Pediatric Exposure Research Articles

Population Pharmacokinetic Modeling and Stochastic Simulations to Support Pediatric Dose Selection of Pimavanserin.

Pimavanserin is a selective serotonin-modulating agent with inverse agonist/antagonist activity at the 5-hydroxytryptamine2A (5-HT2A ) receptor. The safety and efficacy of pimavanserin 34mg once daily were studied in adults with hallucinations and delusions associated with Parkinson's disease psychosis and other neuropsychiatric conditions. This analysis used model-based simulations of pimavanserin steady-state exposures to identify a dose that generated pediatric exposures comparable with adult exposures achieved with 34mg pimavanserin. A population pharmacokinetics model was developed using pooled plasma drug concentration (ie, actual) data from 13 clinical studies, including a phase1 study of adolescent pediatric patients (aged 13-17years) with various psychiatric conditions. Stochastic simulations were performed to predict exposures in a virtual (ie, simulated) group of pediatric patients (aged 5-17years). Steady-state measures of the area under the plasma concentration-time curve (AUC) and maximum drug concentration (Cmax ) were simulated for relevant age and weight stratifications and compared with simulated exposures in adults (aged 18-49years). The simulated mean AUC ranged from 47.41 to 54.73ng d/mL and the mean Cmax ranged from 41.13 to 50.07ng/mL in adults receiving pimavanserin 34mg. The simulated mean (SD) Cmax of 56.54(24.58)ng/mL with pimavanserin 34mg in patients aged 10-17years was similar to that in adults. Pimavanserin 20mg yielded a mean (SD) Cmax of 45.30(21.31)ng/mL in patients aged 5-9years and 49.18(22.91)ng/mL in the pediatric patient weight group of 14-25kg, which are values close to the Cmax in adults treated with 34mg. Pimavanserin 20 and 34mg in pediatric patients aged 5-9 and 10-17years, respectively, yielded exposures similar to daily pimavanserin 34mg in adults aged 18-49years.

Unintentional pediatric exposures to household cleaning products: a cross-sectional analysis of the National Poison Data System (2000–2015)

BackgroundHousehold cleaning products are the second most common cause of unintentional poisoning in children < 6 years old in the United States. The aim of this study is to characterize exposures to household cleaning substances in this age group from data collected from the Nation’s Poison Control Centers.MethodsThis cross-sectional study analyzed all household cleaner calls classified as age < 6 years old made to the American Association of Poison Control Centers between January 1st 2000 and December 31th 2015.ResultsSignificant clinical effects or injury was low, making up only 2.6% of cases with a known medical outcome. Alkali-based cleaning products accounted for the third highest frequency of overall exposures and the highest number of all exposure outcomes determined to have a significant clinical effect or injury.ConclusionsThis study demonstrated particular danger of adverse outcomes after exposure to alkali-based cleaning products, specifically alkali-based oven and drain cleaners. Both of which are readily accessible in many households. This study may be a good starting point for further study and poison prevention efforts.

Perspectives on preparedness for pediatric emergencies after residency: A needs assessment.

General emergency physicians provide most pediatric emergency care in the United States yet report more challenges managing emergencies in children than adults. Recommendations for standardized pediatric emergency medicine (PEM) curricula to address educational gaps due to variations in pediatric exposure during emergency medicine (EM) training lack learner input. This study surveyed senior EM residents and recent graduates about their perceived preparedness to manage pediatric emergencies to better inform PEM curricula design. In 2021, senior EM residents and graduates from the classes of 2020 and 2019 across eight EM programs with PEM rotations at the same children's hospital were recruited and surveyed electronically to assess perceived preparedness for 42 pediatric emergencies and procedures by age: infants under 1 year, toddlers, and children over 4 years. Preparedness was reported on a 5-point Likert scale with 1 or 2 defined as "unprepared." A chi-square test of independence compared the proportion of respondents unprepared to manage each condition across age groups, and a p-value < 0.05 demonstrated significance. The response rate was 53% (129/242), with a higher response rate from senior residents (65%). Respondents reported feeling unprepared to manage more emergency conditions in infants compared to other age groups. Respondents felt least prepared to manage inborn errors of metabolism and congenital heart disease, with 45%-68% unprepared for these conditions across ages. A heat map compared senior residents to recent graduates. More graduates reported feeling unprepared for major trauma, impending respiratory failure, and pediatric advanced life support algorithms. This study, describing the perspective of EM senior residents and recent graduates, offers unique insights into PEM curricular needs during EM training. Future PEM curricula should target infant complaints and conditions with lower preparedness scores across ages. Other centers training EM residents could use our findings and methods to bolster PEM curricula.

