Comprehensive Glycomic and Proteomic Analysis of Mouse Striatum and Lateral Hypothalamus Following Repeated Exposures to Cocaine or Methamphetamine.

Substance use disorder is a major concern, with few therapeutic options. Heparan sulfate (HS) and chondroitin sulfate (CS) interact with a plethora of growth factors and their receptors and have profound effects on cellular signaling. Thus, targeting these dynamic interactions might represent a potential novel therapeutic modality. In the present study, we performed mass spectrometry-based glycomic and proteomic analysis to understand the effects of cocaine and methamphetamine (METH) on HS, CS, and the proteome of two brain regions critically involved in drug addiction: the lateral hypothalamus and the striatum. We observed that cocaine and METH significantly alter HS and CS abundances as well as sulfate contents and composition. In particular, repeated METH or cocaine treatments reduced CS 4-O-sulfation and increased CS 6-O-sulfation. Since C4S and C6S exercise differential effects on axon growth, regeneration, and plasticity, these changes likely contribute to drug-induced neural plasticity in these brain regions. Notably, we observed that restoring these alterations by increasing CS 4-0 levels in the lateral hypothalamus by adeno-associated virus delivery of an shRNA to arylsulfatase B (N-acetylgalactosamine-4-sulfatase) ameliorated anxiety and prevented the expression of preference for cocaine in a novelty induced conditioned place preference test during cocaine withdrawal. Finally, proteomics analyses revealed a number of aberrant proteins in METH- and cocaine-treated versus saline-treated mice, including myelin proteolipid protein, calcium/calmodulin-dependent protein kinase type II subunit alpha, synapsin-2, tenascin-R, calnexin, annexin A7, hepatoma-derived growth factor, neurocan, and CSPG5, and oxidative phosphorylation among the top perturbed pathway. Taken together, these data support the role of HS, CS, and associated proteins in stimulants abuse and suggest that manipulation of HSPGs can represent a novel therapeutic strategy.

A high-affinity cocaine binding site associated with the brain acid soluble protein 1.

Cocaine exerts its stimulant effect by inhibiting dopamine (DA) reuptake, leading to increased dopamine signaling. This action is thought to reflect the binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share cocaine's behavioral actions. Further, recent reports show more potent actions of the drug, implying the existence of a high-affinity receptor for cocaine. We now report high-affinity binding of cocaine associated with the brain acid soluble protein 1 (BASP1) with a dissociation constant (Kd) of 7 nM. Knocking down BASP1 in the striatum inhibits [3H]cocaine binding to striatal synaptosomes. Depleting BASP1 in the nucleus accumbens but not the dorsal striatum diminishes locomotor stimulation in mice. Our findings imply that BASP1 is a pharmacologically relevant receptor for cocaine.

Specific Inhibition of Interpeduncular Nucleus GABAergic Neurons Alleviates Anxiety-Like Behaviors in Male Mice after Prolonged Abstinence from Methamphetamine.

Anxiety is one of the most common withdrawal symptoms of methamphetamine (METH) abuse, which further drives relapse to drugs. Interpeduncular nucleus (IPN) has been implicated in anxiety-like behaviors and addiction, yet its role in METH-abstinence-induced anxiety remains unknown. Here, we found that prolonged abstinence from METH enhanced anxiety-like behaviors in male mice, accompanied by more excited IPN GABAergic neurons, as indicated by the increased c-fos expression and the enhanced neuronal excitability by electrophysiological recording in the GABAergic neurons. Using the designer receptors exclusively activated by designer drugs method, specific inhibition of IPN GABAergic neurons rescued the aberrant neuronal excitation of IPN GABAergic neurons and efficiently reduced anxiety-like behaviors, whereas it did not induce depression-like behaviors in male mice after prolonged abstinence from METH. These findings reveal that IPN GABAergic neurons should be a promising brain target to alleviate late withdrawal symptoms from METH with few side effects.SIGNIFICANCE STATEMENT Prolonged abstinence from METH triggers IPN GABAergic neurons and ultimately increases anxiety in male mice. Suppressing IPN GABAergic neurons rescues METH abstinence-induced aberrant neuronal excitation of IPN GABAergic neurons and efficiently reduces anxiety in mice.

