Assessment of co-ingestion effects on poisoning patterns, drug-drug interactions, and adverse outcomes in acute toxic exposure.

Multiple toxic exposures are increasing nowadays. In cases of acute poisoning involving multiple agents, there is a potential for additional toxicity that goes beyond the effects and toxicity of each drug. Very scarce studies have investigated the problem of multiple toxic exposures where the information on drug-drug interactions (DDIs) originates from clinical experience, which is inconclusive and cannot be generalized to patients. Therefore, the current study aimed to explore the influence of co-ingestion on the clinical presentation of exposed patients and to identify the common associated DDIs and their effect on poisoning outcomes, including the need for mechanical ventilation (MV), intensive care unit (ICU) utilization, and prolonged hospital stay. The current study is a retrospective cross-sectional study that was conducted using medical records of 169 adult patients admitted to a poison control center and diagnosed with acute drug poisoning. Of them, 40.8 % were exposed to multiple drugs. The total number of drugs reported in the current study was 320 preparations, with an average of 1.9 drugs per patient. There were about 726 potential DDIs; more than half of these interactions were significant (n = 486). Antidepressants and psychotropics showed the highest total number of DDIs. Patients with multiple ingestion were significantly older and this pattern of exposure was more frequent among suicidal attempters, substance abusers, cardiac patients, and patients diagnosed with neurological and psychological problems. Moreover, patients with multiple ingestions showed severe presentations indicated by higher grades of Poison Severity Score and lower Glasgow Coma Scale. Multiple ingestion was associated with higher liability for MV, ICU admission, and prolonged length of hospital stay (p < 0.001). There was a significant moderate direct correlation between the number of drugs consumed and the number of resulting DDIs (r = 0.542, p < 0.001). There was a significant direct correlation between the occurrence of significant chronic/chronic drug interactions from one side and the history of substance abuse (r = 0.596, p = 0.041) and psychological illness (r = 0.662, p = 0.019) from the other side. Moreover, significant acute/acute drug interactions were correlated with being male (r = 0.969, p < 0.001) of older age (r = 0.672, p = 0.024). Similarly, significant acute/chronic drug interactions were moderately correlated with being a male (r = 0.692, p = 0.013). The presence of epilepsy and psychological problems were the main significant predictors of multiple acute toxic exposures. Among the patients exposed acutely to more than one agent who were on long-term treatment, exposure to three drugs or more could significantly predict the need for MV with excellent area under the curve (AUC) of 0.896 and 77.0 % accuracy. Moreover, and it was a fair predictor of ICU admission (AUC = 0.625), with an 88.9 % ability to exclude patients unlikely to need ICU admission. Particular attention should be paid to the patients at risk of potential DDIs. When prescribing drugs, the minimum number of drugs with the lowest effective doses, and minimal potential DDIs should be prioritized.

Ethnic-racial disparities in poisoning cases: analysis of drugs of abuse, medicines and pesticides in Brazil.

In Brazil, ethnic-racial inequalities exist in all fields, obstructing access to goods, services, and opportunities, including healthcare services. However, there are no apparent studies that assess, at a national level, ethnic-racial disparities in poisoning cases, emphasizing skin color as a determining factor. The study aimed to examine the relationship between race/ethnicity and general poisoning cases, by medications, pesticides, and drug of abuse in Brazilian states. Poisoning cases data were extracted for the years 2017, 2018, and 2019. Notification data for general poisoning cases and toxic agents were collected: medications, pesticides, and drugs of abuse. Data were categorized between whites and non-whites (blacks, browns, and indigenous) and without information on skin color/ethnicity. Rates of poisonings amongst ethnic-racial groups and cases of not declared skin color as well as relative risk (RR) of poisoning among non-whites were calculated. All states in the North, Northeast (states with the worst Human Development Index), Midwest, and 2 states in the Southeast exhibited higher rates of poisoning cases per 100,000 inhabitants among non-whites. The RR values for nonwhite individuals were higher in the North and Northeast regions for all types of poisonings. The type of poisoning cases that presented the highest RR for non-whites over the 3 years was drugs of abuse (2-2.44), when compared to other types of poisonings from pesticides (2-2.33) and medications (1.5-1.91). The spatial distribution of poisoning cases rates and RR of nonwhite population support public policies to reduce socioeconomic and environmental inequalities.