Bridging the Gap: Utilizing Quality Improvement Tools to Refine a Pediatric Varicella Exposure Investigation

Bridging the Gap: Utilizing Quality Improvement Tools to Refine a Pediatric Varicella Exposure Investigation

A National Survey of the Training and Practice Patterns of Practicing Pediatric Advanced Endoscopists in the United States.

Pediatric advanced endoscopy consists primarily of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) and is becoming more common in pediatrics. This study aims to characterize the current landscape of pediatric advanced endoscopy training and practice by directly surveying independently practicing pediatric advanced endoscopists (PAEs). We also aim to ascertain expert opinion on competency in pediatric ERCP and EUS. A 66-question REDCap survey and a 73-question Qualtrics survey were distributed to members of the ERCP Special Interest Group of North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Respondents currently performing ERCP or EUS independently in children were included. Statistical analysis was performed using Mann-Whitney U test. Of 41 PAEs surveyed, 38 (92.7%) responded and 27 independent practitioners were included. Thirteen respondents performed EUS. PAEs who completed an advanced endoscopy fellowship (AEF) were more comfortable performing American Society for Gastrointestinal Endoscopy grade 3 or grade 4 ERCPs ( P < 0.0008) and felt more prepared to practice EUS independently than other trainees. Expert opinion of PAEs felt a threshold of 200 procedures was needed to attain competency in either ERCP or EUS. Pediatric duodenoscope exposure improved comfort in performing ERCP in children <10 kg ( P = 0.009). Training of pediatric gastroenterologists in ERCP and EUS are highly variable, though the skills attained are similar. AEF-trained specialists reported greater training volumes and felt more prepared to practice independently than those who did not. Competency thresholds determined by expert PAEs for ERCP and EUS agree with American Society for Gastrointestinal Endoscopy guidelines for adult advanced endoscopy trainees.

Assessment of Pediatric Kidney Transplant Experience and Exposure During Pediatric Nephrology Fellowship Training.

Key Points There have been no published studies evaluating competency or perceived competency in kidney transplant–related knowledge and skills among graduates of pediatric nephrology fellowships.There are also no uniform specific transplant requirements within the pediatric nephrology fellowship.We aim to further understand this potential gap to rectify it in the future. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/K360/2023_12_01_KID0000000000000177.mp3

Pediatric hand sanitizer exposures reported to United States poison centers, 2017–2021

