The Toxicology Investigators Consortium 2023 Annual Report.

Since 2010, the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) has maintained the ToxIC Core Registry, a national case registry of in-hospital and clinic patient consultations submitted by medical toxicology physicians. Deidentified patient data entered into the registry includes patient demographics, reason for medical toxicology evaluation, exposure agents, clinical signs and symptoms, treatments and antidotes administered, and mortality. This fourteenth annual report provides data from 7392 patients entered into the Core Registry in 2023 by 36 participating sites comprising 61 distinct healthcare facilities, bringing the total case count to 102331 between 2010 and 2023. Ethanol was the most commonly reported exposure agent class (24.4%), followed by opioids (22.7%), non-opioid analgesics (16.7%), and antidepressants (11.7%). For the first time since the registry's initiation, in 2023, ethanol was the leading agent of exposure. There were 98 fatalities (case fatality rate of 1.3%). Additional descriptive analyses in this annual report were conducted to describe the reasons for medical toxicology consultation by age in 2023, and yearly trends for opioid and psychoactive exposures, physostigmine and rivastigmine treatments, and acetaminophen exposures treated with fomepizole.

Prevalence and predictors of HIV among patients presenting to US emergency departments with opioid overdose.

INTRODUCTION: Opioid overdose deaths in the U.S. have risen dramatically in the past decade, largely due to the surge in illicitly manufactured fentanyl. Injection drug use is a known risk factor for HIV, further complicating the long-term consequences of opioid use. The baseline prevalence of HIV among adults in the US is 0.46 %. The primary purpose of this study was to determine the prevalence and risk factors of HIV among patients presenting to the emergency departments (ED) with an acute opioid overdose. METHODS: This study is a prospective observational cohort study from the ToxIC Fentalog Study group. Patients age 18 years of age or older are included if they present to one of 10 participating U.S. hospitals in 9 states between September 2020 and May 2023 with a suspected opioid overdose and had waste serum available after routine laboratory testing. Clinical data is collected from the medical record and patient serum is sent for comprehensive toxicologic analysis via liquid chromatography quadrupole time-of-flight mass spectroscopy to detect the presence of over 1200 substances including illicit opioids, novel synthetic opioids, medications, and adulterants. Logistic multivariable regression was performed to examine the association between demographic, behavioral, and serum toxicology data with risk factors and HIV status. RESULTS: Among the total cohort (n=1690), 1062 cases had known HIV status (62.8 % of total sample). Among patients with a known HIV status, 60 (5.6 % [95 % CI: 4.2 %, 7.0 %]) were HIV positive. Patients with HIV reported stimulant use more frequently (13.3 %) than those without HIV (6.8 %; p=0.003). After controlling for confounding, bipolar psychiatric history was a significant independent predictor of HIV positivity (aOR: 1.08; 95 % CI: 1.02, 1.13) in this population. CONCLUSIONS: In this large multicenter cohort, the prevalence of HIV for ED patients with illicit opioid overdose was 9 times higher than that expected by the general population. Bipolar disorder appears to be a novel risk factor for HIV positivity in this patient population.

Heroin or fentanyl: Prevalence of confirmed fentanyl in ED patients with suspected heroin overdose.

Background: United States drug overdose deaths are being driven by the increasing prevalence of fentanyl, but whether patients are knowingly using fentanyl is unclear. We examined the analytical confirmation of fentanyl in emergency department (ED) patients with documented heroin overdose. Hypothesis: We hypothesized that the proportion of fentanyl and fentanyl analogs would be higher than that of confirmed heroin. Methods: This is a subgroup analysis from a prospective multicenter consecutive cohort of ED patients age 18+ with opioid overdose presenting to 10 US sites within the Toxicology Investigators Consortium from 2020 to 2021. Toxicology analysis was performed using liquid chromatography quadrupole time-of-flight mass spectrometry. De-identified toxicology results were paired with the clinical database. The primary outcome was the proportion of patients with fentanyl analytes detected in their serum. Results: Of 1006 patients screened, 406 were eligible, and of 168 patients who reported that they had taken heroin or had a documented heroin overdose, 88% (n = 147) were in fact found to have fentanyl and/or a fentanyl analog present on serum analysis (p < 0.0001). In contrast, only 46 of the 168 patients with reported or documented heroin overdose (27%) were found to have heroin biomarkers present. Conclusion: The prevalence of confirmed fentanyl in ED patients with suspected heroin overdose was extremely high, while the prevalence of heroin was very low. There was a high degree of mismatch between the opioids believed to be the overdose agent versus the actual opioids identified on serum toxicology. Clinicians in the United States should presume that fentanyl is involved in all illicit opioid overdoses and should counsel patients on harm reduction measures.

