Toxic Death Research Articles

Efficacy and Safety of Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor T-Cell for the Treatment of Relapsed and Refractory AL Amyloidosis.

The use of anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CART) therapy for AL amyloidosis (AL) is limited owing to patient frailty. HBI0101 anti-BCMA CART was the first proof of concept for its applicability to AL. This report addresses the AL patient cohort treated to date within the phase Ia/Ib clinical trial (ClinicalTrials.gov identifier: NCT04720313). After lymphodepletion, most AL patients were infused with 800 × 106 CARTs. Sixteen patients were treated, with a median of four previous lines of therapy (range, 3-10), 14/16 were triple class refractory, and 6/16 were refractory to belantamab. Most patients (13/16) had cardiac involvement, including five with MAYO stage IIIa/IIIb at study entry. Cytokine release syndrome was frequent (14/16) but mostly low grade (grade 3: 3/16, no grade 4/5). No neurologic toxicity or treatment-related deaths were observed. There were five grade 3 AL-related organ deteriorations resolved quickly with supportive care. The overall hematologic response rate was 15/16 (94%) and complete response (CR) was 12/16 (75%). Minimal residual disease negativity was achieved in 9/14 evaluable patients. Most patients (8/13 evaluable) achieved an objective organ response. Seven patients died during long-term follow-up, three while in CR/very good partial response, and the median overall survival was 10.1 months (95% CI, 5.8 to not reached). This largest clinical trial of AL patients treated with anti-BCMA CART demonstrates acceptable and manageable toxicity in a highly frail and resistant population with remarkable efficacy, leading to fast organ responses. Among patients with baseline advanced cardiac disease, deaths in the first year were frequent, suggesting that this effective therapy should be considered earlier in the course of therapy. Anti-BCMA CART may become a powerful tool for improving organ function and survival in patients with AL.

Chronic disease diagnoses and health service use among people who died of illicit drug toxicity in British Columbia, Canada.

Illicit drug toxicity (i.e., overdose) is the leading cause of death in British Columbia (BC) for people aged 10-59. Stimulants are increasingly detected among drug toxicity deaths. As stimulant useand detection in deaths rises, it is important to understand how people who die of stimulant toxicity differ from people who die of opioid toxicity. BC Coroners Service records were retrieved for all people who died of unintentional illicit drug toxicity (accidental or undetermined) between January 1, 2015, and December 31, 2019, whose coroner investigation had concluded and who had an opioid and/or stimulant detected in post-mortem toxicology and identified by the coroner as relevant to the death (N = 3788). BC Chronic Disease Registry definitions were used to identify people with chronic disease. Multinomial regression models were used to examine the relationship between chronic disease diagnoses and drug toxicity death type. Of the 3788 deaths, 11.1% (N = 422) had stimulants but not opioids deemed relevant to the cause of death (stimulant group), 26.8% (N = 1014) had opioids but not stimulants deemed relevant (opioid group), and 62.1% (N = 2352) had both opioids and stimulants deemed relevant (opioid/stimulant group). People with ischemic heart disease (1.80 (1.14-2.85)) and people with heart failure (2.29 (1.25-4.20)) had approximately twice the odds of being in the stimulant group as compared to the opioid group. Findings suggest that people with heart disease who use illicit stimulants face an elevated risk of drug toxicity death. Future research should explore this association and should identify opportunities for targeted interventions to reduce drug toxicity deaths among people with medical comorbidities.