Introduction The COVID-19 pandemic increased demand for alcohol-based hand sanitizers. We aimed to describe the epidemiological trends in pediatric alcohol-based hand sanitizer cases reported to United States poison centers. We characterized clinically significant pediatric reports involving alcohol-based hand sanitizer products before and during the pandemic and methanol-containing hand sanitizers during the pandemic. Methods We included all single-substance cases involving alcohol-based hand sanitizers reported to the National Poison Data System among children ≤ 19 years from 1 January 2017 to 31 December 2021, and methanol-containing hand sanitizers from 23 June 2020 to 31 December 2021. Multiple product exposures and non-human exposures were excluded. Clinically significant outcomes included moderate or major effects or death. Results There were 95,718 alcohol-based hand sanitizer pediatric cases during the study period. Most (n = 89,521; 94%) were unintentional, occurred by ingestion (n = 89,879; 93.9%), occurred at home, and were managed at the exposure site (n = 89,774; 93.8%). Common symptoms were vomiting (n = 2,969; 3.1%), coughing (n = 1,102; 1.2%), ocular irritation (n = 1,244; 1.3%), and drowsiness (n = 981; 1.0%). Most children (n = 3,937; 66.2%) managed at a health care facility were treated and released; a minority were admitted (n = 527; 9.0%). Few children (n = 81; 1.4%) were admitted to the intensive care unit. The prevalence of clinically significant cases increased in 2020 and 2021, compared to 2017. Population-adjusted rates, by state, of alcohol-based hand sanitizer cases ranged from 280 to 2,700 per million children. Of the 540 reported cases involving methanol-containing hand sanitizers, the majority (n = 255) occurred in July 2020. Thirteen cases (2.4%) had clinically significant outcomes. The prevalence of clinically significant cases remained similar in 2020 and 2021 and exhibited lower prevalence compared to alcohol-based products. Population-adjusted rates, by state, ranged from fewer than 0.9 to 40 per million children. Conclusions Clinically significant pediatric cases involving alcohol-based hand sanitizers increased during the pandemic and remained elevated in 2021. Cases involving methanol-containing products were less frequent. Our findings may inform heightened product quality control and regulatory oversight.

2021 Annual Report of the Kansas Poison Control Center at The University of Kansas Health System.

This is the 2021 Annual Report of the Kansas Poison Control Center (KSPCC) at The University of Kansas Health System. The KSPCC serves the state of Kansas 24-hours a day, 365 days a year with certified specialists in poison information and clinical and medical toxicologists. Encounters reported to the KSPCC from January 1, 2021 through December 31, 2021 were analyzed. Data recorded includes caller demographics, exposure substance, nature and route of exposure, interventions, medical outcome, disposition, and location of care. The KSPCC logged 18,253 total encounters in 2021, including calls from every county in Kansas. A majority of human exposure cases (53.6%) were female. Approximately 59.8% were pediatric exposures (defined as 19 years of age or less). Most encounters occurred at a residence (91.7%) and most were managed there (70.5%). Unintentional exposures were the most common reason for exposures (70.5%). The most common reported substance in pediatric encounters was household cleaning products (n = 815) and cosmetics/personal care products (n = 735). For adult encounters, analgesics (n = 1,241) and sedative/ hypnotics/antipsychotics (n = 1,013) were the most frequently reported. Medical outcomes were 26.0% no effect, 22.4% minor effect, 10.7% moderate effect, and 2.7% major effects. There were 22 deaths. The 2021 KSPCC annual report demonstrated that cases were received from the entire state of Kansas. Pediatric exposures remained most common but cases with serious outcomes continued to increase. This report supported the continued value of the KSPCC to both public and health care providers in the state of Kansas.

Intraday exposure to ambient ozone and emergency department visits among children: a case-crossover study in southern China.

Most existing studies have investigated short-term associations between ozone exposure and acute disease events among children at a daily timescale, which might neglect risk effects happening within several hours after ozone exposure. In this research, we aimed to depict intraday associations between pediatric emergency department visits (PEDVs) and exposure to ozone in order to better detect ultra-short-term effects of ozone exposure on children. We obtained hourly data of all-cause PEDVs, air pollutants, and meteorological factors in Shenzhen and Guangzhou, China, 2015-2018. We applied time-stratified case-crossover design and conditional logistic regression models to estimate odds ratios per 10-μg/m3 rise of ozone concentrations at various exposure periods (e.g., 0-3, 4-6, 7-12, 13-24, 25-48, and 49-72h) prior to PEDVs, controlling for hourly relative humidity and temperature. Subgroup analyses divided by gender, age, and season were undertaken to identify the potential susceptible population and period. A total of 358,285 cases of PEDVs were included in two cities, and hourly average concentration of ozone was 45.5μg/m3 in Guangzhou and 58.9μg/m3 in Shenzhen, respectively. Increased risks of PEDVs occurred within a few hours (0-3h) after exposure to ozone and remained up to 48h. Population risks for PEDVs increased by 0.8% (95% confidence interval, 0.6 to 1.0) in Shenzhen and 0.7% (0.5 to 0.9) in Guangzhou for a 10-μg/m3 increase in ozone concentrations at lag 4-6h and lag 7-12h, respectively. These findings were robust to co-exposure adjustments in our sensitivity analyses. Significantly greater ozone-associated risks were consistently observed during cold months (October to March of the following year) in both cities, while we did not identify evidence for effect modification of children's age and gender. This study provided novel evidence for increased risks of acute disease events among children within several hours after ozone exposure, highlighting the significant implications for policymakers to establish hourly air quality standards for better protecting children's health.

