Increasing severity of medical outcomes and associated substances in cases reported to United States poison centers.

INTRODUCTION: Poison centers provide free expert recommendations on the treatment of a wide variety of toxicological emergencies. Prior studies have called attention to the increasing complexity of cases reported to poison centers. We aimed first, to evaluate the trends in medical outcome severity, over a 15-year period in both the adult and pediatric populations. Second, we described the most frequently reported substances associated with major effect or death. METHODS: This is a retrospective review of exposures reported to the National Poison Data System from 1 January 2007 through 31 December 2021. All closed cases, for human exposures, reported during the study period were included. We assessed trends in frequencies and rates of medical outcomes and level of care received, among the adult (age greater than 19 years) and pediatric (age 19 years and younger) populations by reason for exposure. RESULTS: During the study period, the number of adult unintentional exposures resulting in major effect (37.4 percent) and death (65.3 percent) increased. The number of adult intentional exposures resulting in death increased by 233.9 percent and those resulting in a major effect increased by 133.1 percent. The rates of exposures resulting in major effect and death increased among both intentional and unintentional adult exposures. The number of pediatric unintentional exposures resulting in a major effect increased by 76.6 percent and the number of pediatric intentional exposures resulting in death and major effect increased by 122.7 and 190.1 percent, respectively. Moderate, major effect, and death rates increased in pediatric unintentional exposures and moderate and major effect rates increased in pediatric intentional exposures. CONCLUSIONS: We found a worsening severity of medical outcomes in adult and pediatric cases reported to poison centers. Poison centers are increasingly managing complex cases. Monitoring trends in which substances are associated with severe outcomes is imperative for future strategic prevention efforts.

Psilocybin Exposures Reported to U.S. Poison Centers: National Trends Over a Decade.

PURPOSE: We describe trends in psilocybin exposures among adolescents and young adults as reported to US poison centers over the past decade. METHODS: We queried the National Poison Data System for cases involving psilocybin during January 1, 2013-December 31, 2022. Persons aged 13-25 years were included. We examined exposures to psilocybin by demographics, clinical effects, level of care, and medical outcome. RESULTS: During the 10-year study period, 4,055 psilocybin-involved exposures were reported among adolescents and young adults, 2,667 (65.8%) being single substance exposures. Most single substance cases received medical attention (adolescents: 75.3% [n = 1,176], young adults: 72.1% [n = 797]). We did not find significant change in the number of cases during 2013-2018. Cases started increasing in 2019. In 2022, cases more than tripled among adolescents and more than doubled among young adults, compared to 2018 (p < .0001). DISCUSSION: Continued national surveillance is critical to determine the impact of psilocybin exposures on youth as it becomes increasingly available.

Metabolic modeling of sex-specific liver tissue suggests mechanism of differences in toxicological responses.

Male subjects in animal and human studies are disproportionately used for toxicological testing. This discrepancy is evidenced in clinical medicine where females are more likely than males to experience liver-related adverse events in response to xenobiotics. While previous work has shown gene expression differences between the sexes, there is a lack of systems-level approaches to understand the direct clinical impact of these differences. Here, we integrate gene expression data with metabolic network models to characterize the impact of transcriptional changes of metabolic genes in the context of sex differences and drug treatment. We used Tasks Inferred from Differential Expression (TIDEs), a reaction-centric approach to analyzing differences in gene expression, to discover that several metabolic pathways exhibit sex differences including glycolysis, fatty acid metabolism, nucleotide metabolism, and xenobiotics metabolism. When TIDEs is used to compare expression differences in treated and untreated hepatocytes, we find several subsystems with differential expression overlap with the sex-altered pathways such as fatty acid metabolism, purine and pyrimidine metabolism, and xenobiotics metabolism. Finally, using sex-specific transcriptomic data, we create individual and averaged male and female liver models and find differences in the pentose phosphate pathway and other metabolic pathways. These results suggest potential sex differences in the contribution of the pentose phosphate pathway to oxidative stress, and we recommend further research into how these reactions respond to hepatotoxic pharmaceuticals.

Using an Exposure Call Center to Help Mitigate Outbreaks, Such as COVID-19, on a University Campus.

