Substance abuse by anaesthesiologists, shouldn't we do more?

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Chronic tobacco smoking, impaired reward-based decision-making, and role of insular cortex : a comparison between early-onset smokers and late-onset smokers

Funding: This study was supported by the University of St. Andrews Endowment fund.Introduction: The literature suggests that tobacco smoking may have a neurotoxic effect on the developing adolescent brain. Particularly, it may impair the decision-making process of early-onset smokers ( 0.05) in reward-based decision-making were detected between early-onset smokers and late-onset smokers. VBM results revealed early-onset smokers to present lower GM volume in the bilateral anterior insular cortex (AI) in comparison to late-onset smokers and lower WM volume in the right AI in comparison to late-onset smokers. Conclusion: Impairments in reward-based decision-making may not be affected by tobacco smoking initiation during early adolescence. Instead, lower GM and WM volume in the AI of early-onset smokers may underline a vulnerability to develop compulsive tobacco seeking and smoking behavior during adulthood.Publisher PDFPeer reviewe

Neuropsychological function as a result of chronic exposure to methadone and other opioids

It is increasingly recognised that chronic exposure to opioids has been associated with neuropsychological impairment during both active use and following a period of abstinence. The overall objective of this thesis was to review the relevant prior literature in a systematic manner and subsequently to describe the effects of chronic exposure to prescribed and illicit opioids using an ambispective cohort study design. A systematic literature review was conducted to identify if chronic (defined as a period for more than 3 months) exposure to opioids (prescribed and/or illicit) was associated with measurable neuropsychological deficits. This review was conducted accordingly to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. The results were subsequently described within three cognitive domains of intelligence, executive function and memory and learning. Out of a total of 905 articles extracted between 1964 and 2009, 49 articles were considered appropriate for selection and review. Studies of current and abstinent chronic opioid users (illicit heroin users, patients prescribed methadone for illicit opioid dependence and patients taking opioids as part of the management of chronic pain) have identified performance deficits in measures of executive functioning and memory. These have included impairments within the domains of cognitive and motor impulsivity, strategic planning, cognitive flexibility, attention and memory. However other studies found no clear deficits when comparing the performance of healthy controls. The literature suggested that these neuropsychological deficits may be subject to at least partial recovery following initiation of methadone or total withdrawal from any opioids.This review also highlighted several methodological issues that affect the reliability, validity and clinical relevance of the results obtained. Subsequently a two year ambispective cohort design study was conducted which tested representative opioid exposed participants and healthy controls. Cohorts of participants with validated histories of illicit heroin use (HEROIN, n=24), stabilised methadone maintenance (METHADONE, n=29), chronic opioid prescriptions for pain (CHRONIC PAIN, n=28) and controls (HEALTHY CONTROL, n=28) were recruited. The study was designed to test neuropsychological performance in the HEALTHY CONTROL and CHRONIC PAIN groups on one occasion; and for the HEROIN and METHADONE groups on three and two occasions respectively. The intention was to describe neuropsychological performance in the HEROIN group under conditions of stable illicit heroin use, in controlled opioid withdrawal and when subsequently stabilised on methadone. For the METHADONE group, participants were tested twice, six months apart, to test for changes induced by chronic exposure to methadone. Eligible, screened and consented individuals were tested on nine tests from the CANTAB test battery. Data were analysed using univariate or repeated measures ANCOVA with a between subjects factor of GROUP. Further a priori subgroup analyses were conducted using (1) a two-group factor reflecting DEPENDENCE status and (2) a two-group factor reflecting INJECTING status separately as between subject factors. The homogeneity of variance across groups in repeated-measures design ANCOVAs was assessed by the Mauchly Sphericity Test. NART, age in years, SIMD, total Fagerström score, years in education and past alcohol use in years were used as covariates. A significance level of p<0.01 was applied due to multiple testing, in addition to the post-hoc Bonferroni correction procedure. On the Cambridge Gambling Task (CGT), HEROIN users placed higher bets earlier and risked more. They also showed increased motor impulsivity, impaired strategic planning and visuospatial memory on the Affective Go-NoGo (AGN), Stockings of Cambridge (SOC), and Delayed Matching to Sample(DMS) respectively. METHADONE users deliberated longer and placed higher bets earlier on the CGT, but did not show a tendency to risk more. METHADONE users were also more inattentive and demonstrated poor strategic planning and visuospatial memory on the Spatial Span (SSP) task. The CHRONIC PAIN participants did not exhibit significant impairment in neuropsychological performance on all the CANTAB tasks. Participants from the HEROIN, METHADONE and CHRONIC PAIN groups did not present with impaired cognitive flexibility. Chronic opioid dependence is associated with neuropsychological impairment reflected in altered performance on measures of risk taking and strategic planning. These data support the hypothesis that these neuropsychological impairments reflect an underlying trait vulnerability to drug taking and/or dependence rather than an effect of chronic exposure to opioids. Notably, motor impulsivity and visuo-spatial memory in HEROIN users improved after three weeks stability with methadone. Methadone use seems to confer improvement in some aspects of neuropsychological performance following cessation of heroin and sustains other deficits during long term stable methadone treatment. Dependence and injecting status do not contribute to the causation or deterioration of the identified neuropsychological impairments. Further long term longitudinal studies to help elucidate cognitive endophenotypes responsible for the components in the initiation, continuation and deterioration of neuropsychological deficits present in an opioid dependent population is necessary.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Neuroanatomical correlates of impulsive choices and risky decision making in young chronic tobacco smokers : a voxel-based morphometry study

