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.

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.

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.

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.

Abstinence versus moderation recovery pathways following resolution of a substance use problem: Prevalence, predictors, and relationship to psychosocial well-being in a U.S. national sample.

BACKGROUND: Many people who report resolving an alcohol or other drug (AOD) problem continue some level of substance use. Little information exists, however, regarding the prevalence of this resolution pathway, or how continued substance use after resolving an AOD problem, relative to abstinence, relates to functioning, quality of life, and happiness (i.e., well-being). Greater knowledge of the prevalence and correlates of non-abstinent AOD problem resolution could inform public health messaging and clinical guidelines, while encouraging substance use goals likely to maximize well-being and reduce risks. METHODS: We analyzed data from a nationally representative sample of individuals who endorsed having resolved an AOD problem (N = 2002). Analyses examined: (1) The prevalence of various substance use statuses coded from lowest to highest risk: (a) continuous abstinence from all AOD since problem resolution; (b) current abstinence from all AOD with some use since problem resolution; (c) current use of a substance reported as a secondary substance; (d) current use of the individual's primary substance only; or, (e) current use of a secondary and primary substance; (2) relationships between substance use status and demographic, clinical, and service use history measures; and (3) the relationship between substance use status and well-being. Weighted, controlled, regression analyses examined the influence of independent variables on substance use status. RESULTS: (1) Prevalence: In this sample, 20.3% of patients endorsed continuous abstinence; 33.7% endorsed current abstinence; 21.0% endorsed current use of a secondary substance; 16.2% endorsed current use of a primary substance; and 8.8% endorsed current use of both a secondary and a primary substance. (2) Correlates: Lower-risk substance use status was associated with the initiation of regular substance use at an older age, more years since problem resolution, and fewer lifetime psychiatric diagnoses. (3) Well-Being: Controlling for pertinent confounds, lower-risk substance use status was independently associated with greater self-esteem, happiness, quality of life and functioning, and recovery capital, as well as less psychological distress. CONCLUSIONS: About half of Americans who self-identify as having resolved an AOD problem continue to use AOD in some form. It appears that, although for many abstinence is not necessary to overcome an AOD problem, it is likely to lead to better functioning and greater well-being. Further, people appear to gravitate toward abstinence/lower risk substance use with greater time since problem resolution.

Impacts of the COVID-19 public health restrictions on substance use, mental health, and psychosocial functioning among individuals with alcohol use disorder.

Background: The COVID-19 pandemic has been associated with major psychosocial disruptions and there is particular concern for individuals with substance use disorders.Objectives: This study characterized the psychosocial and experiential impacts of the pandemic on individuals seeking alcohol use disorder (AUD) recovery, including pandemic impacts on self-reported drinking, heavy drinking, tobacco, cannabis, and stimulant use.Methods: Participants were 125 AUD+ individuals (% males: 57.60; Mage = 49.11, SD = 12.13) reporting on substance use from January 1st-24th March, 2020 (pre-pandemic) and since the stay-at-home orders commenced, 24th March-June 28th 2020 (intra-pandemic). Within-subjects changes were examined and a latent profile analysis was performed to identify subgroups differentially impacted by the pandemic.Results: Large proportions reported psychosocial impacts of COVID-19, but drinking and other substance use did not reveal significant changes. Latent profile analyses revealed two subgroups: Profile 1 (n = 41/125), "Moderately Impacted") and Profile 2 (n = 84/125), "Severely Impacted"). Compared to the pre-pandemic period, the group that was moderately impacted by the pandemic exhibited significantly fewer heavy drinking days (p = .02) during the intra-pandemic period, but no other substance use changes. The group showing severe pandemic impacts did not exhibit changes in alcohol or other drug use but evidenced more severe anxiety and depression (ps < .001).Conclusions: We found heterogeneous subtypes of pandemic-related impacts in AUD recovery patients. There is need to provide psychosocial support to this particular population and further monitoring substance use and mental health.

Mutual Help Group Participation for Alcohol and Drug Problems: Uncovering Latent Subgroups.

