Óbitos e internações de vítimas de eventos toxicológicos não medicamentosos no Brasil, 2009 a 2018 / Muertes y hospitalizaciones de víctimas de eventos toxicológicos no medicamentosos en Brasil, 2009 a 2018 / Deaths and hospitalizations of victims of non-drug toxicological events in Brazil, 2009 to 2018

Objetivo: determinar a taxa de internações por eventos agudos de intoxicação não medicamentosa (NMx) e analisar a mortalidade decorrente desses agravos no Brasil, de 2009 a 2018. Métodos: estudo de série temporal, no qual se analisaram registros de internações por "tratamento de intoxicação ou envenenamento por exposição a substâncias de uso não medicamentoso" no Sistema de Informações Hospitalares (SIH), por regressão de Prais-Winsten. Resultados: ocorreram 125.570 internações em virtude de intoxicação NMx. A taxa média de internações foi de 6,3/100 mil habitantes, sendo maior no sexo masculino (8,0/100 mil hab.) comparado ao feminino (4,6/100 mil hab.). A taxa de internações e a mortalidade geral de internações por intoxicação NMx diminuíram de 9,4 para 4,5/100 mil hab. e de 2,5 para 1,6/1 milhão de hab., respectivamente. Conclusões: houve redução da taxa de internações e da mortalidade por intoxicações NMx durante a década analisada.

Objetivo: determinar la tasa de hospitalizaciones por eventos agudos de intoxicación no medicamentosa (NMx) y analizar la mortalidad resultante en Brasil de 2009 a 2018. Métodos: estudio de serie temporal en el que se analizaron los registros de hospitalizaciones por "tratamiento de intoxicación o envenenamiento por exposición a sustancias de uso no farmacológico" del Sistema de Información Hospitalaria (SIH) por la regresión de Prais-Winsten. Resultados: hubo 125.570 hospitalizaciones por intoxicación NMx. La mortalidad promedio de hospitalizaciones fue de 6,3/100 mil hab., siendo más alta en el sexo masculino (8,0/100 mil hab.) en comparación con el femenino (4,6/100 mil hab.). La tasa de hospitalizaciones y la mortalidad global de las hospitalizaciones por NMx disminuyeron de 9,4 a 4,5 por 100 mil hab. y de 2,5 a 1,6 por 1 millón de hab., respectivamente. Conclusiones: hubo reducción en la tasa de hospitalizaciones y en la mortalidad por intoxicaciones NMx durante la década analizada.

Objective: to determine the rate of hospitalizations due to acute non-drug poisoning (NDP) events and to analyze mortality arising from these health conditions in Brazil from 2009 to 2018. Methods: this was a time-series study using Prais-Winsten regression to analyze records of hospitalizations for "treatment of intoxication or poisoning due to exposure to non-drug substances" held on the Hospital Information System. Results: there were 125,570 hospitalizations due to NDP. The average hospitalization rate was 6.3/100,000 inhabitants, although it was higher in males (8.0/100,000 inhab.) compared to females (4.6/100,000 inhab.). The hospitalization rate and the overall mortality rate due NDP to fell from 9.4 to 4.5/100,000 inhab. and from 2.5 to 1.6/1 million inhab., respectively. Conclusions: there was a reduction in the NDP hospitalization rate and in mortality due to NDP during the decade analyzed.

Improvements in Toxicology Testing to Identify Fentanyl Analogs and Other Novel Synthetic Opioids in Fatal Drug Overdoses, Connecticut, January 2016-June 2019.

