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Lancet Regional Health. Americas Aug 2024Manitoba saw the highest number of new HIV diagnoses in the province's history in 2021 and is the only Canadian province not meeting any of the previous UNAIDS 90-90-90...
Sex differences in houselessness, injection drug use, and mental health conditions among people newly diagnosed with HIV in Manitoba, Canada from 2018 to 2021: a retrospective cohort study.
BACKGROUND
Manitoba saw the highest number of new HIV diagnoses in the province's history in 2021 and is the only Canadian province not meeting any of the previous UNAIDS 90-90-90 targets. Our goal was to describe sex differences and syndemic conditions within an incident HIV cohort in Manitoba, and the HIV treatment initiation and undetectable viral load outcomes.
METHODS
This was a retrospective cohort study of all people 18 years and older newly diagnosed with HIV in Manitoba, Canada between January 1st, 2018 and December 31st, 2021. Data was collected as follows: : chlamydia, gonorrhoea, syphilis, and/or hepatitis C antibodies. : age, sex, gender, race/ethnicity, sexual orientation. : CD4 counts, viral load, HIV treatment, hospitalizations, and number of visits to HIV care. Main exposures evaluated: methamphetamine use, injection drug use, houselessness, and mental health conditions. Outcomes: started antiretroviral treatment and achieved an undetectable viral load. A descriptive statistical analysis was used.
FINDINGS
There were 404 new HIV diagnoses in Manitoba from 2018 to 2021; 44.8% were female, 55.2% male; 76.% self-identified as Indigenous, 13.4% white/European, 4.7% African/black; 86.6% cis-gender; 60.9% heterosexual, 13.4% gay, bisexual and men who have sex with men, and 1.7% lesbian. Injection drug use was reported by 71.8% and 43.5% of females and males respectively. Methamphetamine was the most frequently injected drug (62.4%). Amongst females, 81.8% experienced at least one of the following: houselessness (43.1%), mental health comorbidities (46.4%), and injection drug use (71.8%). Only 64.9% of all individuals had an undetectable viral load (61.1% females and 67.9% males), 56.5% among people experiencing houselessness, 59% among young people (≤29 years), and 60.1% among people who inject drugs.
INTERPRETATION
People newly diagnosed with HIV in Manitoba are disproportionately experiencing houselessness, mental illness, and injection drug use (mostly methamphetamine). This pattern is more pronounced for female individuals. These findings highlight the need for syndemic and gender-specific approaches, simultaneously addressing social and health conditions, to treat HIV.
FUNDING
This work was supported by the Canadian Institutes of Health Research, The Manitoba Medical Service Foundation, The James Farley Memorial Fund and the Canada Research Chairs Program.
PubMed: 38912328
DOI: 10.1016/j.lana.2024.100805 -
Trials Jun 2024There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic...
BACKGROUND
There are no approved pharmacotherapies for methamphetamine use disorder. Two preliminary phase 2 randomised controlled trials have found mirtazapine, a tetracyclic antidepressant, to be effective in reducing methamphetamine use. The proposed Tina Trial is the first phase 3 placebo-controlled randomised trial to examine the effectiveness and safety of mirtazapine as an outpatient pharmacotherapy for methamphetamine use disorder.
METHODS
This is a multi-site phase 3 randomised, double-blind, placebo-controlled parallel trial. Participants are randomly allocated (1:1) to receive either mirtazapine (30 mg/day for 12 weeks) or matched placebo, delivered as a take-home medication. The target population is 340 people aged 18-65 years who have moderate to severe methamphetamine use disorder. The trial is being conducted through outpatient alcohol and other drug treatment clinics in Australia. The primary outcome is measured as self-reported days of methamphetamine use in the past 4 weeks at week 12. Secondary outcomes are methamphetamine-negative oral fluid samples, depressive symptoms, sleep quality, HIV risk behaviour and quality of life. Other outcomes include safety (adverse events), tolerability, and health service use. Medication adherence is being monitored using MEMS® Smart Caps fitted to medication bottles.
DISCUSSION
This trial will provide information on the safety and effectiveness of mirtazapine as a pharmacotherapy for methamphetamine use disorder when delivered as an outpatient medication in routine clinical practice. If found to be safe and effective, this trial will support an application for methamphetamine use disorder to be included as a therapeutic indication for the prescription of mirtazapine.
TRIAL REGISTRATION
Australian and New Zealand Clinical Trials Registry ACTRN12622000235707. Registered on February 9, 2022.