Children victims of drug abuser parents: Hair testing as a forensic tool to assess exposure-A cohort of 37 cases from Spain.

Hair testing is a useful tool to investigate suspected pediatric exposure to drugs of abuse. Newborns and young children are at high risk of exposure to drugs of abuse from parents or caregivers who consumed these substances, a fact prosecuted by Spanish authorities as child abuse. A retrospective study based on a cohort of 37 cases classified using several parameters, which involve children under 12years old, were analyzed at the Drugs Laboratory of the National Institute of Toxicology and Forensic Sciences (Madrid, Spain) between 2009 and 2021. Hair samples were tested for the presence of opiates, cocaine, ketamine, amphetamines, methadone, and cannabis using a gas chromatography-mass spectrometry (GC-MS) method. A 59% of the studied children had ages in the range of 1-3years old, and in 81% of cases, victims required hospitalization. In 81% of cases (n = 30), hair was submitted only or in combination with other samples, and these were classified in four categories according to analyzed samples: A (only hair), B (hair and blood), C (hair and urine), and D (hair, blood, and urine). The 93.3% of these cases (n = 28) showed a positive result of cannabinoids (THC and CBN in hair and THC-COOH in urine; 71.4% n = 20), cocaine and metabolites (benzoylecgonine and cocaethylene; 46.4% n = 13), opiates (morphine and 6-acetylmorphine), and amphetamines (MDMA and MDMA; 3.10% n = 1). Hair analysis matched positive results in cases where urine screening test was carried out previously (n = 24) and in those cases where blood and/or urine were also submitted (35.6% n = 11). As a conclusion, hair analysis was confirmed as a useful tool to detect previous exposure to acute poisoning events in children.

Prehospital Recognition and Management of Pediatric Sepsis: A Qualitative Assessment

Background and Purpose Sepsis is a life-threatening disease in children and is a leading cause of morbidity and mortality. Early prehospital recognition and management of children with sepsis may have significant effects on the timely resuscitation of this high-risk clinical condition. However, the care of acutely ill and injured children in the prehospital setting can be challenging. This study aims to understand barriers, facilitators, and attitudes regarding recognition and management of pediatric sepsis in the prehospital setting. Methods This was a qualitative study of EMS professionals participating in focus groups using a grounded theory-based design to gather information on recognition and management of septic children in the prehospital setting. Focus groups were held for EMS administrators and medical directors. Separate focus groups were held for field clinicians. Focus groups were conducted via video conference until saturation of ideas was reached. Using consensus methodology, transcripts were coded in an iterative process. Data were then organized into positive and negative factors based on the validated PRECEDE-PROCEED model for behavioral change. Results Thirty-eight participants in six focus groups identified nine environmental factors, 21 negative factors, and 14 positive factors pertaining to recognition and management of pediatric sepsis. These findings were organized into the PRECEDE-PROCEED planning model. Pediatric sepsis guidelines were identified as positive factors when they did exist and negative factors when they were complicated or did not exist. Six interventions were identified by participants. These include raising awareness of pediatric sepsis, increasing pediatric education, receiving feedback on prehospital encounters, increasing pediatric exposure and skills training, and improving dispatch information. Conclusion This study fills a gap by examining barriers and facilitators to prehospital diagnosis and management of pediatric sepsis. Using the PRECEDE-PROCEED model, nine environmental factors, 21 negative factors, and 14 positive factors were identified. Participants identified six interventions that could create the foundation to improve prehospital pediatric sepsis care. Policy changes were suggested by the research team based on the results of this study. These interventions and policy changes provide a roadmap for improving care in this population and lay the groundwork for future research.

