Adult self-reported childhood maltreatment types are associated with treatment satisfaction and alcohol relapse in patients with comorbid substance use and mental health disorders.

BACKGROUND AND OBJECTIVES: Individuals with comorbid substance use and mental health disorders (concurrent disorders; CD) report poor treatment outcomes, high prevalence of childhood maltreatment, and mostly negative experiences with treatment. No studies to date have examined childhood maltreatment and treatment outcomes in CD. This study investigated self-reported childhood maltreatment as it relates to treatment satisfaction and substance use relapse among CD patients. METHODS: The 258 CD inpatients completed a self-report questionnaire package, comprising the Childhood Trauma Questionnaire and the Inpatient Consumer Survey (ICS). Childhood maltreatment was assessed according to five subtypes and self-perceived treatment satisfaction was rated across six ICS domains. Psychiatric diagnoses, substance use status and relapse data were retrieved via patient medical charts. RESULTS: Emotional neglect was associated with lower ratings across all ICS domains and physical neglect was associated with a lower rating for 'outcome of care'. Childhood sexual abuse was associated with a greater likelihood of alcohol relapse. No other relationships were statistically significant. DISCUSSION AND CONCLUSIONS: The presence of childhood neglect (but not abuse) was more associated with overall treatment dissatisfaction, and sexual abuse alone increased the likelihood of alcohol relapse. These findings suggest some early adverse experiences in CD patients may increase negative experiences in treatment while others contribute to the risk of substance use. Broader longitudinal research is needed to examine the trajectory leading to negative outcomes. SCIENTIFIC SIGNIFICANCE: This is the first study to report differential patterns of association by type of childhood maltreatment on negative outcomes in treatment among CD patients.

What do we know about co-stimulatory and co-inhibitory immune checkpoint signals in ankylosing spondylitis?

Ankylosing spondylitis is the main entity of a family of inflammatory diseases affecting many musculoskeletal (sacroiliac joints, spine, and peripheral joints) and extra-musculoskeletal sites, termed spondyloarthritis. While it is debated whether disease onset is primarily driven by autoimmune or autoinflammatory processes, what is certain is that both innate and adaptive immune responses orchestrate local and systemic inflammation, which leads to chronic pain and immobility. Immune checkpoint signals are one key player in keeping the immune system in check and in balance, but their role in disease pathogenesis is still rather elusive. Therefore, we ran a MEDLINE search utilizing the PubMed platform for a variety of immune checkpoint signals in regard to ankylosing spondylitis. In this review, we summarize the experimental and genetic data available and evaluate the relevance of immune checkpoint signalling in the pathogenesis of ankylosing spondylitis. Markers such as PD-1 and CTLA-4 have been extensively studied and facilitate the concept of an impaired negative immune regulation in ankylosing spondylitis. Other markers are either neglected completely or insufficiently examined, and the data is conflicting. Still, some of those markers remain interesting targets to decipher the pathogenesis of ankylosing spondylitis and to develop new treatment strategies.

The effectiveness of oxytocin in the treatment of stimulant use disorders: a systematic review.

OBJECTIVES: The purpose of this review is to examine human study evidence on the effectiveness of oxytocin in this patient population. Despite stimulant use disorder being a major public health concern, there are no validated pharmacological treatments. Psychosocial interventions show limited effectiveness especially in the more severe cases of stimulant use disorder, whereas animal models suggest that oxytocin may be a useful treatment. METHODS: A literature search using Medline, Embase, and PsychInfo was undertaken. Search results were subsequently imported into Covidence to identify relevant studies. RESULTS: Six studies were included in this review, two of which were pilot studies. Although oxytocin was well tolerated across studies, no study showed a statistically significant reduction in reported cocaine use or cravings. One study suggested oxytocin increased the desire to use cocaine, although the population of participants should be taken into consideration. In contrast, one study showed a trend towards reduced self-reported cocaine use. CONCLUSION: Available research does not support the use of oxytocin in the management of stimulant use disorder; however, included studies are small in sample size and limited in number. There were several noteworthy findings unrelated to this review's primary and secondary outcomes, which are of interest and warrant further research. We provide suggestions for future studies in this area of research. Considering the limited data available at this time, further studies are required before any definitive conclusions can be made regarding the use of oxytocin in stimulant use disorder management.