Contrasting the Reinforcing Effects of the Novel Dopamine Transport Inhibitors JJC8-088 and JJC8-091 in Monkeys: Potential Translation to Medication Assisted Treatment.

Despite considerable efforts, there remains no FDA-approved medications for cocaine use disorder (CUD). One strategy to mitigate cocaine craving and relapse is to elevate dopamine (DA). The DA transport inhibitor and releaser d-amphetamine has been shown to decrease cocaine self-administration (SA), although it has abuse liability. Recently, several modafinil analogues reduced cocaine SA in rats and monkeys, including JJC8-088, characterized as "cocaine like" in rats, and JJC8-091, characterized as "atypical" and not SA by rats. The present studies evaluated the reinforcing effects of both compounds in monkeys under several conditions. For Experiment 1, four male cocaine-experienced rhesus monkeys self-administered cocaine (0.001-0.3 mg/kg/injection), JJC8-088 (0.001-0.3 mg/kg/injection), and JJC8-091 (0.1-3.0 mg/kg/injection) under a progressive-ratio (PR) schedule of reinforcement. Both JJC compounds functioned as reinforcers with equal reinforcing strength to cocaine. Although JJC8-091 was less potent than cocaine, JJC8-088 and cocaine had similar potencies. For Experiment 2, one male and two females drug-naïve cynomolgus monkeys responded on a fixed-ratio schedule of food reinforcement. JJC8-091 was self-administered at rates higher than saline in all three monkeys. In Experiment 3, monkeys from Experiment 2 responded under a concurrent drug vs. food choice paradigm and given access to cocaine or JJC8-091 under these conditions. At doses equal to or one-half log-units higher than doses used in Experiment 2, cocaine, but not JJC8-091, was chosen over food. Together, these results demonstrate that while JJC8-091 may be reinforcing under some conditions, its reinforcing strength, in the presence of an alternative reinforcer, is substantially less than cocaine. Significance Statement JJC8-088 and JJC8-091 have shown efficacy is reducing cocaine self-administration in rats and in nonhuman primates. This study found that both compounds maintained self-administration in monkeys responding under several conditions. However, when given access to an alternative reinforcer during the self-administration session, JJC8-091 was not reinforcing, suggesting that JJC8-091 may be a viable candidate for CUD since, in the human population, alternatives to drug use are often available.

Neurovascular dysfunction in psychiatric disorders: Underlying mechanisms and therapeutic approaches.

BACKGROUND: Neurovascular interfaces, specifically the blood-brain barrier (BBB) and blood-retinal barrier (BRB), play pivotal roles in maintaining the homeostasis of the central nervous system (CNS). For a long time, these structures were seen only as a way of protection, but we currently know that they have a critical role in CNS (dys)function. Several studies have identified neurovascular alterations in early stages of brain and eye diseases, contributing to the pathophysiology of such conditions. More recently, interesting data have also highlighted the importance of neurovasculature in psychiatric disorders. METHODS: Using the PubMed database, we brought together the evidence concerning the changes in BBB and BRB under psychiatric conditions, with a focus on anxiety, major depressive disorder (MDD), attention-deficit/hyperactivity disorder (ADHD) and drug abuse, specifically related with methamphetamine (METH) and cocaine consumption. RESULTS: We summarized the main findings obtained from in vitro and animal studies, as well as clinical research that has been undertaken to identify neurovascular abnormalities upon such neuropsychiatric disorders. The drivers of barrier alterations were examined, namely the role of neuroinflammation, while reporting putative barrier-associated biomarkers of these disorders. CONCLUSION: This review underscores the critical need for a deeper understanding of BBB and BRB function in neuropsychiatric conditions and their potential as therapeutic targets while elucidating the key players involved. The innovative approaches to managing these complex disorders are also addressed while bridging the gap concerning what is currently known regarding the association between neuropsychiatric conditions and their vascular implications.