This study has been supported by a University of St. Andrews Endowment fund and by a self-funded PhD scholarship.Introduction : Impairments in the multifaceted neuropsychological construct of cognitive impulsivity are a main feature of chronic tobacco smokers. According to the literature, these cognitive impairments are relevant for the initiation andmaintenance of the smoking behavior. However, the neuroanatomical correlates of cognitive impulsivity in chronic smokers remain under-investigated. Methods : A sample of 28 chronic smokers (mean age = 28 years) not affectedby polysubstance dependence and 24 matched non-smoker controls was recruited. Voxel Based Morphometry (VBM) was employed to assess Gray Matter (GM) volume differences between smokers and non-smokers. The relationships between GM volume and behavioral manifestations of impulsive choices (5 trial adjusting delay discounting task, ADT-5) and risky decision making (Cambridge Gambling Task, CGT) were also investigated.  Results : VBM results revealed GM volume reductions in cortical and striatal brainregions of chronic smokers compared to non-smokers. Additionally, smokers showed heightened impulsive choices (p < 0.01, Cohen’s f = 0.50) and a riskier decision- making process (p < 0.01, Cohen’s f = 0.40) compared to non-smokers. GM volume reductions in the left Anterior Cingulate Cortex (ACC) correlated with impaired impulsive and risky choices, while GM volume reductions in the left Ventrolateral Prefrontal Cortex (VLPFC) and Caudate correlated with heightened impulsive choices. Reduced GM volume in the left VLPFC correlated with younger age at smoking initiation (mean = 16 years).  Conclusion : Smokers displayed significant GM volume reductions and related cognitive impulsivity impairments compared to non-smoker individuals. Longitudinal studies would be required to assess whether these impairments underline neurocognitive endophenotypes or if they are a consequence of tobacco exposure on the adolescent brain.Publisher PDFPeer reviewe

Early onset smoking theory of compulsivity development : a neurocognitive model for the development of compulsive tobacco smoking

Funding: This manuscript has been supported by a self-funded PhD scholarship and by a University of St Andrews endowment fund.According to the literature, individuals who start tobacco smoking during adolescence are at greater risk of developing severe tobacco addiction and a heavier smoking behaviour in comparison to individuals who uptake tobacco smoking during subsequent developmental stages. As suggested by animal models, this may be related to the unique neuroadaptive and neurotoxic effects of nicotine on adolescents’ fronto-striatal brain regions modulating cognitive control and impulsivity. Previous research has proposed that these neuroadaptive and neurotoxic effects may cause a heightened reward-oriented impulsive behaviour that may foster smoking relapses during quit attempts. However, developments in the field of Addiction Neuroscience have proposed drug addiction to represent a type of compulsive behaviour characterised by the persistent use of a particular drug despite evident adverse consequences. One brain region that has received increased attention in recent years and that has been proposed to play a central role in modulating such compulsive drug seeking and using behaviour is the insular cortex. Lesion studies have shown that structural damages in the insular cortex may disrupt the smoking behaviour, while neuroimaging studies reported lower Gray Matter volume in the anterior insular cortex of chronic smokers compared to non-smokers, in addition to correlations between Gray Matter volume in the anterior insular cortex and measures of compulsive cigarette smoking. Based on the finding of our recent study reporting early onset smokers (mean age at regular smoking initiation= 13.2 years) to display lower Gray Matter and White Matter volume in the anterior insular cortex compared to late onset smokers (mean age at regular smoking initiation=18.0 years), we propose that the anterior insular cortex may play a central role in mediating the association between smoking uptake during adolescence and smoking heaviness/tobacco addiction during adulthood.Publisher PDFPeer reviewe

Understanding fatal and non-fatal drug overdose risk factors : overdose risk questionnaire pilot study—validation

