Psychometric Evaluation of an Adapted Short-Form Spirituality Scale in a Sample of Predominantly White Adults in an Inpatient Substance Use Disorder Treatment Program.

Spirituality is an important aspect of treatment and recovery for substance use disorders (SUDs), but ambiguities in measurement can make it difficult to incorporate as part of routine care. We evaluated the psychometric properties of an adapted short-form version of the Spirituality Scale (the Spirituality Scale-Short-Form; SS-SF) for use in SUD treatment settings. Participants were adult patients (N = 1,388; Mage = 41.23 years, SDage = 11.55; 68% male; 86% White) who entered a large, clinically mixed inpatient SUD treatment program. Factor analysis supported the two-dimensional structure, with factors representing Self-Discovery and Transcendent Connection. Tests of measurement invariance demonstrated that the scale was invariant across age and gender subgroups. The SS-SF exhibited convergent and concurrent validity via associations with participation in spiritual activities, hopefulness, life satisfaction, 12-step participation, and depressive symptoms. Finally, scores on the SS-SF were significantly higher at discharge compared to admission, demonstrating short-term sensitivity to change. These findings support use of the SS-SF as a concise, psychometrically sound measure of spirituality in the context of substance use treatment.

The Clinical Relevance of Impulsivity in Substance Use Disorder Treatment: Examining Within-Treatment Changes and Relationship to Psychiatric Symptoms and Cravings in a Large Inpatient Sample.

OBJECTIVE: Impulsivity is a multidimensional construct consistently associated with problematic substance use, but less is known about its relevance to clinical outcomes. The current study examined whether impulsivity changed over the course of addiction treatment and whether the changes were associated with changes in other clinical outcomes. METHOD: Participants were patients in a large inpatient addiction medicine program (N = 817; 71.40% male). Impulsivity was assessed using a self-report measure of delay discounting (i.e., overvaluation of smaller immediate rewards) and the UPPS-P Impulsive Behavior Scale, a self-report measure of impulsive personality traits. Outcomes were psychiatric symptoms including depression, anxiety, posttraumatic stress disorder, and drug cravings. RESULTS: Within-subjects analyses of variance revealed significant within-treatment changes in all UPPS-P subscales, all psychiatric indicators, and craving (ps < .005), but not delay discounting. Changes in all UPPS-P traits, except for sensation seeking, were significantly positively associated with changes in psychiatric symptoms and cravings over the course of treatment (ps < .01). CONCLUSIONS: These findings reveal that facets of impulsive personality change across addiction treatment and are generally related to positive changes in other clinically relevant outcomes. Evidence of change despite no explicit intervention targeting suggests that impulsive personality traits may be viable treatment targets in substance use disorder treatment.

Assessing the Financial Value of Decentralized Clinical Trials.

BACKGROUND: Deployment of remote and virtual clinical trial methods and technologies, referred to collectively as decentralized clinical trials (DCTs), represents a profound shift in clinical trial practice. To our knowledge, a comprehensive assessment of the financial net benefits of DCTs has not been conducted. METHODS: We developed an expected net present value (eNPV) model of the cash flows for new drug development and commercialization to assess the financial impact of DCTs. The measure of DCT value is the increment in eNPV that occurs, on average, when DCT methods are employed in comparison to when they are not. The model is populated with parameter values taken from published studies, Tufts CSDD benchmark data, and Medable Inc. data on DCT projects. We also calculated the return on investment (ROI) in DCTs as the ratio of the increment in eNPV to the DCT implementation cost. RESULTS: We found substantial value from employing DCT methods in phase II and phase III trials. If we assume that DCT methods are applied to both phase II and phase III trials the increase in value is $20 million per drug that enters phase II, with a seven-fold ROI. CONCLUSIONS: DCTs can provide substantial extra value to sponsors developing new drugs, with high returns to investment in these technologies. Future research on this topic should focus on expanding the data to larger datasets and on additional aspects of clinical trial operations not currently measured.