Associations of the P300 Event-Related Potentials and Self-Reported Craving in Substance Use Disorders: A Systematic Review.

INTRODUCTION: The phenomenon of craving and attention bias towards drug cues is theorized to operate cooperatively, owing to the principles of associative learning. In this context, the conditioned response to drug-related stimuli activates reward mechanisms within the brain, consequently inducing craving and fostering the underlying mechanisms that contribute to relapse in individuals with substance use disorders. Multiple studies have assessed the relationship between attention to substance-related cues and subjective craving through electroencephalography (EEG), but their findings have yet to be synthesized and examined. This review summarizes the association between the amplitude of the P300 event-related potential (ERP) and substance use craving, compares discrepancies in results by type of substance, and discusses gaps in the literature to inform future research. METHODS: A systematic search was conducted on Embase, Web of Science, CINAHL, and PsychINFO databases. Studies were published in English and included peer-reviewed human research investigating the relationship between EEG P300 ERP and self-reported substance use craving. The included study samples comprised of in treatment or non-treatment-seeking participants who use substances. The primary outcomes of interest were those derived from inferential statistics assessing P300 amplitude and substance use craving. RESULTS: Ten studies were included in the final search and were organized by substance type: three alcohol, three cocaine, two tobacco, one heroin, and one cannabis. Results were mixed for alcohol and cocaine. Studies on tobacco, heroin, and cannabis use were congruent for associations between the P300 amplitude and craving. CONCLUSIONS: Overall findings are mixed between studies addressing the association of the EEG P300 amplitude and craving. These results should be considered in the context of the limited sample size, underpowered analyses, and methodological differences that potentially contribute to discrepancies in outcomes. Further research is required to assess the role of craving assessment, EEG methodology, and substance-related factors on the association between P300 amplitude and self-reported craving.

Sleep and Rest-Activity Rhythms in Recovering Patients with Severe Concurrent Mental and Substance Use Disorder: A Pilot Study.

Objective: Mental health and substance use disorders are commonly associated with disrupted sleep and circadian rest-activity rhythms. How these disorders in combination relate to sleep and circadian organization is not well studied. We provide here the first quantitative assessment of sleep and rest-activity rhythms in inpatients with complex concurrent disorders, taking into account categories of substance use (stimulant vs. stimulant and opioid use) and psychiatric diagnosis (psychotic disorder and mood disorder). We also explore how sleep and rest-activity rhythms relate to psychiatric functioning. Methods: A total of 44 participants (10 female) between the age of 20-60 years (median = 29 years) wore wrist accelerometers over 5-70 days and completed standardized questionnaires assessing chronotype and psychiatric functioning (fatigue, psychiatric symptom severity, and impulsiveness). To examine potential influences from treatment, we computed (1) length of stay; (2) days of abstinence from stimulants and opioids as a measure of withdrawal; and (3) a sedative load based on prescribed medications. Results: Participants exhibited a sustained excessive sleep duration, frequent nighttime awakenings, and advanced rest-activity phase related to sedative load. Sleep disruptions were elevated in participants with a history of opioid use. Patients with a psychotic disorder showed the longest sleep and most fragmented and irregular rest-activity patterns. Non-parametric circadian rhythm analysis revealed a high rhythm amplitude by comparison with population norms, and this was associated with greater psychiatric symptom severity. Psychiatric symptom severity was also associated with greater fatigue and later MCTQ chronotype. Conclusions: This pilot study provides initial information on the prevalence and severity of sleep and circadian rhythm disturbances in individuals with severe concurrent disorders. The results underline the need for further studies to start to understand the role of sleep in the disease and recovery process in this understudied population.

The relationship between outpatient service use and emergency department visits among people treated for mental and substance use disorders: analysis of population-based administrative data in British Columbia, Canada.

