Toxicology Investigators Consortium Case Registry Research Articles

Descriptive Analysis of Inpatient and Outpatient Cohorts Seeking Treatment After Prescription Opioid Misuse and Medical Toxicology Evaluation.

Medical toxicology expertise has expanded into the addiction medicine realm including outpatient medication for opioid use disorder (MOUD) and addiction treatment. Concomitantly, the emergency department (ED) and hospital are increasingly seen as important sites for the screening, prevention, and treatment of patients with substance use disorders and addiction. This analysis seeks to characterize patients seen by medical toxicologists for opioid use and opioid use disorder (OUD) in the ED and inpatient consultation setting (inpatient) versus in the OUD clinic (outpatient) setting. We searched the American College of Medical Toxicology's Toxicology Investigators Consortium Case Registry, a prospective, de-identified, national dataset that includes patients receiving medical toxicology consultation following prescription opioid misuse. The dataset also includes patients seen in outpatient MOUD clinics during the same period between June 2013 and November 2015. Intentional self-harm patients were excluded. We analyzed medical history, drug use patterns, and other factors with odds ratios and confidence intervals. Of 110 patients identified, 60 (54.5%) were inpatients and 50 (45.5%) outpatients. Mean age (39 years), gender (68% male), and race breakdown (60% white/non-Hispanic) were similar. The outpatient group was more likely to have Medicare/Medicaid coverage (p<0.0001). By history, the outpatient group was more likely to have past alcohol misuse, intravenous drug use, prescription drug misuse, and prescription opioid misuse. Most inpatient group members sought a recreational high compared to avoiding withdrawal or treating dependence in the outpatient group. Patients treated in the outpatient compared to inpatient setting were more likely to report adverse sequelae from their drug use including long-term drug use, depression, previous rehabilitation attempts, and seeking to avoid withdrawal.

Clinical characteristics and time trends of hospitalized methadone exposures in the United States based on the Toxicology Investigators Consortium (ToxIC) case registry: 2010\u20132017

BackgroundMethadone is well known for its long duration of action and propensity for mortality after an overdose. The present research was aimed at evaluating the clinical manifestations and time trends of methadone exposure in patients in US hospitals.MethodsWe queried the American College of Medical Toxicology’s Toxicology Investigators Consortium case registry for all cases of methadone exposure between January 1, 2010, and December 31, 2017. The collected information included demographic features, clinical presentations, therapeutic interventions, poisoning type (acute, chronic, or acute on chronic), and the reason(s) for exposure. Descriptive data and relative frequencies were used to investigate the participants’ characteristics.Our data analysis was performed using SPSS version 19 and Prism software. The trends and clinical manifestations of methadone poisoning over the time period of the study were specifically investigated.ResultsNine hundred and seventy-three patients who met our inclusion criteria, with a mean age of 41.9 ± 16.6 years (range: 11 months-78 years) were analyzed. Five hundred eighty-two (60.2%) were male. The highest rate of methadone poisoning was observed in 2013. There was an increasing rate of methadone exposures in 2010–2013, followed by a decline in 2014–2017. The most common clinical manifestations in methadone-poisoned patients were coma (48.6%) and respiratory depression (33.6%). The in-hospital mortality rate of methadone poisoning was 1.4%.ConclusionToxIC Registry data showed that inpatient methadone exposures enhanced from 2010 to 2013, after which a reduction occurred in the years 2014 to 2017.