Impact of social media "challenges" on poison center case volume for intentional ingestions among school-aged children: an observational study.

INTRODUCTION: Mental health problems among youth have escalated over the past decade, with increased rates of self-harm, including suicide attempts by ingestion. Social media use has been linked to youth mental health, including "challenges" urging youth to ingest substances for recreational and other purposes. We hypothesized that social media challenges for particular substances would temporally correspond with increased ingestions of these substances. METHODS: We identified peak Google Trends search times for social media ingestion challenges involving diphenhydramine, laundry pods, nutmeg, and cinnamon, and used data from America's Poison Centers National Poison Data System to plot reported ingestions 3 months before and after peak searches in school-aged children. RESULTS: There were 2,169 individuals in the analysis. Diphenhydramine was the most frequently reported ingestion for misuse/abuse and suicidal purposes (n = 266 and 1,609, respectively). For all ingestions together, 45 percent (n = 979) had a moderate health effect, and 6.35 percent (n = 137) had a major health effect. Time of peak searches corresponded with increased ingestions for each substance. DISCUSSION: We found a temporal relationship between peak Google Trends searches for ingestion challenges and ingestions of that substance reported to United States poison centers. Compared to misuse/abuse ingestions, most suicidal ingestions peaked 1-2 months later, suggesting a public health opportunity for intervention. LIMITATIONS: This retrospective observational study does not establish causal effect. All data are a result of self-reporting of the exposures, which may lead to a reporting bias. Google Trends is not the only search engine and likely underestimates the true incidence of social media posts. CONCLUSIONS: Additional research is needed on the relationship between social media and youth mental health, particularly around "challenges" that place youths' health at risk. There may be opportunities for intervention to decrease medical and mental health sequelae of these challenges.

A systematic evaluation of physical activity and diet policies in Scotland: results from the 2021 Active Healthy Kids Report Card.

BACKGROUND: Policymaking regarding physical activity (PA) and diet plays an important role in childhood health promotion. This study provides a detailed examination of Scottish government and policy for child and adolescent PA and diet and discusses strengths and areas for improvement. METHODS: Scottish policy documents (n = 18 [PA]; n = 10 [diet])-published in 2011-20-were reviewed for grading using an adapted version of the Health-Enhancing Physical Activity Policy Audit Tool Version 2. RESULTS: There is clear evidence of leadership and commitment to improving PA and diet and tackling obesity in children and adolescents. The allocation of funds and resources for policy implementation has increased substantially over the past decade. Progress through early key stages of public policymaking-policy agenda and formation-has improved. However, there is limited information on later key stages, including policy monitoring and evaluation. CONCLUSIONS: Childhood PA and diet are a clear priority in Scotland, and PA and diet policies clearly support the desire to achieve other goals, including reducing inequalities and increasing active travel in Scotland. Nonetheless, future policies should be further strengthened through clear(er) plans of implementation, and monitoring and evaluation to support their societal impact.

Opioid overdoses involving xylazine in emergency department patients: a multicenter study.

INTRODUCTION: Illicit opioids, consisting largely of fentanyl, novel synthetic opioids, and adulterants, are the primary cause of drug overdose fatality in the United States. Xylazine, an alpha-2 adrenergic agonist and veterinary tranquilizer, is being increasingly detected among decedents following illicit opioid overdose. Clinical outcomes in non-fatal overdose involving xylazine are unexplored. Therefore, among emergency department patients with illicit opioid overdose, we evaluated clinical outcome differences for patients with and without xylazine exposures. METHODS: This multicenter, prospective cohort study enrolled adult patients with opioid overdose who presented to one of nine United States emergency departments between 21 September 2020, and 17 August 2021. Patients with opioid overdose were screened and included if they tested positive for an illicit opioid (heroin, fentanyl, fentanyl analog, or novel synthetic opioid) or xylazine. Patient serum was analyzed via liquid chromatography quadrupole time-of-flight mass spectroscopy to detect current illicit opioids, novel synthetic opioids, xylazine and adulterants. Overdose severity surrogate outcomes were: (a) cardiac arrest requiring cardiopulmonary resuscitation (primary); and (b) coma within 4 h of arrival (secondary). RESULTS: Three hundred and twenty-one patients met inclusion criteria: 90 tested positive for xylazine and 231 were negative. The primary outcome occurred in 37 patients, and the secondary outcome occurred in 111 patients. Using multivariable regression analysis, patients positive for xylazine had significantly lower adjusted odds of cardiac arrest (adjusted OR 0.30, 95% CI 0.10-0.92) and coma (adjusted OR 0.52, 95% CI 0.29-0.94). CONCLUSIONS: In this large multicenter cohort, cardiac arrest and coma in emergency department patients with illicit opioid overdose were significantly less severe in those testing positive for xylazine.