Objective: This report aims to identify US mutual help group (MHG) participants' psycho-socio-behavioral profiles. Method: We used data from the 2015-2018 National Survey on Drug Use and Health and the sample included 1022 adults with past-year substance use disorders (SUD). We conducted a latent class analysis to identify subgroups of MHG participants and estimated multinomial logistic regression models to examine the associations between sociodemographic/intrapersonal characteristics and class membership. Results: Analyses identified three latent classes. Class 1 (Low-Risk group, 54%) reported low risks in all correlates except for serious psychological distress (SPD, 33%). Class 2 (Psychological Distress group, 30%) demonstrated high risks of major depressive episodes (86%) and SPD (93%). Class 3 (Criminal Justice System Involvement group, 16%) showed high involvement in arrests (100%) and drug-related arrests (67%) and moderate risks for SPD (54%) and behavioral problems, e.g., drug selling (46%) and theft (35%). Compared to Class 1, Class 2 was more likely to be female, out of the labor force, and to show high risk propensity, and Class 3 was more likely to have lower education and drug use disorders. Class 3 was also less likely to be older, belong to the "other" racial/ethnic category, have lower English proficiency, and report alcohol use disorder. Conclusions: The three subgroups of the US MHG participant population illustrate the complex and heterogeneous psycho-social-behavioral profiles of MHG participants with SUD. MHG referral's effectiveness may be augmented by tailoring it to the patient/client's specific psycho-socio-behavioral profile.

Identification of a novel N-linked glycan on the archaellins and S-layer protein of the thermophilic methanogen, Methanothermococcus thermolithotrophicus.

Motility in archaea is facilitated by a unique structure termed the archaellum. N-Glycosylation of the major structural proteins (archaellins) is important for their subsequent incorporation into the archaellum filament. The identity of some of these N-glycans has been determined, but archaea exhibit extensive variation in their glycans, meaning that further investigations can shed light not only on the specific details of archaellin structure and function, but also on archaeal glycobiology in general. Here we describe the structural characterization of the N-linked glycan modifications on the archaellins and S-layer protein of Methanothermococcus thermolithotrophicus, a methanogen that grows optimally at 65 °C. SDS-PAGE and MS analysis revealed that the sheared archaella are composed principally of two of the four predicted archaellins, FlaB1 and FlaB3, which are modified with a branched, heptameric glycan at all N-linked sequons except for the site closest to the N termini of both proteins. NMR analysis of the purified glycan determined the structure to be α-d-glycero-d-manno-Hep3OMe6OMe-(1-3)-[α-GalNAcA3OMe-(1-2)-]-ß-Man-(1-4)-[ß-GalA3OMe4OAc6CMe-(1-4)-α-GalA-(1-2)-]-α-GalAN-(1-3)-ß-GalNAc-Asn. A detailed investigation by hydrophilic interaction liquid ion chromatography-MS discovered the presence of several, less abundant glycan variants, related to but distinct from the main heptameric glycan. In addition, we confirmed that the S-layer protein is modified with the same heptameric glycan, suggesting a common N-glycosylation pathway. The M. thermolithotrophicus archaellin N-linked glycan is larger and more complex than those previously identified on the archaellins of related mesophilic methanogens, Methanococcus voltae and Methanococcus maripaludis This could indicate that the nature of the glycan modification may have a role to play in maintaining stability at elevated temperatures.

Methadone and buprenorphine discontinuation among postpartum women with opioid use disorder.

BACKGROUND: The postpartum year is a vulnerable period for women with opioid use disorder, with increased rates of fatal and nonfatal overdose; however, data on the continuation of medications for opioid use disorder on a population level are limited. OBJECTIVE: This study aimed to examine the effect of discontinuing methadone and buprenorphine in women with opioid use disorder in the year following delivery and determine the extent to which maternal and infant characteristics are associated with time to discontinuation of medications for opioid use disorder. STUDY DESIGN: This population-based retrospective cohort study used linked administrative data of 211,096 deliveries in Massachusetts between 2011 and 2014 to examine the adherence to medications for opioid use disorder. Individuals receiving medications for opioid use disorder after delivery were included in the study. Here, demographic, psychosocial, prenatal, and delivery characteristics are described. Kaplan-Meier survival analysis and Cox regression modeling were used to examine factors associated with medication discontinuation. RESULTS: A total of 2314 women who received medications for opioid use disorder at delivery were included in our study. Overall, 1484 women (64.1%) continued receiving medications for opioid use disorder for a full 12 months following delivery. The rate of continued medication use varied from 34% if women started on medications for opioid use disorder the month before delivery to 80% if the medications were used throughout pregnancy. Kaplan-Meier survival curves differed by maternal race and ethnicity (the 12-month continuation probability was .65 for White non-Hispanic women and .51 for non-White women; P<.001) and duration of use of prenatal medications for opioid use disorder (12-month continuation probability was .78 for women with full prenatal engagement and .60 and .44 for those receiving medications for opioid use disorder ≥5 months [but not throughout pregnancy] and ≤4 months prenatally, respectively; P<.001). In all multivariable models, duration of receipt of prenatal medications for opioid use disorder (≤4 months vs throughout pregnancy: adjusted hazard ratio, 3.26; 95% confidence interval, 2.72-3.91) and incarceration (incarceration during pregnancy or after delivery vs none: adjusted hazard ratio, 1.79; 95% confidence interval, 1.52-2.12) were most strongly associated with the discontinuation of medications for opioid use disorder. CONCLUSION: Almost two-thirds of women with opioid use disorder continued using medications for opioid use disorder for a full year after delivery; however, the rates of medication continuation varied significantly by race and ethnicity, degree of use of prenatal medications for opioid use disorder, and incarceration status. Prioritizing medication continuation across the perinatal continuum, enhancing sex-specific and family-friendly recovery supports, and expanding access to medications for opioid use disorder despite being incarcerated can help improve postpartum medication adherence.