Fatalities in poisoned patients managed by medical toxicologists

Background: Poisoning is a leading cause of injury-related death in the United States. The Toxicology Investigators Consortium (ToxIC) Case Registry, established by the American College of Medical Toxicology, prospectively captures patients who were directly cared for and managed at the bedside by medical toxicology services. We sought to describe exposure cases who presented to Emergency Departments (EDs) across ToxIC sites, received direct bedside care by medical toxicologists; however, the intoxication resulted in fatality.Methods: We identified all cases in the ToxIC Case Registry that resulted in fatality after hospital presentation over the 6-year study period. We collected data on patient demographics and clinical information including age group, sex, circumstances of exposure, route of exposure, substances involved, presenting signs and symptoms and management prior to death.Results: Of 44,567 recorded cases in the registry over the study period, 268 (0.6%) fatalities met the inclusion criteria and comprise the study cohort. There was no sex predominance (138 females; 51.5%) and 27 (10.1%) were pediatric fatalities. In 195 (72.7%) patients, exposure was intentional. In 175 (65.3%) patients, fatality was associated with exposure to pharmaceuticals. The leading substances resulting in death were non-opioid analgesics, followed by opioids (72% prescription opioids), cardiovascular medications, sedatives, antipsychotics, antidepressants, and sympathomimetics. At time of consult, the central nervous system was the most common system affected in both fatal and non-fatal cases. Compared with non-fatal ToxIC cases (n = 44,299), fatal cases involved significantly less children (27.7% vs. 10.1%, respectively; p < .001), and were managed more aggressively (e.g., mechanical ventilation 8.3% vs. 69.8%, p < .001). Both non-opioid analgesics (25.3% vs. 14.7%; p < .001) and opioids (17.8% vs. 7.5%; p < .001) were significantly more likely to be ingested in fatal compared with non-fatal cases, although analgesics, opioids, and non-opioids, were the most common agents implicated in both groups.Conclusions: Most ToxIC registry exposures resulting in death involve intentional exposure, without sex predominance. One in 10 fatalities involved a child. Analgesics, non-opioids, and opioids are the most commonly implicated agents in both fatal and non-fatal intoxications, which highlights the centrality of these agents as major sources of both morbidity and mortality.

Neuropsychiatric Sequelae in Adolescents With Acute Synthetic Cannabinoid Toxicity.

Adolescents represent the largest age group that presents to emergency departments (ED) for synthetic cannabinoid (SC) toxicity; however, the neurotoxic effects of acute SC exposures in this group are understudied. Our aim was to characterize the neuropsychiatric presentation of adolescents with SC-related exposure in the ED compared with those with traditional cannabis exposure. A multicenter registry of clinical information prospectively collected by medical toxicologists (Toxicology Investigators Consortium Case Registry) was reviewed for adolescents presenting to the ED after SC or cannabis exposure from 2010 through 2018. Associations were measured between drug exposures and neuropsychiatric symptoms and/or signs. Exposures were classified into 4 groups: SC-only exposure, SC-polydrug exposures, cannabis-only exposure, and cannabis-polydrug exposures. Adolescents presenting to the ED with SC-only exposure (n = 107) had higher odds of coma and/or central nervous system depression (odds ratio [OR] 3.42; 95% confidence interval [CI] 1.51-7.75) and seizures (OR 3.89; 95% CI 1.39-10.94) than those with cannabis-only exposure (n = 86). SC-only drug exposure was associated with lower odds of agitation than cannabis-only exposure (OR 0.18; 95% CI 0.10-0.34). In contrast, the group with SC-polydrug exposures (n = 38) had higher odds of agitation (OR 3.11; 95% CI 1.56-7.44) and seizures (OR 4.8; 95% CI 1.80-12.74) than the cannabis-polydrug exposures group (n = 117). In this multisite cohort of US adolescents assessed in the ED, SC exposure was associated with higher odds of neuropsychiatric morbidity than cannabis exposure providing a distinct neurospychiatric profile of acute SC toxicity in adolescents.

From Pot to Pods: Accidental Ingestions in the Elderly

Accidental ingestions in the geriatric population are likely more common than recognized. In Virginia, 2.3% of the exposures reported to a poison center in a 6 months period involved adults aged ≥60 years and 84% of those were unintentional. A nationwide study identified similar findings and found that cognitive dysfunction was the possible reason for the incident in 16% of cases. In 2013, The Toxicology Investigators Consortium Case Registry reported that adults older than 66 years accounted for 5.7% of the reported cases.