Acute Oral Toxicity Assessment of Repchol in Wistar Rats: A Liver-protective Herbal Premix for Poultry

The present study was conducted for the assessment of acute oral toxicity and safety analysis of Repchol Premix (M/s Ayurvet Limited) according to OECD-423 guidelines. Six adult Wistar rats, weighing 113-134 g, were used for the study. After oral administration of Repchol@ 300 and 2000mg/kg body weight, the animals were observed for manifestation of toxic effect and death upto14 days. Evaluation of safety analysis and toxicity was assessed on the basis of presence of mortality or toxicity symptoms. Every animal in group served as its own control. At the end of experiment blood biochemical parameters and histopathological changes in heart, liver, kidney and lung were studied. The results showed that Repchol did not produce toxic effects or mortality during the experimental period. The body weight changes observed for two weeks were in the normal range. In Repchol treated rats biochemical parameters like AST, ALT, ALP and creatinine were observed within normal range and in histopathological examination no significant microscopic alterations were observed. Thus, the observations indicated that Repchol Premix did not produce toxic effect or acute oral toxicity and the LD50 of compound is beyond 2000mg/kg.

Pediatric Mature B-Cell Non-Hodgkin Lymphomas in India: A Retrospective Multicenter Pooled Analysis of Treatment Approaches and Outcomes

BackgroundPublished data on outcomes ofpediatric mature B-cell non-Hodgkin lymphoma (B-NHL) from India is limited and difficult to interpret due to small sample size and non-uniform treatment protocols.This study aims to do a pooled analysis of published patient data from multiplecenters across India to provide a clearer understanding of survival rates and treatment-related toxicities with respect to the treatment protocols in this population. MethodsA pooled analysis of patient-level data from 505 children with mature B-NHL, including Burkitt lymphoma (n=395), diffuse large B-cell lymphoma (DLBCL, n=52), and other subtypes (n=58), treated from 2000 to 2022 at seven major cancer centers in India, was conducted. Outcomes assessed were grade 3/4 toxicities, toxic deaths, relapse/progression, and survival rates. ResultsMost patients (401/505) presented with advanced disease; bone marrow and CNS involvement were observed in 13.9% and 6.9% of cases, respectively. Treatment protocols primarily included LMB (n=208), BFM (n=191), and MCP (n=61). Grade 3/4 toxicities were reported in 79.2% of patients, with higher rates observed with LMB protocol (92.1%) compared to BFM (70.8%) and MCP (70.1%) (p<0.001). Toxic death rates were similar across protocols. Overall survival (OS) and event-free survival (EFS) at a median follow-up of 17 months were 69.4±2.2% and 64.9±2.2%, respectively, with no significant differences in relapse/progression rates or stage-specific OS between protocols (p=0.28 and 0.51). ConclusionsThis pooled analysis shows that although treatment-related toxicities differ by protocol, overall survival outcomes were similar across the LMB, BFM, and MCP regimens, despite being lower than those reported in Western studies.Uniform standardized protocols may further improve outcomes for pediatric B-NHL in India.

A scoping review on barriers and facilitators to harm reduction care among youth in British Columbia, Canada

BackgroundProgressive harm reduction policies have been implemented in British Columbia, Canada. However, youth who use drugs face barriers to receiving harm reduction care, resulting in increasing opioid-related hospitalizations and drug toxicity deaths. This scoping review collates peer-reviewed evidence to understand the barriers and facilitators faced by youth who use drugs when accessing harm reduction programming in British Columbia, Canada.MethodsThis scoping review entailed conducting a systematic search of relevant databases to identify relevant articles. Articles were included if they: (i) contained youth falling between the ages of 12 and 26 years old; (ii) explored accessibility, barriers, and/or facilitators to harm reduction care or related topics; (iii) were empirical research articles using primary data (i.e., reviews, grey literature, theoretical or conceptual papers, books, etc. were excluded); and (iv) were available in the English language, given the geographic focus on British Columbia.ResultsA total of 398 sources were identified and ultimately, data from 13 sources were charted and extracted. When investigating barriers to harm reduction care among youth, four themes emerged: self-stigma, service navigation, service delivery, and negative provider interactions. Furthermore, in exploring factors that facilitate harm reduction care for youth, four themes surfaced: ability to meet basic needs, positive provider interactions, social networks, and risk mitigation guidance.ConclusionsThe expansion of harm reduction services in 2016 did not fully address accessibility challenges faced by youth who use drugs. Barriers continue to hinder harm reduction engagement, while supportive networks, positive provider interactions, and the ability to meet basic needs facilitated sustained access. Tailored policy interventions rooted in equity are crucial to improving access to harm reduction services for youth who use drugs.