Brain, behavioral, affective, and sex correlates of recovery from alcohol use disorders.

BACKGROUND: Recovery from alcohol use disorders (AUDs) consists of salutary changes in behavior and affect. While evidence suggests that recovery-related behavioral changes, such as abstinence, emerge in tandem with both neural and affective changes, the precise relationships among these changes are unknown. To understand these relationships, we examined associations between the duration of abstinence (DOA), affective states, and neuroimaging-based structural measures of the brain reward system (BRS) in AUD men (AUDM ) and AUD women (AUDW ). METHODS: Participants were community respondents from the Boston area comprising right-handed abstinent individuals with AUD (n = 60; 30 men) and controls without AUD (NC; n = 60; 29 men). Multivariate linear regressions compared short-/mid-term abstainers (≤5 years), long-term abstainers (>5 years), and the NC group on measures of BRS volume (3T magnetic resonance imaging scans) and measures of affect (Profile of Mood States [POMS]; Multiple Affect Adjective Check List [MAACL]; Hamilton Rating Scale for Depression [HRSD]). Analyses contrasted sex differences and accounted for age, education, drinking severity, and verbal IQ. RESULTS: Compared to the NC group, short-/mid-term abstainers exhibited larger posterior insular volume (total (ß = 0.019, 95% CI: 0.004, 0.034)), higher negative affect (POMS Mood Disturbance (ß = 27.8, 95% CI: 11.56, 44.04), and lower positive affect (POMS Vigor (ß = -4.89, 95% CI: -9.06, -0.72)). Compared to the NC group, Long-term abstainers exhibited significantly smaller volumes of aggregate anterior cingulate cortex (ß = -0.06, 95% CI: -0.113, -0.008) and higher HRSD scores (ß = 1.56, 95% CI: 0.14, 2.98). Relative to AUDM , AUDW exhibited significantly larger right anterior insular volumes (ß = 0.03, 95% CI: 0.01, 0.06) and significantly greater MAACL Positive Affect scores (ß = 7.56, 95% CI: 0.59, 11.55) in association with DOA. CONCLUSIONS: We found that differences in abstinence from alcohol were correlated with differences in both neural recovery and affective dimensions of recovery from AUDs. The observed sex differences extend evidence of dimorphic effects of AUDs and recovery on brain structure and function. Future longitudinal research will test inferences concerning the directionality of these relationships.

Feasibility of a Mobile Health App for Routine Outcome Monitoring and Feedback in SMART Recovery Mutual Support Groups: Stage 1 Mixed Methods Pilot Study.

