Ketamine has recently become an anesthetic drug used in human and veterinary clinical medicine for illicit abuse worldwide, but the detection of illicit abuse and inference of time intervals following ketamine abuse are challenging issues in forensic toxicological investigations. Here, we developed methods to estimate time intervals since ketamine use is based on significant metabolite changes in rat serum over time after a single intraperitoneal injection of ketamine, and global metabolomics was quantified by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Thirty-five rats were treated with saline (control) or ketamine at 3 doses (30, 60, and 90 mg/kg), and the serum was collected at 21 time points (0 h to 29 d). Time-dependent rather than dose-dependent features were observed. Thirty-nine potential biomarkers were identified, including ketamine and its metabolites, lipids, serotonin and other molecules, which were used for building a random forest model to estimate time intervals up to 29 days after ketamine treatment. The accuracy of the model was 85.37% in the cross-validation set and 58.33% in the validation set. This study provides further understanding of the time-dependent changes in metabolites induced by ketamine abuse.

The increasing prevalence of substance misuse in modern culture is contributing to the growth in neonatal abstinence syndrome (NAS) cases in India. NAS can be challenging to diagnose due to nonspecific symptoms and maternal suppression of drug history. Only a few reports of NAS have been published from India. This is a case series of three newborns from India who all had symptoms like restlessness, high-pitched crying, excessive sweating, vigorous sucking, tremors, and diarrhea. The investigations did not lead to any conclusions. In the first case, the mother was treated with a combination of psychotropic medications, including selective serotonin reuptake inhibitors (SSRIs), atypical antipsychotics, and tricyclic antidepressants. In the second case, the mother was a nicotine addict, while in the third case, the mother had an opiate addiction. It was only after being asked several times that the abuse background of the last two cases was revealed. As a result, three cases of NAS were diagnosed, successfully managed with phenobarbitone, and discharged.

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UNASSIGNED: Because of their similar appearance and inexpensive cost, sulfonylureas can cause hypoglycemia when substituted for benzodiazepines by the illicit drug market. We present a patient who developed hypoglycemia after ingestion of what she thought to be Valium; work-up revealed sulfonylurea exposure.
UNASSIGNED: A 33-year-old patient was brought to the hospital after being found unresponsive by paramedics with a reported venous blood glucose level of 18 mg/dL (reference range, 70-140 mg/dL). This prompted treatment with 12.5 g of dextrose administered intravenously. At the hospital, the venous blood glucose level was 15 mg/dL resulting in intravenous dextrose infusion initiation. Once stable, the patient endorsed a medical history of substance use disorder and anxiety. She reported ingesting 2 blue pills given to her by a friend as Valium for her anxiety. Laboratory values showed an elevated insulin level of 47.4 mIU/mL (2.6-24.9), an elevated C-peptide level of 5.4 ng/mL (1.1-4.4), and a glucose level of 44 mg/dL (>70 mg/dL). The patient underwent a 72-hour fasting test. Blood hypoglycemia agent screening showed positive results for glyburide (>5 ng/mL). The patient was discharged home in stable condition.
UNASSIGNED: There are approximately 2 to 5 case reports of hypoglycemia among persons taking illicit drugs containing sulfonylureas. Laboratory values consistent with the use of a hypoglycemic agent include elevated insulin and C-peptide levels, a low glucose level, and positive results for hypoglycemia agent screening.
UNASSIGNED: Sulfonylurea-induced hypoglycemia may lead to clinical sedation, mimicking the effects of benzodiazepines. Sulfonylurea substitution or drug contamination should be suspected when severe hypoglycemia is diagnosed in unresponsive patients suspected of taking illicit drugs.