Data collection and analysis was supported by the Health Informatics Centre, Farr Institute, the University of Dundee. In addition, NHS Fife R&D, NHS Education for Scotland, and the Medical School of the University of St Andrews supported the project.Background: Drug overdoses (fatal and non-fatal) are among the leading causes of death in population with substance use disorders. The aim of the current study was to identify risk factors for fatal and non-fatal drug overdose for predominantly opioid-dependent treatment–seeking population. Methods: Data were collected from 640 adult patients using a self-reported 25-item Overdose Risk (OdRi) questionnaire pertaining to drug use and identified related domains. The exploratory factor analysis (EFA) was primarily used to improve the interpretability of this questionnaire. Two sets of EFA were conducted; in the first set of analysis, all items were included, while in the second set, items related to the experience of overdose were removed. Logistic regression was used for the assessment of latent factors’ association with both fatal and non-fatal overdoses. Results: EFA suggested a three-factor solution accounting for 75 and 97% of the variance for items treated in the first and second sets of analysis, respectively. Factor 1 was common for both sets of EFA analysis, containing six items (Cronbach’s α = 0.70) focusing around “illicit drug use and lack of treatment.” In the first set of analysis, Factors 2 (Cronbach’s α = 0.60) and 3 (Cronbach’s α = 0.34) were focusing around “mental health and emotional trauma” and “chronic drug use and frequent overdose” domains, respectively. The increase of Factor 2 was found to be a risk factor for fatal drug overdose (adjusted coefficient = 1.94, p = 0.038). In the second set of analysis, Factors 2 (Cronbach’s α = 0.65) and 3 (Cronbach’s α = 0.59) as well as Factor 1 were found to be risk factors for non-fatal drug overdose ever occurring. Only Factors 1 and 3 were positively associated with non-fatal overdose (one in a past year). Conclusion: The OdRi tool developed here could be helpful for clinical studies for the overdose risk assessment. However, integrating validated tools for mental health can probably help refining the accuracy of latent variables and the questionnaire’s consistency. Mental health and life stress appear as important predictors of both fatal and non-fatal overdoses.Publisher PDFPeer reviewe

Understanding the use of telemedicine across different Opioid Use Disorder (OUD) treatment models : a scoping review

Introduction The COVID-19 pandemic has instigated the development of telemedicine-mediated provision of medications for opioid use disorder such as buprenorphine and methadone, referred to as TMOUD in this study. As services start to return to pre-pandemic norms, there is a debate around the role of TMOUD as addition to or replacement of the conventional cascade of care for people with opioid use disorder (PWOUD). This scoping review is designed to characterize existing TMOUD services and provide insights to enable a more nuanced discussion on the role of telemedicine in the care of PWOUD. Methods The literature search was conducted in OVID Medline, CINAHL, and PsycINFO, from inception up to and including April 2023, using the Joanna Briggs Institute methodology for scoping reviews. The review considered any study design that detailed sufficient descriptive information on a given TMOUD service. A data extraction form was developed to collect and categorize a range of descriptive characteristics of each discrete TMOUD model identified from the obtained articles. Results A total of 45 articles met the inclusion criteria, and from this, 40 discrete TMOUD services were identified. In total, 33 services were US-based, three from Canada, and one each from India, Ireland, the UK, and Norway. Through a detailed analysis of TMOUD service characteristics, four models of care were identified. These were TMOUD to facilitate inclusion health, to facilitate transitions in care, to meet complex healthcare needs, and to maintain opioid use disorder (OUD) service resilience. Conclusions Characterizing TMOUD according to its functional benefits to PWOUD and OUD services will help support evidence-based policy and practice. Additionally, particular attention is given to how digital exclusion of PWOUD can be mitigated against.Publisher PDFPeer reviewe

Staff regard towards working with patients with co-morbid depression and substance misuse : an exploratory study

Funding: Funding was received from the European Commission (contract number 2005322).Background. Patients having co-morbid mental health and substance misuse experience poorer treatment outcomes than those treated for either condition alone. Studies suggest health professionals regard towards these patients is a factor. Aims. To compare regard towards patients with co-morbid depression and substance misuse across different health professions and services, relative to independent conditions (depression, diabetes, alcohol and/or drug misuse). Methods. A cross-sectional comparative exploratory study of regard towards five patient groups conducted on multi-disciplinary staff (general practitioners, psychiatrists, psychologists, nurses and social workers. Total n=113) in three Scottish NHS board regions-NHS Fife, Tayside and Forth Valley. Services from three main treatment entry points were recruited in each region - 10 primary care services (43.5%), 7 mental health (70%) and 4 specialist addiction (100%). Descriptive statistics were calculated for regard towards each patient group. Multifactorial between subjects ANOVA examined influences on Medical Condition Regard Scale (MCRS) scores. Results. Regard towards patients with co-morbid depression and substance misuse was frequently lower than towards patients with independent conditions. Male professionals held lower regard towards these patients than female (p=0.03). Addiction services held the highest regard and general practice lowest (p >0.001). Over-45‘s held the lowest regard towards these patients (p=0.02). Health professional’s satisfaction with working with these patients was also low (mean 1.98, sd 1.22) compared to other conditions. Conclusions. Regard towards patients with co-morbid depression and substance misuse is lower than either condition independently, particularly among older, male professionals and those in general practice.Publisher PDFPeer reviewe