Characterizing Clinical Heterogeneity in a Large Inpatient Addiction Treatment Sample: Confirmatory Latent Profile Analysis and Differential Levels of Craving and Impulsivity.

Background: Individuals with substance use disorders (SUDs) have highly heterogeneous presentations and identifying more homogeneous subgroups may foster more personalized treatment. This study used SUD and other psychiatric indicators to characterize latent subgroups of patients in a large inpatient addiction treatment program. The resulting subgroups were then analyzed with respect to differences on clinically informative motivational mechanisms. Methods: Patients (n = 803) were assessed for severity of SUD (ie, alcohol use disorder, drug use disorder), post-traumatic stress disorder, anxiety disorders, and major depressive disorder. Confirmatory latent profile analysis (CLPA) was used to identify latent subgroups, hypothesizing 4 subgroups. Subgroups were then characterized with respect to multiple indicators of impulsivity (ie, delay discounting and impulsive personality traits via the UPPS-P) and craving. Results: The CLPA confirmed the hypothesized 4-profile solution according to all indicators (eg, entropy = 0.90, all posterior probabilities ⩾.92). Profile 1 (n = 229 [32.2%], 24.9% female, median age in range of 45-49) reflected individuals with high alcohol severity and low psychiatric severity (HAlc/LPsy). Profile 2 (n = 193 [27.1%], 29.3% female, median age in range of 35-39) reflected individuals with high drug and psychiatric severity (HDrug/HPsy). Profile 3 (n = 160 [22.5%], 37.6% female, median age in range of 45-49) reflected individuals with high alcohol severity and psychiatric severity (HAlc/HPsy). Profile 4 (n = 130 [18.3%], 19.4% female, median age in range of 35-39) reflected individuals with high drug severity and low psychiatric severity (HDrug/LPsy). Both high comorbid psychiatric severity subgroups exhibited significantly higher craving and facets of impulsivity. Conclusions: The results provide further evidence of 4 latent subgroups among inpatients receiving addiction treatment, varying by alcohol versus other drugs and low versus high psychiatric comorbidity. Furthermore, they reveal the highest craving and impulsivity in the high psychiatric comorbidity groups, suggesting targets for more intensive clinical intervention in these patients.

Health-related quality of life and assessment in patients with lower limb lymphoedema: a systematic review.

OBJECTIVE: To determine the impact of lower limb lymphoedema (LLL) on health-related quality of life (HRQoL), and to identify the methodologies used to assess HRQoL and their adherence to the World Health Organization (WHO)-recommended HRQoL dimensions. METHOD: A systematic review was used following the PRISMA guidance. Studies were eligible if they assessed HRQoL in adult patients with LLL. The search was conducted between September 2019 and February 2020 using CINAHL, PubMed, Scopus, EMBASE and the Cochrane Library database. Data were placed onto a pre-developed data extraction table and analysed using a narrative synthesis. Evidence-based Librarianship (EBL) was used for quality appraisal. RESULTS: A total of 18 studies were identified, among which 10 were cross-sectional and eight were longitudinal studies. Twelve HRQoL questionnaires were identified and the Lymphoedema Quality of Life tool (LYMQoL) was the most commonly used. All of the studies except one had an EBL validity score of ≥75%. Although LLL causes a considerable impairment in HRQoL, the findings varied across the studies. All the studies considered at least four of the six WHO recommended dimensions, with none considering the spirituality dimension. Furthermore, physical functioning and wellbeing were discovered to be the worst affected HRQoL dimensions. CONCLUSION: LLL adversely affects physical function, wellbeing and thus the HRQoL. The LYMQoL is the most commonly used questionnaire; despite this, all elements of the WHO recommendations were not captured in the included studies. However, accurate information on HRQoL indicating the impact of the disease on survivors' lives and complete wellbeing is needed to inform evidence-based decision-making. Furthermore, having a universally accepted, disease-specific methodology will facilitate comparison and contrasting of HRQoL in patients with LLL. DECLARATION OF INTEREST: The authors have no conflicts of interest.

