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Background: The 2009 cystic fibrosis (CF) infant care guidelines recommend breastmilk as the initial feeding but do not address if/when it should be fortified or supplemented with formula to promote optimal growth and pulmonary health., Methods: We conducted a prospective multi-center cohort study in breastfed and formula-fed infants that included 172 infants with CF who were born during 2012-17, enrolled after newborn screening at age 1.9 ± 1.0 months, and evaluated growth and lung disease manifestations in the first 3 years of life., Results: Seventy-two percent of our study cohort was breastfed at birth, but 64 % transitioned to receiving fortified feedings (breastmilk, formula, or a combination) by 6 months of age to reverse the downward trajectory of their growth curves. Fortified feedings accelerated catch-up growth to normal weight-for-age (0.12 ± 0.80 z-score) and near normal height-for-age (-0.13 ± 0.90 z-score) at 3 years of age. Within the fortified group, breastmilk and formula were similarly effective in promoting catch-up growth, but proportionately fewer infants with CF fed predominantly breastmilk (30 %) experienced severe or moderate early-onset lung disease compared to those fed predominantly formula (62 %), p = 0.02., Conclusions: Most infants with CF require fortified feedings to recuperate from growth faltering and achieve normal growth at 3 years of age. For these infants, the proactive/preventive strategy of fortified breastmilk feedings starting soon after CF diagnosis, an alternative to the reactive/monitoring approach, can minimize the risk of prolonged postnatal growth faltering, accelerate the potential of attaining catch-up growth, and decrease the likelihood of experiencing more severe early-onset lung disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Background: The diagnosis of toxic alcohol poisoning is often based on clinical presentation and nonspecific surrogate laboratory studies due to limited testing availability. Fomepizole is the recommended antidote and often administered empirically. The objective of this study is to identify substances that mimic toxic alcohols and compare key clinical factors between toxic alcohol and non-toxic alcohol exposures when fomepizole was administered., Methods: This study was a retrospective evaluation using the National Poison Data System from January 1, 2010 through December 31, 2021. Exposures were included if fomepizole was administered. Toxic alcohol exposures had ethylene glycol or methanol as a coded substance. For exposures not coded as a toxic alcohol, the first substance was described. Paracetamol (acetaminophen) exposures from 2020 and 2021 were excluded., Results: Fomepizole was reportedly used 25,110 times over 12 years. Use increased from 1,955 in 2010 to 2,710 in 2021. Most administrations were for reported toxic alcohol poisoning (60 percent) but use in reported non-toxic alcohol poisoning was greater starting in 2020. Toxic alcohol exposures were older (43.3 versus 39.8 years; P  < 0.001) and more likely male (65.7 percent versus 58.2 percent). Level of care was mostly a critical care unit (67.7 percent), which was less common in toxic alcohol (63.3 percent) than non-toxic alcohol exposures (74.2 percent). The most common non-toxic alcohol substances were ethanol (24.9 percent) or an unknown drug (17.5 percent). Acidosis, increased creatinine concentration, anion gap, and osmolal gap, and kidney failure were coded in a lower proportion of toxic alcohol exposures than non-toxic alcohol exposures ( P  < 0.001)., Discussion: The inability to provide rapid clinical confirmation of toxic alcohol poisoning results in the empiric administration of fomepizole to many patients who will ultimately have other diagnoses. Although fomepizole is relative well tolerated we estimated that this practice costs between $1.5 to $2.5 million. The major limitations of this work include the biases associated with retrospective record review, and the inability to confirm the exposures which may have resulted in allocation error., Conclusion: Most fomepizole use was for a presumed toxic alcohol. This recently shifted to greater use in likely non-toxic alcohol poisoning. Key difference between the groups suggest fomepizole administration was likely due to the difficulty in diagnosis of toxic alcohol poisoning along with the efficacy and safety of fomepizole. Increased toxic alcohol laboratory testing availability could improve timely diagnosis, reserving fomepizole use for toxic alcohol poisoning.