Topics: Humans; Mirtazapine; Double-Blind Method; Amphetamine-Related Disorders; Methamphetamine; Adult; Middle Aged; Adolescent; Clinical Trials, Phase III as Topic; Male; Young Adult; Randomized Controlled Trials as Topic; Aged; Female; Treatment Outcome; Multicenter Studies as Topic; Australia; Time Factors; Medication Adherence; Antidepressive Agents, Tricyclic
PubMed: 38907288
DOI: 10.1186/s13063-024-08238-y -
Harm Reduction Journal Jun 2024Retention in substance use treatment is essential to treatment success. While programmatic factors are known to influence retention, less is known about the role of...
BACKGROUND
Retention in substance use treatment is essential to treatment success. While programmatic factors are known to influence retention, less is known about the role of involuntary discharges from drug or alcohol treatment programs. Therefore, we sought to identify the prevalence of and factors associated with involuntary discharge due to ongoing substance use.
METHODS
Data were derived from two community-recruited prospective cohort studies of people who use drugs in Vancouver, Canada. Generalized estimating equation (GEE) analyses were used to identify variables associated with involuntary discharge from treatment programs due to ongoing substance use.
RESULTS
Between June 2017 and March 2020, 1487 participants who accessed substance use treatment and completed at least one study interview were included in this study. Involuntary discharge from a treatment program due to ongoing substance use was reported by 41 (2.8%) participants throughout the study, with 23 instances reported at baseline and another 18 reported during study follow-up. In a multivariable GEE analysis, involuntary discharge was positively associated with homelessness (Adjusted Odds Ratio [AOR] = 3.22, 95% Confidence Interval [95% CI]: 1.59-6.52), daily injection drug use (AOR = 1.87, 95% CI 1.06-3.32) and recent overdose (AOR = 2.50, 95% CI 1.38-4.53), and negatively associated with age (AOR = 0.93, 95% CI 0.90-0.96). In sub-analyses, participants have most commonly been discharged from in-patient treatment centres (52.2%), recovery houses (28.3%) and detox programs (10.9%), and for using heroin (45.5%) and/or crystal methamphetamine (36.4%).
CONCLUSIONS
While involuntary discharge was a relatively rare occurrence, those who were discharged due to active substance use possessed several markers of risk, including high-intensity injection drug use, homelessness, and recent non-fatal overdose. Our findings highlight the need for increased flexibility within treatment programs to account for those who re-initiate or continue to use substances during treatment.
Topics: Humans; Male; Female; Adult; Middle Aged; Ill-Housed Persons; Substance-Related Disorders; Prospective Studies; Canada; British Columbia; Substance Abuse Treatment Centers; Patient Discharge; Cohort Studies
PubMed: 38907209
DOI: 10.1186/s12954-024-01036-4 -
Harm Reduction Journal Jun 2024The current fourth wave of the United States opioid overdose epidemic is characterized by the co-use of opioids and stimulants, including illicit opioids and...
BACKGROUND
The current fourth wave of the United States opioid overdose epidemic is characterized by the co-use of opioids and stimulants, including illicit opioids and methamphetamine. The co-use of these two drugs, known as "goofballing," is associated with higher risk for several adverse outcomes, including more frequent injections, greater health risks, and higher morbidity. Considering these differences, this unique subpopulation of people who inject drugs (PWID) may also have unique unmet needs and harm reduction preferences.
METHODS
We collected self-reported data from participants (N = 50) of a syringe services program (SSP), including basic needs and harm reduction preferences. Using bivariate analyses, we examined differences between SSP participants who do and do not co-use illicit opioids and methamphetamine. Co-use was defined as reporting the use of both drugs, which may or may not have been used simultaneously.
RESULTS
In the overall sample, the mean level of need was highest for bus passes or other transportation, a person who can help you get the services you need, medication for opioid use disorder, and a job or job training. Additionally, all participants reported being either interested or very interested in fentanyl test strips, safe consumption sites, delivery of syringe service supplies, and delivery of naloxone. Those who endorsed co-use had a greater need for food, healthcare, substance use disorder treatment, a support person to help them access needed services, and bus passes or transportation.
CONCLUSIONS
Unmet needs were prevalent, and the desire for more harm reduction services was high among these PWID. Results also suggest people who co-use illicit opioids and methamphetamine may have the greatest unmet needs and desire for additional harm reduction services.