Opioid deaths in children in Ontario: A province-wide study

Abstract Objectives Opioid-related deaths are an ongoing concern. There have been increasing numbers of fentanyl-related adult deaths with limited knowledge of the characteristics and circumstances of opioid toxicity deaths in children. Our aim was to address this using province-wide data capturing all deaths in children under the age of 10 years in Ontario. Methods Data were extracted from the opioid investigative aid database at the Office of the Chief Coroner from the implementation of the system from October 1, 2017, to October 31, 2021. This collects all opioid-related deaths in Ontario (population 14.7 million). A chart review was undertaken on all deaths under 10 years of age. Patient characteristics were calculated as percentages; descriptive analysis was conducted. Results Ten deaths in children under the age of 10 occurred during the study period. The average age was 1.9 years with the oldest being 4 years and 9 months. The causative opioid was fentanyl alone in four cases (40%), fentanyl and other drugs in four cases (40%), and hydromorphone and methadone in one case each (10%). Most cases involved improperly stored medication or illicit substances. All children who died had previous child protection service involvement, and at least 70% of their families had previous police involvement. Conclusions Fentanyl was the primary substance involved in 80% of deaths. Several potential areas of system change include education on fentanyl risk to young children, careful storage of illicit substances, and implications for how the child protection system intervenes in homes where the use of opioids and illicit substance use is reported to occur.

Aspirin reduces Ponatinib-induced cardiovascular toxic phenotypes and death in zebrafish

BackgroundPonatinib (Iclusig) is an oral tyrosine kinase BCR-ABL inhibitor for treating patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myeloid leukemia (CML) who are resistant to the therapies with other tyrosine kinase inhibitors. However, adverse cardiovascular events caused by Ponatinib are a serious issue that affects patients' survival rates. Thus, it is necessary to search for candidate drugs to reduce the cardiovascular toxicity of Ponatinib. PurposeTo investigate the effects of Aspirin on Ponatinib-induced cardiovascular toxicity in zebrafish. MethodsAB strain of wild type zebrafish (Danio rerio), Tg (cmlc2: GFP) transgenic zebrafish, and Tg (gata1: dsRed) transgenic zebrafish were used as in vivo models to assess survival, blood flow, cardiac morphology, and function. Thrombus formation was detected using O-dianisidine staining. The transcriptome of zebrafish larvae treated with Ponatinib was assessed using RNA sequencing. ResultsPonatinib not only reduced survival rate but also caused cardiovascular toxic events such as pericardial edema, abnormal heart structure, low heart rate, and thrombosis. In addition, whole-body transcriptome analysis showed that Ponatinib up-regulated the expression of cyclooxygenase-1 (COX-1). Compared with other antithrombotic drugs, a COX-1 inhibitor Aspirin more effectively reduced ponatinib-induced cardiovascular toxicity events and improved the survival rate of zebrafish larvae. ConclusionOur findings suggest that Aspirin exhibits the potential to reduce Ponatinib-induced cardiovascular toxicity.

