Search Results (25)

Xylazine, commonly called “tranq” or “sleep cut”, is a strong α2-adrenergic agonist used in veterinary practice as a sedative, analgesic, and muscle-relaxing agent. It has never been approved by the Food and Drug Administration for human use, but its use by people is on the rise. In the last decades, due to its low cost and ease of availability, it has often been illicitly used due to its abuse potential as a drug for attempted sexual assault and intended poisoning. In addition, xylazine’s presence in the human body has also been related to domestic accidental events. Generally, it is combined with multiple other drugs, typically by intravenous injection, potentiating the doping effects. Xylazine’s mechanism of action is different from that of other illicit opioids, such as heroin and fentanyl, and it has no known antidote approved for use in humans. The combination with fentanyl prolongs the euphoric sensation and may heighten the risk of fatal overdose. Furthermore, it may cause adverse effects, including central nervous system (CNS) and respiratory depression, bradycardia, hypotension, and even death. Recent reports of xylazine misuse have risen alarmingly and describe people who become “zombies” because of the drug’s harmful effects on the human body, including serious wound formation that could even lead to limb amputation. This paper is an extensive review of the existing literature about xylazine and specifically deals with the chemistry, pharmacokinetics, pharmacodynamic, and toxicological aspects of this compound, highlighting the most recent studies. Full article

Background: Cocaine and illicit amphetamines (disguised as “Adderall”) are being laced with fentanyl and producing accidental and intentional fatal overdoses. Vaccines can prevent these overdoses, but 33% of humans generate insufficient anti-drug antibody (AB) levels. Plasma microRNAs (miRs) can be used to predict non-responders. We have plasma stored from 152 cocaine vaccine trial participants following three vaccinations over 9 weeks and examined miRs as potential response biomarkers. Methods: We compared 2517 miRs before anti-cocaine vaccination in participants with the highest (n = 25) to the lowest (n = 23) antibody levels. False Discovery Rates (FDRs) were applied to identify differentially expressed (DE) miRs. We used miR target prediction pipelines to identify the miR-regulated genes. Results: Using a DE-FDR < 0.05 and a >3-fold difference between high- and low-AB responders yielded 12 miRs down and 3 miRs up compared to low-AB patients. Furthermore, 11 among 1673 genes were targeted by 3 or more of the 12 down DE-miRs. Conclusions: A significant DE-miR for identifying optimal antibody responders replicated previous vaccine study predictors (miR-150), and several more miRs appear to be strong candidates for future consideration in replications based upon significance of individual DE-miRs and upon multiple miRs converging on individual genes. Full article

Background/Objectives: Acute drug intoxications (ADIs) are a significant concern in pediatric healthcare, contributing to both accidental and intentional morbidity. This study aimed to analyze the demographic, clinical, and therapeutic characteristics of pediatric ADI cases to identify trends and inform preventive strategies. Methods: This retrospective study included 120 cases of pediatric ADI admitted to the Second Pediatric Clinic of Craiova County Emergency Clinical Hospital in 2022 and 2023. The inclusion criteria encompassed children aged 0–17 years with confirmed pharmaceutical intoxications. Cases involving mixed poisonings or non-pharmaceutical substances were excluded. Clinical severity was classified using the Poisoning Severity Score (PSS). Data on demographics, substances involved, clinical presentations, interventions, and outcomes were analyzed. Results: The majority of cases occurred in females (73.3%) and urban residents (77.5%). Accidental intoxications were prevalent in children aged 1–5 years (45%), while intentional ingestions were common in adolescents (47.5%). The most frequently implicated substances included antibiotics (46.7%), benzodiazepines (20.8%), and acetaminophen (15.8%). Severity was classified as mild (44.2%), moderate (26.6%), or severe (29.2%), while treatment primarily included supportive care, intravenous fluids (62.5%), and antidotes (35.8%). Severe cases required respiratory support in 29.2% of the instances. Hospitalization duration significantly decreased from 2022 (3.8 ± 1.9 days) to 2023 (2.3 ± 0.9 days) (p < 0.05), and no fatalities were recorded. Conclusions: Pediatric ADIs predominantly involve accidental ingestions in young children and intentional overdoses in adolescents. Targeted public health strategies, such as parental education, adolescent mental health support, and improved rural healthcare access, are essential to reduce incidence and severity. These findings underscore the need for focused prevention and optimized clinical management. Full article

