resolution; and (b) a demographic profile of those reporting problem resolution. Stage 2: social surveying organisation YouGov used the demographic data from stage 1 to guide the administration of the UK National Recovery Survey to a representative subsample from its online panel. RESULTS: In stage 1 (n = 2061), 102 (5%) reported lifetime AOD problem resolution. In the weighted sample (n = 1373) who completed the survey in stage 2, 49.9% reported 'assisted' pathway use via formal treatment (35.0%), mutual help (29.7%) and/or recovery support services (22.6%). Use of an assisted pathway was strongly correlated with lifetime AOD diagnosis (adjusted odds ratio [AOR] = 9.54) and arrest in the past year (AOR = 7.88) and inversely correlated with absence of lifetime psychiatric diagnosis (AOR = 0.17). Those with cocaine (AOR = 2.44) or opioid problems (AOR = 3.21) were more likely to use assisted pathways compared with those with primary alcohol problems. CONCLUSION: Nearly three million people have resolved an AOD problem in the UK. Findings challenge the therapeutic pessimism sometimes associated with these problems and suggest a need to learn from community-based self-change that can supplement and enhance existing treatment modalities.

A Nationwide Survey Study of Recovery Community Centers Supporting People in Recovery From Substance Use Disorder.

OBJECTIVE: The medical community has become aware of its role in contributing to the opioid epidemic and must be part of its resolution. Recovery community centers (RCCs) represent a new underused component of recovery support. METHODS: This study performed an online national survey of all RCCs identified in the United States, and used US Census ZIP code tabulation area data to describe the communities they serve. RESULTS: Residents of areas with RCCs were more likely to be Black (16.5% vs 12.6% nationally, P = 0.005) and less likely to be Asian (4.7% vs 5.7%, P = 0.005), American Indian, or Alaskan Native (0.6% vs 0.8%, P = 0.03), or live rurally (8.5% vs 14.0%, P < 0.0001). More than half of RCCs began operations within the past 5 years. Recovery community centers were operated, on average, by 8.8 paid and 10.2 volunteer staff; each RCC served a median of 125 individuals per month (4-1,500). Recovery community centers successfully engaged racial/ethnic minority groups (20.8% Hispanic, 22.5% Black) and young adults (23.5% younger than 25 years). Recovery community centers provide addiction-specific support (eg, mutual help, recovery coaching) and assistance with basic needs, social services, technology access, and health behaviors. Regarding medications for opioid use disorder (MOUDs), RCC staff engaged members in conversations about MOUDs (85.2%) and provided direct support for taking MOUD (77.0%). One third (36.1%) of RCCs reported seeking closer collaboration with prescribers. CONCLUSIONS: Recovery community centers are welcoming environments for people who take MOUDs. Closer collaboration between the medical community and community-based peer-led RCCs may lead to significantly improved reach of efforts to end the opioid epidemic.

A systematic qualitative study investigating why individuals attend, and what they like, dislike, and find most helpful about, smart recovery, alcoholics anonymous, both, or neither.