Accuracy of the Infectious Diseases Society of America and British Thoracic Society Criteria for Acute Pneumonia in Differentiating Chemical and Bacterial Complications of Aspiration in Comatose Ventilated Patients Following Drug Poisoning.

Drug poisoning frequently leads to admission to intensive care units, often resulting in aspiration, a potentially life-threatening condition if not properly managed. Aspiration can manifest as either bacterial aspiration pneumonia (BAP) or aspiration pneumonitis (AP), which are challenging to distinguish potentially leading to overprescription of antibiotics and the emergence of multidrug-resistant bacteria. This study aims to assess the accuracy of the Infectious Diseases Society of America (IDSA) and British Thoracic Society (BTS) criteria in differentiating BAP from AP in comatose ventilated patients following drug poisoning. This cross-sectional study included 95 patients admitted for drug poisoning at the Lille University Hospital intensive care department, between 2013 and 2017, requiring mechanical ventilation and receiving antibiotics for aspiration. Patients were categorized as having bacterial complications if tracheal sampling yielded positive culture results, and if they were otherwise considered to have chemical complications. The sensitivity, specificity, positive predictive value, and negative predictive value of IDSA and BTS criteria in identifying patients with bacterial complications were evaluated. Among the patients, 34 (36%) experienced BAP. The IDSA criteria demonstrated a sensitivity of 62% and specificity of 33%, while the BTS criteria showed a sensitivity of 50% and specificity of 38%. Both the IDSA and BTS criteria exhibited poor sensitivity and specificity in identifying microbiologically confirmed pneumonia in comatose ventilated patients following drug poisoning.

A case of lacosamide and mirtazapine self-poisoning.

Lacosamide is a relatively new antiepileptic drug that exerts its anticonvulsant effect by selectively inactivating sodium channels. Since its launch, it has been used widely for the treatment of intractable epilepsy, but there are scant data on the toxic or lethal blood concentrations. Here, we report a case of drug poisoning following simultaneous high-dose self-administration of lacosamide and mirtazapine. We developed and validated an approach that uses liquid chromatography coupled with electrospray ionization-tandem mass spectrometry to determine the concentrations of lacosamide and mirtazapine in cadaveric blood, urine and liver. Calibration curves showed good linearity (r2 > 0.995), and our method enabled repeatable and accurate quantification, with intra- and inter-assay coefficients of variation not exceeding 10.9 % and 12.8 %, respectively, for each target drug. We used the method to measure the drug concentrations in the blood of a dead victim and found a lacosamide concentration of 91.9 µg/mL and a mirtazapine concentration of 12.0 µg/mL. The blood mirtazapine concentration was in the lethal range, and that of lacosamide was about 10 times the therapeutic range. The synergistically central nervous system depressive and cardiotoxic effects of these drugs may have contributed to the cause of death. We concluded that the cause of death in this case was lacosamide and mirtazapine poisoning.

Prediction of naloxone dose in opioids toxicity based on machine learning techniques (artificial intelligence).

BACKGROUND: Treatment management for opioid poisoning is critical and, at the same time, requires specialized knowledge and skills. This study was designed to develop and evaluate machine learning algorithms for predicting the maintenance dose and duration of hospital stay in opioid poisoning, in order to facilitate appropriate clinical decision-making. METHOD AND RESULTS: This study used artificial intelligence technology to predict the maintenance dose and duration of administration by selecting clinical and paraclinical features that were selected by Pearson correlation (filter method) (Stage 1) and then the (wrapper method) Recursive Feature Elimination Cross-Validated (RFECV) (Stage2). The duration of administration was divided into two categories: A (which includes a duration of less than or equal to 24 h of infusion) and B (more than 24 h of naloxone infusion). XGBoost algorithm model with an accuracy rate of 91.04%, a prediction rate of 91.34%, and a sensitivity rate of 91.04% and area under the Curve (AUC) 0.97 was best model for classification patients. Also, the best maintenance dose of naloxone was obtained with XGBoost algorithm with R2 = 0.678. Based on the selected algorithm, the most important features for classifying patients for the duration of treatment were bicarbonate, respiration rate, physical sign, The partial pressure of carbon dioxide (PCO2), diastolic blood pressure, pulse rate, naloxone bolus dose, Blood Creatinine(Cr), Body temperature (T). The most important characteristics for determining the maintenance dose of naloxone were physical signs, bolus dose of 4.5 mg/kg, Glasgow Coma Scale (GCS), Creatine Phosphokinase (CPK) and intensive care unit (ICU) add. CONCLUSION: A predictive model can significantly enhance the decision-making and clinical care provided by emergency physicians in hospitals and medical settings. XGBoost was found to be the superior model.