Risk for psychiatric and substance use disorders as a function of transitions in Sweden's public educational system: a national study.

BACKGROUND: To clarify, in a national sample, associations between risk for seven psychiatric and substance use disorders and five key transitions in Sweden's public educational system. METHODS: Swedish-born individuals (1972-1995, N = 1 997 910) were followed through 12-31-2018, at mean age 34.9. We predicted, from these educational transitions, risk for major depression (MD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), anorexia nervosa (AN), alcohol use disorder (AUD), and drug use disorder (DUD), assessed from Swedish national registers, by Cox regression, censoring individuals with onsets ⩽17. We also predicted risk from the deviation of grades from family-genetic expectations (deviation 1) and from changes in grades from ages 16 to 19 (deviation 2). RESULTS: We observed four major risk patterns across transitions in our disorders: (i) MD and BD, (ii) OCD and SZ, (iii) AUD and DUD, and (iv) AN. Failing early educational transitions had the greatest impact on risk for OCD and SZ while for other disorders, not progressing from basic to upper high school had the largest effect. Completing vocational v. college-prep upper high school was strongly associated with risk for AUD and DUD, had little relation with MD, OCD, BD, and SZ risk, and was protective for AN. Deviation 1 predicted risk most strongly for SZ, AN, and MD. Deviation 2 predicted risk most strongly for SZ, AUD, and DUD. CONCLUSIONS: The pattern of educational transitions and within family and within person development deviations are strongly and relatively specifically associated with future risk for seven psychiatric and substance-use disorders.

Modelling the progression of illicit substance use patterns from real-world evidence.

AIMS: To investigate an innovative pharmacometrics approach that addresses the challenges of using real-world evidence to model the progression of illicit substance use. METHODS: The modelling strategy analysed real-world data from the National Longitudinal Study of Adolescent to Adult Health (AddHealth) survey using survival analyses and differential equations. Respondents were categorized into drug-naïve, active users and nonusers. The transitions between categories were modelled using interval-censored parametric survival analysis. The resulting hazard rate functions were used as time-dependent rate constants in a differential equation system. Covariate models for sex and depression status were assessed. RESULTS: AddHealth enrolled 6504 American teenagers (median age 16 years, range 11-21 years); this cohort was followed with five interviews over a 22-year period; the median age at the last interview was 38 years (range 34-45 years). The percentages of illicit drug users at Interviews 1-5 were 7.7%, 5.9%, 15.8%, 21.4% and 0.98%, respectively. The generalized gamma distribution emerged as the preferred model for the survival functions for transitions between categories. Age-dependent prevalence was obtained from the differential equation system. Active drug use was more prevalent in males, increased in adolescence and college years, peaked at 24 years, and decreased to low levels by 35 years. Depression, which was more frequent in females, increased the drug-naïve-active user transition rates but not the active user-nonuser and nonuser-active user transition rates. The evidence did not support an interaction between sex and depression. CONCLUSIONS: The model provided a satisfactory approximation for the age-dependent progression of illicit substance use from preadolescence to early middle age.

The effect of combat deployments on veteran opioid abuse.

Grim national statistics about the U.S. opioid crisis are increasingly well known to the American public. Far less well known is that U.S. servicemembers are at ground zero of the epidemic, with veterans facing an overdose death rate of up to twice that of civilians. Exploiting a quasi-experiment in overseas deployment assignment, this study estimates the causal impact of combat exposure among the deployed in the Global War on Terrorism on opioid abuse. We find that exposure to war theater substantially increased the risk of prescription painkiller abuse and illicit heroin use among active duty servicemen. The magnitudes of our estimates imply lower-bound combat exposure-induced healthcare costs of $1.04 billion per year for prescription painkiller abuse and $470 million per year for heroin use.