OBJECTIVE: The abuse of prescription drugs and over-the-counter medicines has been a major issue addressed as a serious public health problem worldwide. This study explored factors contributing to substance abuse in Korea by examining the status of substance abuse among Korean adults and evaluating their knowledge, attitudes, and intentions toward substance abuse.
METHODS: Data were collected online from a sample of participants 19 years old or older from May 20 to June 1, 2020 (n=1,020). The survey consisted of questions on demographics, perceptions of drug risk, motives for drug use, and attitudes toward drug addiction treatment. Principal component and multiple logistic regression analyses were used to explore the factors contributing to the perception of drug abuse.
RESULTS: In the multivariate regression analysis, overconfidence in handling drug usage, acceptance of addictive substances, and affirmation of public support for drug abuse were associated with opioid abuse (Nagelkerke R2=0.486), and additionally affirmation of legal cannabis usage and motivation to use diet pills were associated with diet pill abuse (Nagelkerke R2=0.569).
CONCLUSIONS: The findings of this study suggest that the actual situation of substance abuse among Korean adults increases awareness of and attitudes toward drug use related to substance abuse.

BACKGROUND: The enormous consequences of drugs include suicides, traffic accidents, and violence, affecting the individual, family, society, and country. Therefore, it is necessary to constantly identify and monitor the drug abuse rate among school-going youth. A geospatial dashboard is vital for the monitoring of drug abuse and related crime incidence in a decision support system.
OBJECTIVE: This paper mainly focuses on developing MyAsriGeo, a geospatial drug abuse risk assessment and monitoring dashboard tailored for school students. It introduces innovative functionality, seamlessly orchestrating the assessment of drug abuse usage patterns and risks using multivariate student data.
METHODS: A geospatial drug abuse dashboard for monitoring and analysis was designed and developed in this study based on agile methodology and prototyping. Using focus group and interviews, we first examined and gathered the requirements, feedback, and user approval of the MyAsriGeo dashboard. Experts and stakeholders such as the National Anti-Drugs Agency, police, the Federal Department of Town and Country Planning, school instructors, students, and researchers were among those who responded. A total of 20 specialists were involved in the requirement analysis and acceptance evaluation of the pilot and final version of the dashboard. The evaluation sought to identify various user acceptance aspects, such as ease of use and usefulness, for both the pilot and final versions, and 2 additional factors based on the Post-Study System Usability Questionnaire and Task-Technology Fit models were enlisted to assess the interface quality and dashboard sufficiency for the final version.
RESULTS: The MyAsriGeo geospatial dashboard was designed to meet the needs of all user types, as identified through a requirement gathering process. It includes several key functions, such as a geospatial map that shows the locations of high-risk areas for drug abuse, data on drug abuse among students, tools for assessing the risk of drug abuse in different areas, demographic information, and a self-problem test. It also includes the Alcohol, Smoking, and Substance Involvement Screening Test and its risk assessment to help users understand and interpret the results of student risk. The initial prototype and final version of the dashboard were evaluated by 20 experts, which revealed a significant improvement in the ease of use (P=.047) and usefulness (P=.02) factors and showed a high acceptance mean scores for ease of use (4.2), usefulness (4.46), interface quality (4.29), and sufficiency (4.13).
CONCLUSIONS: The MyAsriGeo geospatial dashboard is useful for monitoring and analyzing drug abuse among school-going youth in Malaysia. It was developed based on the needs of various stakeholders and includes a range of functions. The dashboard was evaluated by a group of experts. Overall, the MyAsriGeo geospatial dashboard is a valuable resource for helping stakeholders understand and respond to the issue of drug abuse among youth.

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).
CONCLUSIONS: 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.

Estrogen related receptors (ERRs) agonist GSK-9089 (DY-131) reported to pose a potential in increasing exercise endurance. High resolution mass spectrometry (HRMS) based analysis has utmost importance in the detection, identification, or characterization of a molecule including its metabolites in human body. In this study, in vitro metabolism profile of GSK-9089 was investigated after incubation with liver microsomes and S9 fractions. Additionally, in vivo metabolites of the molecule were identified in plasma, urine, and faeces samples of rats. Structures of all the potential metabolites were revealed by employing an in silico tool and HRMS based analysis through data-dependent and data-independent mining strategies. Nine unknown metabolites of GSK-9089 have been identified which were found to be present in a trace amount in in vivo matrices. Most of the in vitro and in vivo phase I metabolites of the molecule were formed after imine bond hydrolysis followed by deamidation, oxidation, and N-oxidation. The molecule underwent phase II metabolism to generate more polar metabolites mainly through glucuronide, sulfate conjugation biotransformation reactions. The in vitro and in vivo metabolites of GSK-9089 could be useful to identify the abuse of this ERRs agonist in the future.