Trends in intentional abuse and misuse ingestions in school-aged children and adolescents reported to US poison centers from 2000-2020.

CONTEXT: Childhood and adolescent misuse and abuse exposures remain a serious public health challenge in the United States. This study aimed to describe recent trends and patterns of intentional substance misuse and abuse exposures among school-aged children and adolescents in the United States. METHODS: This study was a retrospective cohort study of intentional misuse and abuse exposures in children 6 through 18 years reported to the National Poison Data System (NPDS) from January 1, 2000, through December 31, 2020. Demographic trends, reported clinical effects, treatments, management sites, and health outcomes were assessed overall and within four age categories: 6-9, 10-12, 13-15, and 16-18. RESULTS: Between 2000 and 2020, there were 338,727 cases regarding intentional misuse and abuse exposures for children ages 6 through 18 years old. Overall, misuse/abuse ingestions fluctuated over time, with a peak in 2011. The majority of intentional misuse/abuse ingestions occurred in males (58.3%), and more than 80% of all reported exposure cases occurred in youth aged 13 to 18. 32.6% of ingestions resulted in worse than minor clinical outcomes. Older age groups had a greater number of severe medical outcomes compared to younger age groups. Major or life-threatening exposures (including those resulting in death) were more common in males. Overall, deaths were rare (n = 450), 0.1%). Male sex, older age, abuse ingestions, exposure site of a public area or other residence, and multiple ingested substances were other factors associated with increased mortality. Marijuana exposure rates had the highest average monthly increase overall, with the most dramatic rise occurring from 2017 to 2020. Edible marijuana preparations accounted for the highest increase in call rates compared with all other forms of marijuana. DISCUSSION AND CONCLUSION: With over 330,000 poison center cases reported during the 20-year study period, intentional substance misuse and abuse exposures substantially impact the pediatric population. The substances most commonly misused/abused are more widely available substances such as over-the-counter medications, household products and pharmaceuticals commonly prescribed to youth. Differences in age and sex were evident, with males and adolescents more likely to abuse and misuse substances. Our study describes an upward trend in marijuana misuse/abuse exposures among youth, especially those involving edible products. These findings highlight an ongoing concern about the impact of rapidly evolving cannabis legalization on this vulnerable population.

Trends Over 2 Decades in Adolescent Suicidal and Recreational Ingestions of Over-the-Counter Coricidin Preparations.

OBJECTIVE: The aim of this study was to assess national trends in recreational and suicidal ingestions of over-the-counter cough preparations that contain Coricidin. METHODS: Using the American Association of Poison Control Center's National Poison Data System, we obtained data from 2004 to 2017 on patients aged 13 to 19 years with an ingestion of "Coricidin." We examined trends over time overall and ingestion intent (recreational vs suicidal) using linear regression. We compared patient characteristics, substances ingested, clinical effects and therapies, and outcomes by suicidal versus misuse or recreational intention. RESULTS: An initial search with the inclusion criteria found 19,213 calls that matched study inclusion criteria. On average, there was a yearly linear increase of 180.0 (95% confidence interval [CI], 136.6-223.3; P < 0.01) ingestions per year. Within suicide ingestions, there was an average yearly increase of 97.9 (95% CI, 66.9-128.9; P < 0.01) ingestions, and within misuse/recreational ingestions, there was an average yearly increase of 82.1 (95% CI, 60.3-103.9; P < 0.01) ingestions. The most common clinical effect was tachycardia, which occurred in 42.4% of ingestions. Altered mental status, mydriasis, and ataxia were all more common in misuse/recreational ingestions. Suicidal ingestions resulted in more hospital admissions and need for medical treatment. Recreational-use coded calls peaked in 2013, whereas calls coded for suicide attempts have continued to rise dramatically, with a 50% increase in the 14-year study period. CONCLUSION: Combination Coricidin products are a major source of morbidity in adolescents. Targeted preventive measures in primary care offices or larger-scale policy/legislative efforts may be helpful to address this.