Trends in Pregnancy-Associated Opioid Toxicity and Mortality

ObjectivesTo examine trends in pregnancy-associated non-fatal and fatal opioid toxicity and all-cause mortality, and identify associated factors. ApproachWe conducted a population-based study of 1,555,370 pregnancies in Ontario, Canada, 2013-2022. We analyzed linked administrative datasets, including coroner data, and calculated pregnancy-associated (during pregnancy or within one-year post-pregnancy) non-fatal/fatal opioid toxicity and all-cause mortality ratios per 100,000 livebirths by year and timing (pregnancy, post-pregnancy). Poisson regression models analyzed trends in outcomes and generated adjusted relative risks (aRR) of opioid toxicity by socio-demographic and clinical factors. ResultsPregnancy-associated non-fatal opioid toxicity increased 220% between 2013 and 2020 (45.5-145.4/100,000 livebirths) before declining by 30% in 2021. Over the study period, fatal opioid toxicity increased 150% (6.8-17.5/100,000) and all-cause mortality increased 120% (32.8-71.2/100,000). Our methods did not identify any opioid toxicity deaths in pregnancy, and most non-fatal (66.6%) and fatal (88.9%) opioid toxicity and all-cause mortality (73.9%) occurred 43-365 days post-pregnancy. The percent of deaths attributed to opioids increased from 12.7% in 2015 to 25.0% in 2020. Substance use disorder (aRR 19.52, 95% CI 16.87-22.58), pre-pregnancy opioid toxicity (aRR 4.69, 3.81-5.78), mental illness (aRR 2.01, 1.75-2.29), high neighbourhood deprivation (aRR 1.45, 1.28-1.64), and social disadvantage (aRR 3.21, 2.77-3.71) were associated with elevated risk of opioid toxicity. ConclusionsPregnancy-associated opioid toxicity and mortality have increased substantially. In 2020, 1 in 4 pregnancy-associated deaths involved opioids. ImplicationsFindings highlight the need for comprehensive care and perinatal harm reduction services. System-level improvements to reduce poor outcomes must include complete data capture of all pregnancy-associated deaths.

Plinabulin plus docetaxel versus docetaxel in patients with non-small-cell lung cancer after disease progression on platinum-based regimen (DUBLIN-3): a phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial

There is an unmet need for second-line and third-line treatments that are effective and tolerable for advanced or metastatic non-small-cell lung cancer (NSCLC) with no driver mutations. In this phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial, we enrolled patients from 58 medical centres in Australia, China, and the USA. Eligible patients were adults with epidermal growth factor receptor (EGFR) wild-type NSCLC who had progressed after first-line platinum-based therapy. Patients were randomly assigned (1:1) using an independent stratified randomisation schedule with a block size of four to receive intravenous docetaxel 75 mg/m2 on day 1 and either plinabulin (30 mg/m2) or placebo on days 1 and 8 in 21-day cycles until progression, unacceptable toxic effects, withdrawal, or death. The primary endpoint was overall survival (OS) in the intention-to-treat (ITT) population. Safety was analysed in all patients who had received at least one dose of study drug or placebo. This trial is registered with ClinicalTrials.gov (NCT02504489) and is now closed. Between Nov 30, 2015, and Jan 6, 2021, 919 patients were screened for inclusion. 360 patients were excluded, and 559 were enrolled and randomly assigned to receive either docetaxel and plinabulin (n=278) or docetaxel and placebo (n=281). 406 (73%) of 559 patients were male, 153 (27%) were female, and 488 (87%) were Asian. Median OS was 10·5 months (95% CI 9·34-11·87) in the plinabulin group compared with 9·4 months (8·38-10·68) in the control group (stratified HR 0·82, 95% CI 0·68-0·99; p=0·0399). Mean OS was 15·08 months (13·42-16·74) in the plinabulin group compared with 12·77 months (11·45-14·10) in the placebo group using restricted mean survival time analysis (difference 2·31 months, 95% CI 0·18-4·44; p=0·0332). Treatment-emergent adverse events occurred in 273 (>99%) of 274 patients in the plinabulin group and 276 (99%) of 278 patients in the control group. Grade 3 or 4 gastrointestinal disorders occurred more frequently in the plinabulin group than in the placebo group, with the most frequent being diarrhoea (24 [9%] of 274 patients vs three [1%] of 278) and vomiting (six [2%] vs one [<1%]), as did transient grade 3 hypertension (50 [18%] vs eight [3%]). Treatment-emergent death was reported in 12 patients (4%) in the plinabulin group and ten patients (4%) in the placebo group. Plinabulin plus docetaxel significantly improved OS as second-line and third-line treatment in patients with advanced or metastatic EGFR wild-type NSCLC and could be considered as a new treatment option in this population. BeyondSpring Pharmaceuticals.