Rapid identification and management of close contacts is an important component of an effective university mitigation strategy for highly contagious infectious diseases such as measles and coronavirus disease-2019 (COVID-19). Institutions of higher education must plan for an associated large influx of calls that can overwhelm standard student health and local public health operations. In fall 2020, a large state public university's Department of Student Health and Wellness created a dedicated exposure call center (ECC), in close collaboration with the local public health department, to quickly assess students who learned of a COVID-19 exposure outside of the formal contact tracing process. The ECC operated 7 days a week and fielded 3361 calls: 3187 from students and 174 from staff, faculty, and parents. The ECC provided rapid assessment and guidance for students with COVID-19 exposure, allowing for prompt quarantine and medical assessment when warranted. Call centers can increase the bandwidth of university health centers and also reduce the burden on health care providers and other public health resources during periods of crisis or high demand.

Suspected Suicide Attempts by Self-Poisoning Among Persons Aged 10-19 Years During the COVID-19 Pandemic - United States, 2020-2022.

The World Health Organization declared COVID-19 a global pandemic on March 11, 2020 (1). As strategies to mitigate the pandemic were implemented, concerns were raised that the containment efforts through quarantine and social distancing practices were negatively affecting the mental and physical health of children and adolescents (2). Suicide is a growing public health problem in the United States. In 2020, suicide was the second leading cause of death among persons aged 10-14 years and the third leading cause among those aged 15-24 years (3). The National Poison Data System (NPDS) database was used to examine trends in suspected suicide attempts by self-poisoning among persons aged 10-19 years before and during the COVID-19 pandemic. Compared with 2019 (prepandemic), during 2021, the overall rate of suspected suicide attempts by self-poisoning increased by 30.0% (95% CI = 28.6%-30.9%), rates among children aged 10-12 years, adolescents aged 13-15 years, and females increased 73.0% (67.4%-80.0%), 48.8% (46.7%-50.9%), and 36.8% (35.4%-38.2%), respectively, and these trends continued into the third quarter of 2022. Substances most frequently involved in overdoses were acetaminophen, ibuprofen, sertraline, fluoxetine, and diphenhydramine. Acetaminophen-involved overdoses increased 71% (67.4%-74.9%) in 2021 and 58.0% (54.5%-61.6%) in 2022. Diphenhydramine-involved overdoses increased 24.2% (19.9%-28.7%) in 2021 and 35.8% (31.2%-40.5%) in 2022. A comprehensive public health approach to suicide prevention, focused on children and adolescents and involving a partnership between families, school teachers, mental health professionals, and public health leadership is needed. The 9-8-8 Suicide and Crisis Lifeline provides crisis support for persons experiencing mental health-related distress and assists community members who are concerned about persons experiencing a mental health crisis.

Metabolic modeling of sex-specific tissue predicts mechanisms of differences in toxicological responses.

Male subjects in animal and human studies are disproportionately used for toxicological testing. This discrepancy is evidenced in clinical medicine where females are more likely than males to experience liver-related adverse events in response to xenobiotics. While previous work has shown gene expression differences between the sexes, there is a lack of systems-level approaches to understand the direct clinical impact effect of these differences. Here, we integrate gene expression data with metabolic network models to characterize the impact of transcriptional changes of metabolic genes in the context of sex differences and drug treatment. We used Tasks Inferred from Differential Expression (TIDEs), a reaction-centric approach to analyzing differences in gene expression, to discover that androgen, ether lipid, glucocorticoid, tryptophan, and xenobiotic metabolism have more activity in the male liver, and serotonin, melatonin, pentose, glucuronate, and vitamin A metabolism have more activity in the female liver. When TIDEs is used to compare expression differences in treated and untreated hepatocytes, we see little response in those sex-altered subsystems, and the largest differences are in subsystems related to lipid metabolism. Finally, using sex-specific transcriptomic data, we create individual and averaged male and female liver models and find differences in the import of bile acids and salts. This result suggests that the sexually dimorphic behavior of the liver may be caused by differences in enterohepatic recirculation, and we suggest an investigation into sex-specific microbiome composition as an avenue of further research. Author Summary: Male-bias in clinical testing of drugs has led to a disproportionate number of hepatotoxic events in women. Previous works use gene-by-gene differences in biological sex to explain this discrepancy, but there is little focus on the systematic interactions of these differences. To this end, we use a combination of gene expression data and metabolic modeling to compare metabolic activity between the male and female liver and treated and untreated hepatocytes. We find several subsystems with differential activity in each sex; however, when comparing these subsystems with those pathways altered by hepatotoxic agents, we find little overlap. To explore these differences on a reaction-by-reaction basis, we use the same sex-specific transcriptomic data to contextualize the previously published Human1 human cell metabolic model. In these models we find a difference in flux for the import of bile acids and salts, suggesting a potential difference in enterohepatic circulation. These findings can help guide future drug design, toxicological testing, and sex-specific research to better account for the entire human population.

Identifying vulnerable populations at a university during the COVID-19 pandemic.