Background: Gastrointestinal (GI) complications in lung transplant recipients can occur any time during the post-operative period, leading to prolonged morbidity and mortality. Despite the negative association between GI complications and patient outcomes, little is known about their incidence and risk factors for their development in pediatric lung transplant recipients., Methods: We performed a retrospective chart review at one pediatric tertiary center to describe the frequency of GI complications in lung transplant recipients. We identified potential risk factors for the diagnosis of gastroparesis, gastroesophageal reflux disease (GERD) and aspiration in the post-transplant period. Lastly, we investigated the association of these complications with mortality and graft survival., Results: 84.3% of lung transplant recipients experienced at least one GI complication in the post-transplant period. Gastroparesis (52.9%), GERD (41.2%), and oropharyngeal dysphagia/laryngeal penetration (33.3%) were the most common complications diagnosed. Post-operative opioid exposure was a risk factor for gastroparesis, with the odds increasing 3.0% each day a patient was prescribed opioids (p = .021). The risk of death or retransplant in individuals who experienced gastroparesis was 2.7 times higher than those not diagnosed with gastroparesis (p = .027)., Conclusion: Exposure to opioids in the post-operative period is a risk factor for gastroparesis and a prolonged hospitalization placed patients at risk for aspiration. Gastroparesis was associated with increased patient mortality and graft failure, while aspiration and GERD had no effect on long term outcomes. Future prospective studies investigating the relationship between opioid use and the development of a gastroparesis are necessary to improve patient outcomes., (© 2024 Wiley Periodicals LLC.)

Introduction: Increased prescribing of antipsychotics and availability of new antipsychotics has resulted in increased exposures in children. Current data on aripiprazole, brexpiprazole, and cariprazine are limited., Methods: This was a retrospective database study utilizing the National Poison Data System from 2015 through 2021. We included cases of single substance exposures to aripiprazole, brexpiprazole, cariprazine, or lumateperone in children ages 0 to 5 years old with follow-up to a known outcome. Key outcomes were medical outcomes, clinical effects, and level of care if treated in a healthcare facility., Results: There were 3,573 aripiprazole, 137 brexpiprazole, 249 cariprazine, and one lumateperone exposure over the period. Primary outcomes were evaluated in 2,655 cases (2,390 aripiprazole, 96 brexpiprazole, and 169 cariprazine). Fifty-one percent were male and 77% were between 0 and 2 years old. Moderate effect was coded in 16.6% of aripiprazole, 23% of brexpiprazole, and 12% of cariprazine exposures. Major effect was coded in 0.6% of aripiprazole, 1% of brexpiprazole, and 2.4% of cariprazine exposures. Duration of symptoms was mostly between 8 and 24 h for 34.6% of aripiprazole, 30% of brexpiprazole, and 32% of cariprazine exposures. Over 60% of the children seen in a health care facility were discharged from the emergency department. The lowest doses resulting in at least a moderate effect and admission to a health care facility was 0.46 mg/kg for aripiprazole, 2.1 mg/kg for brexpiprazole, and 1.9 mg/kg for cariprazine. Important clinical effects included central nervous system depression, tremors, tachycardia, agitation, and vomiting., Conclusion: Reported ingestions of aripiprazole, brexpiprazole, or cariprazine may result in neurologic symptoms like central nervous system depression or seizures in children. The prolonged duration of symptoms resulted in admission for at least a day for many cases. Further research should address optimal monitoring time and location for these exposures.

Objective: The aim of this study was to perform an updated description of adolescent occupational exposures reported to the US poison centers., Methods: We performed a descriptive analysis of adolescents aged 13 to 19 years with unintentional occupational exposures from 2011 to 2020 using the National Poison Data System. A clinically significant occupational poisoning (CSOP) case is defined as exposures with moderate effect, major effect, or death. Differences in substance categories between younger (13 to 17 years) and older (18 to 19 years) adolescents with CSOP were compared., Results: There were 14,374 adolescent occupational exposures. There were 2151 CSOPs. The most common substance categories associated with CSOP were household cleaners (22.3%), chemicals (20.8%), industrial cleaners (14.2%), fumes/gases/vapors (10.8%), and hydrocarbons (5.9%). Categories of exposures were similar across age groups., Conclusions: This study found that, despite a reduction in the number of adolescent occupational exposures, CSOPs persist., Competing Interests: Conflict of interest: None declared., (Copyright © 2022 American College of Occupational and Environmental Medicine.)