Topics: Humans; Needle-Exchange Programs; Harm Reduction; Female; Male; Adult; Methamphetamine; Substance Abuse, Intravenous; Opioid-Related Disorders; Patient Preference; Middle Aged; Amphetamine-Related Disorders; Health Services Needs and Demand; Illicit Drugs; Analgesics, Opioid
PubMed: 38890736
DOI: 10.1186/s12954-024-01038-2 -
The International Journal on Drug Policy Jun 2024This review examines a series of twelve studies led by James K. Cunningham and his team, focusing on the effects of precursor regulation on illicit drug markets. Their...
This review examines a series of twelve studies led by James K. Cunningham and his team, focusing on the effects of precursor regulation on illicit drug markets. Their research shows that the regulation of chemicals essential for the production of drugs such as heroin, cocaine, and methamphetamine is associated with several positive outcomes. These include a decrease in drug purity, a reduction in seizures, lower demand for treatment and hospitalization, and an increase in drug prices. According to the research, this decrease in harmful outcomes results from a combination of diminished overall consumption and a reduction in harm per dose. However, this review identifies some inconsistencies within their studies. These inconsistencies include premature assumptions about the timing of intervention impacts, uneven influences of similar interventions, variations in the implementation of these interventions, and the disregard of alternate explanations for sudden shifts in drug markets. Cunningham's work can be considered one of the most substantial contributions in this field. However, to secure the full confidence of the drug policy community in the authenticity of their findings, they must effectively address the issues identified in this review.
PubMed: 38890057
DOI: 10.1016/j.drugpo.2024.104498 -
Inquiry : a Journal of Medical Care... 2024Use of heroin, prescription painkillers, methamphetamines, and fentanyl led to a national health crisis in 2017, resulting in 1852 overdose deaths in Indiana. Governor...
Use of heroin, prescription painkillers, methamphetamines, and fentanyl led to a national health crisis in 2017, resulting in 1852 overdose deaths in Indiana. Governor Eric J. Holcomb made tackling substance use in the state one of his highest priorities, calling on all Hoosiers to collaborate. In October 2017, Indiana University (IU) President Michael A. McRobbie responded, announcing that the University would be initiating the Responding to the Addictions Crisis Grand Challenge (AGC). Partners included Governor Holcomb, IU Health, and Eskenazi Health. Leveraging the university's research strengths and partnering with more than 160 community organizations across the state, the AGC sought to address substance use facing Indiana and beyond. Fifty interdisciplinary research projects were created through the AGC, focusing on IU's greatest strength in five areas: (1) education, training, and certification; (2) data science and analysis; (3) policy analysis, economics, and law; (4) basic, applied, and translational research; (5) community engagement and workforce development. Diversity, equity, and inclusion implications were often considered. This supplement describes the IU approach to address the health of the people of the State, investigator initiated projects and research conducted to inform practice, strategy and policy.
Topics: Indiana; Humans; Universities; Substance-Related Disorders; Health Policy
PubMed: 38881186
DOI: 10.1177/00469580241254993 -
Molecular & Cellular Proteomics : MCP Jun 2024Substance 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...
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 (LH) and the striatum (ST). 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 LH by adeno-associated virus (AAV) delivery of an shRNA to Arylsulfatase B (N-acetylgalactosamine-4-sulfatase, ARSB) 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 vs. saline-treated mice, including MYPR, KCC2A, SYN2, TENR, CALX, ANXA7, HDGF, NCAN, 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.
PubMed: 38880242
DOI: 10.1016/j.mcpro.2024.100803 -
Journal of Arthropod-borne Diseases Sep 2023It is possible to identify drugs and poisons present in cadavers by analyzing blowfly larvae and pupae collected during forensic autopsies. The main purpose of this...
BACKGROUND
It is possible to identify drugs and poisons present in cadavers by analyzing blowfly larvae and pupae collected during forensic autopsies. The main purpose of this study was to use larvae and pupae to identify drugs and poisons present in human cadavers.
METHODS
In an investigation, immature fed meat treated with methamphetamine (MA) at various concentrations (45, 90, and 180 ng/mg) were analyzed to detect MA. Acetylation derivatization and liquid-liquid extraction (LLE) were used as sample preparation methods prior to gas chromatography-mass spectrometry (GC-MS) analytical instrumentation to find MA.
RESULTS
According to this study, can be used in toxicological testing to identify MA in a host body. All larval stages, particularly the third stage larva, pupa and empty pupa tested were positive for MA. Larvae in their first instar produced weak peaks. The post-feeding instar following the 45 ng/mg treatment showed the highest MA concentration. For the first time, derivatization using the acetylation approach was used to prepare samples, and successfully, excellent results were obtained.