Safety and outcome of children, adolescents and young adults participating in phase I/II clinical oncology trials: a 9-year center experience.

Enrolling children with cancer in early phase trials is crucial to access innovative treatments, contributing to advancing pediatric oncology research and providing tailored therapeutic options. Our objective is to analyze the impact of these trials on patient outcomes and safety, and to examine the evolution and feasibility of trials in pediatric cancer over the past decade. All patients recruited in pediatric anticancer phase I/II clinical trials from January 2014 to December 2022 were included. Clinical records and trial protocols were analyzed. A total of 215 patients (median age 11.2 years, range 1-29.5) were included in 52 trials (258 inclusions). Patients with extracranial solid tumors (67%), central nervous system (CNS) tumors (24%), and leukemia (9%) were included. The most common investigational drugs were small molecules (28.3%) and antibodies (20.5%). Serious adverse events were experienced by 41% of patients, 4.4% discontinued treatment because of toxicity and two had toxic deaths. Median event-free survival was 3.7 months (95%CI: 2.8-4.5), longer in phase II trials than in phase I (2 vs. 6.3 months; p ≤ 0.001). Median overall survival was 12 months (95%CI: 9-15), higher in target-specific vs. non-target-specific trials (14 vs. 6 months; p ≤ 0.001). A significant and increasing number of patients have been included in early clinical trials, suggesting that both oncologists and families consider it valuable to be referred to specialized Units to access new therapies. Moreover, our data suggests that participation in early clinical trials, although not without potential toxicities, might have a positive impact on individual outcomes.

Clinical Profile and Outcomes of Childhood Wilms Tumors Treated in a Tertiary Cancer Center from North India

In India and other lower-middle-income countries, the progress in the management of Wilms tumor (WT) has lagged behind when compared to the developed countries. In the current study, we highlight the outcomes of 61 children with WT treated at an oncological center in northern India. Our study found that the patient demographics, including age and gender distribution, closely paralleled other Indian studies. Notably, 24% of patients had distant metastasis at diagnosis. An upfront biopsy was performed in majority of the patient with a remarkable concordance rate of over 90%, with no significant complications associated with the procedure. Our surgical approach, guided by image-defined risk factors, resulted in 84% of patients undergoing delayed surgery after chemotherapy. Notably, the incidence of intraoperative complications, including tumor spill, was minimal. Treatment abandonment and toxic death due to sepsis emerged as significant challenges, affecting 22% and 7% of our patient cohort, respectively. The 3-year event-free survival (EFS) and overall survival were 70% and 84%, respectively. The age group of 6 to 8 years and stage V disease emerged as adverse factors influencing EFS. In summary, our study highlights the multifaceted nature of WT management in resource-constrained settings with survival rates promising but still lagging behind high-income countries. Addressing challenges such as treatment abandonment and reducing toxic death is imperative to enhance outcomes of WT in India.

Underlying Polysubstance Classes and Associated Sociodemographic Characteristics and Health Histories among People who Died from Substance-Related Acute Toxicity in Canada: A Latent Class Analysis

AbstractThe aim of this study was to examine underlying patterns of substances detected among accidental acute toxicity deaths in Canada and their associations with sociodemographic characteristics, location, and substance use and health history. Data abstracted from coroner and medical examiner files for all accidental acute toxicity deaths across Canada (2016 to 2017) were analyzed. Six classes emerged from a latent class analysis conducted to characterize detected substance classes: (1) cocaine and alcohol, (2) benzodiazepines and other pharmaceutical substances, (3) pharmaceutical opioids, (4) multiple pharmaceutical and non-pharmaceutical substances, (5) methamphetamine and fentanyl or analogues, and (6) fentanyl or analogues. Differences were identified between latent classes by sex, age, marital status, location of death, place of residence, and substance use and health history. Patterns of detected substances among deaths characterized in this study emphasize the complex nature of substance-related acute toxicity deaths across Canada and can inform future research and public health action.