OBJECTIVES: Drug overdose deaths in Connecticut increasingly involve a growing number of fentanyl analogs and other novel nonfentanyl synthetic opioids (ie, novel synthetics). Current postmortem toxicology testing methods often lack the sophistication needed to detect these compounds. We examined how improved toxicology testing of fatal drug overdoses can determine the prevalence and rapidly evolving trends of novel synthetics. METHODS: From 2016 to June 2019, the Connecticut Office of the Chief Medical Examiner increased its scope of toxicology testing of suspected drug overdose deaths in Connecticut from basic to enhanced toxicology testing to detect novel synthetics. The toxicology laboratory also expanded its testing panels during this time. We analyzed toxicology results to identify and quantify the involvement of novel synthetics over time. RESULTS: From 2016 to June 2019, 3204 drug overdose deaths received enhanced toxicology testing; novel synthetics were detected in 174 (5.4%) instances. Ten different novel synthetics were detected with 205 total occurrences. Of 174 overdose deaths with a novel synthetic detected, most had 1 (n = 146, 83.9%) or 2 (n = 26, 14.9%) novel synthetics detected, with a maximum of 4 novel synthetics detected. Para-fluorobutyrylfentanyl/FIBF, furanylfentanyl, and U-47700 were most identified overall, but specific novel synthetics came in and out of prominence during the study period, and the variety of novel synthetics detected changed from year to year. CONCLUSIONS: Enhanced toxicology testing for drug overdose deaths is effective in detecting novel synthetics that are not identified through basic toxicology testing. Identifying emerging novel synthetics allows for a timely and focused response to potential drug outbreaks and illustrates the changing drug market.

Toxicological Analysis of Gonad Development in Green Mussels (Perna viridis) in Jakarta Bay, Indonesia.

<b>Background and Objective:</b> The accumulation of heavy metals such as cadmium and lead in mussels is very high compared to that in another marine biota. The mussels are sessile, widely distributed filter-feeding organisms, with the ability to sequester many lipophilic organic compounds, absorb anything in their surroundings. The very low mobility allows heavy metal bioaccumulation to occur and cannot avoid pollutants, which increase over time. This bioaccumulation can be toxic to mussels. This study aimed to evaluate the effect of different toxic chemicals and histological changes in green mussels. <b>Materials and Methods:</b> All archive gonad sample of green mussels in 2015 was fixed in paraformaldehyde 4% solution and were sliced by a rotary microtome at 8 µm thickness and finally, the slides were stained with a solution of hematoxylin-eosin. <b>Results:</b> The obtained results demonstrated that developmental disorders in the testes are characterized by the arrangement of follicle cells in a relatively less dense state and some follicles are not fully filled with spermatozoa. It means that the male gonad samples of green mussels in the port of Muara Angke undergoing toxicity and the process of gonad developmental was disrupted. <b>Conclusion:</b> The effects of toxicity of the male gonad of green mussels were more sensitive and were more susceptible than the female gonad of the green mussels.

The Toxicology Investigators Consortium 2020 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology in 2010. The registry collects data from participating sites with the agreement that all bedside and telehealth medical toxicology consultation will be entered. This eleventh annual report summarizes the Registry's 2020 data and activity with its additional 6668 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from January 1 to December 31, 2020. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. Gender distribution included 50.6% cases in females, 48.4% in males, and 1.0% identifying as transgender. Non-opioid analgesics were the most commonly reported agent class, followed by opioid and antidepressant classes. Acetaminophen was once again the most common agent reported. There were 80 fatalities, comprising 1.2% of all registry cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe race and ethnicity demographics and exposures in the registry, telemedicine encounters, and cases related to the COVID-19 pandemic.

Expanding the toxicologist's statistical toolbox: Using effect size estimation and dose-response modelling for holistic assessments instead of generic testing.

It is tempting to base (eco-)toxicological assay evaluation solely on statistical significance tests. The approach is stringent, objective and facilitates binary decisions. However, tests according to null hypothesis statistical testing (NHST) are thought experiments that rely heavily on assumptions. The generic and unreflected application of statistical tests has been called "mindless" by Gigerenzer. While statistical tests have an appropriate application domain, the present work investigates how unreflected testing may affect toxicological assessments. Dunnett multiple-comparison and Williams trend testing and their compatibility intervals are compared with dose-response-modelling in case studies, where data do not follow textbook behavior, nor behave as expected from a toxicological point of view. In such cases, toxicological assessments based only on p-values may be biased and biological evaluations based on plausibility may be prioritized. If confidence in a negative assay outcome cannot be established, further data may be needed for a robust toxicological assessment.