Psychometric evaluation of the treatment entry questionnaire to assess extrinsic motivation for inpatient addiction treatment.

Introduction: Valid multi-faceted measurement of motivation for substance use disorder (SUD) treatment is needed to help inform treatment approaches and predict outcomes. This study examined evidence of validity for the Treatment Entry Questionnaire (TEQ-9). Methods: Data represented individuals entering inpatient SUD treatment (n = 1455). We used confirmatory factor analysis (CFA) to assess the three-factor structure of the TEQ-9 [identified (i.e., values/personally chooses treatment), introjected (i.e., internally controlled by guilt/shame) and external motivations (i.e., external pressure/demands)], and examined measurement invariance across gender, age, and ethno-racial identity. Correlation with readiness and confidence assessed convergent validity, while correlations with substance use problem severity and previous substance use treatment assessed meaningful group differences. Results: A three-factor structure was confirmed with all items loading significantly onto their respective factors (ps < 0.001). Each subscale demonstrated high internal consistency (Identified α = 0.90; Introjected α = 0.79; External α = 0.85). Each subscale demonstrated measurement invariance up to the scalar level across all sub-groups. Readiness, confidence, and substance use problem severity correlated as expected across various substances with the identified (rs = 0.098 - 0.262, ps < 0.05), and external (rs = -0.096 - -0.178, ps < 0.05) subscales. Additionally, the mean Identified subscale score was significantly higher among those who previously engaged in SUD treatment (p < 0.001). Findings for the Introjected subscale were more ambiguous. Conclusions: Findings provide evidence for factorial validity, measurement invariance, convergent validity and group differences of the TEQ-9 in a large clinically mixed inpatient SUD treatment population, providing further support of its clinical and research utility.

Using conventional and machine learning propensity score methods to examine the effectiveness of 12-step group involvement following inpatient addiction treatment.

BACKGROUND: Continuing care following inpatient addiction treatment is an important component in the continuum of clinical services. Mutual help, including 12-step groups like Alcoholics Anonymous, is often recommended as a form of continuing care. However, the effectiveness of 12-step groups is difficult to establish using observational studies due to the risks of selection bias (or confounding). OBJECTIVE: To address this limitation, we used both conventional and machine learning-based propensity score (PS) methods to examine the effectiveness of 12-step group involvement following inpatient treatment on substance use over a 12-month period. METHODS: Using data from the Recovery Journey Project - a longitudinal, observational study - we followed an inpatient sample over 12-months post-treatment to assess the effect of 12-step involvement on substance use at 12-months (n = 254). Specifically, PS models were constructed based on 34 unbalanced confounders and four PS-based methods were applied: matching, inverse probability weighting (IPW), doubly robust (DR) with matching, and DR with IPW. RESULTS: Each PS-based method minimized the potential of confounding from unbalanced variables and demonstrated a significant effect (p < 0.001) between high 12-step involvement (i.e., defined as having a home group; having a sponsor; attending at least one meeting per week; and, being involved in service work) and a reduced likelihood of using substances over the 12-month period (odds ratios 0.11 to 0.32). CONCLUSIONS: PS-based methods effectively reduced potential confounding influences and provided robust evidence of a significant effect. Nonetheless, results should be considered in light of the relatively high attrition rate, potentially limiting their generalizability.

Trends in youth cannabis use across cannabis legalization: Data from the COMPASS prospective cohort study.