Cannabis Toxicity in Children and Adolescents.

The legalization of recreational and medical cannabis has increased the availability and potency of cannabis products in homes and communities. Although state laws regarding legalization and commercial sale often encompass adult use only, pediatric toxicity from unintentional exposures to cannabis edibles and adolescent harm from chronic use are increasing in states and countries that have relaxed laws on use. Unintentional edible ingestions are shown to increase in regions that legalize and commercialize cannabis products at the retail level. Long-term effects on teenagers regarding psychiatric changes as well as acute gastrointestinal effects from hyperemesis syndrome are well documented in the medical literature. This article provides clinical information on the presentation, evaluation, and management of adverse effects from pediatric and adolescent teen exposures to cannabis seen in acute care and emergent settings. [Pediatr Ann. 2023;52(5):e181-e186.].

Risks of leukemia, intracranial tumours and lymphomas in childhood and early adulthood after pediatric radiation exposure from computed tomography.

Children are more susceptible to radiation-induced damage than adults, but little research has compared the risk of cancer after exposure to radiation during computed tomography (CT) among children at different ages. We aimed to explore the risk of intracranial tumours, leukemia or lymphoma among children, adolescents and young adults (aged < 25 yr) after radiation exposure from CT at or before the age of 18 years. We conducted a nested, population-based case-control study using data from Taiwan's publicly funded health care system. We identified participants younger than 25 years with newly diagnosed intracranial tumours, leukemia or lymphoma, from Jan. 1, 2000, to Dec. 31, 2013. We assigned 10 non-cancer controls for each case, matching by sex, date of birth and day of entry to the cohort. We considered CT scans received at or before the age of 18 years and 3 or more years before the index date (the date of cancer diagnosis for cases) as exposure. We used conditional logistic regression models and incidence rate ratios (IRRs) to estimate the relationship between risk of these cancers and CT radiation exposure. We identified 7807 cases and matched to 78 057 controls. Compared with no exposure, exposure to a single pediatric CT scan did not increase risk of intracranial tumours, leukemia or lymphoma. However, participants exposed to 4 or more CT scans had an elevated incidence (IRR 2.30, 95% confidence interval 1.43-3.71) of one of the cancer outcomes of interest. Receiving 4 or more CT scans at or before 6 years of age was associated with the highest risks of cancer, followed by ages 7-12 years and 13-18 years (p for trend < 0.001). Exposure to a single CT scan was not associated with increased risks of subsequent intracranial tumours, leukemia or lymphoma among children; however, we observed increased cancer risks among those with 4 or more CT scans, especially among younger children. Although these cancers are uncommon, the findings of this study underscore the importance of prudent use of CT in the pediatric population.

Exploring Survey-Based Water, Sanitation, and Animal Associations With Enteric Pathogen Carriage: Comparing Results in a Cohort of Cases With Moderate-to-Severe Diarrhea to Those in Controls in the Vaccine Impact on Diarrhea in Africa (VIDA) Study, 2015–2018