Use compatibility intervals in regulatory toxicology.

Recently it was recommended to avoid significance tests, in particular dichotomization into significant/non-significant on the basis of a p-value and a fixed 5% significance level (i.e. false positive rate). As an alternative, the interpretation of a suitable effect size and its compatibility interval is recommended, i.e. confidence intervals whose compatibility with the data, the assumptions, and the models is shown. This concept is used for the evaluation of assays in regulatory toxicology with special emphasis on the proof of hazard and proof of safety. Three case studies for multiple endpoints, multiple models and the consideration of historical controls illustrate the applicability of this concept. The corresponding software code for the open-source R project for statistical computing (www.r-project.org) is provided.

Revealing cytotoxic substructures in molecules using deep learning.

In drug development, late stage toxicity issues of a compound are the main cause of failure in clinical trials. In silico methods are therefore of high importance to guide the early design process to reduce time, costs and animal testing. Technical advances and the ever growing amount of available toxicity data enabled machine learning, especially neural networks, to impact the field of predictive toxicology. In this study, cytotoxicity prediction, one of the earliest handles in drug discovery, is investigated using a deep learning approach trained on a highly consistent in-house data set of over 34,000 compounds with a share of less than 5% of cytotoxic molecules. The model reached a balanced accuracy of over 70%, similar to previously reported studies using Random Forest. Albeit yielding good results, neural networks are often described as a black box lacking deeper mechanistic understanding of the underlying model. To overcome this absence of interpretability, a Deep Taylor Decomposition method is investigated to identify substructures that may be responsible for the cytotoxic effects, the so-called toxicophores. Furthermore, this study introduces cytotoxicity maps which provide a visual structural interpretation of the relevance of these substructures. Using this approach could be helpful in drug development to predict the potential toxicity of a compound as well as to generate new insights into the toxic mechanism. Moreover, it could also help to de-risk and optimize compounds.

15 Years of Small: Research Trends in Nanosafety.

In the field of nano- and microscale science and technology, Small has become one of the worldwide leading journals since its initiation 15 years ago. Among all the topics covered in Small, "nanosafety" has received growing interest over the years, which accounts for a large proportion of the total publications of Small. Herein, inspired by its coming Special Issue "Rethinking Nanosafety," a general bibliometric overview of the nanosafety studies that have been published in Small is presented. Using the data derived from the Web of Science Core Collection, the annual publication growth, most influential countries/institutions as well as the visualized collaborations between different countries and institutions based on CiteSpace software are presented. A special emphasis on the impact of the previous Special Issue from Small that is related to nanosafety research is given and the research trend from the most highly cited papers during last 15 years is analyzed. Lastly, future research directions are also proposed.

Bisfenol-A: cuantificacion en orina de mujeres embarazadas por cromatografia gaseosa-espectrometria de masa / Bisfenol-A: quantification in urine of pregnant women by gas chromatography-mass spectrometry / Bisfenol-A: quantificacao em urina de gestantes por cromatografia gasosa-espectrometria de massa

El uso de bisfenol-A (BPA) a nivel de la industria global se ha venido incrementando en los ultimos anos, y fueron los mercados emergentes los impulsores de esta demanda creciente. Las aplicaciones de BPA en la industria de los alimentos y bebidas representan solo del 3 al 4% del consumo global de policarbonato, pero su uso esta siendo reexaminado debido a que se conocieron varios trabajos cientificos que indican la existencia de una relacion directa entre el BPA y los efectos adversos para la salud. La contaminacion de los alimentos y bebidas se produce por migracion del BPA desde los envases que los contienen (alimentos enlatados, vinos, etc.), y es la principal fuente de exposicion en el humano. Para evaluar dicha exposicion se desarrollo y valido un metodo analitico por cromatografia gaseosa acoplada a espectrometria de masa para la cuantificacion de BPA total en orina de mujeres embarazadas atendidas en el Hospital Italiano de Buenos Aires en el ano 2013, con un limite de cuantificacion de 2,0 ng/mL y un limite de deteccion de 0,8 ng/mL. De las 149 muestras de orina analizadas, el 66,4% fueron cuantificables, con la mediana de BPA total de 4,8 ng/mL (4,3 ng/mg de creatinina) y la media geometrica de 4,8 ng/mL (4,7 ng/mg de creatinina).