Introduction: Almost half of exposures reported to United States (US) poison centers are exploratory ingestions in children under the age of 5 years. Pediatric cannabis exposures reported to US poison centers have risen over the last twenty years, with greater increases in the last 5 years. In 2020, the Coronavirus disease 2019 (COVID-19) pandemic resulted in widespread stay-at-home orders and subsequent changes in work, education, and daycare. This study describes the changes in pediatric cannabis exposures during the first nine months of the COVID-19 pandemic relative to the three years before the pandemic., Methods: Cases were identified from the National Poison Data System. Inclusion criteria was unintentional cannabis exposure in children aged 6 months to 5 years between January 1, 2017 and December 31, 2020. Analysis was performed with segmented regression of interrupted time series analysis comparing January 2017-March 2020 (pre-COVID-19) to April 2020-December 2020 (COVID-19 period). Autocorrelation was assessed using Dubin-Watson test., Results: There were 7,679 unintentional pediatric exposures from January 1, 2017 through December 31, 2020. There was a significant increase of 3.1% per month during the pre-COVID-19 period ( p  < .0001). A statistically significant immediate increase in number of exposures per month occurred in April 2020 (58.4%; p  < .0001). The slope in the COVID-19 period was -0.01% ( p  = .99). No autocorrelation was detected., Discussion and Conclusions: Unintentional cannabis exposures in children aged 6 months to 5 years reported to United States poison centers increased significantly after the initial COVID-19 stay-at-home orders. This trend may be associated with COVID-19 quarantines, increased time children are spending at home, increased availability of cannabis products in homes, or other reasons. Future efforts should evaluate specific factors that resulted in the observed increases in pediatric exposures.

Background: Individual case reports describe trazodone overdose resulting in QTc prolongation and cardiac arrhythmias. The clinical effects and outcomes associated with trazodone exposures on a large-scale basis are less well known., Objective: The primary objective was to characterize the severity of single substance trazodone exposures and identify any relationships that may exist between dose of trazodone and severity of exposure. The secondary objective was to describe these exposures from a demographic and clinical symptom standpoint., Methods: A retrospective review of single-substance trazodone exposures reported to the National Poison Data System (NPDS) from 1 January 2000 to 31 December 2019 was performed. The primary objective was to characterize the severity of trazodone exposures and relationships between ingested dose and level of care required or medical outcome., Results: A total of 118,773 cases were included in the analysis of demographics and level of care required. A majority (59.5%) of cases did not require medical admission. Of the 81,698 cases with known medical outcomes, the most common clinical effects included mild-moderate CNS depression (49.7%), QTc prolongation (12.2% of cases in 2019), vomiting (9.0%), hypotension (7.0%), and tachycardia (7.0%). The median ingested dose associated with treatment, and release from the emergency department was 600 mg compared to 1500 mg in those admitted to the intensive care unit (ICU). Regarding medical outcome, median ingested dose ranged from 600 mg in those experiencing no effect to 1500 mg in those experiencing major effects. Cardiac-related clinical effects and the need for cardiac-specific interventions were overall infrequent. A dose-response relationship was identified for level of care and medical outcome., Conclusions: Many trazodone exposures can be characterized as low severity due to the infrequent need for healthcare facility admission and large proportion of cases that experienced no effects or only minor effects.

Background: Cannabis exposures in children have risen sharply in recent years, resulting in increased hospital visits and admission to pediatric intensive care units (PICUs). The intent of this study was to describe the proportion of pediatric patients admitted to the PICU after unintentional cannabis ingestion that received critical care interventions (CCIs) along with describing trends over time in hospitalization, admission to the PICU, and clinical effects and treatments outside of the PICU., Methods: This was a retrospective database study utilizing the National Poison Data System (NPDS) from 1/1/2000 to 12/31/2020. Children 6 months to 12 years of age with single substance cannabis exposures were included., Results: A total of 12,882 cases were included. There was an increase in the proportion of cases seen in a hospital over time from 43.8% in 2000 to 54.6% in 2020 (range 29.1-62.6%). In patients seen in a HCF, the proportion admitted to the PICU was 9.5% in 2000 and 14% in 2020 (range: 5.6-29.0%). The 875 (6.8%) children admitted to the PICU were analyzed for the primary outcome. CCIs were performed in 69/875 (7.9%) cases that were admitted to the PICU. The most common CCIs in the PICU were intubation and sedation, 4.9 and 3.7%, respectively., Conclusions: Unintentional pediatric cannabis exposures are associated with clinically significant effects, including respiratory depression, hypotension, and bradycardia, but fewer than 5% of exposures were treated with CCIs, like intubation or vasopressors, in patients admitted to the PICU. Further work should assess specific reasons for admission to the PICU.