CircRNA: a rising therapeutic strategy for lung injury induced by pulmonary toxicants.

Lung injury has been a serious medical problem that requires new therapeutic approaches and biomarkers. Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) that exist widely in eukaryotes. CircRNAs are single-stranded RNAs that form covalently closed loops. CircRNAs are significant gene regulators that have a role in the development, progression, and therapy of lung injury by controlling transcription, translating into protein, and sponging microRNAs (miRNAs) and proteins. Although the study of circRNAs in lung injury caused by pulmonary toxicants is just beginning, several studies have revealed their expression patterns. The function that circRNAs perform in relation to pulmonary toxicants (severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2), drug abuse, PM2.5, and cigarette smoke) is the main topic of this review. A variety of circRNAs can serve as potential biomarkers of lung injury. In this review, the biogenesis, properties, and biological functions of circRNAs were concluded, and the relationship between circRNAs and pulmonary toxicants was discussed. It is expected that the new ideas and potential treatment targets that circRNAs provide would be beneficial to research into the molecular mechanisms behind lung injury.

Smoking, alcohol consumption, drug abuse, and osteoporosis among older adults: a cross-sectional study on PERSIAN cohort study in Fasa.

BACKGROUND: With increasing life expectancy and a growing population of older adults, the prevalence of osteoporosis has risen, resulting in a higher incidence of bone fractures, which necessitate extended treatment and specialized medical care. This study investigates the relationship between smoking, alcohol consumption, drug abuse, and osteoporosis among older adults in southern Iran, utilizing cohort data. METHODS: This cross-sectional study is derived from the Fasa Adult Cohort Study (FACS), which included 10,133 individuals. From this cohort, we selected 1,631 older adults using census sampling methods. Our study aimed to explore the correlation between smoking, alcohol consumption, and drug abuse among older adults and the incidence of osteoporosis. We collected demographic information, nutritional indexes, medical history, glucocorticoid usage, and self-reported data on smoking, alcohol consumption, drug abuse, and osteoporosis through questionnaires. To investigate the relationship between smoking, alcohol, and drug use with osteoporosis while accounting for confounding factors, we employed logistic regression analysis. RESULTS: The average age of the study participants was 64.09 ± 3.8 years, with a majority (898 (55.1%)) being female. Osteoporosis prevalence among the subjects was 25.20%. The results did not reveal a significant correlation between smoking, alcohol consumption, drug abuse, and osteoporosis (p > 0.05). Regression analysis identified gender, recent history of fractures within the past five years, history of using glucocorticoids, and physical activity as significant predictive risk factors for osteoporosis within the study population (p < 0.05). CONCLUSION: The study underscores the significance of addressing osteoporosis risk factors in older adults. Healthcare policymakers and administrators can use these findings to identify and mitigate influential factors contributing to osteoporosis in this demographic.

Factors predicting the intention of drug abuse avoidance among adolescents in Pinlaung Township, Myanmar: predictive correlational design.