Recognising inaccuracies in Australian suicide and 'hidden suicide' data.

OBJECTIVE: To examine the effects of revision of Australian mortality statistics every year since 2007 on numbers and rates of suicide and 'hidden suicide'. METHOD: Nine months after the end of each year, the Australian Bureau of Statistics releases preliminary statistics concerning deaths registered in that year, together with revised and finalised data regarding previous years. Numbers and rates of suicide and of deaths coded to selected categories of accidental, undetermined and unknown cause deaths were tabled. RESULTS: Upward revision of suicide and accidental drug poisoning death numbers, three years after first release, show that true rates are substantially higher than initially released data suggested. Concomitant downward revision of rates of undetermined and unknown cause deaths supports evidence that at first release some suicides are coded to these categories. CONCLUSIONS: Australia's finalised suicide data are likely to be more accurate than equivalent data from nations that do not revise mortality data. More comprehensive investigation (including verbal or psychological autopsy) in doubtful cases in Australia and elsewhere would probably lead to reported suicide rates being higher.

Preference for hotline versus mobile application/countdown-based mobile overdose response services: a qualitative study.

BACKGROUND: In response to the exacerbated rates of morbidity and mortality associated with the overlapping overdose and COVID-19 epidemics, novel strategies have been developed, implemented, operationalized and scaled to reduce the harms resulting from this crisis. Since the emergence of mobile overdose response services (MORS), two strategies have aimed to help reduce the mortality associated with acute overdose including staffed hotline-based services and unstaffed timer-based services. In this article, we aim to gather the perspectives of various key interest groups on these technologies to determine which might best support service users. METHODS: Forty-seven participants from various interested groups including people who use substances who have and have not used MORS, healthcare workers, family members, harm reduction employees and MORS operators participated in semi-structured interviews. Transcripts were coded and analyzed using a thematic analysis approach. RESULTS: Four major themes emerged regarding participant perspectives on the differences between services, namely differences in connection, perceived safety, privacy and accessibility, alongside features that are recommended for MORS in the future. CONCLUSIONS: Overall, participants noted that individuals who use substances vary in their desire for connection during a substance use session offered by hotline and timer-based service modalities. Participants perceived hotline-based approaches to be more reliable and thus potentially safer than their timer-based counterparts but noted that access to technology is a limitation of both approaches.

Drug poisoning deaths by occupation and drug type, Massachusetts 2010-2019.

OBJECTIVE: To investigate variation in drug poisoning mortality rates by drug type and occupation in Massachusetts. METHODS: Death certificates for deaths by drug poisonings occurring between 2010 and 2019 in Massachusetts were coded based on the decedent's occupation. Mortality rates and rate ratios (with all other occupations as the reference group) were calculated based on the occupation of the workers according to drug type. Poisson regression was used to determine significantly elevated mortality rates and trends in drug poisoning deaths by occupation and drug type. RESULTS: The rate of drug poisoning deaths increased from 2010 to 2016 after which they plateaued. With respect to specific substances, fentanyl- and cocaine-related deaths increased throughout the surveillance period. For drug poisoning deaths overall, workers in construction trades (3,017); food preparation and serving (1,116); transportation and material moving (1,062) occupations had the highest number of drug poisoning deaths. When adjusting for age, sex, race/ethnicity, and educational attainment, workers in 7 occupations had significantly elevated mortality rate ratios for drug poisonings overall: farming, fishing, and forestry (3.42, P < 0.001); construction trades (2.58, P < 0.001); health care support (1.61, P < 0.001); community and social service (1.60, P < 0.001); food preparation and serving related (1.54, P < 0.001); personal care and service (1.37, P < 0.001); and arts, design, entertainment, sports, and media (1.21, P = 0.010). In many cases, workers in these same occupations had elevated mortality rate ratios for poisonings from specific substances. Health care practitioners and technical occupation workers only had elevated rates for methadone-related poisonings (1.73, P = 0.010). CONCLUSIONS: These findings highlight that workers in certain occupations have an elevated risk for drug poisonings and that the patterns differ with respect to the drug type. These findings can be useful for providing services to workers in high-risk occupations and in identifying occupational factors that may be related to the risk of drug poisoning death. While previous research has begun to uncover work-related factors that may contribute to opioid use, further work is needed to identify occupational factors that may contribute to psychostimulant and benzodiazepine use.