BACKGROUND: Some individuals seeking recovery from alcohol use disorder (AUD) attend Alcoholics Anonymous (AA) while others choose newer alternatives such as Self-Management and Recovery Training ("SMART" Recovery). Some even attend both, while some choose not to attend either. Little is known about why people choose which pathway(s), and what they like, dislike, and find helpful. Greater knowledge could provide insights into the phenomenology of recovery experiences and enhance the efficiency of clinical linkage to these resources. METHODS: Cross-sectional, qualitative, investigation (N = 80; n = 20 per condition; 50%female) of individuals attending either AA-only, SMART-only, both, or neither. Participants were asked why they initially chose that pathway, what they like and dislike, and what helps. Responses were coded using an inductive grounded theory approach with utterances recorded and categorized into superordinate domains and rank-ordered in terms of frequency across each question and recovery pathway. RESULTS: AA participants reported attending due to, as well as liking and finding most helpful, the common socio-community aspects, whereas SMART attendees went initially due to, as well as found most helpful, the different format as well as the CBT/science-based approach. Similar to AA, however, SMART participants liked the socio-community aspects most. "Both" participants reported liking and finding helpful these perceived relative strengths of each organization. "Neither" participants reported reasons for non-attendance related to lower problem severity - perceiving no need to attend, and anxiety about privacy, but reported using recovery-related change strategies similar to those prescribed by AA, SMART and treatment (e.g., stimulus control, competing behaviors). Common dislikes for AA and SMART centered around irritation due to other members behaviors, a need for more SMART meetings, and negative experiences with SMART facilitators. CONCLUSION: Common impressions exist among individuals selecting different recovery pathway choices, but also some differences in keeping with the group dynamics and distinct approaches inherent in AA and SMART. AA attendees appear to go initially for the recovery buoyancy derived from the social ethos and camaraderie of lived experience and may end up staying for the same reason; those choosing SMART, in contrast, appear to attend initially for the CBT/science-based content and different approach but, like AA participants, may end up staying due to the same camaraderie of lived experience. Those participating in both AA and SMART appear to capitalize on the strengths of each organization, suggesting that some can psychologically accommodate and make use of theoretically distinct, and sometimes opposing, philosophies and practices.

Meeting-makers make meaning: alcoholics anonymous participation and personal meaningfulness.

AIMS: The central aim of this study was to determine whether intentional, voluntary alcoholics anonymous (AA) participation showed any independent association with affect, over and above that which has been observed in association with other recovery-related behaviors, such as abstinence, among individuals with a history of alcohol use disorder. Additionally, we sought to determine the nature of the affective changes associated with specific dimensions of AA participation (i.e. meeting  attendance, fellowship  involvement, 12-step  work). METHODS: Thirty abstinent alcohol use disorder individuals were recruited and evaluated. Multivariate linear regressions were used to examine associations between dimensions of AA participation, measured using the Multidimensional Mutual-Help Assessment Scale and standardized measures of affective experiences, including the Profile of Mood States, Subjective Happiness Scale, and the Twelve Promises Scale. RESULTS AND CONCLUSIONS: Increase in AA participation was associated with higher positive affective experiences. These associations were observed independently with AA meeting  attendance and fellowship  involvement, but not 12-step work. This study's findings suggest that greater AA meeting  attendance and fellowship  involvement are correlated with enhancements in the meta-emotional experience of personal meaningfulness. This study extends evidence on AA-related changes by considering affective improvements as a primary clinical outcome, thereby laying the foundation for subsequent, more comprehensive research into the relationship between dimensions of AA participation and recovery-related affective changes.

Sexual minority disparities in psychosocial functioning following substance use recovery among a representative sample of US adults.

Purpose: Sexual minority (SM; e.g., gay, lesbian, bisexual) individuals are disproportionately impacted by alcohol and other drug (AOD) use disorders and psychosocial factors that can exacerbate AOD use disorders and hinder recovery. This study examines SM sub-group differences (monosexual [gay/lesbian] versus bisexual) regarding adaptation to recovery measured by indices of psychosocial functioning. Identifying differential needs of gay/lesbian versus bisexual individuals could improve services to better meet the needs of SM individuals in recovery. Methods: Using data from the National Recovery Study, a nationally representative cross-sectional sample of US adults who reported resolving an AOD problem (N = 2,002), we compared heterosexual to monosexual and bisexual SM individuals on socio-demographic characteristics, AOD use and treatment, and psychosocial variables. Results: Bisexual individuals were significantly younger than heterosexual individuals (p = .002 and p ≤ 0.001 among men and women, respectively) and reported significantly fewer years since AOD problem resolution compared to heterosexual individuals (p = .004 and p = .003 among men and women, respectively). Most notably, bisexual individuals, but not gay/lesbian individuals, reported significantly lower quality of life (QOL), happiness, self-esteem, and significantly higher distress compared to heterosexual individuals. Conclusion: Bisexual, but not monosexual, SM individuals in recovery from an AOD use disorder, were younger and reported worse psychosocial functioning than heterosexual individuals. Findings highlight significant differences between monosexual versus bisexual identified individuals with a notable disadvantage experienced by bisexual individuals. More needs to be learned about the challenges faced by bisexual individuals in recovery to better address their needs and support long-term AOD recovery.