Evaluation of Acute and Sub-acute Toxicity Analysis of Root Powder of &lt;i&gt;Pygmaeopremna herbacea&lt;/i&gt; (Roxb.) Moldenke

Background: Root powder of Pygmaeopremna herbacea (Roxb.) In traditional medicine, Moldenke, the Verbenaceae family, is widely used for managing respiratory-related disorders like bronchial asthma and pneumonia. Aim: This study aimed to assess the acute and subacute toxicity of the root powder of P. herbacea. The drug powder was prepared according to the standard traditional classical textbook. Methods: Sub-acute and acute toxicity were evaluated using WHO standards in Wistar albino rats and Swiss albino mice, respectively. The animals were administered 2000 mg/kg of the test drug in the acute toxicity trial, and for up to 14 days, any toxic symptoms and death were monitored. The test drug was administered to the animals for up to 28 days at dosages of 200, 100, and 50 mg/kg/BW/p.o./day in a sub-acute toxicity trial, and their morbidity and mortality were evaluated. The study was concluded with the sacrifice of all experimental animals and the completion of the evaluation of all hematological, biochemical, and histopathological assessments. Results: The acute toxicity investigation revealed no potentially dangerous signs of mortality. Animals in the sub-acute toxicity study did not show noteworthy variations in body weight alterations, water and food consumption, or haematological, biochemical, or histopathological features among the experiment and the control groups. Conclusion: According to this study, experimental animals receiving a long-term oral dosage of 200 mg/kg/BW of root powder of P. herbacea did not experience any harmful adverse reactions, stating that the human utilisation of the test drug is safe.

20-year trends in Australian methamphetamine-related deaths, 2001–2020

BackgroundOver the past two decades methamphetamine-related harms have increased in Australia. Previous analysis of methamphetamine-related deaths has covered limited timeframes, and largely focused on drug-toxicity deaths. This paper examines long-term trends in methamphetamine-related deaths over 20 years, including deaths due to a range of specific causes. MethodsDescriptive analyses were conducted on Australian methamphetamine-related deaths (2001–2023) by cause, extracted from the National Coronial Information System, an online database containing deaths reported to coroners in Australia and New Zealand. Joinpoint trend analyses were used to assess changes over time between 2001 and 2020 (with data from 2021 to 2023 likely incomplete and thus excluded). ResultsUnintentional drug toxicity was the cause of 49.8 % of methamphetamine-related deaths, intentional self-harm (including toxicity) 23.3 %, unintentional injury 15.1 %, natural causes 9.6 %, and assaults 2.3 %. Between 2001 and 2020, joinpoint analysis showed three trend change points among all-cause methamphetamine-related mortality rates, resulting in four distinct periods: two periods where they increased (2001–2006 – annual percentage change (APC) = 15.4 %; 2009–2016 – APC 25.5 %), and two where they decreased (2006–2009 – APC = –11.8 %; 2017–2020 – APC = –2.9 %). Similar patterns were evident among rates of intentional self-harm and unintentional injury. Deaths caused by unintentional drug toxicity saw two trend change points (2011, 2016), and rates increased across all three periods. Natural cause deaths had three trend change points (2007, 2010, 2015), and rates continued to rise after 2015, largely driven by increases in circulatory diseases. ConclusionCause-specific models highlighted diverse trends. Recent trends show unintentional drug toxicity deaths have slightly increased, intentional self-harm stabilised, and unintentional injury and assault deaths have declined. Deaths from natural causes involving methamphetamine continued to increase, highlighting a public health concern and a potential need for early circulatory disease screening among people who use methamphetamine.

Trends in toxicological findings in unintentional opioid or stimulant toxicity deaths in Québec, Canada, 2012-2021: Has Québec entered a new era of drug-related deaths?