BACKGROUND: Mutual support groups are an important source of long-term help for people impacted by addictive behaviors. Routine outcome monitoring (ROM) and feedback are yet to be implemented in these settings. SMART Recovery mutual support groups focus on self-empowerment and use evidence-based techniques (eg, motivational and behavioral strategies). Trained facilitators lead all SMART Recovery groups, providing an opportunity to implement ROM. OBJECTIVE: The aim of this stage 1 pilot study is to explore the feasibility, acceptability, and preliminary outcomes of a novel, purpose-built mobile health ROM and feedback app (SMART Track) in mutual support groups coordinated by SMART Recovery Australia (SRAU) over 8 weeks. METHODS: SMART Track was developed during phase 1 of this study using participatory design methods and an iterative development process. During phase 2, 72 SRAU group participants were recruited to a nonrandomized, prospective, single-arm trial of the SMART Track app. Four modes of data collection were used: ROM data directly entered by participants into the app; app data analytics captured by Amplitude Analytics (number of visits, number of unique users, visit duration, time of visit, and user retention); baseline, 2-, and 8-week follow-up assessments conducted through telephone; and qualitative telephone interviews with a convenience sample of study participants (20/72, 28%) and facilitators (n=8). RESULTS: Of the 72 study participants, 68 (94%) created a SMART Track account, 64 (88%) used SMART Track at least once, and 42 (58%) used the app for more than 5 weeks. During week 1, 83% (60/72) of participants entered ROM data for one or more outcomes, decreasing to 31% (22/72) by the end of 8 weeks. The two main screens designed to provide personal feedback data (Urges screen and Overall Progress screen) were the most frequently visited sections of the app. Qualitative feedback from participants and facilitators supported the acceptability of SMART Track and the need for improved integration into the SRAU groups. Participants reported significant reductions between the baseline and 8- week scores on the Severity of Dependence Scale (mean difference 1.93, SD 3.02; 95% CI 1.12-2.73) and the Kessler Psychological Distress Scale-10 (mean difference 3.96, SD 8.31; 95% CI 1.75-6.17), but no change on the Substance Use Recovery Evaluator (mean difference 0.11, SD 7.97; 95% CI -2.02 to 2.24) was reported. CONCLUSIONS: Findings support the feasibility, acceptability, and utility of SMART Track. Given that sustained engagement with mobile health apps is notoriously difficult to achieve, our findings are promising. SMART Track offers a potential solution for ROM and personal feedback, particularly for people with substance use disorders who attend mutual support groups. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12619000686101; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377336. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/15113.

One-Stop Shopping for Recovery: An Investigation of Participant Characteristics and Benefits Derived From U.S. Recovery Community Centers.

BACKGROUND: Recovery community centers (RCCs) are the "new kid on the block" in providing addiction recovery services, adding a third tier to the 2 existing tiers of formal treatment and mutual-help organizations (MHOs). RCCs are intended to be recovery hubs facilitating "one-stop shopping" in the accrual of recovery capital (e.g., recovery coaching; employment/educational linkages). Despite their growth, little is known about who uses RCCs, what they use, and how use relates to improvements in functioning and quality of life. Greater knowledge would inform the field about RCC's potential clinical and public health utility. METHODS: Online survey conducted with participants (N = 336) attending RCCs (k = 31) in the northeastern United States. Substance use history, services used, and derived benefits (e.g., quality of life) were assessed. Systematic regression modeling tested a priori theorized relationships among variables. RESULTS: RCC members (n = 336) were on average 41.1 ± 12.4 years of age, 50% female, predominantly White (78.6%), with high school or lower education (48.8%), and limited income (45.2% <$10,000 past-year household income). Most had either a primary opioid (32.7%) or alcohol (26.8%) problem. Just under half (48.5%) reported a lifetime psychiatric diagnosis. Participants had been attending RCCs for 2.6 ± 3.4 years, with many attending <1 year (35.4%). Most commonly used aspects were the socially oriented mutual-help/peer groups and volunteering, but technological assistance and employment assistance were also common. Conceptual model testing found RCCs associated with increased recovery capital, but not social support; both of these theorized proximal outcomes, however, were related to improvements in psychological distress, self-esteem, and quality of life. CONCLUSIONS: RCCs are utilized by an array of individuals with few resources and primary opioid or alcohol histories. Whereas strong social supportive elements were common and highly rated, RCCs appear to play a more unique role not provided either by formal treatment or by MHOs in facilitating the acquisition of recovery capital and thereby enhancing functioning and quality of life.

Psychometric Validation of the Brief Alcohol Social Density Assessment in an Adult Community Sample.