BACKGROUND: Adolescence is a critical transition period and is at high risk for drug/substance abuse. In Myanmar, drug use is common among adolescents and is a public health concern. There are no studies of drug abuse prevention among Myanmar adolescents. Intentions to avoid drug abuse can be a protective factor for preventing drug abuse among adolescents. This study investigated the effects of sex, parental history of drug/alcohol abuse, self-efficacy, parental marital status, and family functioning on the intention of drug abuse avoidance among Myanmar adolescents. METHODS: This is a predictive correlational study. The Biopsychosocial model was used as the theoretical framework of this study. A convenient sampling method was used to collect data from 157 students aged 13-18 years in a government school, middle school level and high school level, Pinlaung Town, Southern Shan State, Myanmar during the COVID-19 pandemic and political protests. G* power software was used to calculate the sample size. Data was collected by four self-administered questionnaires: a socio-demographic questionnaire, Thai Family Functioning Scale (TFFS), General Self-Efficacy Scale (GSE), and Intention of Drug Avoidance Scale (IDAS). Multiple linear regression was employed to analyze the data. RESULTS: Five predictors, including biological sex, parental history without drug/alcohol abuse, self-efficacy, parental marital status, and family functioning, explained 24.4% of the variance in the intention of drug abuse avoidance among Myanmar adolescents (R 2 = .244, F (5,151) = 9.738, p = .000). In addition, only three factors, family functioning (ß = .31, p < .001), biological sex (ß = -.25, p < .01), and self-efficacy (ß = .16, p < .05) statistically and significantly predicted the intention of drug abuse avoidance among Myanmar adolescents. CONCLUSIONS: Family functioning, female gender, and self-efficacy predicted the intention of drug abuse avoidance among Myanmar adolescents in Pinlaung Township, Southern Shan State, Myanmar. IMPLICATIONS OF THIS STUDY: The results of this study have implications for all stakeholders through research, education, practice, and policymaking leading to improve the intentions of drug abuse avoidance among Myanmar adolescents. Furthermore, the results of this study specifically contribute to create psychoeducational intervention programs for increasing intention to avoid substance use by promoting family functioning and self-efficacy of adolescents. This is especially proper for male adolescents who have less intention to avoid substance use.

Psychometric properties of the modified Drug Abuse Screening Test Sinhala version (DAST-SL): evaluation of reliability and validity in Sri Lanka.

BACKGROUND: Psychoactive drug use is an important public health issue in Sri Lanka as it causes substantial health, social and economic burden to the country. Screening for substance use disorders in people who use drugs is vital in preventive health care, as it can help to identify problematic use early. Screening can aid in referring those in need, for the most appropriate treatment and care. Thus, preventing them from developing severe substance use disorders with complications. The Drug Abuse Screening Test (DAST-10) is an evidence-based tool widely used to assess the severity of psychoactive drug use. This study aimed to culturally adapt and evaluate the validity and reliability of the Drug Abuse Screening Test (DAST-10) in Sri Lanka. METHODS: The DAST-10 was culturally adapted, and the nine-item Sinhala version (DAST-SL) was validated using exploratory and confirmatory factor analysis. The validation study was conducted in the Kandy district among people who use drugs, recruited using respondent-driven sampling. Criterion validity of the questionnaire was assessed by taking the diagnosis by a psychiatrist as the gold standard. Cut-off values for the modified questionnaire were developed by constructing Receiver Operating Characteristic (ROC) curves. The reliability of the DAST-SL was assessed by measuring its internal consistency and test re-test reliability. RESULTS: The validated DAST-SL demonstrated a one-factor model. A cut-off value of ≥ 2 demonstrated the presence of substance use disorder and had a sensitivity of 98.7%, specificity of 91.7%, a positive predictive value of 98.8% and a negative predictive value of 91.3%. The area under the curve of the ROC curve was 0.98. A cut-off score of ≤ 1 was considered a low level of problems associated with drug use. The DAST-SL score of 2-3 demonstrated a moderate level of problem severity, a score of 4-6 demonstrated a substantial level of problems, and a score of ≥ 7 demonstrated a severe level of drug-related problems. The questionnaire demonstrated high reliability with an internal consistency of 0.80 determined by Kuder-Richardson Formula-20 and an inter-class correlation coefficient of 0.97 for test re-test reliability. CONCLUSION: The DAST-SL questionnaire is a valid and reliable tool to screen for drug use problem severity in people who use drugs in Sri Lanka.

Adulterants present in the San Diego county fentanyl supply: a laboratory analysis of seized law enforcement samples.