We aimed to describe rates and toxicological findings of unintentional opioid and stimulant toxicity deaths, 2012-2021. The dataset included accidental deaths determined by the Coroner to be due to opioids or stimulants. We calculated annual crude mortality rates and described combinations of drugs identified in toxicological examinations of these deaths. We described temporal trends in the detection of specific opioids, stimulants, benzodiazepines (including novel benzodiazepines), gabapentinoids and z-drugs in deaths due to opioids and stimulants. Mortality rates increased over time, reaching their peak in 2020 and remaining high in 2021. In deaths due to opioids, there was a decline in the proportion of deaths involving pharmaceutical opioids after 2019, and a corresponding increase in the proportion of deaths with fentanyl detected. Benzodiazepines were often present in deaths due to opioids, with novel benzodiazepines increasing rapidly from 2019 onwards. Cocaine was the most frequently detected drug in deaths due to stimulants, but amphetamine/methamphetamine was detected in around half of all stimulant deaths from 2016 onwards. Despite availability of a multitude of overdose prevention interventions, mortality rates due to drug toxicity have increased in Québec. Toxicological findings of these deaths suggest concerning shifts in the illicit drug market, with Québec potentially having entered a new era of elevated overdose mortality. Intervention scale-up is essential, but unlikely to be sufficient, to reduce drug-related mortality. Policy reform to address the root causes of drug toxicity deaths, including an unpredictable drug supply, strained health systems and socio-economic precarity, is essential.

Chronic pain and accidental acute toxicity deaths in Canada, 2016-2017.

Multiple Canadian jurisdictions have reported a pattern of chronic pain among people who died from substance-related acute toxicity. This study examined the prevalence and characteristics of those with chronic pain using data from a national study of people who died of accidental acute toxicity. A cross-sectional analysis of accidental substance-related acute toxicity deaths that occurred in Canada between 1 January 2016 and 31 December 2017 was conducted. The prevalence of pain and pain-related conditions were summarized as counts and percentages of the overall sample. Subgroups of people with and without a documented history of chronic pain were compared across sociodemographic characteristics, health history, contextual factors and substances involved. From the overall sample (n = 7902), 1056 (13%) people had a history of chronic pain while 6366 (81%) had no documented history. Those with chronic pain tended to be older (40 years and older), unemployed, retired and/or receiving disability supports around the time of death. History of mental health conditions, trauma and surgery or injury was significantly more prevalent among people with chronic pain. Of the substances that most frequently contributed to death, opioids typically prescribed for pain (hydromorphone and oxycodone) were detected in toxicology more often among those with chronic pain than those without. Findings underscore the cross-cutting role of multiple comorbidities and unmanaged pain, which could compound the risk of acute toxicity death. Continued prioritization of harm reduction and regular patient engagement to assess ongoing needs are among the various opportunities for intervention.

Housing status and accidental substance-related acute toxicity deaths in Canada, 2016-2017.

There is a complex relationship between housing status and substance use, where substance use reduces housing opportunities and being unhoused increases reasons to use substances, and the associated risks and stigma. In this descriptive analysis of people without housing who died of accidental substance-related acute toxicity in Canada, we used death investigation data from a national chart review study of substance-related acute toxicity deaths in 2016 and 2017 to compare sociodemographic factors, health histories, circumstances of death and substances contributing to death of people who were unhoused and people not identified as unhoused, using Pearson chi-square test. The demographic distribution of people who died of acute toxicity was compared with the 2016 Nationally Coordinated Point-In-Time Count of Homelessness in Canadian Communities and the 2016 Census. People without housing were substantially overrepresented among those who died of acute toxicity in 2016 and 2017 (8.9% versus <1% of the overall population). The acute toxicity event leading to death of people without housing occurred more often in an outdoor setting (24%); an opioid and/or stimulant was identified as contributing to their death more frequently (68%-82%; both contributed in 59% of their deaths); and they were more frequently discharged from an institution in the month before their death (7%). We identified several potential opportunities to reduce acute toxicity deaths among people who are unhoused, including during contacts with health care and other institutions, through harm reduction supports for opioid and stimulant use, and by creating safer environments for people without housing.

A comparison of the characteristics of accidental substance-related acute toxicity deaths in Canada across life stages, 2016-2017.