Geographically specific associations between county-level socioeconomic and household distress and mortality from drug poisoning, suicide, alcohol, and homicide among working-age adults in the United States.

Background: Mortality rates from drug poisoning, suicide, alcohol, and homicide vary significantly across the United States. This study explores localized relationships (i.e., geographically specific associations) between county-level economic and household distress and mortality rates from these causes among working-age adults (25-64). Methods: Mortality data were from the National Vital Statistics System for 2014-2019. County-level socioeconomic distress (poverty, employment, income, education, disability, insurance) and household distress (single-parent, no vehicle, crowded housing, renter occupied) were from the 2009-2013 American Community Survey. We conducted Ordinary Least Squares (OLS) regression to estimate average associations and Geographically Weighted Regression (GWR) to estimate localized spatial associations between county-level distress and working-age mortality. Results: In terms of national average associations, OLS results indicate that a one standard deviation increase in socioeconomic distress was associated with an average of 6.1 additional drug poisoning deaths, 3.0 suicides, 2.1 alcohol-induced deaths, and 2.0 homicides per 100,000 population. A one standard deviation increase in household distress was associated with an average of 1.4 additional drug poisonings, 4.7 alcohol-induced deaths, and 1.1 homicides per 100,000 population. However, the GWR results showed that these associations vary substantially across the U.S., with socioeconomic and household distress associated with significantly higher mortality rates in some parts of the U.S than others, significantly lower rates in other parts of the U.S., and no significant associations in others. There were also some areas where distress overlapped to influence multiple causes of death, in a type of compounded disadvantage. Conclusions: Socioeconomic and household distress are significant and substantial predictors of higher rates of drug poisoning mortality, suicide, alcohol-induced deaths, and homicide in specific regions of the U.S. However, these associations are not universal. Understanding the place-level factors that contribute to them can inform geographically tailored strategies to reduce rates from these preventable causes of death in different places.

Perfil dos casos suspeitos de intoxicação exógena em cães e gatos atendidos no hvu ufpi de Teresina-Pi no período de 2017 a 2021 / Profile of suspected cases of exogenous intoxication in dogs and cats treated at the hvu ufpi in Teresina-Pi from 2017 to 2021 / Perfil de los casos sospechosos de intoxicación exógena en perros y gatos atendidos en el hvu ufpi de Teresina-Pi de 2017 a 2021

Os casos suspeitos de intoxicações exógenas são frequentes na clínica de cães e gatos. O presente trabalho objetivou realizar um estudo retrospectivo dos casos suspeitos de intoxicação em cães e gatos atendidos no Hospital Veterinário Universitário da UFPI, localizado em Teresina PI, durante o período de 2017 a 2021. Os casos foram classificados por agente tóxico suspeito, espécie, idade e ano de ocorrência. No total foram registrados 324 casos, sendo 58 em 2017, 88 em 2018, 94 em 2019, 50 em 2020 e 34 em 2021. A maioria dos casos ocorreu em 2019 (29,01%) tendo como causa principal a intoxicação medicamentosa (16,04%), seguida da intoxicação por agrotóxicos (10,80%). A maior prevalência foi em animais com idade inferior a cinco anos (87,03%); machos (56,79%); cães (68,20%). Foram observados: elevado número de casos sem agente tóxico identificado (28,08%) e de fichas de atendimento não preenchidas (8,33%) pelos médicos veterinários em atendimento. A prevenção, a educação continuada dos tutores e a capacitação dos médicos veterinários são destacadas como essenciais para a redução dos casos de intoxicações exógenas em cães e gatos.(AU)

Suspected cases of exogenous poisoning are frequent in the clinic of dogs and cats. The present study aimed to perform a retrospective study of suspected cases of intoxication in dogs and cats treated at the University Veterinary Hospital of UFPI, located in Teresina PI, during the period from 2017 to 2021. The cases were classified by suspected toxic agent, species, age and year of occurrence. A total of 324 cases were recorded, being 58 in 2017, 88 in 2018, 94 in 2019, 50 in 2020 and 34 in 2021. Most cases occurred in 2019 (29.01%) with drug intoxication (16.04%) as the main cause, followed by pesticide intoxication (10.80%). The highest prevalence was in animals less than five years old (87.03%); males (56.79%); dogs (68.20%). It was observed: high number of cases without identified toxic agent (28.08%) and unfilled attendance forms (8.33%) by the attending veterinarians. Prevention, continued education of guardians and training of veterinarians are highlighted as essential for the reduction of cases of exogenous poisoning in dogs and cats.(AU)

