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Clinica Chimica Acta; International... Jun 2024The number of xylazine-involved overdose deaths tremendously increased from 2019 onwards in the US. This is due to the "tranq-dope" trend consisting in mixing opioids...
BACKGROUND AND AIMS
The number of xylazine-involved overdose deaths tremendously increased from 2019 onwards in the US. This is due to the "tranq-dope" trend consisting in mixing opioids with the sedative to reduce drug manufacturing costs and enhance their effects. In this study, we report the first fatality involving xylazine-adulterated heroin in the EU.
MATERIALS AND METHODS
The subject was a 33-year-old Caucasian male with a documented history of drug abuse who was found dead in a public area with puncture marks at the elbow. Peripheral blood and urine were collected at the autopsy and analyzed by liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) after protein precipitation.
RESULTS
6-Monoacetylmorphine, total/free morphine, and codeine blood concentrations of 20.3, 236/105, and 38.3 ng/mL, respectively, indicated recent heroin consumption. Methadone blood concentration was below 10 ng/mL. Alprazolam, nordiazepam, and flurazepam blood concentrations were 23.9, 61.4, and 55.0 ng/mL, respectively. Benzoylecgonine blood concentration was below 5 ng/mL. Xylazine blood and urine concentrations were 105 and 72.6 ng/mL, respectively.
CONCLUSION
The combination of central nervous system depressants, i.e., opioids, benzodiazepines, and xylazine, was the principal cause of death by cardiorespiratory failure. The case was promptly reported to the UE Early Warning System on drugs.
PubMed: 38909977
DOI: 10.1016/j.cca.2024.119826 -
Medicina 2024Acetaminophen is a commonly used analgesic and antipyretic drug, which has experienced an increase in its consumption in recent years in our environment. There has also...
Acetaminophen is a commonly used analgesic and antipyretic drug, which has experienced an increase in its consumption in recent years in our environment. There has also been an increase in the number of accidental and intentional overdoses that were treated by the health system. Its toxicity is dose-dependent and can cause fulminant liver failure, becoming one of the main reasons for liver transplantation in English-speaking countries. The case of a 28-year-old woman with a history of major depression and five previous suicide attempts, who deliberately ingested a significant amount of paracetamol tablets, is here presented. She developed fulminant liver failure and metabolic acidosis, for which she underwent an emergency liver transplant due to the severity of her condition, from which she evolved favorably. The decision to perform a liver transplant in serious cases like this and under a condition of severe psychiatric vulnerability is challenging and must be carefully considered. This particular case illustrates the importance of multidisciplinary care including psychiatric evaluation in patients with acetaminophen poisoning.
Topics: Humans; Acetaminophen; Female; Adult; Liver Transplantation; Liver Failure, Acute; Suicide, Attempted; Analgesics, Non-Narcotic; Drug Overdose
PubMed: 38907980
DOI: No ID Found -
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 -
Cureus May 2024Lance-Adams syndrome (LAS) is a rare clinical presentation of hypoxic-ischemic brain injury typically occurring in the setting of cardiac arrest. It is rare for it to be...
Lance-Adams syndrome (LAS) is a rare clinical presentation of hypoxic-ischemic brain injury typically occurring in the setting of cardiac arrest. It is rare for it to be associated with respiratory failure. The advent of the COVID-19 pandemic heralded a new cause of respiratory failure, and not much is known about the occurrence of Lance-Adams syndrome in the context of COVID-19 pneumonia. A 23-year-old male was brought to the emergency department (ED) after being found unconscious at home. He had prominent generalized myoclonus in the context of COVID-19 pneumonia and a possible clonazepam overdose. Magnetic resonance imaging (MRI) of the brain with and without contrast revealed findings suggestive of hypoxic-ischemic brain injury. A diagnosis of LAS was made based on electroencephalography (EEG). As LAS typically carries a relatively favorable prognosis, aggressive treatment was pursued. This resulted in a fairly good outcome, although he had to be maintained on several antiseizure medications. Our case is a rare occurrence of Lance-Adams syndrome in the setting of respiratory failure and COVID-19 pneumonia in the absence of cardiac arrest. It is critical to distinguish myoclonic status epilepticus (MSE) from Lance-Adams syndrome due to the difference in prognosis. Our case can provide future direction for studies in a larger cohort of patients to see if LAS is frequently associated with respiratory failure secondary to COVID-19 pneumonia in the absence of cardiac arrest. It is important to consider Lance-Adams syndrome as one of the emerging neurological complications of COVID-19 pneumonia.