The use of bisphenol-A (BPA) at the level of the global industry has been increasing in recent years, with emerging markets being the drivers of this growing demand. BPA applications in the food and beverage industry represent only 3 to 4% of the global consumption of polycarbonate, but its use is being reexamined because several scientific works were reported indicating the existence of a direct relationship between BPA and adverse effects on health. The contamination of food and beverages is produced by the migration of BPA from the containers that hold them (canned foods, wines, etc.) and it is the main source of exposure in humans. To evaluate this exposure, an analytical method was developed by gas chromatography coupled to mass spectrometry for the quantification of total BPA in urine of pregnant women treated at the Hospital Italiano de Buenos Aires in 2013, with a limit of quantification of 2.0 ng/mL and of detection of 0.8 ng/mL. Of the 149 urine samples analyzed, 66.4% were quantifiable, with a median total BPA of 4.8 ng/mL (4.3 ng/mg creatinine) and a geometric mean of 4.8 ng/mL (4.7 ng/mg creatinine).

O uso de bisfenol-A (BPA) ao nivel da industria global foi aumentando nos ultimos anos, e foram os mercados emergentes que deram impulso a essa demanda crescente. As aplicacoes de BPA na industria de alimentos e bebidas representam apenas 3 a 4% do consumo global de policarbonato, mas seu uso esta sendo reexaminado visto que varios trabalhos cientificos indicando a existencia de uma relacao direta entre o BPA e os efeitos adversos na saude foram conhecidos. A contaminacao dos alimentos e bebidas e produzida pela migracao de BPA das embalagens que os contem (alimentos enlatados, vinhos, etc.) e e a principal fonte de exposicao em humanos. Para avaliar esta exposicao, foi desenvolvido e avaliado um metodo analitico por cromatografia gasosa acoplada a espectrometria de massas para a quantificacao do BPA total na urina de gestantes atendidas no Hospital Italiano de Buenos Aires em 2013, com um limite de quantificacao de 2,0 ng/mL e um limite de deteccao de 0,8 ng/mL. Das 149 amostras de urina analisadas, 66,4% foram quantificaveis, com uma mediana de BPA total de 4,8 ng/mL (4,3 ng/mg de creatinina) e a media geometrica de 4,8 ng/mL (4,7 ng/mg de creatinina).

Dose-response analysis of toxicological and pharmacological mixtures with the model deviation ratio method: Problems and solutions.

Risk assessment for mixtures of chemicals requires to investigate the magnitude of their potential adverse effects on living organisms. This is usually done by assessing how experimental toxicological mixture data depart from the model of Loewe additivity. Several recent scientific studies propose to perform this task using an ad hoc method known as model deviation ratio (MDR) method. Moreover, the first official European regulatory document for the study of combined exposures explicitly recommends the use of the MDR method (EFSA Scientific Committee et al. Guidance on harmonised methodologies for human health, animal health and ecological risk assessment of combined exposure to multiple chemicals. EFSA Journal, 2019). We show here that the MDR method is not rooted in statistical principles and can lead to erroneous claims. We show however that the distribution of the MDR can be evaluated by simulations and show how this allows us to devise and carry out a bona fide statistical test. The proposed method accounts for uncertainty in the estimation of ED/EC50 and does not require a minimum sample size. The computer code developped in this study is made available as an R package called MDR.

Toxicological exposures reported to a telephonic consultation service at a tertiary care hospital in Lebanon.

