The Shift to Toxicological-Related Deaths Over Natural During the COVID-19 Pandemic-An Ontario, Canada, Experience.

Study Design: Retrospective review of deaths in Ontario where there was Coroner's investigation and a postmortem examination between 2018 and 2021 to compare year by year changes before and during the COVID-19 pandemic. Objective: To establish the changes in patterns of toxicological deaths over the pandemic. Methods: Using the database of the Office of the Chief Coroner for Ontario to determine the numbers of postmortem examinations for the province of Ontario as well as the primary cause and manner of death. Those with a toxicological primary cause of death were isolated from 2003 to the first half of 2022 and divided by year. For those between the years 2018 and 2021 deaths were divided by manner of death. Further all deaths with either a toxicological primary cause of death or unfinalized investigations which were highly suspicious for a toxicological cause based on circumstance with a positive toxicology were isolated. From these the data on demographics and substances detected were compiled by year for comparison. Results: Comparing two years prior to the COVID-19 pandemic to the following two years there was an increase in total case load of 22%. Comparing the year before the pandemic to the first year of the pandemic deaths from natural causes fell from 52% to 47% of total cases, while drug-related cases increased from 24% to 36%. Fentanyl remained as the most prevalent detected substance in toxicological deaths. Combined opioid toxicity with stimulants increased, as well as the detection of nonpharmaceutical benzodiazepines. Deaths in men increased to comprise 3 in 4 drug-related deaths with the 30 to 39 years age-group remaining the most impacted. Conclusions: There was an increase in numbers and relative proportions of cases attributed to drug-related deaths which remained high over the two years of the pandemic.

Maternal Deaths Using Coroner's Data: A Latent Class Analysis.

OBJECTIVE: Knowledge regarding the antecedent clinical and social factors associated with maternal death around the time of pregnancy is limited. This study identified distinct subgroups of maternal deaths using population-based coroner's data, and that may inform ongoing preventative initiatives. METHODS: A detailed review of coroner's death files was performed for all of Ontario, Canada, where there is a single reporting mechanism for maternal deaths. Deaths in pregnancy, or within 365 days thereafter, were identified within the Office of the Chief Coroner for Ontario database, 2004-2020. Variables related to the social and clinical circumstances surrounding the deaths were abstracted in a standardized manner from each death file, including demographics, forensic information, nature and cause of death, and antecedent health and health care factors. These variables were then entered into a latent class analysis (LCA) to identify distinct types of deaths. RESULTS: Among 273 deaths identified in the study period, LCA optimally identified three distinct subgroups, namely, (1) in-hospital deaths arising during birth or soon thereafter (52.7% of the sample); (2) accidents and unforeseen obstetric complications also resulting in infant demise (26.3%); and (3) out-of-hospital suicides occurring postpartum (21.0%). Physical injury (22.0%) was the leading cause of death, followed by hemorrhage (16.8%) and overdose (13.3%). CONCLUSION: Peri-pregnancy maternal deaths can be classified into three distinct sub-types, with somewhat differing causes. These findings may enhance clinical and policy development aimed at reducing pregnancy mortality.

Pharmacogenetics of Lethal Opioid Overdose: Review of Current Evidence and Preliminary Results from a Pilot Study.

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.

Reviewing pharmacogenetics to advance precision medicine for opioids.

BACKGROUND: Adequate opioid prescribing is critical for therapeutic success of pain management. Despite the widespread use of opioids, optimized opioid therapy remains unresolved with risk of accidental lethal overdosing. With the emergence of accumulating evidence linking genetic variation to opioid response, pharmacogenetic based treatment recommendations have been proposed. OBJECTIVE: The aim of this review is to evaluate pharmacogenetic evidence and provide an overview on genes involved in the pharmacokinetics and pharmacodynamics of opioids. METHODS: For this review, a systematic literature search of published articles was used in PubMed®, with no language restriction and between the time period of January 2000 to December 2020. We reviewed randomized clinical studies, study cohorts and case reports that investigated the influence of genetic variants on selected opioid pharmacokinetics and pharmacodynamics. In addition, we reviewed current CPIC clinical recommendations for pharmacogenetic testing. RESULTS: Results of this review indicate consistent evidence supporting the association between selected genetic variants of CYP2D6 for opioid metabolism. CPIC guidelines include recommendations that indicate the avoidance of tramadol use, in addition to codeine, in CYP2D6 poor metabolizers and ultrarapid metabolizers, and to monitor intermediate metabolizers for less-than-optimal response. While there is consistent evidence for OPRM1 suggesting increased postoperative morphine dosing requirements in A118G G-allele carriers, the clinical relevance remains limited. CONCLUSION: There is emerging evidence of clinical relevance of CYP2D6 and, to a lesser extent, OPRM1 polymorphism in personalized opioid drug dosing. As a result, first clinics have started to implement pharmacogenetic guidelines for CYP2D6 and codeine.