BACKGROUND: Research findings on the association between outpatient service use and emergency department (ED) visits for mental and substance use disorders (MSUDs) are mixed and may differ by disorder type. METHODS: We used population-based linked administrative data in British Columbia, Canada to examine associations between outpatient primary care and psychiatry service use and ED visits among people ages 15 and older, comparing across people treated for three disorder categories: common mental disorders (MDs) (depressive, anxiety, and/or post-traumatic stress disorders), serious MDs (schizophrenia spectrum and/or bipolar disorders), and substance use disorders (SUDs) in 2016/7. We used hurdle models to examine the association between outpatient service use and odds of any ED visit for MSUDs as well count of ED visits for MSUDs, stratified by cohort in 2017/8. RESULTS: Having had one or more MSUD-related primary care visit was associated with lower odds of any ED visit among people treated for common MDs and SUDs but not people treated for serious MDs. Continuity of primary care was associated with slightly lower ED use in all cohorts. One or more outpatient psychiatrist visits was associated with lower odds of ED visits among people treated for serious MDs and SUDs, but not among people with common MDs. CONCLUSION: Findings highlight the importance of expanded access to outpatient specialist mental health services, particularly for people with serious MDs and SUDs, and collaborative models that can support primary care providers treating people with MSUDs.

Prescription-related risk factors for opioid-related overdoses in the era of fentanyl contamination of illicit drug supply: A retrospective case-control study.

Background:We sought to quantify the association between clinical, physiological, and contextual factors and opioid-related overdose, specifically focusing on current and past use of select prescription medications. Methods: We conducted a case-control study of individuals who experienced a non-fatal opioid-related overdose between January 2015 and November 2016 in British Columbia, Canada. We matched 8,831 cases to 44,155 controls on birth year, sex, and local health area of residence and examined 5-year prescribing history for opioids for pain, medications for opioid use disorder (MOUD), benzodiazepines/z-drugs, and other psychoactive medications. Results: The overall prevalence of prescription opioid drug use was generally low in the study population. Cases had a relatively higher use of selected prescription medications, a higher physical and mental morbidity burden, and were less connected to health services compared with controls. For opioids for pain, current therapy was associated with experiencing an overdose (OR = 8.5, 95%CI: 7.3-10); history of long-term use had a stronger association than history of short-term use (OR = 2.9, 95%CI: 2.6-3.3 vs OR = 1.7, 95%CI: 1.5-1.8, respectively). While persons on MOUD were more likely to overdose compared to persons who were not on therapy (OR = 2.0, 95%CI 1.7-2.4), recent discontinuation of MOUD greatly increased the likelihood of overdose (OR = 25.6, 95%CI 17.5-37.4). Active therapy of benzodiazepines/z-drugs and other sedating medications also significantly increased the likelihood of overdose. Conclusions: While this study supports expansion of efforts to prevent overdoses among individuals actively using opioids for pain and improve retention among those on MOUD, it is also important to address other clinical, physiological, and contextual risk and protective factors to help curb the current overdose crisis.

Enzymatic Cß-H Functionalization of l-Arg and l-Leu in Nonribosomally Derived Peptidyl Natural Products: A Tale of Two Oxidoreductases.

Muraymycins are peptidyl nucleoside antibiotics that contain two Cß-modified amino acids, (2S,3S)-capreomycidine and (2S,3S)-ß-OH-Leu. The former is also a component of chymostatins, which are aldehyde-containing peptidic protease inhibitors that─like muraymycin─are derived from nonribosomal peptide synthetases (NRPSs). Using feeding experiments and in vitro characterization of 12 recombinant proteins, the biosynthetic mechanism for both nonproteinogenic amino acids is now defined. The formation of (2S,3S)-capreomycidine is shown to involve an FAD-dependent dehydrogenase:cyclase that requires an NRPS-bound pathway intermediate as a substrate. This cryptic dehydrogenation strategy is both temporally and mechanistically distinct in comparison to the biosynthesis of other capreomycidine diastereomers, which has previously been shown to proceed by Cß-hydroxylation of free l-Arg catalyzed by a member of the nonheme Fe2+- and α-ketoglutarate (αKG)-dependent dioxygenase family and (eventually) a dehydration-mediated cyclization process catalyzed by a distinct enzyme(s). Contrary to our initial expectation, the sole nonheme Fe2+- and αKG-dependent dioxygenase candidate Mur15 encoded within the muraymycin gene cluster is instead demonstrated to catalyze specific Cß hydroxylation of the Leu residue to generate (2S,3S)-ß-OH-Leu that is found in most muraymycin congeners. Importantly, and in contrast to known l-Arg-Cß-hydroxylases, the Mur15-catalyzed reaction occurs after the NRPS-mediated assembly of the peptide scaffold. This late-stage functionalization affords the opportunity to exploit Mur15 as a biocatalyst, proof of concept of which is provided.