The treatment landscape for opioid use disorder (OUD) faces challenges stemming from the limited efficacy of existing medications, poor adherence to prescribed regimens, and a heightened risk of fatal overdose post-treatment cessation. Therefore, there is a pressing need for innovative therapeutic strategies that enhance the effectiveness of interventions and the overall well-being of individuals with OUD. This study explored the therapeutic potential of nor-Levo-α-acetylmethadol (nor-LAAM) to treat OUD. We developed sustained release nor-LAAM-loaded poly (lactic-co-glycolic acid) (PLGA) microparticles (MP) using a hydrophobic ion pairing (HIP) approach. The nor-LAAM-MP prepared using HIP with pamoic acid had high drug loading and exhibited minimal initial burst release and sustained release. The nor-LAAM-MP was further optimized for desirable particle size, drug loading, and release kinetics. The lead nor-LAAM-MP (F4) had a relatively high drug loading (11 wt%) and an average diameter (19 μm) and maintained a sustained drug release for 4 weeks. A single subcutaneous injection of nor-LAAM-MP (F4) provided detectable nor-LAAM levels in rabbit plasma for at least 15 days. We further evaluated the therapeutic efficacy of nor-LAAM-MP (F4) in a well-established fentanyl-addiction rat model, and revealed a marked reduction in fentanyl choice and withdrawal symptoms in fentanyl-dependent rats. These findings provide insights into further developing long-acting nor-LAAM-MP for treating OUD. It has the potential to offer a new effective medication to the existing sparse armamentarium of products available to treat OUD.

Amidst far-reaching COVID-19 effects and social constraints, this study leveraged wastewater-based epidemiology to track 38 conventional drugs and 30 new psychoactive substances (NPS) in northern Taiwan. Analyzing daily samples from four Taipei wastewater plants between September 2021 and January 2024-encompassing club reopenings, holidays, Lunar New Year, an outbreak, and regular periods-thirty-one drugs were detected, including 5 NPS. Tramadol, zolpidem tartrate, CMA, and MDPV were newly detected in Taiwanese sewage with frequency of 1.4 %- 89.0 %. Conventional drug use typically increased post-pandemic, aside from benzodiazepines and methadone. Methamphetamine showed 100 % frequency, indicating ongoing daily consumption despite COVID-19 measures. Methamphetamine and morphine\'s consumption dipped then rose around club reopening, hinting at limited access. The consumption trend of methadone appeared to compensate for the use of morphine. Ketamine and NPS demonstrated similar patterns throughout the entire period. NPS as party drugs seemed influenced by an unstable supply chain and complexities in implementation. Benzodiazepines, commonly abused alongside synthetic cathinones in Taiwan exhibited an opposing trend to NPS while aligned with acetaminophen, suggesting elevated stress and anxiety levels during the pandemic. No significant differences were observed in drug consumption between weekdays and weekends, potentially indicating that COVID-19 measures blurred the traditional distinctions between these timeframes. ENVIRONMENTAL IMPLICATION: New psychoactive substances refer to chemically modified variants of controlled drugs designed to mimic the effects of the original drugs while evading modern detection methods, categorizing them as hazardous materials. The study presents a sewage monitoring project conducted from 2021 to 2024, collecting samples from four WWTPs to analyze NPS and conventional drug trends during and after the COVID-19 pandemic. The findings uncovered connections between drug consumption patterns and pandemic-related policies. In light of the persistent drug abuse and their environmental presence, the results bear critical importance for both environmental and public health. We provide a thorough assessment of these relationships and prioritize areas for future research.