CONCLUSION
Low quantities of MA can be easily found in immature fly samples using GC-MS. It is important to analyze all samples including human tissues and insect samples, for postmortem drug testing. They can be utilized to find entire MA before they are excreted in excretory samples such as urine. Also, third instar larvae are a great and reliable sample for toxicological study.
PubMed: 38860200
DOI: 10.18502/jad.v17i3.14984 -
Water Research Aug 2024The determination of illicit drugs in urban influent wastewater (IWW) enables the monitoring of spatial and temporal drug usage trends and assessment of community...
The determination of illicit drugs in urban influent wastewater (IWW) enables the monitoring of spatial and temporal drug usage trends and assessment of community lifestyle habits. The increasing number of wastewater surveillance studies has emphasized the necessity for the development of rapid, high-throughput methods that maintain high quality data. This work evaluates the use of a dilute-and-shoot methodology, based on direct injection (DI) of centrifuged samples, as an alternative approach to the widely applied sample pre-treatment based on solid-phase extraction, for the liquid chromatography-tandem mass spectrometry determination of seven widely consumed illicit drugs and their metabolites in IWW (amphetamine; cocaine metabolite, benzoylecgonine; ketamine; 3,4-methylenedioxymethamphetamine (MDMA); methamphetamine; cannabis metabolite, 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THCCOOH); heroin metabolite, 6-acetylmorphine (6-MAM)). Comparison of both approaches in terms of matrix effects, sensitivity and accuracy, demonstrates the DI method suitability to correctly quantify these analytes in IWW, with a limit of quantification lower than 30 ng L for most compounds. After validation of the method and participation in an interlaboratory exercise, the DI method was applied to the analysis of 54 IWW samples collected from different Spanish wastewater treatment plants. Additionally, quality controls were incorporated in each analysis batch to support the DI method applicability and robustness. The use of a 10 μL-DI reduces time-consuming sample preparation, analysis time and measurement uncertainty. Moreover, it supports green chemistry by reducing the consumption of organic solvents and it facilitates logistics by collecting, transporting, and storing less sample volume. The methodology is therefore especially appropriate for monitoring illicit drugs in large wastewater-based epidemiology sampling campaigns or when fast near real-time results are needed.
Topics: Illicit Drugs; Tandem Mass Spectrometry; Chromatography, Liquid; Wastewater; Water Pollutants, Chemical; Wastewater-Based Epidemiological Monitoring; Substance Abuse Detection; Liquid Chromatography-Mass Spectrometry
PubMed: 38852386
DOI: 10.1016/j.watres.2024.121864 -
Biochimica Et Biophysica Acta.... Jun 2024Methamphetamine (METH) chronic exposure is an important risk factor for hypertension development. However, the mechanisms behind METH-induced hypertension remain...
AIM
Methamphetamine (METH) chronic exposure is an important risk factor for hypertension development. However, the mechanisms behind METH-induced hypertension remain unclear. Therefore, we aimed to reveal the potential mechanisms underlying METH-induced hypertension.
METHODS AND RESULTS
We structured the mouse hypertension model by METH, and observed that METH-treated mice have presented vascular remodeling (large-and small-size arteries) with collagen deposit around the vessel and increasing blood pressure (BP) and Sigma1 receptor (Sigmar1) in vascular tissue. We hypothesized that Sigmar1 is crucial in METH-induced hypertension and vascular remodeling. Sigmar1 knockout (KO) mice and antagonist (BD1047) pretreated mice exposed to METH for six-week showed higher BP and more collagen deposited around vessels than wild-type (WT) mice exposed to METH for six-week, in contrast, mice pretreated with Sigmar1 agonist (PRE-084) had unchanged BP and perivascular collagen despite the six-week METH exposure. Furthermore, we found that METH exposure induced vascular smooth muscle cells (VSMCs) and mesenchymal stem cells to differentiate into the myofibroblast-like cell and secrete collagen into surrounding vessels. Mechanically, Sigmar1 can suppress the COL1A1 expression by blocking the classical fibrotic TGF-β/Smad2/3 signaling pathway in METH-exposed VSMCs and mesenchymal stem cells.
CONCLUSION
Our results suggest that Sigmar1 is involved in METH-induced hypertension and vascular fibrosis by blocking the activation of the TGF-β/Smad2/3 signaling pathway. Accordingly, Sigmar1 may be a novel therapeutic target for METH-induced hypertension and vascular fibrosis.
PubMed: 38851304
DOI: 10.1016/j.bbadis.2024.167284