PubMed: 38903282
DOI: 10.7759/cureus.60621 -
BMC Public Health Jun 2024In Canada, substance-related accidental acute toxicity deaths (AATDs) continue to rise at the national and sub-national levels. However, it is unknown if, where, when,...
OBJECTIVES
In Canada, substance-related accidental acute toxicity deaths (AATDs) continue to rise at the national and sub-national levels. However, it is unknown if, where, when, and to what degree AATDs cluster in space, time, and space-time across the country. The objectives of this study were to 1) assess for clusters of AATDs that occurred in Canada during 2016 and 2017 at the national and provincial/territorial (P/T) levels, and 2) examine the substance types detected in AATD cases within each cluster.
METHODS
Two years of person-level data on AATDs were abstracted from coroner and medical examiner files using a standardized data collection tool, including the decedent's postal code and municipality information on the places of residence, acute toxicity (AT) event, and death, and the substances detected in the death. Data were combined with Canadian census information to create choropleth maps depicting AATD rates by census division. Spatial scan statistics were used to build Poisson models to identify clusters of high rates (p < 0.05) of AATDs at the national and P/T levels in space, time, and space-time over the study period. AATD cases within clusters were further examined for substance types most present in each cluster.
RESULTS
Eight clusters in five regions of Canada at the national level and 24 clusters in 15 regions at the P/T level were identified, highlighting where AATDs occurred at far higher rates than the rest of the country. The risk ratios of identified clusters ranged from 1.28 to 9.62. Substances detected in clusters varied by region and time, however, opioids, stimulants, and alcohol were typically the most commonly detected substances within clusters.
CONCLUSION
Our findings are the first in Canada to reveal the geographic disparities in AATDs at national and P/T levels using spatial scan statistics. Rates associated with substance types within each cluster highlight which substance types were most detected in the identified regions. Findings may be used to guide intervention/program planning and provide a picture of the 2016 and 2017 context that can be used for comparisons of the geographic distribution of AATDs and substances with different time periods.
Topics: Humans; Canada; Female; Male; Adult; Spatio-Temporal Analysis; Middle Aged; Adolescent; Young Adult; Substance-Related Disorders; Cluster Analysis; Aged
PubMed: 38898445
DOI: 10.1186/s12889-024-18883-2 -
BioRxiv : the Preprint Server For... Jun 2024Hepatic endothelial cell (EC) dysfunction and centrilobular hepatocyte necrosis occur with acetaminophen (APAP) overdose. The protease thrombin, which is acutely...
BACKGROUND & AIMS
Hepatic endothelial cell (EC) dysfunction and centrilobular hepatocyte necrosis occur with acetaminophen (APAP) overdose. The protease thrombin, which is acutely generated during APAP overdose, can signal through protease-activated receptors 1 and 4 (PAR1/PAR4). PAR1 is a high-affinity thrombin receptor that is known to signal on ECs, whereas PAR4 is a low-affinity thrombin receptor, and evidence for its expression and function on ECs is mixed. This study aims to exploit the high levels of thrombin generated during APAP overdose to determine (1) if hepatic endothelial PAR4 is a functional receptor, and (2) endothelial-specific functions for PAR1 and PAR4 in a high thrombin setting.
METHODS
We generated mice with conditional deletion(s) of in ECs and overdosed them with APAP. Hepatic vascular permeability, erythrocyte congestion/bleeding, and liver function were assessed following overdose. Additionally, we investigated the expression levels of endothelial PARs and how they influence transcription in APAP-overdosed liver ECs using endothelial Translating Ribosome Affinity Purification followed by next-generation sequencing (TRAPseq).