Impact of opioid agonist treatment on mental health in patients with opioid use disorder: a systematic review and network meta-analysis of randomized clinical trials.

Background: There is a knowledge gap in systematic reviews on the impact of opioid agonist treatments on mental health.Objectives: We compared mental health outcomes between different opioid agonist treatments and placebo/waitlist, and between the different opioids themselves.Methods: This meta-analysis of randomized clinical trials (RCTs) was pre-registered at PROSPERO (CRD42018109375). Embase, MEDLINE, PsychInfo, CINAHL Complete, and Web of Science Core Collection were searched from inception to May 2020. RCTs were included if they compared opioid agonists with each other or with placebo/waitlist in the treatment of patients with opioid use disorder and reported at least one mental health outcome after 1-month post-baseline. Studies with psychiatric care, adjunct psychotropic medications, or unbalanced psychosocial services were excluded. The primary outcome was overall mental health symptomatology, e.g. Symptom Checklist 90 total score, between opioids and placebo/waitlist. Random effects models were used for all the meta-analyses.Results: Nineteen studies were included in the narrative synthesis and 15 in the quantitative synthesis. Hydromorphone, diacetylmorphine (DAM), methadone, slow-release oral morphine, buprenorphine, and placebo/waitlist were among the included interventions. Based on the network meta-analysis for primary outcomes, buprenorphine (SMD (CI95%) = -0.61 (-1.20, -0.11)), DAM (-1.40 (-2.70, -0.23)), and methadone (-1.20 (-2.30, -0.11)) were superior to waitlist/placebo on overall mental health. Further direct pairwise meta-analysis indicated that overall mental health improved more in DAM compared to methadone (-0.23 (-0.34, -0.13)).Conclusions: Opioid agonist treatments used for the treatment of opioid use disorder improve mental health independent of psychosocial services.

Psychiatry and the Opioid Crisis in Canada.

A position statement developed by the Canadian Psychiatric Association's Professional Standards and Practice Committee and approved by the CPA's Board of Directors on April 18, 2019.

Examining the Relationships between Cumulative Childhood Adversity and the Risk of Criminal Justice Involvement and Victimization among Homeless Adults with Mental Illnesses after Receiving Housing First Intervention.

OBJECTIVES: Exposure to adverse childhood experiences (ACEs) is associated with increased risk of criminal justice involvement and repeated victimization among homeless individuals. This study aimed to (1) examine whether the relationship between cumulative ACE score and odds of experiencing criminal justice involvement and victimization remains significant over time after receiving the Housing First (HF) intervention and (2) investigate the moderating effect of cumulative ACE score on the effectiveness of the HF intervention on the likelihood of experiencing these outcomes among homeless individuals with mental illnesses. METHODS: We used longitudinal data over the 2-year follow-up period from the At Home/Chez Soi demonstration project that provided HF versus treatment as usual (TAU) to homeless adults with mental illness in five Canadian cities (N = 1,888). RESULTS: In all 4 follow-up time points, the relationship between cumulative ACE score and both outcomes remained significant, regardless of study arm (HF vs. TAU) and other confounding factors. However, cumulative ACE score did not moderate intervention effects on odds of experiencing either outcome, suggesting that the effectiveness of HF versus TAU, with regard to the odds of being victimized or criminal justice involvement, did not differ by cumulative ACE scores over the course of study. CONCLUSIONS: Findings suggest that providing services for homeless individuals with mental illness should be trauma informed and include specialized treatment strategies targeting the experience of ACEs and trauma to improve their treatment outcomes. An intensive approach is required to directly address the problem of criminal justice involvement and victimization in these individuals.