Objective: Persons with high-risk for severe COVID-19 illness require special attention when considering university operations during the novel coronavirus pandemic. The objective of this study was to determine the number of students who fall within a high-risk category according to Centers for Disease Control and Prevention (CDC) guidelines using linked databases. Participants: Students enrolled at a large public University and who accessed the student health center between 2016 and 2020. Methods: Clinical data were linked with both university student enrollment and disability services databases to provide a comprehensive, de-identified dataset of students at higher medical risk of severe COVID-19 illness. Results: 1902 unique students (14% of the student health center population) were identified as having one or more high-risk condition. Conclusions: Utilizing a large and longitudinally linked student database provides universities with valuable information to make critical administrative decisions about how best to accommodate high-risk students to reduce their medical risk when returning to in-person instruction.

Toxic Alcohol Poisoning.

This article reviews the background, metabolism, clinical effects, and treatment of toxic alcohols, specifically ethylene glycol, methanol, diethylene glycol, propylene glycol, and isopropyl alcohol. This article also reviews the importance of an anion gap metabolic acidosis in relation to toxic alcohols and explores both the utility and the limitations of the osmol gap in patient management.

Chemical Agents Encountered in Protests.

The most common chemicals used in riot control agents are chlorobenzylidene malononitrile, chloroacetophenone, dibenz[b,f]-[1,4]-oxazepine, and oleoresin capsicum. They cause ocular, respiratory, and dermal effects usually within seconds to minutes of exposure, but delayed effects have been reported. In addition, the canisters containing these chemicals can cause traumatic injuries when launched as projectiles. Although most effects are mild, some may be serious, especially in those with preexisting respiratory disease. Treatment consists of removing the patient from the source of exposure, removing contaminated clothes, and copiously irrigating the affected areas with water.

Utilizing the Toxicology Laboratory in the Poisoned Patient.

When evaluating a potentially poisoned patient, there is no substitute for a thorough history and physical examination. Clues from the examination are generally more likely to be helpful than a "shotgun" laboratory approach that involves indiscriminate testing of blood or urine for multiple agents. When used appropriately, diagnostic tests may be of help in the management of the intoxicated patient. When a specific toxin or even class of toxins is suspected, requesting qualitative or quantitative levels may be appropriate. The purpose of this review is to examine the role of common diagnostic tests in the evaluation of the poisoned patient.

Pediatric suicides reported to U.S. poison centers.

INTRODUCTION: As the pediatric mental health crisis worsens, the rate of adolescent suicide-related cases is increasing, including adolescent cases of self-poisoning. METHODS: Data from the National Poison Data System was analyzed for trends in rates and frequencies of all pediatric suspected suicides between 2015 and 2020. RESULTS: There were 514,350 pediatric suspected suicides analyzed, with the largest increase in rate of suspected suicides occurring in children ages 10 to 12 years (109.3%, p = 0.002). Rates also increased significantly in children ages 13 to 15 years (30.3%, p < 0.001) and 16 to 19 years (18.1%, p < 0.05). The most commonly utilized substances were ibuprofen and acetaminophen, with the largest increase in rate of exposures seen for acetaminophen. Discussion: This data demonstrates concerning rises in cases of self-poisoning, suggesting that the pediatric mental health crisis is worsening and extending into younger populations. Pediatric populations have easier access to over-the-counter medications, potentially explaining the likelihood of utilization of these medications in pediatric suspected suicides. CONCLUSIONS: Initiation of appropriate mental health screenings and interventions should be considered in these young age groups in order to prevent further rises in self-poisoning cases and associated morbidity and mortality.

Predictors of severe outcome following opioid intoxication in children.

INTRODUCTION: While the opioid crisis has claimed the lives of nearly 500,000 in the U.S. over the past two decades, and pediatric cases of opioid intoxications are increasing, only sparse data exist regarding risk factors for severe outcome in children following an opioid intoxication. We explore predictors of severe outcome (i.e., intensive care unit [ICU] admission or in-hospital death) in children who presented to the Emergency Department with an opioid intoxication. METHODS: In this prospective cohort study we collected data on all children (0-18 years) who presented with an opioid intoxication to the 50 medical centers in the US and two international centers affiliated with the Toxicology Investigators Consortium (ToxIC) of the American College of Medical Toxicology, from August 2017 through June 2020, and who received a bedside consultation by a medical toxicologist. We collected relevant demographic, clinical, management, disposition, and outcome data, and we conducted a multivariable logistic regression analysis to explore predictors of severe outcome. The primary outcome was a composite severe outcome endpoint, defined as ICU admission or in-hospital death. Covariates included sociodemographic, exposure and clinical characteristics. RESULTS: Of the 165 (87 females, 52.7%) children with an opioid intoxication, 89 (53.9%) were admitted to ICU or died during hospitalization, and 76 did not meet these criteria. Seventy-four (44.8%) children were exposed to opioids prescribed to family members. Fentanyl exposure (adjusted OR [aOR] = 3.6, 95% CI: 1.0-11.6; p = 0.03) and age ≥10 years (aOR = 2.5, 95% CI: 1.2-4.8; p = 0.01) were independent predictors of severe outcome. CONCLUSIONS: Children with an opioid toxicity that have been exposed to fentanyl and those aged ≥10 years had 3.6 and 2.5 higher odds of ICU admission or death, respectively, than those without these characteristics. Prevention efforts should target these risk factors to mitigate poor outcomes in children with an opioid intoxication.