BACKGROUND: The opioid overdose crisis is one of the worst public health crises ever to face the US and emerging evidence suggests its effects are compounded by the presence of drug adulterants. Here we report our efforts to characterize the adulterants present within the local fentanyl supply of San Diego County, obtained from undifferentiated drug samples seized by local law enforcement over the calendar year 2021. METHODS: Thirty-two participating local law enforcement agencies across San Diego submitted 4838 unknown individual illicit drug samples (total of 312 kg) to the San Diego County Sheriff's Department Regional Crime Laboratory for identification. RESULTS: Qualitative analysis of these samples via FTIR and GC-MS identified methamphetamine (38.7%), fentanyl (20.8%), diacetylmorphine (heroin) (10.2%), codeine (5.8%) and alprazolam (4.3%) as the most common illicit substances and the presence of 52 unique adulterants. The most common adulterants included 4-methylaminoantipyrine (4-MAAP) (10.9%), mannitol (9%), acetaminophen (8.5%), methamphetamine (4.2%), diacetylmorphine (heroin) (3.6%), tramadol (1.9%), and xylazine (1.7%). Several additional pharmacologically active adulterants and contaminants of interest were also identified. CONCLUSION: This analysis is vital for public health use and harm reduction efforts at the level of the individual consumer. Continued direct surveillance of the drug supply is necessary for the detection of potentially harmful adulterants that may pose serious threats to the public.

Adapting a health facility HIV stigma-reduction participatory training intervention to address drug use stigma in HIV care and treatment clinics in Dar es Salaam, Tanzania.

BACKGROUND: HIV prevalence among people who use drugs (PWUD) in Tanzania is 4-7 times higher than in the general population, underscoring an urgent need to increase HIV testing and treatment among PWUD. Drug use stigma within HIV clinics is a barrier to HIV treatment for PWUD, yet few interventions to address HIV-clinic drug use stigma exist. Guided by the ADAPT-ITT model, we adapted the participatory training curriculum of the evidence-based Health Policy Plus Total Facility Approach to HIV stigma reduction, to address drug use stigma in HIV care and treatment clinics (CTCs). METHODS: The first step in the training curriculum adaptation process was formative research. We conducted 32 in-depth interviews in Dar es Salaam, Tanzania: 18 (11 men and 7 women) with PWUD living with HIV, and 14 with a mix of clinical [7] and non-clinical [7] CTC staff (5 men and 9 women). Data were analyzed through rapid qualitative analysis to inform initial curriculum adaptation. This initial draft curriculum was then further adapted and refined through multiple iterative steps of review, feedback and revision including a 2-day stakeholder workshop and external expert review. RESULTS: Four CTC drug use stigma drivers emerged as key to address in the curriculum adaptation: (1) Lack of awareness of the manifestations and consequences of drug use stigma in CTCs (e.g., name calling, ignoring PWUD and denial of care); (2) Negative stereotypes (e.g., all PWUD are thieves, dangerous); (3) Fear of providing services to PWUD, and; (4) Lack of knowledge about drug use as a medical condition and absence of skills to care for PWUD. Five, 2.5-hour participatory training sessions were developed with topics focused on creating awareness of stigma and its consequences, understanding and addressing stereotypes and fears of interacting with PWUD; understanding drug use, addiction, and co-occurring conditions; deepening understanding of drug use stigma and creating empathy, including a panel session with people who had used drugs; and working to create actionable change. CONCLUSION: Understanding context specific drivers and manifestations of drug use stigma from the perspective of PWUD and health workers allowed for ready adaptation of an existing evidence-based HIV-stigma reduction intervention to address drug use stigma in HIV care and treatment clinics. Future steps include a pilot test of the adapted intervention.

The Drug Overdose Epidemic in the U.S.-Mexico Border Region: Shifts, Progression, and Community Characteristics.