BACKGROUND: Individuals' social networks exert a strong influence on alcohol use, but valid assessment of network drinking behavior is typically lengthy and high in participant burden. The aim of this study was to validate the Brief Alcohol Social Density Assessment (BASDA), an efficient measure of perceived alcohol use within a person's social network, in a sample of adult drinkers from the general community. Specifically, the convergent, criterion-related, incremental validity and internal validity were investigated by examining the BASDA in relation to other established measures of drinking motives, weekly drinking level, and severity of involvement. METHODS: Participants were 903 (56% female) adults who reported drinking in the last year and who completed the BASDA, the Drinking Motives Questionnaire, the Daily Drinking Questionnaire, and the Alcohol Use Disorders Identification Test (AUDIT). RESULTS: Significant positive correlations were found between the BASDA and drinking motives, drinking quantity, and the AUDIT (rs = 0.21 to 0.51, ps < 0.001), providing support for convergent validity. There was a significantly higher BASDA score for those scoring at or above an AUDIT cutoff for hazardous drinking (p < 0.001), providing support for criterion-related validity. Finally, beyond motives and covariates, the BASDA was significantly associated with total AUDIT score (ΔR2  = 0.09, p < 0.001), indicating its additive contribution and providing support for incremental validity. Confirmatory factor analysis revealed excellent fit, and all items significantly loaded onto a single factor (p < 0.0001), providing evidence of internal validity. The resulting alcohol social density latent variable was significantly and robustly associated with drinks per week and AUDIT total score. CONCLUSIONS: These findings provide further support for the BASDA as a valid and efficient measure of social network alcohol density for understanding social influences on alcohol misuse.

Alcoholics Anonymous and other 12-step programs for alcohol use disorder.

BACKGROUND: Alcohol use disorder (AUD) confers a prodigious burden of disease, disability, premature mortality, and high economic costs from lost productivity, accidents, violence, incarceration, and increased healthcare utilization. For over 80 years, Alcoholics Anonymous (AA) has been a widespread AUD recovery organization, with millions of members and treatment free at the point of access, but it is only recently that rigorous research on its effectiveness has been conducted. OBJECTIVES: To evaluate whether peer-led AA and professionally-delivered treatments that facilitate AA involvement (Twelve-Step Facilitation (TSF) interventions) achieve important outcomes, specifically: abstinence, reduced drinking intensity, reduced alcohol-related consequences, alcohol addiction severity, and healthcare cost offsets. SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, CINAHL and PsycINFO from inception to 2 August 2019. We searched for ongoing and unpublished studies via ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 15 November 2018. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and bibliographies of included studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs), quasi-RCTs and non-randomized studies that compared AA or TSF (AA/TSF) with other interventions, such as motivational enhancement therapy (MET) or cognitive behavioral therapy (CBT), TSF treatment variants, or no treatment. We also included healthcare cost offset studies. Participants were non-coerced adults with AUD. DATA COLLECTION AND ANALYSIS: We categorized studies by: study design (RCT/quasi-RCT; non-randomized; economic); degree of standardized manualization (all interventions manualized versus some/none); and comparison intervention type (i.e. whether AA/TSF was compared to an intervention with a different theoretical orientation or an AA/TSF intervention that varied in style or intensity). For analyses, we followed Cochrane methodology calculating the standard mean difference (SMD) for continuous variables (e.g. percent days abstinent (PDA)) or the relative risk (risk ratios (RRs)) for dichotomous variables. We conducted random-effects meta-analyses to pool effects wherever possible. MAIN RESULTS: We included 27 studies containing 10,565 participants (21 RCTs/quasi-RCTs, 5 non-randomized, and 1 purely economic study). The average age of participants within studies ranged from 34.2 to 51.0 years. AA/TSF was compared with psychological clinical interventions, such as MET and CBT, and other 12-step program variants. We rated selection bias as being at high risk in 11 of the 27 included studies, unclear in three, and as low risk in 13. We rated risk of attrition bias as high risk in nine studies, unclear in 14, and low in four, due to moderate (> 20%) attrition rates in the study overall (8 studies), or in study treatment group (1 study). Risk of bias due to inadequate researcher blinding was high in one study, unclear in 22, and low in four. Risks of bias arising from the remaining domains were predominantly low or unclear. AA/TSF (manualized) compared to treatments with a different theoretical orientation (e.g. CBT) (randomized/quasi-randomized evidence) RCTs comparing manualized AA/TSF to other clinical interventions (e.g. CBT), showed AA/TSF improves rates of continuous abstinence at 12 months (risk ratio (RR) 1.21, 95% confidence interval (CI) 1.03 to 1.42; 2 studies, 1936 participants; high-certainty evidence). This effect remained consistent at both 24 and 36 months. For percentage days abstinent (PDA), AA/TSF appears to perform as well as other clinical interventions at 12 months (mean difference (MD) 3.03, 95% CI -4.36 to 10.43; 4 studies, 1999 participants; very low-certainty evidence), and better at 24 months (MD 12.91, 95% CI 7.55 to 18.29; 2 studies, 302 participants; low-certainty evidence) and 36 months (MD 6.64, 95% CI 1.54 to 11.75; 1 study, 806 participants; low-certainty evidence). For longest period of abstinence (LPA), AA/TSF may perform as well as comparison interventions at six months (MD 0.60, 95% CI -0.30 to 1.50; 2 studies, 136 participants; low-certainty evidence). For drinking intensity, AA/TSF may perform as well as other clinical interventions at 12 months, as measured by drinks per drinking day (DDD) (MD -0.17, 95% CI -1.11 to 0.77; 1 study, 1516 participants; moderate-certainty evidence) and percentage days heavy drinking (PDHD) (MD -5.51, 95% CI -14.15 to 3.13; 1 study, 91 participants; low-certainty evidence). For alcohol-related consequences, AA/TSF probably performs as well as other clinical interventions at 12 months (MD -2.88, 95% CI -6.81 to 1.04; 3 studies, 1762 participants; moderate-certainty evidence). For alcohol addiction severity, one study found evidence of a difference in favor of AA/TSF at 12 months (P < 0.05; low-certainty evidence). AA/TSF (non-manualized) compared to treatments with a different theoretical orientation (e.g. CBT) (randomized/quasi-randomized evidence) For the proportion of participants completely abstinent, non-manualized AA/TSF may perform as well as other clinical interventions at three to nine months follow-up (RR 1.71, 95% CI 0.70 to 4.18; 1 study, 93 participants; low-certainty evidence). Non-manualized AA/TSF may also perform slightly better than other clinical interventions for PDA (MD 3.00, 95% CI 0.31 to 5.69; 1 study, 93 participants; low-certainty evidence). For drinking intensity, AA/TSF may perform as well as other clinical interventions at nine months, as measured by DDD (MD -1.76, 95% CI -2.23 to -1.29; 1 study, 93 participants; very low-certainty evidence) and PDHD (MD 2.09, 95% CI -1.24 to 5.42; 1 study, 286 participants; low-certainty evidence). None of the RCTs comparing non-manualized AA/TSF to other clinical interventions assessed LPA, alcohol-related consequences, or alcohol addiction severity. Cost-effectiveness studies In three studies, AA/TSF had higher healthcare cost savings than outpatient treatment, CBT, and no AA/TSF treatment. The fourth study found that total medical care costs decreased for participants attending CBT, MET, and AA/TSF treatment, but that among participants with worse prognostic characteristics AA/TSF had higher potential cost savings than MET (moderate-certainty evidence). AUTHORS' CONCLUSIONS: There is high quality evidence that manualized AA/TSF interventions are more effective than other established treatments, such as CBT, for increasing abstinence. Non-manualized AA/TSF may perform as well as these other established treatments. AA/TSF interventions, both manualized and non-manualized, may be at least as effective as other treatments for other alcohol-related outcomes. AA/TSF probably produces substantial healthcare cost savings among people with alcohol use disorder.