The magnitude of pediatric enteric pathogen exposures in low-income settings necessitates substantive water and sanitation interventions, including animal feces management. We assessed associations between pediatric enteric pathogen detection and survey-based water, sanitation, and animal characteristics within the Vaccine Impact on Diarrhea in Africa case-control study. In The Gambia, Kenya, and Mali, we assessed enteric pathogens in stool of children aged <5 years with moderate-to-severe diarrhea and their matched controls (diarrhea-free in prior 7 days) via the TaqMan Array Card and surveyed caregivers about household drinking water and sanitation conditions and animals living in the compound. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using modified Poisson regression models, stratified for cases and controls and adjusted for age, sex, site, and demographics. Bacterial (cases, 93%; controls, 72%), viral (63%, 56%), and protozoal (50%, 38%) pathogens were commonly detected (cycle threshold <35) in the 4840 cases and 6213 controls. In cases, unimproved sanitation (RR, 1.56; 95% CI, 1.12-2.17), as well as cows (RR, 1.61; 95% CI, 1.16-2.24) and sheep (RR, 1.48; 95% CI, 1.11-1.96) living in the compound, were associated with Shiga toxin-producing Escherichia coli. In controls, fowl (RR, 1.30; 95% CI, 1.15-1.47) were associated with Campylobacter spp. In controls, surface water sources were associated with Cryptosporidium spp., Shigella spp., heat-stable toxin-producing enterotoxigenic E. coli, and Giardia spp. Findings underscore the importance of enteric pathogen exposure risks from animals alongside more broadly recognized water and sanitation risk factors in children.

Survey-Based Assessment of Water, Sanitation, and Animal-Associated Risk Factors for Moderate-to-Severe Diarrhea in the Vaccine Impact on Diarrhea in Africa (VIDA) Study: The Gambia, Mali, and Kenya, 2015-2018.

Pediatric exposures to unsafe sources of water, unsafely managed sanitation, and animals are prevalent in low- and middle-income countries. In the Vaccine Impact on Diarrhea in Africa case-control study, we examined associations between these risk factors and moderate-to-severe diarrhea (MSD) in children <5 years old in The Gambia, Kenya, and Mali. We enrolled children <5 years old seeking care for MSD at health centers; age-, sex-, and community-matched controls were enrolled at home. Conditional logistic regression models, adjusted for a priori confounders, were used to evaluate associations between MSD and survey-based assessments of water, sanitation, and animals living in the compound. From 2015 to 2018, 4840 cases and 6213 controls were enrolled. In pan-site analyses, children with drinking water sources below "safely managed" (onsite, continuously accessible sources of good water quality) had 1.5-2.0-fold higher odds of MSD (95% confidence intervals [CIs] ranging from 1.0 to 2.5), driven by rural site results (The Gambia and Kenya). In the urban site (Mali), children whose drinking water source was less available (several hours/day vs all the time) had higher odds of MSD (matched odds ratio [mOR]: 1.4, 95% CI: 1.1, 1.7). Associations between MSD and sanitation were site-specific. Goats were associated with slightly increased odds of MSD in pan-site analyses, whereas associations with cows and fowl varied by site. Poorer types and availability of drinking water sources were consistently associated with MSD, whereas the impacts of sanitation and household animals were context-specific. The association between MSD and access to safely managed drinking water sources post-rotavirus introduction calls for transformational changes in drinking water services to prevent acute child morbidity from MSD.

Awareness raising and dealing with methanol poisoning based on effective strategies

Intoxication with methanol most commonly occurs as a consequence of ingesting, inhaling, or coming into contact with formulations that include methanol as a base. Clinical manifestations of methanol poisoning include suppression of the central nervous system, gastrointestinal symptoms, and decompensated metabolic acidosis, which is associated with impaired vision and either early or late blindness within 0.5–4 h after ingestion. After ingestion, methanol concentrations in the blood that are greater than 50 mg/dl should raise some concern. Ingested methanol is typically digested by alcohol dehydrogenase (ADH), and it is subsequently redistributed to the body's water to attain a volume distribution that is about equivalent to 0.77 L/kg. Moreover, it is removed from the body as its natural, unchanged parent molecules. Due to the fact that methanol poisoning is relatively uncommon but frequently involves a large number of victims at the same time, this type of incident occupies a special position in the field of clinical toxicology. The beginning of the COVID-19 pandemic has resulted in an increase in erroneous assumptions regarding the preventative capability of methanol in comparison to viral infection. More than 1000 Iranians fell ill, and more than 300 of them passed away in March of this year after they consumed methanol in the expectation that it would protect them from a new coronavirus. The Atlanta epidemic, which involved 323 individuals and resulted in the deaths of 41, is one example of mass poisoning. Another example is the Kristiansand outbreak, which involved 70 people and resulted in the deaths of three. In 2003, the AAPCC received reports of more than one thousand pediatric exposures. Since methanol poisoning is associated with high mortality rates, it is vital that the condition be addressed seriously and managed as quickly as feasible. The objective of this review was to raise awareness about the mechanism and metabolism of methanol toxicity, the introduction of therapeutic interventions such as gastrointestinal decontamination and methanol metabolism inhibition, the correction of metabolic disturbances, and the establishment of novel diagnostic/screening nanoparticle-based strategies for methanol poisoning such as the discovery of ADH inhibitors as well as the detection of the adulteration of alcoholic drinks by nanoparticles in order to prevent methanol poisoning. In conclusion, increasing warnings and knowledge about clinical manifestations, medical interventions, and novel strategies for methanol poisoning probably results in a decrease in the death load.