Suicide by Fatal Pentobarbital Intoxication in Ontario, Canada, from 2012 to 2015.

A fatal concentration of pentobarbital found in a coroner's case where the history had not indicated use of this drug prompted a review of fatalities in Ontario from 2012 to 2015. Coroner's case files, including police and toxicology reports, were reviewed in twenty deaths, in which pentobarbital was identified as the primary cause of death. In all of the deaths (11 females, 9 males), the blood concentration of pentobarbital was greater than 10 mg/L. There were three to eight deaths per year and each was classified as suicide. In 11 cases, there was clear evidence that the drug was purchased over the internet from Mexico or China and imported into Canada. In four cases, it appears that the pentobarbital was labeled as a different, innocuous chemical to facilitate crossing the border without scrutiny. The findings underscore the value of a thorough scene investigation, including details of evidence that may be considered unrelated.

Last Words: Are There Differences in Psychosocial and Clinical Antecedents Among Suicide Decedents Who Leave E-Notes, Paper Notes, or No Note?

OBJECTIVE: Only a minority of suicide decedents leave a suicide note. Typically, the notes are handwritten on paper; however, electronic suicide notes have been reported with increasing frequency. This emerging phenomenon remains generally under-researched. The aim of this study was to compare the psychosocial and clinical antecedents of suicide decedents who left E-notes with those who left paper notes or no notes. METHOD: The study was embedded in the Southwestern Ontario Suicide Study (SOSS). The SOSS was a three-year case series of consecutive deaths by suicide that occurred in the region between 2012 and 2014. Data on psychosocial and clinical antecedents were collected with a modified version of the Manchester questionnaire used in the UK. RESULTS: Of the 476 suicides files reviewed, 45.8% contained a suicide note. A total of 383 separate suicide notes were left: 74.3% were paper notes and 25.7% were E-notes. The results of the multivariate regression analyses indicate that the likelihood of leaving a suicide note was negatively associated with a history of admissions to a mental health unit, while the likelihood of leaving an E-note was negatively associated with age, positively associated with presence of a mental disorder, and negatively associated with history of hospital admissions. CONCLUSIONS: Future studies with larger samples need to consider the timing of the text messages, and appraise whether there was the intent of seeking help or rescue in the text messages.

Confidential Survey Into Southwestern Ontario Suicide: Implication for Primary Care Practice.

OBJECTIVE: To describe sociodemographic and clinical characteristics of suicide decedents and to explore the pattern of clinical and suicide risk assessment in primary care settings. METHODS: A 3-year case series of consecutive suicides (January 1, 2012, to December 31, 2014) in Southwestern Ontario, Canada, identified by the Office of the Chief Coroner of Ontario and Ontario Forensic Pathology Service (OCC/OFPS) was conducted. Clinicians who provided care to suicide decedents completed a confidential suicide questionnaire offered online through a secured portal or by hardcopy. RESULTS: A total of 476 suicide cases were analyzed using data extracted from the OCC/OFPS files or provided by clinicians who had completed the survey. Hanging (42.8%) was the most common method of suicide, followed by self-poisoning (17.9%). More than half of the decedents (51.8%) used psychotropic medications, and 29.4% used opiates to self-poison. Typically, these self-poisonings involved prescribed medications (70.6%). Over two-thirds (67.4%) of suicide decedents had consulted their primary care physician prior to their deaths, and 63.6% had been seen by a physician within 28 days of their death. Suicide risk assessments were reportedly conducted in 87.1% of these visits. Of those who were assessed, the immediate risk of suicide was deemed to be absent in 39.8%, low in 50.0%, moderate in 8.3%, and high in only 1.9%. CONCLUSION: The findings from this confidential survey may be important for the formulation of recommendations that could improve suicide prevention in primary care practice.