Introduction: This study aims to describe the epidemiology of toxicological exposures reported to a telephonic medical toxicology service at a tertiary care center in Lebanon during a 46-months period.Methods: This study is a secondary analysis of a database for a telephonic medical toxicology service at a tertiary care center in Lebanon. Clinical information from all pediatric and adult patients, presenting with intentional or unintentional toxicological exposure, was entered into the database by the medical toxicology team.Results: Four hundred and seventy-seven exposures were recorded from 1 March 2015 to 31 December 2018. Female patients were involved in 60.2% of cases. Children less than 5 years old constituted 23.5% of cases and adults aged 20-49 constituted 48.6%. Up to 51.6% of cases were intentional, with 37.7% resulting from suicidal attempts. The majority of patients displayed no effects (33.1%) or minor effects (39.2%). Almost half of patients were treated and discharged from the Emergency Department (ED) without further hospitalization, and another 18.9% of patients left the ED against medical advice. The most common pharmaceutical agents involved were sedative/hypnotics/antipsychotics (14.7%), analgesics (12.6%) and antidepressants (11.3%). The most common non-pharmaceutical agents involved were household cleaning substances (8.0%), pesticides (5.2%) and bites and envenomations (3.8%).Conclusions: The results of this study suggest that sedative/hypnotics/antipsychotics, analgesics, antidepressants and household cleaning substances are the most common agents involved. Adult women and children ≤5 years old constitute a large portion of patients with toxicological exposures. Prevention strategies and policies should be implemented to mitigate these hazards.

Post-mortem toxicology in the diagnosis of sudden death in young and middle-aged victims.

OBJECTIVE: We aimed to investigate the impact of the toxicological results found in cases of sudden death (SD) and to correlate the clinical, autopsy and genetic findings with the toxicology results. MATERIALS AND METHODS: Consecutive SD in people aged between 16 and 50 years with medico-legal autopsies and toxicology studies were included over a 3-year period. The comparison between the toxicological data and demographic characteristics, clinical circumstances, autopsy, and genetic results were taken into account. RESULTS: 101 cases were finally included. They were predominately males (84%) and the mean age was 39.8 years. 52 (51.5%) cases had positive toxicological findings and in 25 cases (24.8%), toxic compounds were considered the first cause of death. Ethanol was the most frequently identified agent (69%), following by licit drugs (56%) and drugs of abuse (39%). Cases with positive toxicology were younger than those with negative results (37.9±9.1 vs. 41.9±7.8; p=0.02). Patients with more than 3 comorbidities showed an association with positive toxicological results (n=14 vs. n=3; p=0.017). The genetic study was performed in 70 (69.3%) SD cases. We identified pathogenic or likely pathogenic variants in 17.1% cases and uncertain significance variants in 42.8% cases. 58% of these variants were probably related to the cause of death. CONCLUSIONS: A large fraction of SD victims had positive toxicological findings and a quarter of deaths were directly caused by toxic substances. The identification of the factors that trigger SD provides a good approach to contribute in avoiding future episodes.

Serotonin Toxicity: Associated Agents and Clinical Characteristics.