America's perceptions of opioid related impairment: A national randomized study examining how different individuals may stigmatize addiction in response to different terminology.

INTRODUCTION: Prior research has found that different ways of describing opioid-related impairment influences the types and degrees of stigmatizing beliefs held by the American public. In this study we examined the extent to which different characteristics of the American public (i.e., age, gender, race/ethnicity, religiosity, sexual orientation, political affiliation, personal history of addiction/mental health problem) are associated with holding different types and degrees of stigmatizing beliefs when asked to consider someone treated for opioid-related impairment. We also assessed whether any observed differences in stigmatizing beliefs related to participant characteristics are dependent on how an opioid-impaired patient is described in terms of both the nature of the impairment (e.g., as a "chronically relapsing brain disease", "brain disease", "disease", "illness", "disorder", or "problem") as well as the gender of the depicted opioid-impaired person. METHODS: A nationally representative sample of the U.S. population (N = 3643) was randomized to one of six vignettes describing a patient being treated for opioid-related impairment that differed only in the way the impairment was described (as a "chronically relapsing brain disease", "brain disease", "disease", "illness", "disorder", or "problem"). Participants subsequently were asked to rate statements assessing five stigma dimensions (blame, prognostic pessimism, continuing care, dangerousness, and social distance). RESULTS: Several characteristics were associated with different types and higher levels of stigmatizing beliefs: older age, male gender, White race, heterosexual orientation, being religious, Republican political affiliation, and having no prior alcohol/drug or mental health problem history (ps < 0.001). With very few exceptions, the way the opioid-impairment was described or whether the depicted patient was a man or a woman did not influence the strength of these associations. CONCLUSIONS: Certain characteristics of members of the US population were associated with holding different types and degrees of stigmatizing attitudes when asked to consider someone receiving treatment for opioid-related impairment and these were largely unaffected by how the impairment was labeled or the opioid-impaired person's gender. Depending on the specific target of clinical and public health anti-stigma campaigns, both addiction terminology and the beliefs held by certain population sub-groups will need to be considered when creating opioid use disorder related anti-stigma campaigns.

Prevalence and correlates of 12-step and second-wave mutual-help attendance in a nationally representative US sample.

BACKGROUND: Mutual-help organizations (MHOs) are effective community-based, recovery support options for individuals with alcohol and other drug use disorders (i.e., substance use disorder; SUD). Greater understanding of second-wave MHOs, such as SMART Recovery, can help build on existing research that has focused primarily on 12-step MHOs, such as Alcoholics Anonymous, to inform scientific, practice, and policy recommendations. METHODS: We conducted a secondary analysis of the National Recovery Study, a representative sample of US adults who resolved a substance use problem (N = 1984). Using survey-weighted estimates, we examined descriptive statistics for any lifetime, weekly lifetime, and past 90-day MHO attendance; we compared rates of 12-step and second-wave MHO attendance over time by descriptively examining distributions for calendar year of the first meeting attended. We also used two logistic regression models to examine demographic, substance use, clinical, and recovery-related correlates of weekly lifetime attendance separately for 12-step (n = 692) and second-wave MHOs (n = 32). RESULTS: For any attendance, 41.4% attended a 12-step MHO and 2.9% a second-wave MHO; for weekly attendance, 31.9% attended a 12-step MHO, and 1.7% a second-wave MHO. Two-thirds (64%) of initial second-wave attendance occurred between 2006 and 2017 compared to 22% of initial 12-step attendance during this time frame. Significant correlates of weekly 12-step MHO attendance included histories of SUD treatment and arrest. Significant correlates of weekly second-wave MHO attendance included Black identity (vs. White) and history of SUD medication. CONCLUSIONS: Attendance at second-wave MHOs is far less common than 12-step MHOs, but appears to be on the rise. Observed correlates of second-wave MHO attendance should be replicated in larger second-wave MHO samples before integrating these findings into best practices. Enhanced linkages from clinical and criminal justice settings to both second-wave and 12-step groups may help to "broaden the base" of MHOs.