Alcoholics Anonymous and 12-Step Facilitation Treatments for Alcohol Use Disorder: A Distillation of a 2020 Cochrane Review for Clinicians and Policy Makers.

AIMS: A recently completed Cochrane review assessed the effectiveness and cost-benefits of Alcoholics Anonymous (AA) and clinically delivered 12-Step Facilitation (TSF) interventions for alcohol use disorder (AUD). This paper summarizes key findings and discusses implications for practice and policy. METHODS: Cochrane review methods were followed. Searches were conducted across all major databases (e.g. Cochrane Drugs and Alcohol Group Specialized Register, PubMed, Embase, PsycINFO and ClinicalTrials.gov) from inception to 2 August 2019 and included non-English language studies. Randomized controlled trials (RCTs) and quasi-experiments that compared AA/TSF with other interventions, such as motivational enhancement therapy (MET) or cognitive behavioral therapy (CBT), TSF treatment variants or no treatment, were included. Healthcare cost offset studies were also included. Studies were categorized by design (RCT/quasi-experimental; nonrandomized; economic), degree of manualization (all interventions manualized versus some/none) and comparison intervention type (i.e. whether AA/TSF was compared to an intervention with a different theoretical orientation or an AA/TSF intervention that varied in style or intensity). Random-effects meta-analyses were used to pool effects where possible using standard mean differences (SMD) for continuous outcomes (e.g. percent days abstinent (PDA)) and the relative risk ratios (RRs) for dichotomous. RESULTS: A total of 27 studies (21 RCTs/quasi-experiments, 5 nonrandomized and 1 purely economic study) containing 10,565 participants were included. AA/TSF interventions performed at least as well as established active comparison treatments (e.g. CBT) on all outcomes except for abstinence where it often outperformed other treatments. AA/TSF also demonstrated higher health care cost savings than other AUD treatments. CONCLUSIONS: AA/TSF interventions produce similar benefits to other treatments on all drinking-related outcomes except for continuous abstinence and remission, where AA/TSF is superior. AA/TSF also reduces healthcare costs. Clinically implementing one of these proven manualized AA/TSF interventions is likely to enhance outcomes for individuals with AUD while producing health economic benefits.