Canada legalized recreational cannabis use for adults on October 17, 2018 with decision-makers emphasising the need to reduce cannabis use among youth. We sought to characterise trends of youth cannabis use before and after cannabis legalization by relying on a quasi-experimental design evaluating cannabis use among high school students in Alberta, British Columbia, Ontario, and Québec who participated in the COMPASS prospective cohort study. Overall trends in use were examined using a large repeat cross-sectional sample (n = 102,685) at two time points before legalization (16/17 and 17/18 school years) and one after (18/19 school year). Further differential changes in use among students affected by legalization were examined using three sequential four-year longitudinal cohorts (n = 5,400) of students as they progressed through high school. Youth cannabis use remains common with ever-use increasing from 30.5% in 2016/17 to 32.4% in 2018/19. In the repeat cross-sectional sample, the odds of ever use in the year following legalization were 1.05 times those of the preceding year (p = 0.0090). In the longitudinal sample, no significant differences in trends of cannabis use over time were found between cohorts for any of the three use frequency metrics. Therefore, it appears that cannabis legalization has not yet been followed by pronounced changes on youth cannabis use. High prevalence of youth cannabis use in this sample remains a concern. These data suggest that the Cannabis Act has not yet led to the reduction in youth cannabis use envisioned in its public health approach.

Non-cancer-related lower limb lymphoedema in complex decongestive therapy: the patient experience.

OBJECTIVE: Lymphoedema is a debilitating condition that results in the swelling of one or more limbs, leading to a significant impairment of mobility. From a psychosocial perspective, body image and quality of life (QoL) are also adversely affected. To date, non-cancer lymphoedema has been under-researched. The primary objectives of this study were to explore QoL and limb volume in patients with primary and secondary non-cancer-related lower limb lymphoedema during the intensive, maintenance and self-care phases of complex decongestive therapy over a 24-week period. Secondary objectives included exploring patients' experiences of living with lymphoedema and the challenges of self-care maintenance. METHOD: A sequential mixed methodology, using quantitative and qualitative methods, was used. The quantitative part of the study involved the use of tape measurements at 4cm intervals to ascertain limb volume alterations. Measurements were taken during the intensive phase at weeks 1, 2, 3 and 4; and during the maintenance phase at weeks 8, 16 and 24. QoL was measured using the lymphoedema QoL (LYMQOL) leg, at baseline and weeks 8 and 24. The qualitative part of the study involved the use of semi-structured interviews with patients at week 8. Interviews explored the experiences of patients living with lymphoedema and their experiences of complex decongestive therapy. RESULTS: A total of 20 patients were recruited, two male and 18 female, with a mean age of 58.8 years (standard deviation (SD): 16 years), and all receiving complex decongestive therapy. At baseline, for all patients, the mean QoL score was 4.3 (SD: 2.4); and 8 (SD: 1.5) after 8 weeks of complex decongestive therapy. Mean difference was 4.00 (95% confidence interval: 2.76-5.24; p=0.00001) indicating a positive treatment effect. Limb volume measurements demonstrated a reduction in oedema from baseline to week 8. However, there were fluctuations in limb volume over the maintenance period of four months after treatment as the patients endeavoured to engage in self-care. Analysis of the interviews identified themes pertaining to lack of knowledge of lymphoedema among health professionals, a negative impact of living with lymphoedema and the positive therapeutic effect of complex decongestive therapy. CONCLUSION: Lower limb lymphoedema is a chronic condition that impacts negatively on the individual. Complex decongestive therapy improves QoL and reduces oedema. However, given the fluctuations in oedema post-treatment, individuals need greater support to maintain active engagement in effective self-care strategies.

Evaluating the Associations Between Exposure to Tobacco Interventions During Inpatient Treatment and Substance Use Outcomes: Findings From a Natural Experiment.