Disclosing Recovery: A pilot randomized controlled trial of a patient decision aid to improve disclosure processes for people in treatment for opioid use disorder.

INTRODUCTION: People engaged in treatment for opioid use disorder (OUD) report struggling with whether and how to disclose, or share information about their OUD history and/or treatment with others. Yet, disclosure can act as a gateway to re-establishing social connection and support during recovery. The current study describes a pilot randomized controlled trial of Disclosing Recovery: A Decision Aid and Toolkit, a patient decision aid designed to facilitate disclosure decisions and build disclosure skills. METHODS: Participants (n = 50) were recruited from a community-based behavioral health organization in 2021-2022 and randomized to receive the Disclosing Recovery intervention versus an attention-control comparator. They responded to surveys immediately after receiving the intervention as well as one month following the intervention at a follow-up appointment. Primary outcome analyses examined indicators of implementation of the intervention to inform a future efficacy trial. Secondary outcome analyses explored impacts of the intervention on the decision-making process, disclosure rates, and relationships. RESULTS: Participants were successfully recruited, randomized, and retained, increasing confidence in the feasibility of future efficacy trials to test the Disclosing Recovery intervention. Moreover, participants in the Disclosing Recovery intervention agreed that the intervention is acceptable, feasible, and appropriate. They additionally reported a higher quality of their decision-making process and decisions than participants in the comparator condition. At their follow-up appointment, participants with illicit opioid use who received the Disclosing Recovery intervention were less likely to disclose than those who received the comparator condition. Moreover, significant interactions between illicit opioid use and the intervention condition indicated that participants without illicit opioid use who received the Disclosing Recovery intervention reported greater closeness to and social support from their planned disclosure recipient than those who received the comparator condition. CONCLUSIONS: The Disclosing Recovery intervention appears to be an acceptable, feasible, and appropriate patient decision aid for addressing disclosure processes among people in treatment for OUD. Moreover, preliminary results suggest that it shows promise in improving relationship closeness and social support in patients without illicit opioid use. More testing is merited to determine the intervention's efficacy and effectiveness in improving relationship and treatment outcomes for people in treatment for OUD.

Coming of age in recovery: The prevalence and correlates of substance use recovery status among adolescents and emerging adults.

BACKGROUND AND AIMS: To date, no epidemiological survey has estimated the prevalence of adolescents identifying as being in recovery. This is necessary for planning and identifying the needs of youth with current and remitted substance use disorders. This study estimated the prevalence of recovery status in a large statewide epidemiological survey administered between January and March 2020. PARTICIPANTS: Participants were high school students in 9th through 12th grades throughout Illinois. MEASUREMENTS: Youth were asked if they were in recovery and if they had resolved problems with substances. Youth who reported recovery and problem resolving dual status (DS), recovery only (RO), and problem resolution only (PRO) were compared to propensity score matched control groups who reported neither status (neither/nor; NN). Outcomes included alcohol use, binge alcohol use, cannabis use, and prescription drug use in the past 30 days. FINDINGS: Prevalence estimates were 884 (1.4%) for DS, 1546 (2.5%) for PRO, and 1,811 (2.9%) for RO. Relative to propensity matched control samples, all three groups had significantly lower odds of prescription drug use. The PRO group had lower odds of past month cannabis use. There were no significant differences for either alcohol outcome. CONCLUSIONS: Prevalence estimates of youth in recovery are slightly lower than those of adults in recovery, and estimates should be replicated. Youth in recovery and those resolving problems have numerous behavioral health needs, and relative to matched controls, have even odds for past 30-day alcohol use. These findings compel us to further define recovery for adolescents and emerging adults to allow for improving treatments and epidemiological research.

A UK national study of prevalence and correlates of adopting or not adopting a recovery identity among individuals who have overcome a drug or alcohol problem.

