Nitazene opioids and the heart: Identification of a cardiac ion channel target for illicit nitazene opioids.

The growing use of nitazene synthetic opioids heralds a new phase of the opioid crisis. However, limited information exists on the toxic effects of these drugs, aside from a propensity for respiratory depression. With restricted research availability of nitazenes, we used machine-learning-based tools to evaluate five nitazene compounds' interaction potential with the hERG potassium channel, a key drug antitarget in the heart.

Innovations to the ECHO model to enhance reach and network-building among addiction clinicians in Western Canada.

Background: Building capacity for evidence-based treatment and support for people with substance use disorders (SUD) is an urgent priority in the context of the toxic drug poisoning crisis. We implemented the first substance use-focused Project Extension for Community Healthcare Outcomes (ECHO) in Western Canada for health care providers, to enhance their clinical addiction skills and knowledge, facilitate practice change, and foster a supportive community of practice. The aims of this article are to describe our innovations to the Project ECHO model in British Columbia (BC) and Yukon, and present key program outcomes.

Perspectives on Diversion of Medications From Safer Opioid Supply Programs.

Importance: Safer supply programs were implemented in Canada to provide pharmaceutical-grade alternatives to the toxic unregulated drug supply. While research shows clinical benefits and reduced overdose mortality among safer supply patients, medication diversion remains a concern.

Objective: To examine provider (prescribing clinicians and allied health professionals) and patient perspectives on diversion of opioids prescribed in safer supply programs.

Self-Harm as a Contributor to the Opioid Epidemic: Data From the Toxicology Investigators Consortium Registry.

Objectives: Although considerable focus has been placed on understanding the causes of opioid drug overdoses, the intentions for such overdoses are not well characterized. We investigated the motivations behind nonfatal opioid exposures resulting in serious adverse health outcomes.

Methods: We analyzed prospectively collected data on nonfatal opioid overdoses in the multicenter Toxicology Investigators Consortium (ToxIC) Core Registry between 2014 and 2021.

The incorporation of MALDI mass spectrometry imaging in studies to identify markers of toxicity following opioid exposures in mouse fetuses.

Introduction: In 2015, the FDA released a Drug Safety Communication regarding a possible link between opioid exposure during early pregnancy and an increased risk of fetal neural tube defects (NTDs). At the time, the indications for opioid use during pregnancy were not changed due to incomplete maternal toxicity data and limitations in human and animal studies. To assess these knowledge gaps, largescale animal studies are ongoing; however, state-of-the-art technologies have emerged as promising tools to assess otherwise non-standard endpoints.

Could chronic opioid use be an additional risk of hepatic damage in patients with previous liver diseases, and what is the role of microbiome?

Among illicit drugs, addiction from opioids and synthetic opioids is soaring in an unparalleled manner with its unacceptable amount of deaths. Apart from these extreme consequences, the liver toxicity is another important aspect that should be highlighted. Accordingly, the chronic use of these substances, of which fentanyl is the most frequently consumed, represents an additional risk of liver damage in patients with underlying chronic liver disease.

In vitro safety evaluation of dopamine D3R antagonist, R-VK4-116, as a potential medication for the treatment of opioid use disorder.

R-VK4-116 is currently being developed as a medication to treat opioid use disorder (OUD). To characterize in vitro safety properties of R-VK4-116, metabolic stability in hepatocytes or liver microsomes, metabolite identification, metabolism/transporter-mediated drug interactions, lysosomal perturbation, mitochondrial toxicity, off-target enzyme effects, cellular and nuclear receptor functional assays, electrophysiological assays, CiPA, KINOMEscanTM, plasma protein binding, phospholipidosis and steatosis assays were performed. Overall, R-VK4-116 was metabolically stable in hepatocytes and microsomes.

Reshaping the Landscape of Locoregional Treatments for Breast Cancer Liver Metastases: A novel, intratumoral, p21-targeted percutaneous therapy increases survival in BALB/c mice inoculated with 4T1 triple negative breast cancer cells in the liver.

Patients with disseminated metastatic disease from breast cancer are likely to have liver involvement in >50% of cases at some point during disease progression. These patients have a poor prognosis; and, when treated with the standard of care systemic therapy they have a median survival of <9-months. Increasing survival in breast cancer patients will likely require the administration of better therapies that are specifically targeted to treat distant metastases.

The efficacy of wound catheter infusion with local anesthetics for the treatment of postoperative pain in children: A systematic review.