If there is one poet who has been widely represented under a legendary light, it is Elizabeth Barrett Browning (1806–1861), mostly through the figure of a secluded invalid. Barrett Browning’s illness and death have been romanticised ever since her own time, with multiple rumours and theories mostly focusing on the fact that her illness was ‘miraculously dispelled’ by ‘love’ and only reappeared gradually to take the poet’s life. This article proposes yet another and quite different diagnosis for Barrett Browning’s illness, theorising on the possibility that Barrett Browning’s ailment was a pulmonary congenital malformation, which remained misdiagnosed due to the lack of medical technology at the time. Several of the diagnoses given to Barrett Browning by her medical practitioners, contemporary and posthumous biographers and other scholars are presented and compared, alongside my own hypothesis. In addition, Barrett Browning’s arguable morphine dependency is reassessed in order to explore its impact on her illness, with the possibility that it exacerbated or even caused some of her symptoms. This reassessment also explores the role that morphine played in Barrett Browning’s death, suggesting an accidental overdose possibly overlooked by Robert Browning. Full article

Pharmaceutical poisoning is a significant global public health concern, causing approximately 190,000 deaths annually. This scoping review aims to comprehensively map the available literature on pharmaceutical poisoning and compare patterns between high-income countries (HICs) and low-middle-income countries (LMICs). A systematic search was performed across the following databases: Embase, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and CINAHL. Studies included were from 1 January 2011 to 31 December 2020, in English, with full text available. Seventy-nine articles were included in the study; 21 were from LMICs and 58 were from HICs. Toxic exposure was largely intentional (77%) in LMICs and accidental (68%) in HICs. Drugs acting on the nervous system were responsible for 95% of toxicities worldwide with analgesics accounting for the largest subtherapeutic group in both LMICs (40%) and HICs (58%). Notable statistics were that HICs accounted for 99% of opioid overdoses, and LMICs accounted for 19% of anti-epileptic-induced toxicities. Overall, the medical outcomes due to poisonings were generally worse in LMICs. The review provides possible interventions to target specific geographic locations, based on the trends identified, to reduce the burden worldwide. Many gaps within the literature were recognised, calling for more robust analytical research. Full article

The European Medicine Agency (EMA) has defined Adverse Drug Reactions (ADRs) as “a noxious and unintended response to a medicine”, not including poisoning, accidental, or intentional overdoses. The ADR occurrence differs based on the approach adopted for defining and detecting them, the characteristics of the population under study, and the research setting. ADRs have a significant impact on morbidity and mortality, particularly among older adults, and represent a financial burden for health services. Between 30% and 60% of ADRs might be predictable and preventable, emerging as a result of inappropriate prescription, drug chemistry inherent toxicity, cell-specific drug toxicity, age- and sex-related anomalies in drug absorption, distribution, metabolism, and elimination (ADME), and drug–drug interactions (DDIs) in combination therapies or when a patient is treated with different drugs for concomitant disorders. This is particularly important in chronic diseases which require long-term treatments. Rapid developments in pharmacogenetics/genomics have improved the understanding of ADRs accompanied by more accurate prescriptions and reduction in unnecessary costs. To alleviate the burden of ADRs, especially in the elderly, interventions focused on pharmaceutical principles, such as medication review and reconciliation, should be integrated into a broader assessment of patients’ characteristics, needs, and health priorities. Digital health interventions could offer valuable solutions to assist healthcare professionals in identifying inappropriate prescriptions and promoting patient adherence to pharmacotherapies. Full article