OBJECTIVE: In this study, we took advantage of a natural experiment that occurred within a substance use disorders (SUD) treatment setting which first saw the implementation of an evidence-based practice (EBP) for tobacco cessation, followed by the implementation of a tobacco-free policy (TFP) that included a campus-wide tobacco ban. We sought to examine how implementation of the EBP and TFP was associated with substances use outcomes, in addition to tobacco use, up to 3-months posttreatment. METHODS: Data were collected from patients in a substance use disorders treatment program at baseline, discharge, 1-, and 3-months posttreatment. Using a quasi-experimental design and generalized estimating equations, we modelled how patients' (N = 480) exposure to one of 3 interventions (1: treatment as usual [TAU], 2: EBP, and 3: EBP + TFP) was associated with overall abstinence from tobacco, alcohol, and other substances over time. Measures of tobacco use frequency, amount, and quit attempts were also modelled among a sub-sample of participants who self-reported using tobacco before treatment. RESULT: Exposure to the EBP + TFP was associated with increased tobacco abstinence (odds ratio [OR] = 1.93, 95% confidence interval [CI] [1.29, 2.90]) over time, including decreases in tobacco use frequency (OR = 0.78, 95% CI [0.68, 0.89]) and amount (OR = 0.80, 95% CI [0.67, 0.96]), and increased in likelihood of making a quit attempt (OR = 1.75, 95% CI [1.10, 2.80]) compared to TAU. Exposure was not associated with alcohol and/or other substance use. CONCLUSIONS: Comprehensive tobacco interventions that include EBP + TFP can promote tobacco cessation and reduced tobacco use following inpatient SUD treatment, without adversely affecting the use of other substances.

Psychometric validation of an adaptation of the Penn Alcohol Craving Scale to assess aggregated drug craving.

PURPOSE: Clinicians need a broad spectrum measurement of psychoactive substance craving (i.e., alcohol and/or drug) to assess collective treatment effects, especially in the context of polysubstance use. In three separate studies, we investigated the psychometric properties of an adapted version of the Penn Alcohol Craving Scale (PACS), designed to measure broad range substance craving. DESIGN: In Study One, we examined the latent factor structure for craving, as well as concurrent validity with measures of frequency and severity of substance use. In Study Two, we examined the short-term test-retest reliability. In Study Three, we examined the long-term sensitivity to treatment effects at 12 month postdischarge. SETTING: An inpatient SUD program in Guelph, Ontario, Canada. PARTICIPANTS: Adult patients receiving treatment for SUD: Study One, n = 971; Study Two, n = 35; Study Three, n = 191. MEASUREMENTS: We used an adapted version of the PACS, termed the Aggregated Drug Craving Scale (ADCS), and measures of substance use frequency, severity, and abstinence. FINDINGS: In Study One, confirmatory factor analysis supported the unidimensional structure of the craving scale (CFI: 0.994, RMSEA: 0.071, SRMR: 0.010). In addition, statistically significant, medium effect size associations provided evidence of concurrent validity with measures of substance use frequency and severity (CFI = 0.992; RMSEA = 0.054; SRMR = 0.015). In Study Two, the ADCS demonstrated good agreement over two time points (ICC = 0.82), exhibiting acceptable short-term retest reliability. In Study 3, the mean craving score decreased significantly from 19.6 at baseline to 7.5 at 12-month follow-up (t = -18.48, p < 0.001), demonstrating an ability to detect long-term sensitivity to treatment effects (Cohen's d = -1.54). CONCLUSIONS: Together, these findings provide initial support for a concise, broad-spectrum measure of aggregated drug cravings among an SUD treatment population.

Survey by TEDDY European Network of Excellence for Paediatric Clinical Research demonstrates potential for Europe-wide trials.

AIM: The European Network of Excellence for Paediatric Clinical Research, known as the TEDDY Network, carried out a survey to determine the capacity and competence of paediatric centres to perform research studies. METHODS: A cross-sectional, web-based pilot survey was conducted from October 2016 to April 2017 with paediatric clinical research centres in 11 countries: Albania, Austria, Belgium, Denmark, Iceland, Ireland, Italy, Norway, Spain, Switzerland and the United Kingdom. All were registered with the TEDDY Network database. RESULTS: We approached 107 centres and 63 provided data on their experiences and expertise in paediatric clinical trials. Four groups of performance indicators were identified, referring to scientific experience, trial readiness, trial competence, regulatory issues, ethics and patients. Most centres were actively involved in paediatric clinical research: 53 centres (84.1%) had received funds for more than five paediatric studies in the last 5 years, and 42 (66.7%) had a specific clinical trial unit and dedicated study coordinators. We concluded that the European centres we studied had the capability and capacity to conduct paediatric trials, but there was still room for improvement, including enhanced collaboration. CONCLUSION: This pilot survey demonstrated that there is potential for performing paediatric trials across Europe, but improvements are possible.