Impact of Physical Activity on Adiposity and Risk Markers for Cardiovascular and Metabolic Disease.

The main aim of the present study was to investigate the impact of physical activity (PA) on adiposity and for cardiovascular and metabolic disease risk markers (CMDRMs). In total, 55 adults (33 lean [L] and 22 overweight/obesity [O/O]) visited the laboratory on two occasions. During the first session, body composition and anthropometric measurements were taken as well as resting blood pressure (BP). Free-living PA intensity was monitored using an ActiGraph accelerometer, which the participants wore for a period of 6 days. During the second visit, blood samples for the analysis of disease risk markers were obtained from the participants in the morning after overnight fasting (≥10 hr). There was no significant difference between groups in the percentage of time spent in PA levels (54.5% ± 1.2% and 54.9% ± 2.1% for L and O/O, respectively). Although, the O/O group was within recommended PA level, they had higher leptin, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hsCRP) levels than the L group (all p < .01). The O/O group had higher levels of triglycerides, low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) and lower levels of high-density lipoprotein (HDL; all p < .01). Interestingly, vigorous activity was positively correlated with HDL (r = .30, p < .05) and negatively with LDL (r = -.26, p = .05) levels and the arachidonic acid to eicosapentaenoic acid (ARA/EPA) ratio (r = -.30, p < .05). Only the O/O group had elevated CMDRMs. However, vigorous activity may improve health-related blood lipids such as HDL, LDL, and ARA/EPA ratio. Regardless of body composition status, low active participants were more likely to have higher level of leptin and hsCRP. Further exploration of the beneficial effects of vigorous exercise on adiposity and CMDRMs is warranted.

Failure to Launch: Predictors of Unfavourable Physical Activity and Sedentary Behaviour Trajectories from Childhood to Adolescence: The Gateshead Millennium Study.

In a previous study based on this cohort, only 15% of the participants belonged to a favourable physical activity/sedentary behaviour trajectory group (characterised by relatively high moderate-vigorous intensity physical activity and relatively low sedentary behaviour across childhood and adolescence). Since this favourable trajectory is protective against obesity, we aimed to identify factors associated with membership of this group. In this longitudinal study, 671 participants were assessed at ages 7, 9, 12 and 15 years. Participants' demographics, socio-economic status (SES) and physical activity environment such as, sports club participation and commuting school were assessed at ages 7, 9 and 12 and analysed with favourable trajectory membership as an outcome using multinomial logistic regression. Sex (male) and SES (higher) were the non-modifiable factors associated with favourable trajectory group. Of the modifiable factors, commuting to school at age 7, a safe environment to play at age 7 and sports club participation at age 12 were all associated with more than 2.0 times increased probability of being in the most favourable trajectory. Future interventions to promote a favourable trajectory could focus on girls and participants with low SES. Promoting active commuting, safe local spaces to play and sports participation should also help lead to a favourable trajectory for physical activity and sedentary behaviour across childhood and adolescence.

Moderate-To-Vigorous Intensity Physical Activity and Sedentary Behaviour across Childhood and Adolescence, and Their Combined Relationship with Obesity Risk: A Multi-Trajectory Analysis.

The combined role of objectively assessed moderate-vigorous intensity physical activity (MVPA) and sedentary behaviour (SB) is unclear in obesity prevention. This study aimed to identify latent groups for MVPA and SB trajectories from childhood to adolescence and examine their relationship with obesity risk at adolescence. From the Gateshead Millennium Study, accelerometer-based trajectories of time spent in MVPA and SB at ages 7, 9, 12, and 15 were derived as assigned as the predictor variable. Fat mass index (FMI), using bioelectrical impedance at age 15, was the outcome variable. From 672 children recruited, we identified three distinct multiple trajectory groups for time spent in MVPA and SB. The group with majority membership (54% of the cohort) had high MVPA and low SB at childhood, but MVPA declined and SB increased by age 15. One third of the cohort (31%) belonged to the trajectory with low MVPA and high time spent sedentary throughout. The third trajectory group (15% of the cohort) that had relatively high MVPA and relatively low SB throughout had lower FMI (-1.7, 95% CI (-3.4 to -1.0) kg/m2, p = 0.034) at age 15 compared to the inactive throughout group. High MVPA and low SB trajectories when combined are protective against obesity.