Acute Poisonings from Synthetic Cannabinoids — 50 U.S. Toxicology Investigators Consortium Registry Sites, 2010–2015

Recent reports suggest that acute intoxications by synthetic cannabinoids are increasing in the United States (1,2). Synthetic cannabinoids, which were research compounds in the 1980s, are now produced overseas; the first shipment recognized to contain synthetic cannabinoids was seized at a U.S. border in 2008 (3). Fifteen synthetic cannabinoids are Schedule I controlled substances (3), but enforcement is hampered by the continual introduction of new chemical compounds (1,3). Studies of synthetic cannabinoids indicate higher cannabinoid receptor binding affinities, effects two to 100 times more potent than Δ(9)-tetrahydrocannabinol (the principal psychoactive constituent of cannabis), noncannabinoid receptor binding, and genotoxicity (4,5). Acute synthetic cannabinoid exposure reportedly causes a range of mild to severe neuropsychiatric, cardiovascular, renal, and other effects (4,6,7); chronic use might lead to psychosis (6,8). During 2010-2015, physicians in the Toxicology Investigators Consortium (ToxIC) treated 456 patients for synthetic cannabinoid intoxications; 277 of the 456 patients reported synthetic cannabinoids as the sole toxicologic agent. Among these 277 patients, the most common clinical signs of intoxication were neurologic (agitation, central nervous system depression/coma, and delirium/toxic psychosis). Relative to all cases logged by 50 different sites in the ToxIC Case Registry, there was a statistically significant association between reporting year and the annual proportion of synthetic cannabinoid cases. In 2015, reported cases of synthetic cannabinoid intoxication increased at several ToxIC sites, corroborating reported upward trends in the numbers of such cases (1,2) and underscoring the need for prevention.

Utilization of Observation Units for the Care of Poisoned Patients: Trends from the Toxicology Investigators Consortium Case Registry.

Many poisoned patients may only require a period of observation after their exposure. There are limited data describing the use of observation units for managing poisoned adult and pediatric patients. We performed a retrospective review of all patients reported to the ToxIC Case Registry between January 1, 2012 and December 31, 2013. Eligible patients included those who received a bedside consultation by a medical toxicologist and whose care was provided in an observation unit, or those who were admitted under the care of a medical toxicologist in an observation unit. A total of 15,562 poisonings were reported to the registry during the study period, of which 340 (2.2%) involved patients who were cared for in an observation unit. Of these patients, 22.1% were 18years of age or younger, and the remaining 77.9% were greater than 18years of age. The most common reason for exposure was the intentional ingestion of a pharmaceutical agent in both adult (30.2%) and pediatric patients (36.0%). Alcohols (ethanol) (24.9%), opioids (20.0%), and sedative-hypnotics (17.7%) were the most common agent classes involved in adult patient exposures. The most common agent classes involved in pediatric exposures were antidepressants (12.0%), anticonvulsants (10.7%), and envenomations (10.7%). In adult patients, the most common signs and symptoms involved the nervous system (52.0%), a toxidrome (17.0%), or a major vital sign abnormality (14.7%). In pediatric patients, the most common signs and symptoms involved the nervous system (53.3%), a toxidrome (21.3%), or a major vital sign abnormality (17.3%). The results of this study demonstrate that a wide variety of poisoned patients have been cared for in an observation unit in consultation with a board-certified medical toxicologist. Patterns for the reasons for exposure, agents responsible for the exposure, and toxicological treatments will continue to evolve. Further study is needed to identify betterthose poisoned patients who can be appropriately managed in an observation unit.

Abuse and Diversion of Gabapentin Among Nonmedical Prescription Opioid Users in Appalachian Kentucky

Gabapentin (Neurontin®) is FDA-approved as an adjunctive anti-epileptic for refractory partial seizures and as an analgesic for post-herpetic neuralgia. It is presumed to interact with calcium channels to regulate various neurotransmitter release (1) and is commonly prescribed off-label for other pain syndromes as well as mood and anxiety disorders (2), with few reports of abuse (2–5). However, with decreasing availability of commonly abused prescription opioids, it has been suggested that non-medical users of prescription opioids are substituting other licit (6) and illicit (7) drugs for abuse.