Building-Level Wastewater Surveillance for SARS-CoV-2 in Occupied University Dormitories as an Outbreak Forecasting Tool: One Year Case Study.

Congregate living poses one of the highest risk situations for the transmission of respiratory viruses including SARS-CoV-2. University dormitories exemplify such high-risk settings. We demonstrate the value of using building-level SARS-CoV-2 wastewater surveillance as an early warning system to inform when prevalence testing of all building occupants is warranted. Coordinated daily testing of composite wastewater samples and clinical testing in dormitories was used to prompt the screening of otherwise unrecognized infected occupants. We overlay the detection patterns in the context of regular scheduled occupant testing to validate a wastewater detection model. The trend of wastewater positivity largely aligned well with the clinical positivity and epidemiology of dormitory occupants. However, the predictive ability of wastewater-surveillance to detect new positive cases is hampered by convalescent shedding in recovered/noncontagious individuals as they return to the building. Building-level pooled wastewater-surveillance and forecasting is most productive for predicting new cases in low-prevalence instances at the community level. For higher-education facilities and other congregate living settings to remain in operation during a pandemic, a thorough surveillance-based decision-making system is vital. Building-level wastewater monitoring on a daily basis paired with regular testing of individual dormitory occupants is an effective and efficient approach for mitigating outbreaks on university campuses.

Trends and risk markers of student hazardous drinking: a comparative analysis using longitudinally linked datasets in a public university.

Aims: This study compares the incidence and risk-markers of student alcohol intoxication-related emergency department (ED) visits and alcohol-related incidents reported to student affairs. Methods: Enrollment data were linked to ED visits with alcohol intoxication and to alcohol-related incidents reported to campus authorities within one year following the first (index) annual enrollment. Incidence, annual trends and associated risk markers were analyzed. Results: The cohort consisted of 204,423 students aged 16-49. Incidence rates of first ED visit with alcohol intoxication and alcohol-related incidents were 59/10,000 and 311/10,000 person-years, respectively. Both outcomes shared common risk-markers including age, gender, race/ethnicity, fraternity and sorority (FSL) membership, an existing diagnosis of depression, etc. Being an athlete was associated with a lower risk of alcohol-related ED visits, and transfer students were at lower risk for alcohol-related incidents. Conclusion: Linking enrollment data with hazardous drinking events can help in better monitoring of student hazardous drinking and targeting interventions.HighlightsFirst longitudinal study documenting the incidence of extreme student alcohol misuse.There were rising trends in student risky drinking based on two independent datasets.Analysis identified a range of risk markers predictive of risky drinking behaviors.Linking multiple student datasets can timely identify high risk students.

A Membrane-Modulated Centrifugal Microdevice for Enzyme-Linked Immunosorbent Assay-Based Detection of Illicit and Misused Drugs.

Increased opioid use and misuse have imposed large analytical demands across clinical and forensic sectors. Due to the absence of affordable, accurate, and simple on-site tests (e.g., point of interdiction and bedside), analysis is primarily conducted in centralized laboratories via time-consuming, labor-intensive methods. Many healthcare facilities do not have such analytical capabilities and must send samples to commercial laboratories, increasing turnaround time and care costs, as well as delaying public health warnings regarding the emergence of specific substances. Enzyme-linked immunosorbent assays (ELISAs) are used ubiquitously, despite lengthy workflows that require substantial manual intervention. Faster, reliable analytics are desperately needed to mitigate the mortality and morbidity associated with the current substance use epidemic. We describe one such alternative─a portable centrifugal microfluidic ELISA system that supplants repetitive pipetting with rotationally controlled fluidics. Embedded cellulosic membranes act as microvalves, permitting flow only when centrifugally generated hydraulic pressure exceeds their liquid entry pressure. These features enable stepwise reagent introduction, incubation, and removal simply by tuning rotational frequency. We demonstrate the success of this platform through sensitive, specific colorimetric detection of opiates, a subclass of opioids naturally derived from the opium poppy. Objective image analysis eliminated subjectivity in human color perception and permitted reliable detection of opiates in buffer and artificial urine at the ng/µL range. Opiates were clearly differentiated from other drug classes without interference from common adulterants known to cause false positive results in current colorimetric field tests. Eight samples were simultaneously analyzed in under 1 h, a marked reduction from the traditional multiday timeline. This approach could permit rapid, automatable ELISA-based drug detection outside of traditional laboratories by nontechnical personnel.