In recent years, the administration of fentanyl (FNTL) implicitly in transdermal drug delivery systems (TDDS) has vastly increased in chronic pain treatment. Non-medical and uncontrolled use of FNTL in TFDS (transdermal fentanyl delivery systems) may reveal toxic effects by the route of exposure, dermal or alternative, by ingestion of patches, and drug release in the stomach. The purpose of this study was to present three different cases of FNTL poisonings, two of which resulted in death due to TFDS abuse. The first case is a 66-year-old woman treated for accidental FTNL poisoning resulting in acute respiratory distress syndrome. Two remaining cases are a 31-year-old woman and a 25-year-old man who died as a result of FNTL overdose after on-skin and ingestion application of the drug patches. During the hospitalization of the 66-year-old patient, in blood samples, FNTL was confirmed at a concentration of 10.0 ng/mL. Tests run on blood taken from the corpses of 25- and 31-year-old patients exhibited FNTL presence in concentrations of 29.1 ng/mL and 38.7 ng/mL, respectively. The various routes of administration and ultimately toxic effects are important to present because, in TDDS, fentanyl can be a reason for severe to fatal poisoning, as shown by the three cases above. Full article

Positive psychology is a rapidly expanding and recent empirical. interdisciplinary research topic (i.e., within the last 25 years). Early evidence supported that targeting positive variables (i.e., empathy or kindness) has numerous benefits, including improving health outcomes, vocational success, psychological well-being, and interpersonal connectedness. Positive Psychological Interventions (PPIs) are activities and behavioral interventions that target positive variables to promote adaptive functioning (e.g., reducing depression or promoting psychological well-being). PPIs may make excellent contributions to treating substance use, substance use disorders (SUDs), and substance use problems because the interventions can partially shift the notable negative treatment focus (e.g., avoiding the consequences of using) onto positive aspects (e.g., pursuing an ideal future). Current substance use treatment outcomes demonstrate a need for improvements (e.g., low abstinence rates and lifetime symptom remission of SUDs), and positive psychology may provide a framework for improving existing treatments. In the current paper, the author reviewed research supporting the use of PPIs in substance use treatments, provide suggestions for PPI applications, examine advantages and practical issues, outline the current limitations, and provide future directions for continuing this line of work. The author aimed to encourage researchers to advance substance use treatment improvements with positive psychology because the growing consequences from substance use (e.g., the growing frequency of accidental fatal overdose) and the variable, limited treatment outcomes, placing those who use substances in a uniquely vulnerable position. Full article

Background: There have been multiple reported pharmacy initiatives to reduce opioid misuse and accidental overdose to address our nation’s public health crisis. To date, there has not been a description in the literature of a community pharmacy follow-up initiative for dispensed opioids. Methods: A follow-up program was designed and implemented in community pharmacies as part of a previously developed opioid overdose and misuse prevention program (ONE Program). Five to twelve days after the dispensing of an opioid, pharmacy technicians called the patient to follow up on opioid safety topics. Pharmacy technicians used a questionnaire to inquire about medication disposal plans, if the patient was taking the medication more than prescribed, medication side effects, and if the patient needed a pharmacist consultation. The results from that questionnaire were documented. Results: During the first 18 months of the follow-up program, 1789 phone calls were completed. Of those contacted, 40% were still using their opioid medication, and over 10% were experiencing side effects which triggered a pharmacist consult. Patients were reminded of proper medication disposal methods, and most patients (78%) desired to dispose of unused medication at the pharmacy medication disposal box. Conclusions: Follow-up phone calls post-opioid medication dispensing were shown to add value to a previously established opioid misuse and accidental overdose prevention program and allowed for the fulfillment of the Pharmacist Patient Care Process. Full article