The acute toxicity (sometimes called "overdose" or "poisoning") crisis has affected Canadians across all stages of life, including youth, adults and older adults. Our biological risks and exposures to substances change as we age. Based on a national chart review study of coroner and medical examiner data on acute toxicity deaths in 2016 and 2017, this analysis compares the burden of deaths and circumstances of death, locations of acute toxicity event and death, health history and substances contributing to death of people, by sex and life stage.

Acute toxicity of chemotherapy in central nervous system germ cell tumour patients according to age.

SIOP-CNS-GCT-II European trial was opened for the treatment of patients of any age with central nervous system germ cell tumour (CNS-GCT). Four courses of pre-irradiation chemotherapy were delivered. The influence of patient age on chemotherapy related acute toxicity (CRAT) was assessed. CRAT was analysed according to age-groups: children (aged ≤11 years), adolescents (aged 12-17 years), adults (aged ≥18 years) and to chemotherapy type: CarboPEI (alternating etoposide-carboplatin/etoposide-ifosfamide) for non-metastatic germinoma; PEI (cisplatin-etoposide-ifosfamide) for standard-risk non-germinomatous GCT (NGGCT); PEI and high-dose PEI (HD-PEI), for high-risk or poorly responsive NGGCTs. 296 patients were assessable for CRAT: 105 children, 121 adolescents, 70 adults (max age: 41 years). Median cumulative doses/m² of chemotherapy were similar among age-groups. The proportion of germinoma over NGGCT (and accordingly use of CarboPEI chemotherapy) was higher in the adult groups (79%) versus the other two groups (62%). Delay in chemotherapy ≥7 days was noticed in 27%, 38%, and 19% of children, adolescents, and adults, respectively. Grade ≥3 haematological and non-haematological adverse events (AEs) were observed in 94%/31%, 97%/36%, and 77%/21% of children, adolescents, and adults, respectively. No toxic death was reported. Grade ≥3 AEs and delayed chemotherapies were significantly rarer in adults when compared with adolescents, even when adjusted on chemotherapy type: odds ratio: 0.1 [95%CI 0.02-0.4], and 0.2 [95%CI 0.1-0.4] in the group treated with CarboPEI. Adult patients can be treated safely with a chemotherapy intensive protocol, with even less toxicity than that observed in adolescents. Further work is required to understand age-related differences regarding toxicity.

Uji Toksisitas Akut Ekstrak Etanol Daun Alpukat (Persea americana Mill.) dan Pengaruhnya Terhadap Hepar Mencit BALB/c

Avocado leaf ethanol extract as a traditional medicine has been proven to have various pharmacological activities, but the safety of its use is not yet known. This study aims to determine the range of LD50 values, toxic symptoms, changes in body weight, and SGPT SGOT levels of Balb/c mice. The research was carried out experimentally using a fixed dose toxicity test method with a randomized matched pre and post-test control group design. EEDA is made by 70% ethanol maceration. The acute toxicity test consists of 2 stages: preliminary and main tests. Preliminary tests were carried out with a dose of extract 300 mg/kg BW once administered. After 24 hours of observation, there were no toxic symptoms, the test dose was increased to 2000 mg/kg BW. The main test was carried out using 10 test animals which were divided into 2 groups, each given a dose of extract 2000 mg/kg BW once and CMC Na 1% (negative control). Observation of toxic symptoms and death was carried out for 14 days. The LD50 value is determined from the results of toxic symptoms and death of test animals. Toxic symptoms were analyzed descriptively, and changes in body weight and SGOT SGPT levels were analyzed statistically (95% confidence level). The research results show that avocado leaf ethanol extract has an LD50 value range of &gt;2000 mg/kg BW. The test dose of 2000 mg/kg BW did not cause toxic symptoms and death. SGOT and SGPT levels were still within normal limits, however, changes in SGPT levels were significantly different from controls. Thus, an extract dose of 2000 mg/kg BW has an acute toxic effect on the liver of mice.