The Feasibility and Clinical Utility of Conducting a Confidential Inquiry Into Suicide in Southwestern Ontario.

BACKGROUND AND AIMS: Given the effectiveness of the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness (NCI) in the UK, the present study evaluated this approach in Southwestern Ontario. A systematic confidential examination of suicides in Ontario was developed to guide quality improvement of services and suicide prevention. METHOD: A 3-year case series of consecutive suicides in Southwestern Ontario identified by the Office of the Chief Coroner was compiled. Clinicians who provided care to suicide decedents completed an online confidential suicide questionnaire offered through a secured portal. RESULTS: A total of 476 suicide cases were analyzed. In all, 270 invitations to clinicians were sent, 237 (87.8%) responded to the invitation and 187 (69.3%) completed the online questionnaire. The majority of the suicide decedents (54.6%, n = 260), were between the ages of 40 and 64 (x = 47.2, SD = 17.1), White (91.4%, n = 416), single (34.2%, n = 439), and male (74.4%, n = 476). Of the 86 cases of self-poisoning, prescription medications were used in 66.3%. Almost two thirds of decedents visited the clinician in the month prior to their death. LIMITATIONS: The results of the survey were drawn from suicides in Southwestern Ontario and generalizing these findings should be done with caution. CONCLUSION: This study highlights (a) the value of the clinicians' survey to identify gaps in clinical services and (b) the necessity of improvements in suicide risk assessment/management and restriction of prescription medications.

Drug Toxicity Deaths after Release from Incarceration in Ontario, 2006-2013: Review of Coroner's Cases.

BACKGROUND: There is an increased risk of death due to drug toxicity after release from incarceration. The purpose of this study was to describe the timing, rate and circumstances of drug toxicity deaths following release from incarceration. This information can be used to help design potential preventive interventions. METHODS AND FINDINGS: We reviewed coroner's files to identify deaths in adults in Ontario between 2006 and 2013 caused by drug toxicity (n = 6,978) and these records were matched with provincial correctional records to identify individuals who died within one year of being released from incarceration (n = 702). Twenty percent (n = 137) of the 702 deaths occurred within one week of release. The majority (77%, n = 538) of deaths after release involved one or more opioids. Of the deaths involving opioids, intervention by another person may have been possible in 318 cases. CONCLUSIONS: Between 2006 and 2013 in Ontario, one in ten drug toxicity deaths in adults occurred within one year of release from provincial incarceration. These findings may help to inform the implemention and assessment of interventions aimed at reducing drug toxicity deaths following release from incarceration.

Differences in spirometry interpretation algorithms: influence on decision making among primary-care physicians.

BACKGROUND: Spirometry is recommended for the diagnosis of asthma and chronic obstructive pulmonary disease (COPD) in international guidelines and may be useful for distinguishing asthma from COPD. Numerous spirometry interpretation algorithms (SIAs) are described in the literature, but no studies highlight how different SIAs may influence the interpretation of the same spirometric data. AIMS: We examined how two different SIAs may influence decision making among primary-care physicians. METHODS: Data for this initiative were gathered from 113 primary-care physicians attending accredited workshops in Canada between 2011 and 2013. Physicians were asked to interpret nine spirograms presented twice in random sequence using two different SIAs and touch pad technology for anonymous data recording. RESULTS: We observed differences in the interpretation of spirograms using two different SIAs. When the pre-bronchodilator FEV1/FVC (forced expiratory volume in one second/forced vital capacity) ratio was >0.70, algorithm 1 led to a 'normal' interpretation (78% of physicians), whereas algorithm 2 prompted a bronchodilator challenge revealing changes in FEV1 that were consistent with asthma, an interpretation selected by 94% of physicians. When the FEV1/FVC ratio was <0.70 after bronchodilator challenge but FEV1 increased >12% and 200 ml, 76% suspected asthma and 10% suspected COPD using algorithm 1, whereas 74% suspected asthma versus COPD using algorithm 2 across five separate cases. The absence of a post-bronchodilator FEV1/FVC decision node in algorithm 1 did not permit consideration of possible COPD. CONCLUSIONS: This study suggests that differences in SIAs may influence decision making and lead clinicians to interpret the same spirometry data differently.