BACKGROUND: The concept of recovery has increasingly become an organizing paradigm in the addiction field in the past 20 years, but definitions of the term vary amongst interested groups (e.g. researchers, clinicians, policy makers or people with lived experience). Although professional groups have started to form a consensus, people with lived experience of alcohol or drug (AOD) problems use the term in a different way, leading to confusion in policy making in the UK. Greater knowledge about the prevalence and correlates of adopting a recovery identity amongst those who have overcome an AOD problem would inform clinical, public health, and policy communication efforts. METHODS: We conducted a cross-sectional nationally representative survey of individuals resolving a significant AOD problem (n = 1,373). Weighted analyses estimated prevalence and tested correlates of label adoption. Qualitative analyses summarized reasons for adopting or not adopting a recovery identity. RESULTS: The proportion of individuals currently identifying as being in recovery was 52.4%, never in recovery 28.6%, and no longer in recovery 19.0%. Predictors of identifying as being in recovery included current abstinence from AOD, formal treatment, recovery support service or mutual-help participation, and history of being diagnosed with AOD or other psychiatric disorders. Qualitative analyses found themes around not adopting a recovery identity related to low AOD problem severity, viewing the problem as resolved, or having little difficulty in stopping. CONCLUSIONS: Despite increasing use of the recovery label and concept in clinical and policy contexts, many resolving AOD problems do not identify in this manner. These are most likely to be individuals with less significant histories of impairment secondary to AOD and who have not engaged with formal or informal treatment systems. The understanding of the term recovery in this UK population did not completely align with abstinence from alcohol or drugs.

Who affiliates with SMART recovery? A comparison of individuals attending SMART recovery, alcoholics anonymous, both, or neither.

BACKGROUND: Mutual-help organizations (MHOs) play a crucial role for many individuals with alcohol use disorder (AUD) or other substance use disorders in achieving stable remission. While there is now substantial research characterizing who uses 12-step MHOs, very little is known about who becomes affiliated with newer and rapidly growing MHOs, such as Self-Management and Recovery Training ("SMART" Recovery). More research could inform knowledge regarding who may be best engaged by these differing pathways. METHODS: We conducted a cross-sectional analysis of participants (N = 361) with AUD recruited mostly from the community who were starting a new recovery attempt and self-selected into one of four different recovery paths: (1) SMART Recovery ("SMART-only"; n = 75); (2) Alcoholics Anonymous ("AA-only"; n = 73); (3) Both SMART and AA ("Both"; n = 53); and (4) Neither SMART nor AA ("Neither"; n = 160). We compared the groups on demographics, clinical history, treatment and recovery support service use, and indices of functioning and well-being. We computed descriptives and conducted inferential analyses according to the data structure. RESULTS: Compared to study participants choosing AA-only or Both, SMART-only participants were more likely to be White, married, have higher income and more education, be full-time employed, and evince a pattern of lower clinical severity characterized by less lifetime and recent treatment and recovery support services usage, lower alcohol use intensity and fewer consequences, and less legal involvement. AUD symptom levels, lifetime psychiatric diagnoses, psychiatric distress, and functioning were similar across MHO-engaged groups. CONCLUSION: SMART Recovery appears to attract individuals with greater psychosocial stability and economic advantage and less severe histories of alcohol-related impairment and legal involvement. Findings suggest that certain aspects specific to the SMART Recovery group approach, format, and/or contents may appeal to individuals exhibiting this type of profile. As such, SMART appears to provide an additional resource that expands the repertoire of options for individuals with AUD who seek recovery.

Sequence tolerance of immunoglobulin variable domain framework regions to noncanonical intradomain disulfide linkages.