BACKGROUND: Serotonin toxicity is a common cause of drug-induced altered mental status. However, data on the causes of serotonin toxicity, symptomatology, complications, and rate of antidotal treatment are limited. METHODS: This study evaluated cases of serotonin toxicity in the ToxIC registry, an international database of prospectively collected cases seen by medical toxicologists. Serotonin toxicity was diagnosed by bedside evaluation of medical toxicology specialists and explicit criteria were not used. The database was searched for "serotonin syndrome" between January 1, 2010, and December 31, 2016. RESULTS: There were 1010 cases included. Females made up 608 (60%) cases. Ages are as follows: younger than 2 years (3, 0.3%), 2 to 6 years (8, 0.8%), 7 to 12 years (9, 0.9%), 13 to 18 years (276, 27.3%), 19 to 65 years (675, 67%), older than 66 years (33, 3.4%), unknown (6, 0.6%). Reasons for encounter: intentional (768, 76%), adverse drug event/reaction (127, 12.6%), unintentional (66, 6%), and unknown (55, 5.4%). Signs/symptoms: hyperreflexia/clonus/myoclonus (601, 59.5%), agitation (337, 33.4%), tachycardia (256, 25.3%), rigidity (140, 13.9%), seizures (139, 13.7%), and hyperthermia (29, 2.9%). COMPLICATIONS: rhabdomyolysis (97, 9.7%), dysrhythmias (8, 0.8%), and death (1, 0.1%). TREATMENTS: benzodiazepines 67% (677/1010), cyproheptadine 15.1% (153/1010). There were 192 different xenobiotics reported with 2046 total exposures. Antidepressants were most common (915, 44.7%) with bupropion the most frequent overall (147, 7.2%). Common non-antidepressants were dextromethorphan (95, 6.9%), lamotrigine (64, 3.1%), and tramadol (60, 2.9%). DISCUSSION: Serotonin toxicity most often occurred in adult patients with intentional overdose. Antidepressants were the most common agents of toxicity. Interestingly, bupropion, a norepinephrine/dopamine reuptake inhibitor, was the most frequently mentioned xenobiotic. Though often cited as a potential antidote, only 15% of patients received cyproheptadine. Severe toxicity was rare. A single death was reported.

Factors associated with incomplete toxicology reporting in drug overdose deaths, 2010-2016.

PURPOSE: Classification of overdose deaths is often geographically and demographically inconsistent. Incomplete surveillance records may distort estimates of drug overdose rates across time and place. We examined incomplete toxicology reporting among drug overdose decedents by demographic and geographic characteristics, measuring changes in missingness rates and their associations with decedent characteristics over time. METHODS: We estimated the percentage of overdose deaths reported in the National Vital Statistics System with missing toxicology results from 2010 to 2016, overall and by decedents' demographic and geographic characteristics. Multilevel logistic regression models evaluated prevalence of missingness by decedent characteristics, accounting for geographic clustering. RESULTS: Overall, 20.3% of death certificates did not indicate a specific drug, declining from 24.4% in 2010 to 14.6% in 2016. Deaths were less likely to have missing information if they occurred in counties with medical examiners versus coroners. Female decedents were more likely to have missing information than males, as were non-Hispanic whites compared with Hispanics and non-Hispanic blacks. CONCLUSIONS: The percentage of deaths with missing toxicology information declined over time, but demographic and geographic differences in missingness persist. This yields detection biases that skew temporal trends and understanding of groups impacted by the opioid epidemic.

The Toxicology Investigators Consortium Case Registry-the 2018 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology (ACMT) in 2010. The Registry collects data from participating sites with the agreement that all bedside medical toxicology consultation will be entered. The objective of this ninth annual report is to summarize the Registry's 2018 data and activity with its additional 7043 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2018. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. A total of 51.5% of cases were female, 48% were male, and 0.6% transgender. Non-opioid analgesics were the most commonly reported agent class, followed by antidepressants and opioids. Acetaminophen was once again the most common agent reported. There were 106 fatalities, comprising 1.5% of all registry cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe exposures in elderly patients, addiction consultation practices, and risk factors for bupropion-induced seizures. The launch of the ToxIC Qualified Clinical Data Registry (TQCDR) is also described.

Adverse Drug Events and Reactions Managed by Medical Toxicologists: an Analysis of the Toxicology Investigators Consortium (ToxIC) Registry, 2010-2016.