COVID-19 Isolation and Quarantine Experience for Residential Students at a Large Four-Year Public University.

Rapid identification and management of students with COVID-19 symptoms, exposure, or disease are critical to halting disease spread and protecting public health. We describe the interdisciplinary isolation and quarantine program of a large, public university, the University of Virginia, Charlottesville. The program provided students with wraparound services, including medical, mental health, academic, and other support services during their isolation or quarantine stay. The program successfully accommodated 844 cases during the fall 2020 semester, thereby decreasing exposure to the rest of the university and the local community. (Am J Public Health. 2021;111(10):1772-1775. https://doi.org/10.2105/AJPH.2021.306424).

Risk factors associated with concussions in a college student population.

PURPOSE: To determine risk factors associated with concussion among the general collegiate population using a unique data linkage methodology. METHODS: Student health medical, counseling, and disability access service data were linked with university enrollment data to provide a comprehensive, deidentified dataset of students who sought care at the student health center for concussion from 2016-2020. Using chi-squared tests and logistic regression, characteristics of students with and without concussion were evaluated. RESULTS: During the study period, 506 concussions from 474 students were identified (cumulative incidence rate of 51.7 per 10,000 students). Significant predictors of concussion included: younger age (<21 years): odds ratio (OR) = 3.52 (95% confidence intervals [CI], 2.78, 4.50), Greek affiliation: OR = 1.89 (95% CI, 1.56, 2.30), and utilization of counseling and psychological services: OR = 1.92 (95% CI 1.59, 2.32). Of the students with concussion, 47% had at least one other concussion within the preceding year. History of prior hospitalization or medical imaging for head injury increased subsequent concussion risk by 4.5 fold. CONCLUSIONS: Linking unique datasets provides a richer understanding of the characteristics and risk factors associated with student concussions than analysis of a single data source. This comprehensive dataset will enable future targeted interventions to prevent and treat college student concussions.

Toxic Alcohols.

This article reviews the background, metabolism, clinical effects, and treatment of toxic alcohols, specifically ethylene glycol, methanol, diethylene glycol, propylene glycol, and isopropyl alcohol. This article also reviews the importance of an anion gap metabolic acidosis in relation to toxic alcohols and explores both the utility and the limitations of the osmole gap in patient management.

Opioid Exposures Reported to U.S. Poison Centers.

OBJECTIVE: Opioid-related deaths are a leading cause of accidental deaths in the United States (U.S.). This study aims to examine the national trends in opioid exposures reported to U.S. poison centers (PCs). METHODS: The National Poison Data System (NPDS) was queried for opioid exposures between 2011 and 2018. We descriptively assessed the demographic and clinical characteristics. Trends in opioid frequencies and rates were analyzed using Poisson regression. Independent predictors of serious adverse events in opioid exposures were studied. RESULTS: There were a total of 604,183 opioid exposure calls made to the PCs during the study period. The frequency of opioid exposures decreased by 28.9% (95% CI: -29.6%, -28.1%; p < 0.001), and the rate of opioid exposures decreased by 21.2% (95% CI: -24.7%, -16.9%; p < 0.001). Multiple substance exposures accounted for 48.9% cases. The most frequent age group was 20-29 years (19.3%). Suspected suicides accounted for 34.9% cases. There were 7,246 deaths in our study sample, with 6.8% of cases demonstrating major effects. Hydrocodone was the most frequently observed opioid causing a toxic exposure and naloxone was used in 20.6% cases. Important predictors of a serious adverse event were age, gender, multi-substance exposures, and reasons for exposure. CONCLUSIONS: Analysis of calls to PCs indicated a decreasing trend of opioid exposures. However, the proportion of SAEs due to such exposures increased. There was a high proportion of intentional exposures and occurred in older age groups. PCs are a vital component of real-time public health surveillance of overdoses in the current opioid crisis.