Most immunoglobulin (Ig) domains bear only a single highly conserved canonical intradomain, inter-ß-sheet disulfide linkage formed between Cys23-Cys104, and incorporation of rare noncanonical disulfide linkages at other locations can enhance Ig domain stability. Here, we exhaustively surveyed the sequence tolerance of Ig variable (V) domain framework regions (FRs) to noncanonical disulfide linkages. Starting from a destabilized VH domain lacking a Cys23-Cys104 disulfide linkage, we generated and screened phage-displayed libraries of engineered VHs, bearing all possible pairwise combinations of Cys residues in neighboring ß-strands of the Ig fold FRs. This approach identified seven novel Cys pairs in VH FRs (Cys4-Cys25, Cys4-Cys118, Cys5-Cys120, Cys6-Cys119, Cys22-Cys88, Cys24-Cys86, and Cys45-Cys100; the international ImMunoGeneTics information system numbering), whose presence rescued domain folding and stability. Introduction of a subset of these noncanonical disulfide linkages (three intra-ß-sheet: Cys4-Cys25, Cys22-Cys88, and Cys24-Cys86, and one inter-ß-sheet: Cys6-Cys119) into a diverse panel of VH, VL, and VHH domains enhanced their thermostability and protease resistance without significantly impacting expression, solubility, or binding to cognate antigens. None of the noncanonical disulfide linkages identified were present in the natural human VH repertoire. These data reveal an unexpected permissiveness of Ig V domains to noncanonical disulfide linkages at diverse locations in FRs, absent in the human repertoire, whose presence is compatible with antigen recognition and improves domain stability. Our work represents the most complete assessment to date of the role of engineered noncanonical disulfide bonding within FRs in Ig V domain structure and function.

Ligamentum teres cardiopexy for post vertical sleeve gastrectomy gastroesophageal reflux.

PURPOSE: Vertical sleeve gastrectomy (VSG) evolved in the early 2000s into the standalone weight loss procedure we see today. While numerous studies highlight VSG's durability for weight loss, and improvements co-morbidities such as type 2 diabetes mellitus and cardiovascular disease, patients with gastroesophageal reflux disease (GERD) have been counseled against VSG due to the concern for worsening reflux symptoms. When considering anti-reflux procedures, VSG patients are unable to undergo traditional fundoplication due to lack of gastric cardia redundancy. Magnetic sphincter augmentation lacks long-term safety data and endoscopic approaches have undetermined longitudinal benefits. Until recently, the only option for patients with a history of VSG with medically refractory GERD has been conversion to roux en Y gastric bypass (RNYGB), however, this poses other risks including marginal ulcers, internal hernias, hypoglycemia, dumping syndrome, and nutritional deficiencies. Given the risks associated with conversion to RNYGB, we have adopted the ligamentum teres cardiopexy as an option for patients with intractable GERD following VSG. METHODS: A retrospective chart review was conducted of patients who had prior laparoscopic or robotic VSG and subsequently GERD symptoms refectory to pharmacological management who underwent ligamentum teres cardiopexy between 2017 and 2022. Pre-operative GERD disease burden, intraoperative cardiopexy characteristics, post-operative GERD symptomatology and changes in H2 blocker or PPI requirements were reviewed. RESULTS: Of the study's 60 patients the median age was 50 years old, and 86% were female. All patients had a diagnosis of GERD through pre-operative assessments and were taking antisecretory medication. Of the 36 patients who have completed their one year follow up, 81% of patients had either a decrease in dosage or cessation of the antisecretory medication at one year following ligamentum teres cardiopexy. CONCLUSION: Ligamentum teres cardiopexy is a viable alternative to RNYGB in patients with a prior vertical sleeve gastrectomy with medical refractory GERD.

Virion glycosylation influences mycobacteriophage immune recognition.

Glycosylation of eukaryotic virus particles is common and influences their uptake, trafficking, and immune recognition. In contrast, glycosylation of bacteriophage particles has not been reported; phage virions typically do not enter the cytoplasm upon infection, and they do not generally inhabit eukaryotic systems. We show here that several genomically distinct phages of Mycobacteria are modified with glycans attached to the C terminus of capsid and tail tube protein subunits. These O-linked glycans influence antibody production and recognition, shielding viral particles from antibody binding and reducing production of neutralizing antibodies. Glycosylation is mediated by phage-encoded glycosyltransferases, and genomic analysis suggests that they are relatively common among mycobacteriophages. Putative glycosyltransferases are also encoded by some Gordonia and Streptomyces phages, but there is little evidence of glycosylation among the broader phage population. The immune response to glycosylated phage virions in mice suggests that glycosylation may be an advantageous property for phage therapy of Mycobacterium infections.