Living With Dual Diagnosis and Homelessness: Marginalized Within a Marginalized Group.

Objective: Concurrent mental and substance use disorders or dual diagnosis are highly prevalent among individuals experiencing homelessness. Studies have indicated that dual diagnosis leads to poorer health outcomes and higher health service utilization among those affected. This study aims to estimate the prevalence of dual diagnoses among homeless populations in British Columbia (BC), Canada, and understand their characteristics and specific factors associated with dual diagnoses. Methods: The BC Health of the Homeless Survey is a cross-sectional study involving the homeless population of three cities in BC. The survey assessed addiction and concurrent disorders with standardized interviews-the Mini-International Neuropsychiatric Interview Plus, the Maudsley Addiction Profile, and the Brief Symptom Inventory-in a sample of 500 individuals who are homeless living in shelters or on the street. We characterized individuals after categorizing them into four groups: those without any current mental disorder, those with substance use disorders only, those with mental disorders only, and those with concurrent substance use and mental disorders. Focusing on the concurrent disorder group, we completed a multivariate analysis comparing individuals with dual diagnosis to those without concurrent disorders. Results: Consistent with previous studies, we found that individuals with dual diagnoses report more severe physical and psychological symptoms. Among the homeless, they were more likely to be Aboriginal and younger and more likely to not make it into a shelter. They also reported substantially more difficulties in getting the health care service that they need. Conclusions: Within this marginalized group, individuals with dual diagnosis were more likely to be from groups considered to be more vulnerable with more complex needs. They were having more problems accessing even basic support, such as shelters and health care. Without a systematic approach in providing appropriate care to individuals with dual diagnosis, the most vulnerable clients are not only the ones likely to suffer the most but also the ones having the most problems meeting their basic needs.

Predictors of Mental Health Recovery in Homeless Adults with Mental Illness.

For people with mental illness, experiences of homelessness can complicate mental health recovery processes. This study used longitudinal data from a randomized controlled trial of housing first (HF) to examine predictors of recovery among homeless people with mental illness. Findings showed that health and community predictors were most strongly associated with mental health recovery. Receipt of HF did not have any effect on changes in recovery scores at follow-up. Overall, the findings suggest that interventions aimed at preventing chronic homelessness, strengthening social networks and community involvement, and providing case management services will facilitate mental health recovery.

Childhood Trauma and Lifetime Traumatic Brain Injury Among Individuals Who Are Homeless.

OBJECTIVES: To study the association of childhood trauma and lifetime prevalence of traumatic brain injury (TBI) among individuals who are homeless. DESIGN: Cross-sectional survey. SETTING: Three cities in British Columbia, Canada. PARTICIPANTS: Five hundred individuals who are homeless and 19 years of age or older in 2009. MEASUREMENTS: Traumatic brain injury was identified with National Survey of Homeless Assistance Providers and Clients (NSHAPC) and childhood trauma using the Childhood Trauma Questionnaire-Short Form (CTQ-SF). The relationship between childhood trauma and TBI was explored using multivariable logistic regression approach, adjusting for age, gender, any psychiatric diagnosis (anxiety disorder, mood disorder, psychosis), alcohol dependence, and substance dependence. The effect of number of childhood trauma types on TBI was also explored using multiple variables logistic regression approach adjusting for the same covariates. RESULTS: The prevalence of TBI was 63.6% and childhood maltreatment was 87.7% among the sample population. During childhood of 487 participants included in the analysis, 57.7% experienced physical abuse, 62.8% physical neglect, 45.8% sexual abuse, 62.4% emotional abuse, and 55.2% emotional neglect. After adjustment, childhood trauma (adjusted odds ratio [aOR] = 2.26; 95% confidence interval [CI], 1.04-5.02), childhood physical abuse (aOR = 2.13; 95% CI, 1.19-3.87; n = 487), and childhood emotional abuse (aOR = 1.95; 95% CI, 1.09-3.51; n = 487) were significantly associated with history of TBI. After adjustment, having 4 different types of childhood trauma (aOR = 2.81; 95% CI, 1.11-7.31) was significantly associated with higher odds of reporting TBI history. CONCLUSIONS: Childhood trauma is significantly associated with lifetime prevalence of TBI in homeless populations in British Columbia, Canada, indicating an added level of vulnerability in this population. In addition, these findings suggest a potential role for childhood trauma prevention strategies and services mindful of the patients' history of trauma for this particularly vulnerable population.