Firearm-related lead exposure and pediatric lead levels in Massachusetts: A decade of evidence (2010–2019)

The US has more firearms than any other country in the world and uses lead ammunition almost exclusively. Lead exposure is a significant public health concern and children are at the greatest risk given their exposure to take-home lead. Firearm-related take-home lead exposure may be one of the greatest influences on elevated pediatric blood lead levels. For this ecological and spatial investigation of the relationship between firearm licensure rates as a proxy for firearm-related lead exposure and prevalence of children with blood lead levels ≥5 μg/dL in 351 cities/towns in Massachusetts, we used 10 years of data (2010–2019). We examined this relationship against other known contributors to pediatric lead exposure including old housing stock (lead paint/dust), occupations, and lead in water. Pediatric blood lead levels were positively correlated with licensure, poverty, and certain occupations and negatively correlated with lead in water and police or firefighter employment. Firearm licensure was a major significant predictor of pediatric blood lead alone (β = 0.13; 95% CI, 0.10, 0.17) and across all regression models. The final model predicted over half the variation in pediatric blood lead (Adjusted R2 = 0.51). Negative binomial analysis found cities/towns with more firearms had higher pediatric blood lead levels (highest quartile fully adjusted prevalence ratio ((aPR) = 1.18; 95% CI, 1.09, 1.30) with a significant increase in pediatric blood lead per increase in firearms (p < 0.001). There were no significant spatial effects, suggesting that although there could be other factors impacting elevated pediatric blood lead, they are unlikely to influence spatial associations. Our paper provides compelling evidence of a potential and dangerous link between lead ammunition and child blood lead levels and is the first to do so using multiple years’ worth of data. More research is required to substantiate this relationship on the individual-level and into prevention/mitigation.

Unintentional ingestion of putative delta-8 tetrahydrocannabinol by two youth requiring critical care: a case report

BackgroundDelta-8 tetrahydrocannabinol (THC) is a psychoactive cannabinoid from the cannabis plant that can be synthetically converted from cannabidiol (CBD). Most states permit the full or restricted sale of hemp and hemp-derived CBD products, and therefore, delta-8 THC products are on the rise. Delta-8 THC consumption can cause intoxication. Products are often sold in edible form and occasionally in packaging that appears similar to candy. Clinical presentations for delta-8 THC ingestions are understudied and may differ from those described for delta-9 THC ingestions.Case presentationThis case report describes unintentional ingestions of putative delta-8 THC by two pediatric patients that results in admission to the pediatric intensive care unit. The ingestions were of putative delta-8 THC infused product that resembled popular candies. Both patients developed periods of bradypnea with continued intermittent periods of agitation. Medical intervention included observation, noninvasive positive pressure ventilation via high flow nasal cannula, and intubation—but was not needed for both patients. Although family noted ongoing irritability for the patients, both were discharged approximately 45 h after ingestion. Delta-8 THC ingestion is reliant on self-report.ConclusionsAs the availability of delta-8 THC increases, along with associated pediatric exposures, it is imperative for health care providers to quickly recognize and provide adequate treatment. While there is no specific antidote for THC intoxication beyond supportive care, providers can play an important role in prevention by educating parents and guardians on safe cannabis storage and by documenting cases for adverse event monitoring.