Los casos sospechosos de intoxicaciones exógenas son frecuentes en la clínica de perros y gatos. El presente estudio tuvo como objetivo realizar un estudio retrospectivo de los casos sospechosos de intoxicación en perros y gatos tratados en el Hospital Veterinario Universitario de la UFPI, ubicado en Teresina PI, durante el período de 2017 a 2021. Los casos se clasificaron por agente tóxico sospechoso, especie, edad y año de ocurrencia. Se registraron un total de 324 casos, 58 en 2017, 88 en 2018, 94 en 2019, 50 en 2020 y 34 en 2021. La mayoría de los casos se produjeron en 2019 (29,01%) siendo la intoxicación por fármacos la principal causa (16,04%), seguida de la intoxicación por plaguicidas (10,80%). La mayor prevalencia se dio en animales menores de cinco años (87,03%); machos (56,79%); perros (68,20%). Se observó un elevado número de casos sin agente tóxico identificado (28,08%) y de formularios asistenciales no cumplimentados (8,33%) por los veterinarios asistentes. Se insiste en que la prevención, la educación continuada de los propietarios de animales de compañía y la formación de los veterinarios son esenciales para reducir los casos de intoxicación exógena en perros y gatos.(AU)

Associations with experience of non-fatal opioid overdose in British Columbia, Canada: a repeated cross sectional survey study.

INTRODUCTION: Lives lost in North America due to the unregulated drug poisoning emergency are preventable and those who survive an opioid overdose may suffer long-term disability. Rates of opioid overdose more than doubled following the onset of the COVID-19 pandemic in British Columbia, Canada. MATERIALS AND METHODS: Our analytical sample was comprised of 1447 participants from the 2018, 2019, and 2021 Harm Reduction Client Survey who responded yes or no to having experienced an opioid overdose in the past 6 months. Participants were recruited from harm reduction sites from across British Columbia. We used logistic regression to explore associations of experiencing an opioid overdose. RESULTS: Overall, 21.8% of participants reported experiencing an opioid overdose in the last six months (18.2% in 2019 and 26.6% in 2021). The following factors were positively associated with increased adjusted odds of experiencing a non-fatal opioid overdose: cis men relative to cis women (AOR 1.49, 95% CI 1.10-2.02), unstably housed compared to people with stable housing (AOR 1.87, 95% CI 1.40-2.50), and participants from 2021 compared to those from 2019 (AOR 3.06, 95% CI 1.57-5.97). The effects of both previous experience of a stimulant overdose and having witnessed an opioid overdose depended on the year of study, with both effects decreasing over subsequent years. CONCLUSIONS: Overdoses have increased over time; in 2021 more than one in four participants experienced an overdose. There is an urgent need for policy and program development to meaningfully address the unregulated drug poisoning emergency through acceptable life-saving interventions and services to prevent overdoses and support overdose survivors.

Investigating uses of peer-operated Virtual Overdose Monitoring Services (VOMS) beyond overdose response: a qualitative study.

Background: Virtual overdose monitoring services (VOMS) are novel technologies that allow remote monitoring of individuals while they use substances (especially those who use alone) electronically.Objectives: The authors explored key partner perspectives regarding services offered by VOMS beyond overdose response with the aim of understanding the breadth and perception of the services amongst those that use these services and are impacted by them.Methods: Forty-seven participants from six key partner groups [peers who had used VOMS (25%), peers who had not used VOMS (17%), family members of peers (11%), health professionals (21%), harm reduction sector employees (15%), and VOMS operators (15%)] underwent 20-to-60-minute semi-structured telephone interviews. Of peer and family groups, thirteen participants identified as female, eleven as male and one as non-binary, gender data was not recorded for other key partner groups. Interview guides were developed and interviews were conducted until saturation was reached across all participants. Themes and subthemes were identified and member checked with partner groups.Results: Participants indicated that uses of VOMS beyond overdose monitoring included: (1) providing mental health support and community referral; (2) methamphetamine agitation de-escalation; (3) advice on self-care and harm reduction; and (4) a sense of community and peer support. Respondents were divided on how VOMS might affect emergency services (5).Conclusions: VOMS are currently being used for purposes beyond drug poisoning prevention, including community methamphetamine psychosis de-escalation, mental health support, and community peer support. VOMS are capable of delivering a broad suite of harm reduction services and referring clients to recovery-oriented services.