Clinical and patient characteristics associated with severe outcome in diphenhydramine toxicity.

BACKGROUND: Diphenhydramine is frequently misused and ingested recreationally for its antihistaminergic and antimuscarinic effects and is often involved in both serious and fatal poisonings, either in isolation or in combination with other xenobiotics. OBJECTIVE: This analysis sought to determine which patient and encounter characteristics were associated with severe outcome after diphenhydramine overdose. METHODS: This is an analysis of the multi-center ToxIC registry (2010-2016). Descriptive analysis of all cases with diphenhydramine listed as the "primary agent" contributing to toxicity were included. Analysis sought to determine which patient and encounter characteristics were associated with severe outcome, defined as occurrence of seizure, ventricular dysrhythmia, or intubation. To determine which patient and encounter characteristics were individually associated with severe outcome, we performed chi-square tests. Fisher's exact tests were used in the case of sparse data. We also performed multivariable logistic regression to further determine independent risk factors for severe outcome in diphenhydramine overdose. RESULTS: Eight hundred and sixty-three cases remained after exclusion with 15.6% (n = 135) of all patients having one or more severe outcome. The most common severe outcome was seizures which occurred in 98 (11.6%) of all ingestions. Females comprised 59.1% (n = 510) of all ingestions. Most ingestions were intentional (86.0%, n = 742) with the most common known reason for an intentional ingestion being self-harm, accounting for 37.5% (n = 324) of all ingestions. Self-harm ingestions and ingestions in males were more commonly associated with intubation. When examining outcomes by age, there were no significant differences overall or in any individual outcome except intubation in which children 0-12 were less likely to be intubated as compared to teens and adults. Signs and symptoms most strongly associated with a severe outcome included acidemia (pH < 7.2), QRS prolongation (QRS > 120 ms), and elevated anion gap (AG > 20). DISCUSSION: Acidemia, QRS prolongation, and elevated anion gap are associated with severe outcomes in diphenhydramine toxicity. Further research is warranted to determine their predictive characteristics.

Trends in socioeconomic inequalities in underweight and obesity in 5-year-old children, 2011-2018: a population-based, repeated cross-sectional study.

OBJECTIVE: To explore trends in prevalence and socioeconomic inequalities in underweight and obesity in 5-year-old schoolchildren in Scotland between 2011/2012 and 2017/2018. DESIGN: A population-based, repeated cross-sectional study. SETTING: Local authority primary schools in Scotland. PARTICIPANTS: 373 189 5-year-old schoolchildren in Scotland between 2011/2012 and 2017/2018. METHODOLOGY: Trends in prevalence and inequalities in underweight and obesity were examined across seven school years (2011/2012-2017/2018) for 373 189 5-year-old schoolchildren in Scotland. Body mass index SD scores were calculated, and epidemiological cut-offs relative to the UK 1990 references categorised underweight and obesity. Slope/relative indices of inequality (SII/RII) were calculated for underweight and obesity by school year using the area-based Scottish Index of Multiple Deprivation. RESULTS: The prevalence of obesity rose slightly overall during the study period (9.8% in 2011/2012; 10.1% in 2017/2018). However, this masked a widening of inequalities, with children from the most deprived areas experiencing a greater risk of obesity in 2017/2018 than in 2011/2012 (risk ratio=1.14, 95% CI 1.04 to 1.25) compared with an unchanged risk in children from the least deprived areas (risk ratio=0.95, 95% CI 0.82 to 1.11). SII and RII indicate widening inequalities for obesity, with RII rising from 1.95 (95% CI 1.71 to 2.22) in 2011/2012 to 2.22 (95% CI 1.93 to 2.56) in 2017/2018. The prevalence of underweight was consistently low (compared with the UK 1990 references) and remained unchanged over the study period (1.2% in 2011/2012; 1.1% in 2017/2018), with no consistent evidence of social patterning over time. CONCLUSIONS: Inequalities in obesity in schoolchildren in Scotland are large and have widened from 2011, despite only a slight rise in overall prevalence. In contrast there has been little change in underweight prevalence or inequalities during the study period. Extra resources for policy implementation and measures which do not widen inequalities and focus on reaching the most deprived children are required to tackle the high prevalence and growing inequalities in childhood obesity in Scotland.