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.

Keeping cool in the heat: Behavioral thermoregulation and body temperature patterns in wild vervet monkeys.

OBJECTIVES: Climate change is having a significant impact on biodiversity and increasing attention is therefore being devoted to identifying the behavioral strategies that a species uses to cope with climatic stress. We explore how wild vervet monkeys (Chlorocebus pygerythrus) respond to heat stress, and how behavioral adaptations are used to regulate body temperature. MATERIALS AND METHODS: We implanted wild vervet monkeys with temperature-sensitive data loggers and related the body temperature rhythms of these animals to their use of thermoregulatory behaviors. RESULTS: Environmental temperature had a positive effect on the mean, minima and maxima of daily body temperatures. Environmental temperature had a positive effect on the amount of time that vervet monkeys spent in the shade, and animals that spent more time in the shade had lower body temperature maxima. Drinking water did not have a proximate effect on body temperature, most likely a consequence of their regular access to drinking water. Body temperatures were observed to decrease after swimming events, but tended to return to pre-swim temperatures within 1 hr, suggesting a limited thermal benefit of this behavior. CONCLUSIONS: Our data support the view that vervet monkeys cope well in the heat, and use behavior as a means to aid thermoregulation. The ability of primates to be flexible in their use of thermoregulatory behaviors can contribute positively to their capacity to cope with environmental variability. However, given its broad effect on plant productivity and habitat loss, climate change is a major threat to species' biogeographical distribution and survival.

Evaluating the short-term impact of a tobacco-free policy in an inpatient addiction treatment setting.

PURPOSE: Tobacco use is highly prevalent within addiction treatment settings, despite the potential benefits that cessation may provide to patients' psychosocial functioning and overall sobriety. Moreover, tobacco cessation is often insufficiently addressed in addiction treatment programs, although evidence suggests that tobacco control policies, such as access to evidence-based treatment or tobacco-free policies, may be effective. The objective of our study was to evaluate the impact of the implementation of these two tobacco control policies in an inpatient addiction treatment centre. METHODS: Using a 3-group quasi-experimental design, we examined how the implementation of the Ottawa Model for Smoking Cessation (OMSC) and a subsequent campus-wide tobacco ban influenced patients' overall smoking status, frequency, amount used per day, and quit attempts during treatment, compared to usual care. Participants (N = 397) responded to a comprehensive questionnaire upon admission and discharge from an addiction treatment program. We used generalized linear mixed modelling to measure changes over time while accounting for relevant sociodemographic covariates. RESULTS: Patients exposed to a more comprehensive tobacco control environment (i.e., the OMSC, plus complete tobacco ban) were over 80% less likely to report having used tobacco during treatment, compared to patients exposed to usual care (AOR = 0.17, 95% CI [0.05-0.63]). Receiving treatment in this setting also contributed to a 35% decrease in the average number of days patients used tobacco compared to usual care (AOR = 0.65, 95% CI [0.53-0.98]), and a 27% decrease in the average number of cigarettes used per day compared to usual care (AOR = 0.73, 95% CI [0.58-0.93]). CONCLUSION: Comprehensive tobacco control policy interventions within inpatient addiction treatment hospitals promote tobacco cessation. Such interventions should include a combination of evidence-based treatment for patients and environmental restrictions to discourage tobacco use. The results of our study suggest that, within inpatient addiction treatment settings, use of the OMSC in combination with a campus-wide tobacco ban may be more effective than usual care or the OMSC alone.

Effects of 12-step mutual support and professional outpatient services on short-term substance use outcomes among adults who received inpatient treatment.