There has been a worldwide substantial increase in accidental opioid-overdose deaths. The aim of this review, along with preliminary results from our pilot study, is to highlight the use of pharmacogenetics as a tool to predict causes of accidental opioid-overdose death. For this review, a systematic literature search of PubMed^® between the time period of January 2000 to March 2023 was carried out. We included study cohorts, case–controls, or case reports that investigated the frequency of genetic variants in opioid-related post-mortem samples and the association between these variants and opioid plasma concentrations. A total of 18 studies were included in our systematic review. The systematic review provides evidence of the use of CYP2D6, and to a lower extent, CYP2B6 and CYP3A4/5 genotyping in identifying unexpectedly high or low opioid and metabolite blood concentrations from post-mortem samples. Our own pilot study provides support for an enrichment of the CYP2B6*4-allele in our methadone-overdose sample (n = 41) compared to the anticipated frequency in the general population. The results from our systematic review and the pilot study highlight the potential of pharmacogenetics in determining vulnerability to overdose of opioids. Full article

The year 2021 was the most deadly year for overdose deaths in the USA and Canada. The stress and social isolation stemming from the COVID-19 pandemic coupled with a flood of fentanyl into local drug markets created conditions in which people who use drugs were more susceptible to accidental overdose. Within territorial, state, and local policy communities, there have been longstanding efforts to reduce morbidity and mortality within this population; however, the current overdose crisis clearly indicates an urgent need for additional, easily accessible, and innovative services. Street-based drug testing programs allow individuals to learn the composition of their substances prior to use, averting unintended overdoses while also creating low threshold opportunities for individuals to connect to other harm reduction services, including substance use treatment programs. We sought to capture perspectives from service providers to document best practices around fielding community-based drug testing programs, including optimizing their position within a constellation of other harm reduction services to best serve local communities. We conducted 11 in-depth interviews from June to November 2022 via Zoom with harm reduction service providers to explore barriers and facilitators around the implementation of drug checking programs, the potential for integration with other health promotion services, and best practices for sustaining these programs, taking the local community and policy landscape into account. Interviews lasted 45–60 min and were recorded and transcribed. Thematic analysis was used to reduce the data, and transcripts were discussed by a team of trained analysts. Several key themes emerged from our interviews: (1) the instability of drug markets amid an inconsistent and dangerous drug supply; (2) implementing drug checking services in dynamic environments in response to the rapidly changing needs of local communities; (3) training and ongoing capacity building needed to create sustainable programs; and (4) the potential for integrating drug checking programs into other services. There are opportunities for this service to make a difference in overdose deaths as the contours of the drug market itself have changed over time, but a number of challenges remain to implement them effectively and sustain the service over time. Drug checking itself represents a paradox within the larger policy context, putting the sustainability of these programs at risk and challenging the potential to scale these programs as the overdose epidemic worsens. Full article

Potassium overdose usually occurs accidentally, but potassium is also used for judicial executions, assisted death, and, rarely, suicides. In addition to exogenous overdose, various drugs, and renal failure, diabetic ketoacidosis can cause hyperkalemia. Potassium tablets are used in most cases of suicidal potassium overdose. Suicide by intravenous administration of potassium is rare but usually fatal. The author reports a rare case of suicide with potassium infusion. Autopsy and histology findings, along with post-mortem biochemical analysis of different body fluids and fluid from the infusion set, are reported. Previously published reports of potassium overdose were reviewed, and the detection possibilities of potassium overdose are discussed. The detection possibilities of lethal hyperkalemia are very limited since hyperkalemia produces only nonspecific autopsy and histology findings. Post-mortem potassium concentrations are not indicative of ante-mortem potassium concentrations; therefore, post-mortem biochemical analysis has limited value in determining potassium overdose. The best way to prove potassium overdose is via the collection and analysis of circumstantial evidence. Full article