Background: Previous literature suggests a laboratory interference of n-acetylcysteine (NAC) with prothrombin time (PT) and the international normalized ratio (INR). Early publications focused on this interaction in the setting of an acetaminophen overdose and evaluated the INR of patients receiving intravenous NAC. However, there is limited literature describing the concentration-effect relationship of NAC to INR measurement in the absence of acetaminophen-induced hepatotoxicity at therapeutic NAC concentrations. The purpose of the study is to quantify the degree of interference of NAC on INR values at therapeutic concentrations correlating to each infusion of the regimen (ex. bag 1: 550 mcg/mL, bag 2: 200 mcg/mL, bag 3: 35 mcg/mL, double bag 3: 70 mcg/mL) and at supratherapeutic concentrations in vitro ., Methods: Blood samples were obtained from study volunteers. Each blood sample was transferred into vials containing 0.3 mL buffered sodium citrate 3.2% and spiked with various concentrations of NAC for final concentrations of 0, 35, 70, 200, 550, 1000, 2000, and 4000 mcg/mL. The samples were centrifuged and tested to determine PT and INR on two separate machines: Siemens CS-2500 and Stago SN1114559. We would require a sample size of 6 to achieve a power of 80% and a level of significance of 1.7% (two-sided). Differences between INRs at varying concentrations were determined by Friedman's test. For multiple comparisons, post hoc analysis was performed using Wilcoxon signed-rank test with Bonferroni adjustment. Analyses were performed with SAS version 9.4 (SAS Institute, Cary, NC)., Results: Participants included 11 healthy subjects: 8 males, 3 females, median age 30 years (range 25 - 58). Median and interquartile ranges (IQR) INR for the baseline samples were 1.09 (IQR 1.05, 1.16) for Siemens and 1.03 (IQR 0.99, 1.11) for Stago analyzers. There was a significant difference in INR between the therapeutic concentrations (baseline, 35, 70,200, or 550 µg/mL) (Siemens p  = .0008, Stago p  < .0001). The 550 µg/mL concentration with the Siemens analyzer was the only one compared separately and found to be significantly greater than the baseline (1.07 vs 1.22, p  = .02). For the Stago analyzer the 200 µg/mL and 500 µg/mL were compared and found to be significantly different from baseline (1.00 vs 1.07 and 1.19, adjusted p  = .02 and p  = .03, respectively). The largest INR increase seen was in one subject from a baseline of 1.07-1.32 with the 550 µg/mL concentration. Increases in concentrations to supratherapeutic levels resulted in a statistically significant non-linear increase in INR for all concentrations (Siemens p  < .0001, Stago p  < .0001). All of these concentrations were found to be significantly different from baseline (all adjusted p  < .05)., Conclusion: Although it was found that at therapeutic concentrations the in vitro presence of NAC affects INR measurements on two different machines, the change is of little clinical relevance. Supratherapeutic concentrations of NAC affect INR significantly, but the clinical utility of those results is limited by the rarity of those concentrations being measured.

Background: Limited data describe poisoning exposures in pregnant women. Previous studies are limited to inpatient populations, those seen only by toxicologists, or single poison centers. This study aimed to describe poison exposures reported to U.S. poison control centers in pregnant patients compared to non-pregnant controls., Methods: This was a retrospective observational study of exposures reported to the American Association of Poison Control Centers National Poison Data System from 2000 through 2019. Pregnant patients were included from 15-44 years along with a random sampling of 5:1 age and year matched control group of non-pregnant exposures. Demographics, primary substance, and known medical outcomes were described. Chi square analysis was performed for comparisons., Results: From 2000 to 2019, a total of 131,619 pregnant cases and 658,095 non-pregnant controls were identified. The median age was 27 years (IQR: 22, 31) for the matched groups. For known trimester of pregnancy: 29.8, 37.0, and 28.2% were in the first, second, and third trimester, respectively. Most common exposures were analgesics and cleaning products. Intentional exposures were more common in non-pregnant compared to pregnant cases (41.2 vs 21.9%; OR 2.71, 95% CI 2.67-2.75), mostly self-harm attempts (31.5 vs. 15.8%). Notably, there was a large discrepancy in the proportion of environmental exposures, with fewer in non-pregnant controls compared with pregnant cases (3.8 vs. 12.1%; OR 0.29, 95% CI 0.28-0.29). More non-pregnant cases had multiple substance exposures compared with pregnant cases (22.2 vs. 10.9%; OR 2.34, 95% CI 2.29-2.38). There were more moderate effect outcomes in non-pregnant compared with pregnant cases (13.2 vs. 6.3%; OR 2.25, 95% CI 2.20-2.30)., Conclusions: Outcomes of poisoning exposures in pregnant patients reported to U.S. poison centers are less serious compared to non-pregnant controls, likely due to the lower rates of intentional abuse and self-harm exposures and greater number of minimally toxic environmental exposures.