How Many Recovery Attempts Does it Take to Successfully Resolve an Alcohol or Drug Problem? Estimates and Correlates From a National Study of Recovering U.S. Adults.

BACKGROUND: Alcohol and other drug (AOD) problems are commonly depicted as chronically relapsing, implying multiple recovery attempts are needed prior to remission. Yet, although a robust literature exists on quit attempts in the tobacco field, little is known regarding patterns of cessation attempts related to alcohol, opioid, stimulant, or cannabis problems. Greater knowledge of such estimates and the factors associated with needing fewer or greater attempts may have utility for health policy and clinical communication efforts and approaches. METHODS: Cross-sectional, nationally representative survey of U.S. adults (N = 39,809) who reported resolving a significant AOD problem (n = 2,002) and assessed on number of prior serious recovery attempts, demographic variables, primary substance, clinical histories, and indices of psychological distress and well-being. RESULTS: The statistical distribution of serious recovery attempts was highly skewed with a mean of 5.35 (SD = 13.41) and median of 2 (interquartile range [IQR] = 1 to 4). Black race, prior use of treatment and mutual-help groups, and history of psychiatric comorbidity were associated with higher number of attempts, and more attempts were associated independently with greater current distress. Number of recovery attempts did not differ by primary substance (e.g., opioids vs. alcohol). CONCLUSIONS: Estimates of recovery attempts differed substantially depending on whether the mean (5.35 recovery attempts) or median (2 recovery attempts) was used as the estimator. Implications of this are that the average may be substantially lower than anticipated because cultural expectations are often based on AOD problems being "chronically relapsing" disorders implicating seemingly endless tries. Depending on which one of these estimates is reported in policy documents or communicated in public health announcements or clinical settings, each may elicit varying degrees of help-seeking, hope, motivation, and the use of more assertive clinical approaches. The more fitting, median estimate of attempts should be used in clinical and policy communications given the distribution.

Risk Factors for Overdose in Young People Who Received Substance Use Disorder Treatment.

BACKGROUND AND OBJECTIVES: To identify substance and psychiatric predictors of overdose (OD) in young people with substance use disorders (SUDs) who received treatment. METHODS: We conducted a retrospective review of consecutive medical records of young people who were evaluated in a SUD program between 2012 and 2013 and received treatment. An independent group of patients from the same program who received treatment and had a fatal OD were also included in the sample. OD was defined as substance use associated with a significant impairment in level of consciousness without intention of self-harm, or an ingestion of a substance that was reported as a suicide attempt. t Tests, Pearson's χ2 , and Fisher's exact tests were performed to identify predictors of OD after receiving treatment. RESULTS: After initial evaluation, 127 out of 200 patients followed up for treatment and were included in the sample. Ten (8%) of these patients had a nonfatal OD. Nine patients who received treatment and had a fatal OD were also identified. The sample's mean age was 20.2 ± 2.8 years. Compared with those without OD, those with OD were more likely to have a history of intravenous drug use (odds ratio [OR]: 36.5, P < .001) and mood disorder not otherwise specified (OR: 4.51, P = .01). DISCUSSION AND CONCLUSIONS: Intravenous drug use and mood dysregulation increased risk for OD in young people who received SUD treatment. SCIENTIFIC SIGNIFICANCE: It is important to identify clinically relevant risk factors for OD specific to young people in SUD treatment due to the risk for death associated with OD. (Am J Addict 2019;28:382-389).

Using the text-messaging program SmokefreeTXT to support smoking cessation for nondaily smokers.