RESULTS
We found that mice deficient in high-expressing endothelial or low-expressing had equivalent reductions in APAP-induced hepatic vascular instability but no effect on hepatocyte necrosis. Additionally, mice with loss of endothelial and had reduced permeability at an earlier time point after APAP overdose when compared to mice singly deficient in either receptor in ECs. We also found that endothelial PAR1-but not PAR4-can regulate transcription in hepatic ECs.
CONCLUSIONS
Low-expressing PAR4 can react similarly to high-expressing PAR1 in APAP-overdosed hepatic ECs, demonstrating that PAR4 is a potent thrombin receptor. Additionally, these receptors are functionally redundant but act divergently in their expression and ability to influence transcription in hepatic ECs.
PubMed: 38895465
DOI: 10.1101/2024.06.07.598028 -
International Journal of Molecular... Jun 2024Acute liver failure is an infrequent yet fatal condition marked by rapid liver function decline, leading to abnormalities in blood clotting and cognitive impairment...
Acute liver failure is an infrequent yet fatal condition marked by rapid liver function decline, leading to abnormalities in blood clotting and cognitive impairment among individuals without prior liver ailments. The primary reasons for liver failure are infection with hepatitis virus or overdose of certain medicines, such as acetaminophen. (PT), a type of microalgae known as a diatom species, has been reported to contain an active ingredient with anti-inflammatory and anti-obesity effects. In this study, we evaluated the preventive and therapeutic activities of PT extract in acute liver failure. To achieve our purpose, we used two different acute liver failure models: acetaminophen- and D-GalN/LPS-induced acute liver failure. PT extract showed protective activity against acetaminophen-induced acute liver failure through attenuation of the inflammatory response. However, we failed to demonstrate the protective effects of PT against acute liver injury in the D-GalN/LPS model. Although the PT extract did not show protective activity against two different acute liver failure animal models, this study clearly demonstrates the importance of considering the differences among animal models when selecting an acute liver failure model for evaluation.
Topics: Animals; Acetaminophen; Mice; Chemical and Drug Induced Liver Injury; Microalgae; Disease Models, Animal; Liver Failure, Acute; Male; Protective Agents; Ethanol; Diatoms; Liver; Lipopolysaccharides
PubMed: 38892435
DOI: 10.3390/ijms25116247 -
International Journal of Molecular... May 2024Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis...
Acetaminophen overdose is a leading cause of acute liver failure (ALF), and effective treatment depends on early prediction of disease progression. ALF diagnosis currently requires blood collection 24-72 h after APAP ingestion, necessitating repeated tests and hospitalization. Here, we assessed earlier ALF diagnosis using positron emission tomography (PET) imaging of translocator proteins (TSPOs), which are involved in molecular transport, oxidative stress, apoptosis, and energy metabolism, with the radiotracer [F]GE180. We intraperitoneally administered propacetamol hydrochloride to male C57BL/6 mice to induce ALF. We performed in vivo PET/CT imaging 3 h later using the TSPO-specific radiotracer [F]GE180 and quantitatively analyzed the PET images by determining the averaged standardized uptake value (SUV) in the liver parenchyma. We assessed liver TSPO expression levels via real-time polymerase chain reaction, Western blotting, and immunohistochemistry. [F]GE180 PET imaging 3 h after propacetamol administration (1500 mg/kg) significantly increased liver SUV compared to controls ( = 0.001). Analyses showed a 10-fold and 4-fold increase in TSPO gene and protein expression, respectively, in the liver, 3 h after propacetamol induction compared to controls. [F]GE180 PET visualized and quantified propacetamol-induced ALF through TSPO overexpression. These findings highlight TSPO PET's potential as a non-invasive imaging biomarker for early-stage ALF.
Topics: Animals; Liver Failure, Acute; Acetaminophen; Male; Mice; Mice, Inbred C57BL; Receptors, GABA; Positron-Emission Tomography; Liver; Positron Emission Tomography Computed Tomography; Fluorine Radioisotopes; Radiopharmaceuticals; Disease Models, Animal; Carbazoles
PubMed: 38892130
DOI: 10.3390/ijms25115942 -
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