Introduction: Perampanel is indicated for partial onset seizures in children and adults. The mechanism is unique among antiepileptic agents as it inhibits glutamate activity on AMPA receptors. Currently, there are few published case reports describing overdose., Methods: This is a retrospective observational study of all single substance perampanel ingestions from January 2014 to December 2019 reported to the national poison data system (NPDS). The primary outcome is to describe the clinical effects of perampanel exposures. Secondary outcomes include evaluation of management and investigation of a dose-effect relationship for the purpose of triaging acute unintentional exposures., Results: A total of 138 exposures were reported to NPDS since the release of the agent. Median age was 20 years (IQR 10-38) with 68 (49.3%) males. The reason for exposure was most commonly therapeutic error (80, 58.0%), followed by exploratory ingestion (24, 17.4%), and suicidal ingestion (14, 10.1%). A total of six (4.3%) patients developed major effects, 20 (14.5%) moderate, 32 (23.2%) minor effects and 22 (15.9%) no effect. An additional 54 (39.1%) cases were not followed. Almost half of cases were managed at home. Of those that were in a healthcare facility (HCF) ( n  = 72), most were treated/evaluated and released (31, 43.1%), followed by admission to a non-critical care unit (20, 27.8%), and critical care unit (13, 18.1%). Most frequently reported symptoms were drowsiness (27, 19.6%), agitation (20, 14.5%), ataxia (13, 9.4%), and confusion (12, 8.7%). The most common therapies provided in a HCF were intravenous fluids (22,30.6%), followed by benzodiazepines (14, 19.4%), then other types of sedation (9, 12.5%). There were too few cases to determine a dose cut off for triaging., Conclusions: While drowsiness, agitation, ataxia, and confusion were the most often reported symptoms, close to 19% developed moderate/major effects and almost 4% of patients received potentially life-saving interventions.

Abstract: Guidelines exist on the management of supratherapeutic/subtherapeutic international normalized ratio (INR) values for patients on warfarin. However, there is a paucity of the literature relating to an acute overdose of warfarin. This is a retrospective cohort study for all acute and acute-on-chronic (AOC) warfarin overdoses reported to the Maryland Poison Center in patients ≥12 years between January 1st, 2000, until October 31st, 2019, managed in a health care facility. The primary outcome was to determine the time after presentation to peak INR. Secondary outcomes included risk factors associated with INR >10 and describing patient characteristics. A total of 163 overdoses were included, 68 acute and 95 AOC. In patients who did not receive reversal therapies, INR peaked at a median value of 3.8 (interquartile range 2.6-5.5) between 24 and 36 hours. The median time to phytonadione was 22.0 hours. Most patients received phytonadione (62.0%), with fewer receiving blood products (16.6%). The median warfarin dose ingested was 75 mg. The AOC group had a greater mean age (56 vs. 43 years), median INR value (2.4 vs. 1.4), and men (62.1% vs. 41.2%). Factors associated with an INR > 10 included initial INR and reported quantity ingested. Peak INR was greater in the AOC than the acute overdose group (6.1 vs. 3.4), although the bleeding rate was similar. Peak INR values after warfarin overdose occur between 24 and 36 hours after presentation. Initial INRs and reported quantity ingested may be useful to predict those needing treatment., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Flecainide is a class 1C antiarrhythmic with a narrow therapeutic window and thereby a high-risk medication for causing acute toxicity. Dysrhythmias secondary to flecainide ingestion are often refractory to antiarrhythmics and cardioversion, and patients commonly require extracorporeal support. We review the successful resuscitation of two brothers aged 2 and 4 who presented two years apart with unstable wide-complex tachyarrhythmia suspicious for severe flecainide toxicity. Each patient received sodium bicarbonate and 20% intravenous lipid emulsion with a full recovery. While extracorporeal support is often required following flecainide ingestion, we present two cases where it was avoided due to aggressive multimodal management with sodium bicarbonate, electrolyte repletion, and 20% intravenous lipid emulsion. In addition, avoidance of agitation-induced tachycardia may be beneficial., Competing Interests: The authors have no conflicts of interest to report., (Copyright © 2021 Sarah E. Gardner Yelton et al.)