CLINICAL AND PATHOHISTOLOGICAL MANIFESTATIONS OF ACUTE KIDNEY INJURY AMONG PATIENTS WITH ACUTE DRUG POISONING (OVERDOSE).

OBJECTIVE: The aim: To investigate clinical and pathohistological manifestations of acute kidney injury among patients with drug poisoning (overdose). PATIENTS AND METHODS: Materials and methods: A cohort retrospective analysis of medical data of 86 patients treated in 2017-2021 with a diagnosis of "acute drug poisoning" com¬plicated by the development of acute kidney injury syndrome was conducted. A forensic medical examination of deceased patients (7 persons) was carried out. Histological samples were examined using an microscope OPTON Axioskop (Germany) in transmitted light, at magnifications of 100 and 400 times. Statistical analysis of the obtained data was carried out using the IBM SPSS Statistics 29.0.0.0 program, Pearson's correlation analysis was used, p≤0.05. RESULTS: Results: Acute renal failure in drug poisoning occurs under the influence of prerenal (hypoxia, r=0,66, р=0,0021; hypovolemia, r=0,61, р=0,0333) and renal factors (toxic effect of chemical components of the drug and rhabdomyolysis, r=0,743, р=0,0034). In the tissue samples, erythrocyte stasis in the capillaries, general fullness of blood vessels, signs of the sludge effect and small diapedesis hemorrhages were found; vasculitis and perivascular sclerosis are noted; foci of mononuclear infiltration of the stroma, focal edema, necrosis and interstitial fibrosis; desquamation, degenerative-dystrophic changes of the nephrothelium, tubular atrophy were found; hyaline casts in separate tubules; focal glomerular changes with segmental increase of the mesangial matrix and proliferation of endothelial cells, atrophy and hyalinosis of individual glomeruli were noted. CONCLUSION: Conclusions: The multifactorial effect of opioids is confirmed by microcirculation disorders, vascular, interstitial, tubular and glomerular changes in the kidneys.

A cost benefit analysis of a virtual overdose monitoring service/mobile overdose response service: the national overdose response service.

BACKGROUND: The overdose crisis continues across Canada which calls for novel harm reduction strategies. Previous research indicates that a majority of eHealth solutions are cost-effective however current literature on the cost-benefit of eHealth for harm reduction is sparse. The National Overdose Response Service (NORS) is a Canada-wide telephone-based harm reduction service. Service users can call the phone number and connect to a peer who can virtually monitor the substance use session and dispatch appropriate interventions in the case of overdose. OBJECTIVES OF THE RESEARCH/PROJECT: We aim to assess the cost-benefit of NORS by comparing the estimated cost-savings from prevented overdose mortality to the operating costs of the program, alongside healthcare costs associated with its operation. METHODS: Data around systems costs and operational costs were gathered for our calculations. Our primary outcome was cost-benefit ratios, derived from estimates and models of mortality rates in current literature and value of life lost. We presented our main results across a range of values for costs and the probability of death following an unwitnessed overdose. These values were utilized to calculate cost-benefit ratios and value per dollar spent on service provision by NORS over the length of the program's operation (December 2020-2022). RESULTS: Over the total funded lifespan of the program, and using a Monte Carlo estimate, the benefit-to-cost ratio of the NORS program was 8.59 (1.53-15.28) per dollar spent, depending on estimated mortality rates following unwitnessed overdose and program operation costs. Further, we conservatively estimate that early community-based naloxone intervention results in healthcare system savings of $4470.82 per overdose response. CONCLUSIONS: We found the NORS program to have a positive benefit-to-cost ratio when the probability of death following an unwitnessed overdose was greater than 5%. NORS and potentially other virtual overdose monitoring services have the potential to be cost-effective solutions for managing the drug poisoning crisis.

Drugs involved in Kentucky drug poisoning deaths and relation with antecedent controlled substance prescription dispensing.