The published health benefits of Cannabis sativa has caught the attention of health-conscious consumers and the food industry. Historically, seeds have long been utilized as a food source and currently there is an increasing number of edibles on the market that contain cannabis. Cannabinoids include the psychoactive constituent, delta-9-tetrahydrocannabinol (THC), and the non-psychoactive cannabidiol (CBD) that are both compounds of interest in Cannabis sativa. This paper looks at the distribution of nutrients and phytocannabinoids in low-THC Cannabis sativa, the historical uses of hemp, cannabis edibles, and the possible side-effects and concerns related to cannabis edibles. Several authors have pointed out that even though the use of cannabis edibles is considered safe, it is important to mention their possible side-effects and any concerns related to its consumption that negatively influence consumer acceptance of cannabis edibles. Such risks include unintentional overdose by adults and accidental ingestion by children and adolescents resulting in serious adverse effects. Therefore, cannabis edibles should be specifically packaged and labelled to differentiate them from known similar non-cannabis edibles so that, together with tamperproof packaging, these measures reduce the appeal of these products to children. Full article

Background and Objectives: Insulin and oral hypoglycemic agents are drugs widely used in the world population due to their therapeutic effects on diabetes mellitus. Despite these benefits, they can also cause accidental or voluntary drug overdose. This review aims to evaluate post-mortem investigations in cases of suspected hypoglycemic drug overdose. Materials and Methods: We performed a comprehensive search using the Preferred Reporting Items for Systematic Review (PRISMA) standards; we systematically searched the PubMed, Science Direct Scopus, Google Scholar, and Excerpta Medica Database (EM-BASE) databases from the point of database inception until August 2022. The following inclusion criteria were used: (1) original research articles, (2) reviews and mini-reviews, (3) case reports/series, (4) and only papers written in English. Results: Thirty-three scientific papers, including original research articles, case reports, and case series, fulfilled the inclusion criteria. A total of 109 cases of insulin or hypoglycemic drug overdose were found. There were 71 cases of suicide (65%), 25 cases of accidental poisoning (23%), and 13 cases of homicide (12%). The most commonly used drug was insulin (95.4%). Autopsy and post-mortem examinations were performed in 84 cases, while toxicological investigations were performed in 79 cases. The most common gross findings in the autopsy were pulmonary edema (55.7%) and congestion (41.8%), while the most common histological finding was neuronal depletion or necrosis (29.1%). Conclusions: In the suspicion of death from insulin or overdose from oral hypoglycemic agents, autopsy findings may be nonspecific, and the search for injection marks can be positive at the external examination. Significant post-mortal alterations can interest biological samples and an early autopsy investigation is recommended. Full article

Regional anaesthesia is well established as a standard method in clinical practice. Currently, the local anaesthetics of amino-amide types such as prilocaine are frequently used. Despite routine use, complications due to overdose or accidental intravenous injection can arise. A non-invasive method that can indicate such complications early would be desirable. Breath gas analysis offers great potential for the non-invasive monitoring of drugs and their volatile metabolites. The physicochemical properties of o-toluidine, the main metabolite of prilocaine, allow its detection in breath gas. Within this study, we investigated whether o-toluidine can be monitored in exhaled breath during regional anaesthesia in an animal model, if correlations between o-toluidine and prilocaine blood levels exist and if accidental intravenous injections are detectable by o-toluidine breath monitoring. Continuous o-toluidine monitoring was possible during regional anaesthesia of the cervical plexus and during simulated accidental intravenous injection of prilocaine. The time course of exhaled o-toluidine concentrations considerably differed depending on the injection site. Intravenous injection led to an immediate increase in exhaled o-toluidine concentrations within 2 min, earlier peak and higher maximum concentrations, followed by a faster decay compared to regional anaesthesia. The strength of correlation of blood and breath parameters depended on the injection site. In conclusion, real time monitoring of o-toluidine in breath gas is possible by means of PTR-ToF-MS. Since simulated accidental intravenous injection led to an immediate increase in exhaled o-toluidine concentrations within 2 min and higher maximum concentrations, monitoring exhaled o-toluidine may potentially be applied for the non-invasive real-time detection of accidental intravenous injection of prilocaine. Full article