Trends in pediatric nonprescription analgesic/antipyretic exposures during the COVID-19 pandemic

Objective To examine pediatric exposure trends involving selected nonprescription analgesics/antipyretics, before and during the COVID-19 pandemic. Methods Using descriptive and interrupted time-series analyses, we assessed monthly United States poison center data involving pediatric (<18 years) exposures to nonprescription paracetamol (acetaminophen), ibuprofen, acetylsalicylic acid, and naproxen before (January 2015-February 2020) and during (March 2020-April 2021) the pandemic. Statins and proton pump inhibitors (prescription or nonprescription) served as controls. Results Most nonprescription analgesic/antipyretic exposures (75–90%) were single-substance; unintentional exposures typically involved children <6 years (84–92%), while intentional exposures involved females (82–85%) and adolescents, 13–17 years (91–93%). Unintentional exposures among children <6 years, declined for all four analgesics/antipyretics immediately after the World Health Organization declared COVID-19 a pandemic (March 11, 2020), but most significantly for ibuprofen (30–39%). Most intentional exposures were classified as suspected suicide. Intentional exposures were relatively low and stable among males. Intentional exposures in females declined immediately after the pandemic was announced but subsequently increased to pre-pandemic levels for acetylsalicylic acid and naproxen and above pre-pandemic levels for paracetamol and ibuprofen. For paracetamol, female intentional exposures increased from 513 average monthly cases in the pre-pandemic to 641 average monthly cases during the pandemic; and reached 888 cases by the end of the study period in April 2021. While for ibuprofen, average monthly cases rose from 194 in the pre-pandemic, to 223 during the pandemic; and reached 352 cases in April 2021. Patterns were similar among females 6–12 and 13–17 years. Conclusion Nonprescription analgesic/antipyretic unintentional exposure cases declined among young children, while intentional exposure cases increased among females, 6–17 years, during the pandemic. Findings highlight the importance of safely storing medications and being alert to signs that adolescents may be in need of mental health support services; caregivers should seek medical care or call poison control centers for any suspected poisoning event.

Entrectinib dose confirmation in pediatric oncology patients: pharmacokinetic considerations

PurposeEntrectinib is a central nervous system-active potent inhibitor of tropomyosin receptor kinase (TRK), with anti-tumor activity against neurotrophic NTRK gene fusion-positive tumors. This study investigates the pharmacokinetics of entrectinib and its active metabolite (M5) in pediatric patients and aims to understand whether the pediatric dose of 300 mg/m2 once daily (QD) provides an exposure that is consistent with the approved adult dose (600 mg QD).MethodsForty-three patients aged from birth to 22 years were administered entrectinib (250–750 mg/m2 QD) orally with food in 4-week cycles. Entrectinib formulations included capsules without acidulant (F1) and capsules with acidulant (F2B and F06).ResultsAlthough there was interpatient variability with F1, entrectinib and M5 exposures increased dose dependently. Lower systemic exposures were observed in pediatric patients receiving 400 mg/m2 QD entrectinib (F1) versus adults receiving either the same dose/formulation or the recommended flat dose of 600 mg QD (~ 300 mg/m2 for a 70 kg adult) due to suboptimal F1 performance in the pediatric study. The observed pediatric exposures following 300 mg/m2 QD entrectinib (F06) were comparable to those in adults receiving 600 mg QD.ConclusionsOverall, the F1 formulation of entrectinib was associated with lower systemic exposure in pediatric patients compared with the commercial acidulant formulation (F06). Systemic exposures achieved in pediatric patients with the F06 recommended dose (300 mg/m2) were within the known efficacious range in adults, confirming the adequacy of the recommended dose regimen with the commercial formulation.