BACKGROUND: The shift from prescription to illicit drugs involved in drug poisoning deaths raises questions about the current utility of prescription drug monitoring program (PDMP) data to inform drug poisoning (overdose) prevention efforts. In this study, we describe relations between specific drugs involved in Kentucky drug poisoning deaths and antecedent controlled substance (CS) dispensing. METHODS: The study used linked death certificates and PDMP data for 2,248 Kentucky resident drug poisoning deaths in 2021. Death certificate literal text analysis identified drugs mentioned with involvement (DMI) in drug poisoning deaths. We characterized the concordance between each DMI and the CS dispensing history for this drug at varying timepoints since 2008. RESULTS: Overall, 25.5% of all decedents had dispensed CS in the month before fatal drug poisoning. Over 80% of decedents were dispensed opioid(s) since 2008; the percentage was similar regardless of opioid involvement in the poisoning death. One-third of decedents had dispensed buprenorphine for treatment of opioid use disorder since 2008, but only 6.1% had dispensed buprenorphine in the month preceding death. Fentanyl/fentanyl analogs were DMI in 1,568 (69.8%) deaths, yet only 3% had received a fentanyl prescription since 2008. The highest concordance in the month preceding death was observed for clonazepam (43.6%). CONCLUSION: Overall, concordance between CS dispensing history and the drugs involved in poisoning deaths was low, suggesting a need to reevaluate the complex relationships between prescription medication exposure and overdose death and to expand harm reduction interventions both within and outside the healthcare system to reduce drug poisoning mortality.

Changing dynamics of drug overdoses in the United Kingdom: An attempt to replicate the Jalal et al. findings of steady exponential growth.

BACKGROUND: Jalal et al. discovered that between 1979 and 2020 total rates and counts of fatal drug overdoses in the United States exhibited exponential growth at a very steady rate even though deaths from individual drugs did not. That is a startling result because it means that the different drugs are in effect "taking turns", with one growing faster just as another drug's death rate growth ebbs. That raises the question of whether this steadiness in the all-drug death rates is in some sense just a coincidence peculiar to the United States or whether it might reflect some more general phenomenon and so manifest in other countries. METHODS: We fit the same model used by Jalal et al. to data on drug-related death rates for the countries of the United Kingdom. RESULTS: The main finding is largely a failure to replicate the United States result. Simple graphical display of the trends and a number of statistical measures show that the growth in the United Kingdom was not only slower than in the United States, it was also less steady, with the exception of Northern Ireland. CONCLUSIONS: Steady exponential growth in the all-drugs mortality rate may be a phenomenon specific to certain contexts. It remains an open question whether the explanation of steady exponential growth in the United States and Northern Ireland relates to demand and supply mechanisms, to social and political conditions, or to coincidence.

[Rapid determination of acetaminophen in plasma by LC-MS/MS].

Objective: To establish a method for the rapid determination of acetaminophen (APAP) in human plasma by LC-MS/MS. Methods: The plasma samples were extracted by methanol and acetonitrile (1: 1) and purified directly. C(18) column was used for sample separation. The mobile phase were methanol (5 mmol/L ammonium acetate) and water (5 mmol/L ammonium acetate). Samples were analyzed by LC MS/MS with the electrospray ionization multi reaction monitoring (MRM) mode. Results: The calibration curves of APAP was linear in the concentration range of 0~10 mg/L, the correlation coefficient (r) was greater than 0.999 0. The relative standard deviation within and between batches was less than 10%. The recovery rate were 96.81%~101.7%. The detection limit of the method was 0.1 µg/L and the lower limit of quantification was 0.3 µg/L. Conclusion: This method has strong specificity, high sensitivity and reliable determination results. It is suitable for the rapid analysis of clinical plasma samples.

Prognostic factors in acute poisoning with central nervous system xenobiotics: development of a nomogram predicting risk of intensive care unit admission.

Background: Acute intoxication with central nervous system (CNS) xenobiotics is an increasing global problem. Predicting the prognosis of acute toxic exposure among patients can significantly alter the morbidity and mortality. The present study outlined the early risk predictors among patients diagnosed with acute exposure to CNS xenobiotics and endorsed bedside nomograms for identifying patients requiring intensive care unit (ICU) admission and those at risk of poor prognosis or death. Methods: This study is a 6-year retrospective cohort study conducted among patients presented with acute exposure to CNS xenobiotics. Results: A total of 143 patients' records were included, where (36.4%) were admitted to the ICU, and a significant proportion of which was due to exposure to alcohols, sedative hypnotics, psychotropic, and antidepressants (P = 0.021). ICU admission was associated with significantly lower blood pressure, pH, and HCO3 levels and higher random blood glucose (RBG), serum urea, and creatinine levels (P < 0.05). The study findings indicate that the decision of ICU admission could be determined using a nomogram combining the initial HCO3 level, blood pH, modified PSS, and GCS. HCO3 level < 17.1 mEq/L, pH < 7.2, moderate-to-severe PSS, and GCS < 11 significantly predicted ICU admission. Moreover, high PSS and low HCO3 levels significantly predicted poor prognosis and mortality. Hyperglycemia was another significant predictor of mortality. Combining initial GCS, RBG level, and HCO3 is substantially helpful in predicting the need for ICU admission in acute alcohol intoxication. Conclusion: The proposed nomograms yielded significant straightforward and reliable prognostic outcomes predictors in acute exposure to CNS xenobiotics.