INTRODUCTION: Smoking cessation interventions for nondaily smokers are needed. The current study explores the fit of the text-messaging intervention SmokefreeTXT for nondaily smokers. METHODS: Adult nondaily smokers (N = 32; mean age = 35 ± 12, 64% female, 53% non-Hispanic White) were enrolled in SmokefreeTXT. SmokefreeTXT usage data were recorded passively, theorized mechanisms of change were assessed at baseline and 2, 6, and 12 weeks after the chosen quit day, and EMA protocols captured real-time cigarette reports at baseline, and during the first two weeks after the quit day. RESULTS: Most participants completed the SmokefreeTXT program and responded to system-initiated inquiries, but just-in-time interaction with the program was limited. In retrospective recall at treatment end, content of the text-messages was rated as "neutral" to "helpful." Within-person change was observed in theorized mechanisms, with less craving (p < 0.01), increased abstinence self-efficacy (external: p < 0.01; internal: p < 0.01), and poorer perceptions of pros of smoking (psychoactive benefits: p < 0.01, pleasure p < 0.01; and pros: p < 0.01) reported after SmokefreeTXT initiation compared to baseline. Exploratory analyses of real-time reports of smoking (225 cigarette reports in N = 17 who relapsed) indicated that cigarettes smoked in the first two weeks after quitting were more likely to occur to reduce craving (OR = 2.21[1.21-3.72]), and less likely to occur to socialize (OR = 0.06[0.01-0.24]), between 19:00 and 23:00 (OR = 0.34[0.17-0.66]), and on Saturdays (OR = 0.59[0.35-0.99]) than prior to quitting. CONCLUSIONS: While well accepted by nondaily smokers, SmokefreeTXT could potentially be improved by targeting cons of smoking, enhancing engagement with the just-in-time component of SmokefreeTXT, and tweaking the timing of text-messages.

A novel glycan modifies the flagellar filament proteins of the oral bacterium Treponema denticola.

While protein glycosylation has been reported in several spirochetes including the syphilis bacterium Treponema pallidum and Lyme disease pathogen Borrelia burgdorferi, the pertinent glycan structures and their roles remain uncharacterized. Herein, a novel glycan with an unusual chemical composition and structure in the oral spirochete Treponema denticola, a keystone pathogen of periodontitis was reported. The identified glycan of mass 450.2 Da is composed of a monoacetylated nonulosonic acid (Non) with a novel extended N7 acyl modification, a 2-methoxy-4,5,6-trihydroxy-hexanoyl residue in which the Non has a pseudaminic acid configuration (L-glycero-L-manno) and is ß-linked to serine or threonine residues. This novel glycan modifies the flagellin proteins (FlaBs) of T. denticola by O-linkage at multiple sites near the D1 domain, a highly conserved region of bacterial flagellins that interact with Toll-like receptor 5. Furthermore, mutagenesis studies demonstrate that the glycosylation plays an essential role in the flagellar assembly and motility of T. denticola. To our knowledge, this novel glycan and its unique modification sites have not been reported previously in any bacteria.

Beyond Abstinence: Changes in Indices of Quality of Life with Time in Recovery in a Nationally Representative Sample of U.S. Adults.

BACKGROUND: Alcohol and other drug (AOD) treatment and recovery research typically have focused narrowly on changes in alcohol/drug use (e.g., "percent days abstinent") with little attention on changes in functioning or well-being. Furthermore, little is known about whether and when such changes may occur, and for whom, as people progress in recovery. Greater knowledge would improve understanding of recovery milestones and points of vulnerability and growth. METHODS: National, probability-based, cross-sectional sample of U.S. adults who screened positive to the question, "Did you used to have a problem with alcohol or drugs but no longer do?" (Response = 63.4% from 39,809; final weighted sample n = 2,002). Linear, spline, and quadratic regressions tested relationships between time in recovery and 5 measures of well-being: quality of life, happiness, self-esteem, recovery capital, and psychological distress, over 2 temporal horizons: the first 40 years and the first 5 years, after resolving an AOD problem and tested moderators (sex, race, primary substance) of effects. Locally Weighted Scatterplot Smoothing regression was used to explore turning points. RESULTS: In general, in the 40-year horizon there were initially steep increases in indices of well-being (and steep drops in distress), during the first 6 years, followed by shallower increases. In the 5-year horizon, significant drops in self-esteem and happiness were observed initially during the first year followed by increases. Moderator analyses examining primary substance found that compared to alcohol and cannabis, those with opioid or other drugs (e.g., stimulants) had substantially lower recovery capital in the early years; mixed race/native Americans tended to exhibit poorer well-being compared to White people; and women consistently reported lower indices of well-being over time than men. CONCLUSIONS: Recovery from AOD problems is associated with dynamic monotonic improvements in indices of well-being with the exception of the first year where self-esteem and happiness initially decrease, before improving. In early recovery, women, certain racial/ethnic groups, and those suffering from opioid and stimulant-related problems appear to face ongoing challenges that suggest a need for greater assistance.