The Toxicology Investigators Consortium Case Registry—The 2011 Experience

In 2010, the American College of Medical Toxicology established its Case Registry, the Toxicology Investigators Consortium (ToxIC). ToxIC is a prospective registry, which exclusively compiles suspected and confirmed toxic exposure cases cared for at the bedside by medical toxicologists at its participating sites. The Registry aims to fulfill two important gaps in the field: a real-time toxicosurveillance system to identify current poisoning trends and a powerful research tool in toxicology. ToxIC allows extraction of information from medical records making it the most robust multicenter database on chemical toxicities in existence. All cases seen by medical toxicologists at participating institutions were entered in a database. Information characterizing patients entered in 2011 was tabulated. 2010 data was also included so that cumulative total numbers could be described as well. The current report is a summary of the data collected in 2011 in comparison to 2010 entries and also includes cumulative data through December 31st, 2011. During 2011, 28 sites with 49 specific institutions contributed a total of 6,456 cases to the Registry. The total number of cases entered into the registry at the end of 2011 was 10,392. Emergency departments remained the most common source of consultations in 2011, accounting for 53% of cases. The most common reason for consultation was for pharmaceutical overdoses, which occurred in 48% of patients, including intentional (37%) and unintentional (11%) exposures. The most common classes of agents were sedative-hypnotics (1,492 entries in 23% of cases), non-opioid analgesics (1,368 cases in 21% of cases), opioids (17%), antidepressants (16%), stimulants/sympathomimetics (12%), and ethanol (8%). N-acetylcysteine was the most commonly administered antidote during 2011, similar to 2010, followed by the opioid antagonist naloxone, sodium bicarbonate, physostigmine and flumazenil. Anti-crotalid Fab fragments (CroFab) were administered in 106 out of 131 cases in which an envenomation occurred. There were 35 deaths recorded in the Registry during 2011. The most common associated agents, including when reported as sole agent or in combination with other agents, were opioids and analgesics (acetaminophen, aspirin, NSAIDS) with ten and eight deaths, respectively. Oxycodone was reported in six of the ten opioid-related deaths and heroin in three. Acetaminophen was the most common single agent reported overall being identified in all eight of the death cases attributed to analgesics. There were significant trends identified during 2011. Cases involving designer drugs including psychoactive bath salts and synthetic cannabinoids increased substantially from 2010 to 2011. The psychoactive bath salts were responsible for a large increase in stimulant/sympathomimetic-related cases reported to the Registry in 2011 with overall numbers doubling from 6% of all Registry entries in 2010 to 12% in 2011. Entries involving psychoactive drugs of abuse also increased twofold from 2010 to 2011 jumping 3 to 6%, primarily due to increasing frequency of synthetic cannabinoid ("K2") related intoxications as 2011 progressed. The 2011 Registry included over 600 ADR's (10% of Registry Cases) with 115 agents causing at least 2 ADR's. This is up from only 3% of cases (116 total cases) in 2010. The ToxIC Case Registry continues to grow. At the end of 2011, over 10,000 cases had been entered into the Registry. As demonstrated by the trends identified in psychoactive bath salt and synthetic cannabinoid reports, the Registry is a valuable toxicosurveillance and research tool. The ToxIC Registry is a unique tool for identifying and characterizing confirmed cases of significant or potential toxicity or complexity to require bedside consultation by a medical toxicologist.

Toxico-Surveillance of Infant and Toddler Poisonings in the United States

Infant and toddler poisonings are important to capture and may be challenging to manage. We aim to describe the Toxicology Investigators Consortium (ToxIC) Case Registry as a tool for toxico-surveillance of this problem in the United States. Using the ToxIC Case Registry database of the American College of Medical Toxicology, we identified infant and toddler poisonings over a 15-month period between April 1, 2010 and June 30, 2011 reported to the 31 Registry sites. Of 6,810 poisoning cases reported to the ToxIC registry, 248 (3.6 %) involved children younger than 2 years (51 % males). Fifty-four percent were hospital inpatients, 42 % were in the Emergency Department and 4 % were outpatients. Sixty-three percent were symptomatic. The most common ingested compounds were highly toxic-cardiac drugs (16 %), psychotropics (15 %), recreational drugs, alcohols, and controlled narcotic drugs (13 %), analgesics (9 %), and cleaning compounds (7 %). Fourteen percent of cases involved multiple agents. The ToxIC registry is a potentially useful toxico-surveillance tool to identify and trend clinically significant poisonings in young children, and potentially other populations. These data could be used to target specific preventive interventions.