Introduction : Management of patients with acute agitation or aggressive behavior can pose a significant challenge to health-care providers in emergency departments. Areas covered : This article provides a comprehensive review of the pharmacologic properties, efficacy, and safety profiles of select intramuscular (IM) sedative agents (i.e., antipsychotics, benzodiazepines, and ketamine) for rapid tranquilization. Expert opinion : Using antipsychotics and benzodiazepines - whether a single agent or combined - will have similar efficacy in producing sedation. But there are differences in the time to sedation depending on which agent is used. Based upon the available studies, droperidol (5-10 mg IM) and midazolam (5-10 mg IM) have the fastest onset of sedation when either is used as a single agent. When combination therapy is used, using midazolam with an antipsychotic agent, instead of lorazepam, may result in faster sedative effect. QT prolongation and torsades de pointes are uncommon adverse drug effects of antipsychotic administration. Ketamine is often reserved as a second-line agent when antipsychotics and benzodiazepines fail to produce the desired tranquilization. However, ketamine (5 mg/kg IM) is more frequently associated with airway compromise requiring endotracheal intubation. A low-dose of ketamine (2 mg/kg IM) may reduce the risk of airway compromise while providing adequate sedation.

Purpose: Identify if publication of the 2010 drug safety communication (DSC) regarding benzonatate was associated with a decrease in the incidence of severe benzonatate poisonings reported to United States poison centers., Methods: This retrospective database study utilized the National Poison Data System to compare the incidence of severe benzonatate poisonings before and after the publication of a drug safety communication. We utilized interrupted time series analysis to compare 2000-2010 (pre-DSC) to 2012-2019 (post-DSC)., Results: There were 18 619 benzonatate exposures reported to US poison centers during the time period covered and 11 554 exposures were included. There was an increase in exposures throughout the time period. There was no difference in the incidence of severe outcomes in the two time periods. In the pre-DSC era, rates of severe outcomes increased by 0.4% per year followed by an immediate non-significant drop of 2.9% in incidence of severe outcomes (P = .15). Finally, the slope of severe outcomes in the post-DSC era showed an increase of 0.3% per year, which was not significantly different from the pre-DSC era (P = .78)., Conclusion: Publication of a Drug Safety Communication regarding the risks of benzonatate did not result in a decrease in the proportion of severe benzonatate poisoning reported to US poison centers. Deaths and other severe outcomes continued to occur at a similar rate after the publication., (© 2020 John Wiley & Sons Ltd.)

Objective: This is a descriptive study evaluating fatal iatrogenic and in-hospital medication errors reported to United States poison centers., Methods: A retrospective evaluation of the National Poison Data System from 2000-2017 of all therapeutic errors with a scenario coded as iatrogenic/healthcare professional or occurring in a healthcare facility. Death abstracts were reviewed for details of the exposure and therapeutic error scenarios were recoded or added to the case as appropriate. Cases, where death was considered not related to the exposure, were excluded. Additionally, we created one additional scenario (rate-related) and one additional route of administration (intrathecal) to better describe the cases., Results: A total of 172 cases were evaluated. The majority of the patients were female (52.3%) with a median age of 58.5 years (range: 2 days to 96 years). The most commonly reported medication error was "other incorrect dose" (22.7%) followed by other/unknown error (15.1%). The route of exposure was primarily parenteral (54.9%), followed by ingestion (30.2%), then intrathecal (7.0%). The most common medications were cardiac drugs, chemotherapeutics, opioids, anticoagulants, and sedative-hypnotic/antipsychotics., Conclusions: Iatrogenic and in-hospital medication errors have been studied extensively with goals to reduce their occurrence. Specific controls to prevent incorrect dosing routes, 10-fold overdoses, and incorrect intrathecal administration have been instituted. Despite interventions, all three of these therapeutic errors continued to occur in 2017, suggesting that more preventive controls should be instituted.