OBJECTIVE: Previous studies show the reach of the current drug overdose epidemic into the U.S.-Mexico border region, albeit with a unique border-specific wave pattern compared to national waves and a delayed onset of fentanyl involvement (Wave I: 2002-2011, Wave II: 2012-2016, and Wave III: since 2017). The objective of this study is to examine the community predictors and the progression of overdose deaths across the U.S-Mexico border-specific epidemic waves. METHOD: Descriptive epidemiological profile of border communities across the unfolding of the opioid epidemic, integrated data from the CDC-WONDER multiple causes of death data set, the CDC SVI, Uniform Crime Report, and the Behavioral Risk Factor Surveillance System. Using spatially adjusted Bayes rates by border-specific epidemic waves, we provide a descriptive profile of the spatial unfolding of the drug overdose epidemic. Negative binomial regression models assessed community predictors of overdose deaths across waves. RESULTS: Spatial analysis identified moderate to steep increases in drug overdose deaths over the three waves along the border. The impact and unfolding of the epidemic in the U.S.-Mexico border region were not uniform and affecting communities with differing severity and timing. Our study also finds support for social vulnerability and community violence as predictors of overdose deaths over the current wave of the epidemic. CONCLUSION: Findings suggest that more disadvantaged U.S.-Mexico border communities may encounter increasing rates of overdose death over the coming years. Interventions need to target not only the supply side but also the underlying social root causes for sustainable overdose prevention.

Weight of Evidence: Is an Animal Study Warranted? Assessments for Carcinogenicity, Drug Abuse Liability, and Pediatric Safety.

Nonclinical safety studies are typically conducted to establish a toxicity profile of a new pharmaceutical in clinical development. Such a profile may encompass multiple differing types of animal studies, or not! Some types of animal studies may not be warranted for a specific program or may only require a limited evaluation if scientifically justified. The goal of this course was to provide a practical perspective on regulatory writing of a dossier(s) using the weight of evidence (WOE) approach for carcinogenicity, drug abuse liability and pediatric safety assessments. These assessments are typically done after some clinical data are available and are highly bespoke to the pharmaceutical being developed. This manuscript will discuss key data elements to consider and strategy options with some case studies and examples. Additionally, US FDA experience with dossier(s) including WOE arguments is discussed.

RCEM best practice guideline: suspected cannabinoid hyperemesis syndrome in emergency departments.

Cannabinoid hyperemesis syndrome (CHS) is an episodic syndrome of cyclic vomiting in the context of the prolonged use of cannabis. The Royal College of Emergency Medicine Toxicology Special Interest Group has produced guidance to support emergency medicine clinicians with the recognition and treatment of people experiencing CHS.Considerations regarding recognition, investigation and communication are discussed, and recommendations regarding treatment options (which include haloperidol and capsaicin) are made. There is a focus on making recommendations on the best available evidence.

Predictors of recurrent stroke and subsequent mortality among patients experiencing housing instability.

BACKGROUND: The experience of homelessness has been linked with developing poor health outcomes. Little is known about the risk of recurrent stroke among these individuals. This study investigated the correlates of developing recurrent stroke and subsequent mortality among Veterans with housing instability. METHODS: Using a national sample of Veterans from the U.S. Department of Veterans Affairs who had an indicator of housing instability between 2014-2018 (n=659,987), we identified 15,566 Veterans who experienced incident stroke. We compared characteristics of Veterans who experienced incident stroke and did and did not experience recurrent stroke and conducted logistic regressions using a discrete-time survival framework to assess two outcomes: recurrent stroke and all-cause mortality. RESULTS: Among our cohort, 91.3% did not experience recurrent stroke while 8.7% did during the observation period. The receipt of any level of primary care outpatient visits was associated with a reduction in the odds of recurrent stroke. Several medical diagnoses were also associated with increased odds of recurrent stroke, including hypertension (aOR 1.35, 95% CI 1.15-1.59), diabetes (aOR 1.21, 95% CI 1.07-1.36), and renal disease (aOR 1.17, 95% CI 1.02, 1.35). Veterans who used any level of VA Homeless Programs had reduced odds of all-cause mortality (high level: aOR 0.65, 95% CI 0.60-0.71; low level: aOR 0.66, 95% CI 0.60-0.73). CONCLUSION: Our study found several predictors of developing recurrent stroke and subsequent death in a population of Veterans experiencing housing instability. Implications include the need to monitor closely high-risk patients who have experienced incident stroke and have other co-occurring needs.