An investigation of SMART Recovery: protocol for a longitudinal cohort study of individuals making a new recovery attempt from alcohol use disorder.

INTRODUCTION: Alcohol use disorder (AUD) remains one of the most pervasive of all psychiatric illnesses conferring a massive health and economic burden. In addition to professional treatments to address AUD, mutual-help organisations such as Alcoholics Anonymous (AA) and newer entities like Self-Management and Recovery Training (SMART Recovery) play increasingly important roles in many societies. While much is known about the positive effects of AA, very little is known about SMART. Hence, this study seeks to estimate real-world patterns of utilisation and benefit from SMART Recovery as well as explore for whom (moderators) and how (mechanisms) SMART confers recovery benefits. METHODS AND ANALYSIS: Naturalistic, longitudinal, cohort study (n=368) of individuals with AUD recruited between February 2019 and February 2022, initiating a new recovery attempt who self-select into one of four groups at study entry: (1) SMART Recovery; (2) AA; (3) SMART+AA; (4) Neither SMART nor AA; (stratified by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) severity markers), with assessments conducted at intake, and 3 months, 6 months, 9 months, 12 months, 18 months and 24 months. Primary outcomes are: frequency of SMART and AA meetings attendance; per cent days abstinent and per cent days heavy drinking. Secondary outcomes include psychiatric distress; quality of life and functioning. Moderator variables include sex/gender; race/ethnicity; spirituality. Mediational variables include social networks; coping skills; self-efficacy; impulsivity. Multivariable regression with propensity score matching will test for patterns of attendance and effects of participation over time on outcomes and test for mechanisms and moderators. ETHICS AND DISSEMINATION: This study involves human participants and was approved by the Massachusetts General Hospital Institutional Review Board (Protocol #: 2017P002029/PHS). Results will be published in peer-reviewed journals and presented at conferences. REGISTRATION: This is a non-randomised, naturalistic, longitudinal, cohort study, and thus was not registered in advance. Results, therefore, should be considered exploratory.

A glyco-engineering approach for site-specific conjugation to Fab glycans.

Effective processes for synthesizing antibody-drug conjugates (ADCs) require: 1) site-specific incorporation of the payload to avoid interference with binding to the target epitope, 2) optimal drug/antibody ratio to achieve sufficient potency while avoiding aggregation or solubility problems, and 3) a homogeneous product to facilitate approval by regulatory agencies. In conventional ADCs, the drug molecules are chemically attached randomly to antibody surface residues (typically Lys or Cys), which can interfere with epitope binding and targeting, and lead to overall product heterogeneity, long-term colloidal instability and unfavorable pharmacokinetics. Here, we present a more controlled process for generating ADCs where drug is specifically conjugated to only Fab N-linked glycans in a narrow ratio range through functionalized sialic acids. Using a bacterial sialytransferase, we incorporated N-azidoacetylneuraminic acid (Neu5NAz) into the Fab glycan of cetuximab. Since only about 20% of human IgG1 have a Fab glycan, we extended the application of this approach by using molecular modeling to introduce N-glycosylation sites in the Fab constant region of other therapeutic monoclonal antibodies. We used trastuzumab as a model for the incorporation of Neu5NAz in the novel Fab glycans that we designed. ADCs were generated by clicking the incorporated Neu5NAz with monomethyl auristatin E (MMAE) attached to a self-immolative linker terminated with dibenzocyclooctyne (DBCO). Through this process, we obtained cetuximab-MMAE and trastuzumab-MMAE with drug/antibody ratios in the range of 1.3 to 2.5. We confirmed that these ADCs still bind their targets efficiently and are as potent in cytotoxicity assays as control ADCs obtained by standard conjugation protocols. The site-directed conjugation to Fab glycans has the additional benefit of avoiding potential interference with effector functions that depend on Fc glycan structure.