Wound catheter infusion (WCI) with local anesthetics (LA) is a regional anesthesia technique, which has shown to produce effective postoperative analgesia in adults, without any adverse effects on wound healing. To investigate the efficacy and safety of WCI with LA for the treatment of postoperative pain in children, we conducted a systematic review of literature published until 2020. The literature search included articles concerning subcutaneous WCI with LA, in the surgical wound, as treatment of postoperative pain, in children <18 years of age.

Safety and Tolerability of Intravenous Lidocaine Infusions as Opioid Adjunct for Children Hospitalized With Sickle Cell Vaso-Occlusive Pain.

Sickle cell disease (SCD) vaso-occlusive episode (VOE) pain is treated with opioids, and non-opioid adjuvants may reduce pain severity without opioid side effects. We retrospectively investigated the safety and tolerability of intravenous lidocaine infusions as an adjunct to opioids in children and adolescents during VOE hospitalizations. In 2 years, lidocaine was administered in 64.

Comparison of Laboratory Confirmed Drugs in Acute Recreational Drug Toxicity Presentations to an Urban Hospital in London, UK, 2016/17 versus 2019/20.

Introduction: Novel Psychoactive Substance (NPS) use is increasingly prevalent and is often associated with severe acute recreational drug toxicity (ARDT). 258 UK deaths were attributed to NPS use in 2021. Confirmatory testing which identifies NPS is limited by expense and timeliness.

Revisiting opioid toxicity: Cellular effects of six commonly used opioids.

Objectives: There is an ongoing opioid crisis in the United States where the illicit and non-medical use of prescription opioids is associated with an increasing number of overdose deaths. Few studies have investigated opioid-induced effects on cell viability, and comparative studies are limited. Here, we examine the toxicity of six commonly used opioids: methadone, morphine, oxycodone, hydromorphone, ketobemidone, and fentanyl with respect to mitochondrial and membrane function .

Molecular and Environmental Determinants of Addictive Substances.

Knowledge about determinants of addiction in people taking addictive substances is poor and needs to be supplemented. The novelty of this paper consists in the analysis of innovative aspects of current research about relationships between determinants of addiction in Polish patients taking addictive substances and rare available data regarding the relationships between these factors from studies from recent years from other environments, mainly in Europe, and on the development of genetic determinants of physiological responses. We try to explain the role of the microelements Mn, Fe, Cu, Co, Zn, Cr, Ni, Tl, Se, Al, B, Mo, V, Sn, Sb, Ag, Sr, and Ba, the toxic metals Cd, Hg, As, and Pb, and the rare earth elements Sc, La, Ce, Pr, Eu, Gd, and Nd as factors that may shape the development of addiction to addictive substances or drugs.

Impact of Intrauterine Insults on Fetal and Postnatal Cerebellar Development in Humans and Rodents.

Many children suffer from neurodevelopmental aberrations that have long-term effects. To understand the consequences of pathological processes during particular periods in neurodevelopment, one has to understand the differences in the developmental timelines of brain regions. The cerebellum is one of the first brain structures to differentiate during development but one of the last to achieve maturity.

Continuous Incisional Infusion of Local Anaesthetic (CIILA) Reduces Postoperative Opioid Usage in Children.

Aim: Adequate post-operative pain relief is associated with shorter recovery time and higher patient satisfaction. Universally, opioids have been the mainstay but are associated with many adverse effects. We aimed to assess the safety and effectiveness of Continuous Incisional Infusion of Local Anaesthetic (CIILA) for postoperative pain relief in the paediatric population.

A New Source of Opioid and Lead Toxicity on the Block-Kamini: An Emerging Health Hazard-A Case Series.

Introduction: Illicit drug abuse with opioids can inadvertently lead to refractory anemia and lead poisoning. The absence of adequate regulations for Ayurvedic herbal products has led to the adulteration of opioid-containing drugs with lead. As a result, lead toxicity has become a concern within this seldom-addressed population of opioid users.

The role of Alberta pharmacists working in opioid use disorder and their potential to prescribe buprenorphine-naloxone: A qualitative study.

Objective: Opioid toxicity continues to have significant morbidity and mortality in Alberta. Opioid agonist therapy is an effective treatment for opiate use disorder (OUD), with first-line treatment with buprenorphine-naloxone (BUP-NAL) being both highly effective and safe. Barriers to care limit access to treatment, and more access points for treatment are needed.

Interventional Radiology Management of Bone Metastasis Pain: Strategies and Techniques.

Osseous metastases are common in cancer patients, and pain is one of the most frequent associated symptoms. The management of cancer-related pain is still problematic worldwide with 40 to 50% of patients still being undertreated. A significant proportion of cancer patients will require discontinuation of traditional analgesic treatments such as opioids due to unsuccessful pain relief or severe unmanageable toxicity and may, therefore, benefit from alternative treatments.