INTRODUCTION: Adverse drug events/reactions (ADE/ADRs) cost more than $30 billion annually and are among the leading causes of death in the USA. Little is known about patients treated at the bedside for ADE/ADR by medical toxicologists. METHODS: We conducted a retrospective study of ADE/ADR cases reported to the Toxicology Investigators Consortium (ToxIC) registry between January 1, 2010, and December 31, 2016. Clinical and demographic data were collected including age, sex, circumstances surrounding exposure, suspected offending substance, clinical manifestations, treatment, disposition, and outcome. RESULTS: Among 51,440 ToxIC cases during this time period, 673 ADE/ADR cases were reported (337 females). By age, ADE/ADRs were seen most commonly among adults age 19-65 years (442/673, 65.7% of ADE/ADR) and older adults age 65-89 years (134/673, 19.9% of ADE/ADR). 222/673 (33%) of consults for ADE/ADR were seen in the emergency department (ED); 181/673 (26.9%) were seen in the hospital ward; and 160/673 (23.8%) were seen in the intensive care unit (ICU). The most commonly reported sign for ADE/ADR was tachycardia: 51/673 (7.6%), followed by bradycardia: 49/673 (7.3%). Most commonly reported agents associated with ADE/ADR were as follows: 97/673 (14.4%) due to cardiovascular medications; 76/673 (11.3%) due to antipsychotic medications; and 61/673 (9.1%) due to antidepressants. 429/673 (63.7%) of ADE/ADR were reported as due to a single agent, and 212/673 (31.5%) were reported as due to multiple agents. CONCLUSIONS: 4.2% of cases managed at the bedside by a consulting toxicologist and reported to the ToxIC registry between 2010 and 2016 had ADE/ADR as the reason for consultation. Agents most commonly involved in ADE/ADRs included cardiovascular medications, antipsychotic medications, and antidepressants.

An interprofessional clinical toxicology advanced pharmacy practice experience.

BACKGROUND AND PURPOSE: Clinical toxicology is a blend of science, research, and patient management practices involving human poisonings from exposure to natural and synthetic toxins. The objective of this study was to describe the components of an elective advanced pharmacy practice experience (APPE) in clinical toxicology at California Poison Control System (CPCS). EDUCATIONAL ACTIVITY AND SETTING: The APPE requirements included a mix of active participation in case management and supplemental educational exercises, case presentations and consultations, and a structured self-study component consisting of readings and on-line modules. In addition, there were two active learning activities, high acuity poisoning simulation scenarios utilizing a high-fidelity mannequin, and an antidote tasting session. FINDINGS: From April 2012 to October 2017, 82 student pharmacists completed this APPE. Pharmacy students completed 85 pre-simulation surveys and 80 post-simulation surveys. Survey results showed an increase in pharmacy student beliefs that a clinical pharmacist should be involved in the differential diagnosis and management of patients (60% pre-simulation vs. 78.8% post-simulation, p = 0.009). APPE pharmacy students completed an evaluation of the preceptors(s), site, and learning experience. The average score for all areas on the preceptor and site evaluations was >4.5 on a 5-point Likert scale. Qualitative data themes included student satisfaction with opportunities, feedback, and the interprofessional and collaborative environment. SUMMARY: An APPE in the CPCS was successfully designed and implemented. The APPE provides an interprofessional collaborative learning environment that allows student pharmacists to understand the unique role of the pharmacist in this setting.

Extracting and Benchmarking Emerging Adverse Outcome Pathway Knowledge.

As the community of toxicological researchers, risk assessors, and risk managers adopt the adverse outcome pathway (AOP) framework for organizing toxicological knowledge, the number and diversity of AOPs in the online AOP knowledgebase (KB) continues to grow. To track and investigate this growth, AOPs in the AOP-KB were assembled into a single network. Summary measures on the current state of the AOP-KB and the overall connectivity and structural features of the resulting network were calculated. Our results show that networking the 187 user-defined AOPs currently described in the AOP-KB resulted in the emergence of 9405 unique, previously undescribed, linear AOPs (LAOPs). To investigate patterns in this emerging knowledge, we assembled the AOP-KB network retrospectively by sequentially adding each of the 187 user-defined AOPs and found that the creation of new AOPs that borrowed components from previously existing AOPs in the KB most described emergence of new LAOPs. However, the introduction of nonadjacent key event relationships and cycles among KEs also play key roles in emergent LAOPs. We provide examples of how to identify application-specific critical paths from this large number of LAOPs. Our research shows that the global AOP network may have considerable value as a source of emergent toxicological knowledge. These findings are not only helpful for understanding the nature of this emergent information but can also be used to manage and guide future development of the AOP-KB, and how to tailor this wealth of information to specific applications.