BACKGROUND: Continuing care is increasingly prioritized in the treatment of substance use disorders (SUDs). Ongoing engagement in continuing care, including mutual support (e.g., 12-step groups) and/or professional outpatient services, may enhance treatment outcomes and facilitate recovery. OBJECTIVE: This study investigates how engagement in 12-step mutual support and professional outpatient services is associated with short-term substance use outcomes in a sample of patients who completed inpatient SUDs treatment. METHODS: As part of the Recovery Journey Project - a longitudinal cohort study - participants completed questionnaires upon admission to an inpatient SUDs treatment program, and at 1- and/or 3-months post-discharge (n = 379). Baseline data were collected by self-administered, electronic questionnaires. Follow up data were collected by phone or email. Analyses involved multivariate Generalized Estimating Equations separately modelling self-reported abstinence and percent days abstinent (PDA) over the three time periods. RESULTS: Overall, rates of self-reported abstinence and PDA increased significantly from baseline to 1- and 3-months follow up. Engagement in 12-step activities (i.e., attended 30 meetings in 30 days, had a home group, had a sponsor, did service work) and professional outpatient substance use support were each significantly associated with abstinence and PDA. Participants who reported a higher degree of 12-step involvement (defined as engagement in more 12-step activities) were also more likely to report being abstinence and greater PDA. CONCLUSIONS: Engagement in continuing care, including 12-step activities and professional outpatient substance use support, was highly associated with substance use. Clinical teams should encourage participation in such activities to optimize treatment outcomes.

HLA Alleles Associated With Risk of Ankylosing Spondylitis and Rheumatoid Arthritis Influence the Gut Microbiome.

OBJECTIVE: HLA alleles affect susceptibility to more than 100 diseases, but the mechanisms that account for these genotype-disease associations are largely unknown. HLA alleles strongly influence predisposition to ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Both AS and RA patients have discrete intestinal and fecal microbiome signatures. Whether these changes are the cause or consequence of the diseases themselves is unclear. To distinguish these possibilities, we examined the effect of HLA-B27 and HLA-DRB1 RA risk alleles on the composition of the intestinal microbiome in healthy individuals. METHODS: Five hundred sixty-eight stool and biopsy samples from 6 intestinal sites were collected from 107 healthy unrelated subjects, and stool samples were collected from 696 twin pairs from the TwinsUK cohort. Microbiome profiling was performed using sequencing of the 16S ribosomal RNA bacterial marker gene. All subjects were genotyped using the Illumina CoreExome SNP microarray, and HLA genotypes were imputed from these data. RESULTS: Associations were observed between the overall microbial composition and both the HLA-B27 genotype and the HLA-DRB1 RA risk allele (P = 0.0002 and P = 0.00001, respectively). These associations were replicated using the stool samples from the TwinsUK cohort (P = 0.023 and P = 0.033, respectively). CONCLUSION: This study shows that the changes in intestinal microbiome composition seen in AS and RA are at least partially due to effects of HLA-B27 and HLA-DRB1 on the gut microbiome. These findings support the hypothesis that HLA alleles operate to cause or increase the risk of these diseases through interaction with the intestinal microbiome and suggest that therapies targeting the microbiome may be effective in preventing or treating these diseases.

Cannabidiol as a Novel Candidate Alcohol Use Disorder Pharmacotherapy: A Systematic Review.

There is substantial interest in the therapeutic potential of cannabidiol (CBD), a nonpsychoactive cannabinoid found in plants of the genus Cannabis. The goal of the current systematic review was to characterize the existing literature on this topic and to evaluate the credibility of CBD as a candidate pharmacotherapy for alcohol use disorder (AUD). Using a comprehensive search strategy, 303 unique potential articles were identified and 12 ultimately met criteria for inclusion (8 using rodent models, 3 using healthy adult volunteers, and 1 using cell culture). In both rodent and cell culture models, CBD was found to exert a neuroprotective effect against adverse alcohol consequences on the hippocampus. In rodent models, CBD was found to attenuate alcohol-induced hepatotoxicity, specifically, alcohol-induced steatosis. Finally, findings from preclinical rodent models also indicate that CBD attenuates cue-elicited and stress-elicited alcohol seeking, alcohol self-administration, withdrawal-induced convulsions, and impulsive discounting of delayed rewards. In human studies, CBD was well tolerated and did not interact with the subjective effects of alcohol. Collectively, given its favorable effects on alcohol-related harms and addiction phenotypes in preclinical models, CBD appears to have promise as a candidate AUD pharmacotherapy. This is further bolstered by the absence of abuse liability and its general tolerability. A clear limitation to the literature is the paucity of human investigations. Human preclinical and clinical studies are needed to determine whether these positive effects in model systems substantively translate into clinically relevant outcomes.