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers.

The Gram-negative opportunistic pathogen Pseudomonas aeruginosa causes severe nosocomial infections. It uses quorum sensing (QS) to regulate and coordinate population-wide group behaviours in the infection process like concerted secretion of virulence factors. One very important signalling network is the Pseudomonas quinolone signal (PQS) QS. With the aim to devise novel and innovative anti-infectives, inhibitors have been designed to address the various potential drug targets present within pqs QS. These range from enzymes within the biosynthesis cascade of the signal molecules PqsABCDE to the receptor of these autoinducers PqsR (MvfR). This review shortly introduces P. aeruginosa and its pathogenicity traits regulated by the pqs system and highlights the published drug discovery efforts providing insights into the compound binding modes if available. Furthermore, suitability of the individual targets for pathoblocker design is discussed.

Chronic Pain Among Homeless Persons with Mental Illness.

OBJECTIVE: Chronic pain is an important public health issue. However, characteristics and needs of marginalized populations have received limited attention. Studies on prevalence and correlates of chronic pain among homeless persons are lacking. We assessed chronic pain among homeless persons with mental illness in the At Home/Chez Soi study. DESIGN: Cross-sectional data from a randomized controlled trial on homelessness and mental health. SETTING: Data collected between 2009 and 2013 in three Canadian cities. SUBJECTS: One thousand two hundred eighty-seven homeless persons with mental illness. METHODS: Data on chronic pain and utilization of prescribed and nonprescribed interventions was assessed using a chronic pain screening instrument. Mental illness was diagnosed with the Mini-International Neuropsychiatric Interview. RESULTS: Forty-three percent reported moderate to severe chronic pain, interfering with general daily activities (80%), sleep (78%), and social interactions (61%). Multivariate analysis indicated that increasing age and diagnoses of major depressive disorder, mood disorder with psychotic features, panic disorder, and post-traumatic stress disorder (PTSD) were independent predictors of chronic pain. Chronic pain was further associated with increased suicidality. Among participants reporting chronic pain, 64% had sought medical treatment and 56% treated pain with prescribed drugs, while 38% used illicit drugs for pain relief. CONCLUSIONS: Chronic pain is very common among homeless persons with mental illness and affects activities of daily living. Clinicians treating this population should be aware of the common connections between chronic pain, depression, panic disorder, PTSD, and substance use. While the data indicate the contribution of chronic pain to complex treatment needs, they also indicate a clear treatment gap.

Substance Use Among Homeless Individuals With Schizophrenia and Bipolar Disorder.

Mental illness and substance use are overrepresented within urban homeless populations. This paper compared substance use patterns between homeless individuals diagnosed with schizophrenia spectrum (SS) and bipolar disorders (BD) using the Mini-International Neuropsychiatric Interview. From a sample of 497 subjects drawn from Vancouver, Canada who participated in the At Home/Chez Soi study, 146 and 94 homeless individuals were identified as BD and SS, respectively. In the previous 12 months, a greater proportion of BD homeless reported greater use of cocaine (χ = 20.0, p = 0.000), amphetamines (χ = 13,8, p = 0.000), opiates (χ = 24.6, p = 0.000), hallucinogens (χ = 11.7, p = 0.000), cannabinoids (χ = 5.05, p = 0.034), and tranquilizers (χ = 7.95, p = 0.004) compared to SS. Cocaine and opiates were significantly associated with BD homeless (χ = 39.06, df = 2, p < 0.000). The present study illustrates the relationship between substance use and BD in a vulnerable urban population of homeless, affected by adverse psychosocial factors and severe psychiatric conditions.