Individual-level and neighborhood-level shifts in mortality patterns among drug poisoning deaths in a high-density Asian city: a territory-wide, case-only analysis.

BACKGROUND: The shifts in individual-level and neighborhood-level patterns of drug poisoning deaths in a high-density Asian city over time have been underestimated, although they provide essential information for community-based surveillance and interventions. METHODS: A case-only analysis with a 16-y, territory-wide, population-based registry in Hong Kong was applied to compare drug poisoning deaths from 2001 to 2010 with 2011 to 2016. Drug poisoning deaths, deaths from heroin and deaths from other opioids (codeine or morphine) were extracted (ICD codes: T36-T50, T40.1, T40.2). Binomial regressions were used to estimate the shifts in mortality patterns. RESULTS: Among 3069 drug poisoning deaths, a significant shift in mortality patterns was found despite a decreasing mortality trend in Hong Kong. Overall, drug poisoning deaths shifted towards middle-aged/young-old, widowed/divorced, economically active, white collar and non-local born. Since 2011, more deaths from heroin were in older ages and non-local born, but less were never married and economically inactive. More deaths from other opioids were middle-aged, young-old and divorced. In particular, most decedents shifted towards young-old, especially deaths from other opioids. Compared with deaths during 2001-2010, there were 3.72- and 6.50-fold more deaths from heroin and deaths from other opioids in those aged ≥60 y since 2021 (ORs: 3.72 [2.37, 5.86], 6.50 [3.97, 10.65]), respectively. Additionally, drug poisoning deaths shifted towards areas with less neighborhood deprivation (more high-education individuals and a mix of private/public housing residents), especially deaths from other opioids. CONCLUSION: Misuse of registered drugs (e.g. opioid pain relievers) could be a rising trend among vulnerable subpopulations in Hong Kong other than illegal drug use (heroin). Health officials should provide more advice and support on drug information. Specifically, an improved health system with education regarding the appropriate use of registered drugs for medical treatments should be provided to mid-/high-income and local-born individuals.

Can computed tomography replace or supplement autopsy?

Postmortem computed tomography (PMCT) has been integrated into the practice of many forensic pathologists. To evaluate the utility of PMCT in supplementing and/or supplanting medicolegal autopsy, we conducted a prospective double-blind comparison of abnormal findings reported by the autopsy pathologist with those reported by a radiologist reviewing the PMCT. We reviewed 890 cases: 167 with blunt force injury (BFI), 63 with pediatric trauma (under 5 years), 203 firearm injuries, and 457 drug poisoning deaths. Autopsy and radiology reports were coded using the Abbreviated Injury Scale and abnormal findings and cause of death (COD) were compared for congruence in consensus conferences with novel pathologists and radiologists. Overall sensitivity for recognizing abnormal findings was 71% for PMCT and 74.6% for autopsy. Sensitivities for PMCT/autopsy were 74%/73.1% for BFI, 61.5%/71.4% for pediatric trauma, 84.9%/83.7% for firearm injuries, and 56.5%/66.4% for drug poisoning deaths. COD assigned by reviewing PMCT/autopsy was correct in 88%/95.8% of BFI cases, 99%/99.5% of firearm fatalities, 82.5%/98.5% of pediatric trauma deaths, and 84%/100% of drug poisoning deaths of individuals younger than 50. Both autopsy and PMCT were imperfect in recognizing injuries. However, both methods identified the most important findings and are sufficient to establish COD in cases of BFI, pediatric trauma, firearm injuries and drug poisoning in individuals younger than 50. Ideally, all forensic pathologists would have access to a CT scanner and a consulting radiologist. This would allow a flexible approach that meets the diagnostic needs of each case and best serves decedents' families and other stakeholders.