Ameliorating the adverse cardiorespiratory effects of chemical immobilization by inducing general anaesthesia in sheep and goats: implications for physiological studies of large wild mammals.

Chemical immobilization is necessary for the physiological study of large wild animals. However, the immobilizing drugs can adversely affect the cardiovascular and respiratory systems, yielding data that do not accurately represent the normal, resting state. We hypothesize that these adverse effects can be ameliorated by reversing the immobilizing agent while holding the animal under general anaesthesia. We used habituated sheep Ovis aries (N = 5, 46.9 ± 5.3 kg body mass, mean ± SEM) and goats Capra hircus (N = 4, 27.7 ± 2.8 kg) as ungulate models for large wild animals, and measured their cardiorespiratory function under three conditions: (1) mild sedation (midazolam), as a proxy for the normal resting state, (2) immobilization (etorphine and azaperone), and (3) general anaesthesia (propofol) followed by etorphine antagonism (naltrexone). Cardiac output for both sheep and goats remained unchanged across the three conditions (overall means of 6.2 ± 0.9 and 3.3 ± 0.3 L min-1, respectively). For both sheep and goats, systemic and pulmonary mean arterial pressures were significantly altered from initial midazolam levels when administered etorphine + azaperone, but those arterial pressures were restored upon transition to propofol anaesthesia and antagonism of the etorphine. Under etorphine + azaperone, minute ventilation decreased in the sheep, though this decrease was corrected under propofol, while the minute ventilation in the goats remained unchanged throughout. Under etorphine + azaperone, both sheep and goats displayed arterial blood hypoxia and hypercapnia (relative to midazolam levels), which failed to completely recover under propofol, indicating that more time might be needed for the blood gases to be adequately restored. Nonetheless, many of the confounding cardiorespiratory effects of etorphine were ameliorated when it was antagonized with naltrexone while the animal was held under propofol, indicating that this procedure can largely restore the cardiovascular and respiratory systems closer to a normal, resting state.

Scaling of morphology and ultrastructure of hearts among wild African antelope.

The hearts of smaller mammals tend to operate at higher mass-specific mechanical work rates than those of larger mammals. The ultrastructural characteristics of the heart that allow for such variation in work rate are still largely unknown. We have used perfusion-fixation, transmission electron microscopy and stereology to assess the morphology and anatomical aerobic power density of the heart as a function of body mass across six species of wild African antelope differing by approximately 20-fold in body mass. The survival of wild antelope, as prey animals, depends on competent cardiovascular performance. We found that relative heart mass (g kg-1 body mass) decreases with body mass according to a power equation with an exponent of -0.12±0.07 (±95% confidence interval). Likewise, capillary length density (km cm-3 of cardiomyocyte), mitochondrial volume density (fraction of cardiomyocyte) and mitochondrial inner membrane surface density (m2 cm-3 of mitochondria) also decrease with body mass with exponents of -0.17±0.16, -0.06±0.05 and -0.07±0.05, respectively, trends likely to be associated with the greater mass-specific mechanical work rate of the heart in smaller antelope. Finally, we found proportionality between quantitative characteristics of a structure responsible for the delivery of oxygen (total capillary length) and those of a structure that ultimately uses that oxygen (total mitochondrial inner membrane surface area), which provides support for the economic principle of symmorphosis at the cellular level of the oxygen cascade in an aerobic organ.