Protracted abstinence in males with an opioid use disorder : partial recovery of nucleus accumbens function

Opioid use disorder (OUD) affects more than 27 million people globally accounting for more than 300,000 deaths annually. Protracted abstinence among individuals with OUD is rare due to a high relapse rate among those not receiving medications for OUD. Extensive preclinical studies form the basis of the allostasis theory, which proposes long lasting functional brain abnormalities that persist after opioid withdrawal and contribute to relapse. Few studies have tested the allostasis theory in humans using neuroimaging. Here we used fMRI and an instrumental learning task to test allostasis theory predictions (ATP) of functional abnormalities in both positive valence (PVS) and negative valence (NVS) accumbens systems in OUD patients with protracted abstinence (n=15), comparing them with OUD patients receiving methadone treatment (MT) (n=33), and with healthy controls (n=23). As hypothesized, protracted abstinence OUD patients showed incomplete recovery of nucleus accumbens function, as evidenced by blunted response to aversive events (NVS) during negative reinforcement, as observed in MT patients. In contrast, their accumbens response to rewarding events (PVS) during positive reinforcement was similar to that of controls and different to that in MT patients whose response was blunted. Protracted abstinence OUD patients also showed improvements in depression symptoms compared to MT patients. Residual depressive symptoms and pre-MT intravenous drug measures were associated with worse accumbens function in protracted abstinence. These results support the ATP of long lasting dysfunction of NVS after withdrawal and show preliminary evidence of recovery of PVS function with protracted withdrawal. Therapeutic strategies that target NVS may facilitate recovery.Publisher PDFPeer reviewe

Overdose alert and response technologies : state-of-the-art review

Funding: Technology Enabled Care program of the Scottish Government.Background: Drug overdose deaths, particularly from opioids, are a major global burden, with 128,000 deaths estimated in 2019. Opioid overdoses can be reversed through the timely administration of naloxone but only if responders are able to administer it. There is an emerging body of research and development in technologies that can detect the early signs of an overdose and facilitate timely responses. Objective: Our aim was to identify and classify overdose-specific digital technologies being developed, implemented, and evaluated. Methods: We conducted a “state-of-the-art review.” A systematic search was conducted in MEDLINE, Embase, Web of Science, Scopus, ACM, IEEE Xplore, and SciELO. We also searched references from articles and scanned the gray literature. The search included terms related to telehealth and digital technologies, drugs, and overdose and papers published since 2010. We classified our findings by type of technology and its function, year of publication, country of study, study design, and theme. We performed a thematic analysis to classify the papers according to the main subject. Results: Included in the selection were 17 original research papers, 2 proof-of-concept studies, 4 reviews, 3 US government grant registries, and 6 commercial devices that had not been named in peer-reviewed literature. All articles were published between 2017 and 2022, with a marked increase since 2019. All were based in or referred to the United States or Canada and concerned opioid overdose. In total, 39% (9/23) of the papers either evaluated or described devices designed to monitor vital signs and prompt an alert once a certain threshold indicating a potential overdose has been reached. A total of 43% (10/23) of the papers focused on technologies to alert potential responders to overdoses and facilitate response. In total, 48% (11/23) of the papers and 67% (4/6) of the commercial devices described combined alert and response devices. Sensors monitor a range of vital signs, such as oxygen saturation level, respiratory rate, or movement. Response devices are mostly smartphone apps enabling responders to arrive earlier to an overdose site. Closed-loop devices that can detect an overdose through a sensor and automatically administer naloxone without any external intervention are still in the experimental or proof-of-concept phase. The studies were grouped into 4 themes: acceptability (7/23, 30%), efficacy or effectiveness (5/23, 22%), device use and decision-making (3/23, 13%), and description of devices (6/23, 26%). Conclusions: There has been increasing interest in the research and application of these technologies in recent years. Literature suggests willingness to use these devices by people who use drugs and affected communities. More real-life studies are needed to test the effectiveness of these technologies to adapt them to the different settings and populations that might benefit from them.Publisher PDFPeer reviewe