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.

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.

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.

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.

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.

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.

Genetic association of ankylosing spondylitis with TBX21 influences T-bet and pro-inflammatory cytokine expression in humans and SKG mice as a model of spondyloarthritis.

OBJECTIVES: Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthropathy. Inflammation in AS is poorly understood. TBX21 encodes T-bet, a transcription factor, lying within a locus with genome-wide significant association with AS. T-bet is implicated in innate and adaptive immunity. However, the role of T-bet in AS pathogenesis is unclear. METHODS: We assessed the importance of T-bet in disease development and progression in peripheral blood mononuclear cells from 172 AS cases and 83 healthy controls carrying either risk or protective alleles of the peak AS-associated TBX21 single nucleotide polymorphism. Kinetics and localisation of T-bet expression in the SKG mouse model of spondyloarthropathy was examined, along with the impact of Tbx21 knockout on arthritis development in SKG mice. RESULTS: Patients with AS had higher T-bet expression than healthy individuals, driven predominantly by natural killer and CD8+ T cells, with expression levels in CD8+ T cells completely distinguishing AS cases from healthy controls. T-bet expression was increased in AS cases carrying risk compared with protective alleles of rs11657479. In curdlan-treated SKG mice, T-bet expression increased early after disease initiation and persisted throughout the course of disease. There was marked reduction in gut and peripheral joint inflammation, and less IFNγ-producing and IL-17-producing CD8+ T cells, in Tbx21-/- compared with wild-type SKG mice. CONCLUSIONS: AS-associated variants in TBX21 influence T-bet expression. T-bet+ innate and adaptive immune cells have altered IL-17 and IFNγ, and early activation marker CD69 expression than T-bet cells. This indicates that T-bet is a major component of inflammatory pathways of spondyloarthropathy in humans and mice.

Functional Genomics and Its Bench-to-Bedside Translation Pertaining to the Identified Susceptibility Alleles and Loci in Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a highly heritable disease for which there is a great unmet need for improved therapies. Genetics research has identified several major pathways involved in the disease, from which treatments have either now entered clinical practice or are in development. In particular, therapies targeting the IL-23 pathway were repositioned for use in AS following the discovery of multiple genes in the pathway as determinants of AS risk. Discovery of the association of aminopeptidase genes with AS, and subsequently with psoriasis, inflammatory bowel disease and other conditions, has triggered research into therapies targeting this pathway. The AS-genetic associations point to involvement of gut mucosal immunity in driving disease, and metagenomic studies have provided strong support that AS is a disease driven by interaction between the gut microbiome and host immune system, providing a rationale for the exploration of gut-targeted therapies for the disease.

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.

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.

Effectiveness of pharmacist counseling combined with nicotine replacement therapy: a pragmatic randomized trial with 6,987 smokers.

UNLABELLED: Pharmacists may be effective health care practitioners to deliver smoking cessation interventions. This paper examines the short-term outcomes of smokers randomized to one of two models of a pharmacist-led smoking cessation intervention. METHODS: An open-label pragmatic randomized trial compared two models of a pharmacist-led behavioral intervention [Group A (3-sessions) vs. Group B (1-session)] in conjunction with 5 weeks of nicotine replacement therapy (NRT). Ninety-eight pharmacies in Ontario, Canada delivered the intervention. Baseline demographic and smoking behavior data were recorded, as were intervention characteristics. Self-reported, 7-day point prevalence quit rates were obtained 5-week postintervention start date. RESULTS: 6,987 individuals participated; 51.4% (n = 3588) randomized to Group A; 48.6% (n = 3399) to Group B. Approximately, 50% of Group A participants completed all three sessions. Quit rates were significantly higher among Group A, 3-session completers (27.7%; n = 478) compared to Group B participants (18.0%; n = 604). Multivariable results suggest that even when controlling for possible confounders and clustering across pharmacies, Group A participants who completed all three sessions were more likely to quit compared to Group B [OR = 1.72 (95% CI: 1.53, 1.94)]. CONCLUSIONS: Cessation outcomes are higher among participants completing three intervention sessions compared to one session; however, many do not return for follow-up sessions.

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.

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.

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.

Lateralization of the central circadian pacemaker output: a test of neural control of peripheral oscillator phase.

To evaluate the contribution of neural pathways to the determination of the circadian oscillator phase in peripheral organs, we assessed lateralization of clock gene expression in Syrian hamsters induced to split rhythms of locomotor activity by exposure to constant light. We measured the ratio of haPer1, haPer2, and haBmal1 mRNA on the high vs. low (H/L) side at 3-h intervals prior to the predicted activity onset (pAO). We also calculated expression on the sides ipsilateral vs. contralateral (I/C) to the side of the suprachiasmatic nucleus (SCN) expressing higher haPer1. The extent of asymmetry in split hamsters varied between specific genes, phases, and organs. Although the magnitude of asymmetry in peripheral organs was never as great as that in the SCN, we observed significantly greater lateralization of clock gene expression in the adrenal medulla and cortex, lung, and skeletal muscle, but not in liver or kidney, of split hamsters than of unsplit controls. We observed fivefold lateralization of expression of the clock-controlled gene, albumin site D-element binding protein (Dbp), in skeletal muscle (H/L: 10.7 +/- 3.7 at 3 h vs. 2.2 +/- 0.3 at 0 h pAO; P = 0.03). Furthermore, tyrosine hydroxylase expression was asymmetrical in the adrenal medulla of split (H/L: 1.9 +/- 0.5 at 0 h) vs. unsplit hamsters (1.2 +/- 0.04; P < 0.05). Consistent with a model of neurally controlled gene expression, we found significant correlations between the phase angle between morning and evening components (psi(me)) and the level of asymmetry (H/L or I/C). Our results indicate that neural pathways contribute to, but cannot completely account for, SCN regulation of the phase of peripheral oscillators.