Electronic survey investigating UK veterinarians' perceptions of the potential for veterinary prescription medication misuse or abuse.

OBJECTIVE: To investigate veterinarians' experience and perception of the risk of veterinary prescription medication (VPM) misuse and abuse by the public and veterinary professionals and to determine the clinical context in which respondent veterinarians prescribed certain VPMs. STUDY DESIGN: Anonymous online voluntary survey. POPULATION: A total of 361 of 7126 veterinarians registered as practicing in the UK, who provided e-mail contact details to the Royal College of Veterinary Surgeons Knowledge for participation in research. Respondents included general practitioners, with or without further qualifications, and European specialists, covering charity, private or academic small, large or mixed animal practice. METHODS: The anonymous online survey, open from September to December 2021, posed 27 questions regarding personal experience and perception of VPM misuse or abuse, including which VPMs were considered most at risk of abuse by clients or veterinary staff. Thematic analysis was performed on free-text sections. RESULTS: The participation rate was 5% (361/7126), and the completion rate 60% (216/361 respondents). Of these, 88% of respondents somewhat agreed, agreed or strongly agreed that some VPMs were at risk of abuse. A third (29.9%; 107/358) had suspected an owner of taking VPMs, and one fifth (20.1%; 72/358) had suspected veterinary staff. Perceptions regarding the likelihood of public VPM abuse ranged from not suspecting a problem to having first-hand experience. Drugs considered most at risk of owner abuse were opioids, benzodiazepines and gabapentin, and those for veterinary staff were opioids, benzodiazepines and ketamine. Numerous 'red flags' prompting suspicion of VPM abuse were identified alongside ways of mitigating risk. CONCLUSIONS AND CLINICAL RELEVANCE: Veterinarians in the UK reported varied experiences with, awareness of, and attitudes towards VPM abuse by the public and veterinary staff. Although not quantified, the UK veterinary industry could be a source of abusable drugs.

The experiences of people who use injection drugs with accessing hepatitis c testing and diagnosis in western countries: A scoping review.

BACKGROUND: The purpose of this scoping review was to summarize the literature that reported on the experiences of people who use injection drugs' access to hepatitis C testing and diagnosis in Western countries. METHODS: The initial search was conducted in 2020 and an updated review was completed in 2022. Seven electronic databases were searched using a peer-reviewed search strategy and included: full-text, peer-reviewed studies with people who inject(ed) drugs, hepatitis C testing or diagnosis, conducted in Western countries. Excluded were studies published prior to 2014 and intervention studies. Two-step screening was conducted in duplicate. Conventional content analysis was used. RESULTS: Six studies were found from the search. The studies were published between 2014 and 2021 in Australia, United Kingdom, and United States. A total of 19 participant characteristics were extracted to contextualize their experiences, demonstrating a lack of demographic data. Four themes were found: Awareness and Knowledge, Stigma, Healthcare Service, and Psychological Responses. There were 58 occurrences of client quotes where participants described their experiences, 29 occurrences of quotes describing client-identified barriers, and 14 occurrences of quotes describing client-identified facilitators. CONCLUSION: A scoping review was conducted to present the experiences, barriers, and facilitators of people who use injection drugs to hepatitis C testing. The lack of demographic data and connection to client quotes further exacerbates the inequities among the population by overlooking their intragroup identities. Understanding their experiences of accessing hepatitis C testing and collecting demographic data will help advance health policies and interventions targeting people who use injection drugs.