Background and Objectives: Pediatric ingestions of amphetamines used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) are on the rise. Little data provide an amphetamine dose at which to refer pediatric unintentional ingestions to a healthcare facility for monitoring. We studied the dose at which unintentional ingestions of amphetamines develop symptoms and receive benzodiazepines. Methods: We performed a retrospective study from a single poison center from 1/1/2005 through 11/30/2018. We included single substance ingestion of amphetamine salts to treat ADHD in amphetamine-naïve children age 0-12 years followed to a known outcome. Poison center documentation was reviewed for signs and symptoms related to amphetamine toxicity and use of benzodiazepines. Results: We screened 1,394 cases and 160 met inclusion criteria. The mean age of patients was 1.8 years and 55% were male. The median dose of symptomatic patients (1.38 mg/kg) was greater than those without symptoms (0.83 mg/kg). The median amphetamine dose of patients receiving benzodiazepines (1.58 mg/kg) was also greater than for patients not receiving benzodiazepines (1.0 mg/kg). A dose threshold of greater than 0.75 mg/kg was 100% sensitive and 36.8% specific for benzodiazepine administration and 93.9% sensitive and 47.4% specific for presence of any symptoms. Conclusions: The median dose of amphetamines ingested by patients receiving benzodiazepines was greater than those not receiving benzodiazepines. No child with a dose of ≤0.75 mg/kg received benzodiazepines. Prospective studies should be performed to assess triage guidelines and referral doses.

Objectives: To date, very little literature describes the outcomes of acute unintentional ingestions of lithium in young children. This study aimed to describe the clinical effects and outcomes reported in these patients reported to the National Poison Data System (NPDS). Methods: This is a retrospective observational study of acute unintentional lithium ingestions in children <6 years of age. The primary intent of the study was to characterize acute unintentional exposures to lithium in children in this age group. As a secondary outcome, we sought to identify a weight-based threshold to empirically refer patients into a healthcare facility for symptoms consistent with moderate effect or worse. The American Association of Poison Control Centers' NPDS was queried for all acute ingestions of lithium salts in children <6 years of age from 2000 to 2018. Inclusion criteria were single substance ingestions, unintentional-general exposure (i.e., exploratory ingestion), and followed to a known outcome or coded as potentially toxic exposure unable to follow and the patient was experiencing symptoms. Results: A total of 3045 single-substance exploratory ingestions of lithium were reported to poison centers that showed a decrease over time, consistent with decreasing use of lithium and decreasing calls to poison centers. Of the 3045 cases, we excluded 1178 leaving 1863 cases for analysis. Median age was 2 years (IQR: 1.5, 2) with 51% male cases. Management site was primarily non-health care facility ( n  = 808; 43.4%) with 569 (30.5%) already in a healthcare facility (HCF) when the Poison Control Center (PCC) was called and 477 (25.6%) referred to a HCF. The route of exposure was most commonly ingestion ( n  = 1853; 99.5%) and site of exposure was primarily home (1743; 93.6%). Medical outcomes were predominantly no effect and minor effect. There were 262 related clinical effects were reported in 184 patients (10%). The most frequently reported were vomiting ( n  = 76), drowsiness/lethargy ( n  = 58), other ( n  = 22), and ataxia ( n  = 20). Clinical effects lasted ≤2 h for 65 (33%), 2-8 h for 57 (28.9%), 8-24 h for 51 (25.9%), 1-3 days for 11 (5.6%), and >3 days to ≤1 week for 1 (0.5%); no cases resulted in clinical effects thought to be permanent and no deaths were reported. There were 1173 treatments provided to 857 patients. The most common treatments were basic and are readily performed at home; dilution ( n  = 492) and food/snack ( n  = 180). A smaller subset of patients received care that could likely only be provided in a healthcare facility including IV fluids ( n  = 173), other ( n  = 120), whole bowel irrigation ( n  = 46), single dose activated charcoal ( n  = 41), syrup of ipecac ( n  = 34), and lavage ( n  = 31). No patients received hemodialysis. A total of 425 of the exposures were referred to a healthcare facility by the PCC which had a dose coded. There was no difference in dose that resulted to referral to a healthcare facility over time ( p  = 0.2747). Due to the small number of moderate/major effect cases with dose information, we were unable to identify a dose-based threshold for referral to HCF. Conclusions: Severe outcomes after unintentional ingestion of lithium in pediatric patients are rare. It is likely that most asymptomatic pediatric patients <6 years do not need to be referred to the hospital after ingestion of lithium.

Iron poisoning was a leading cause of pediatric morbidity and mortality. We sought to assess whether the removal of strict iron packaging requirements in 2003 resulted in an increase in iron-related morbidity and mortality in pediatric exposures. We performed a retrospective cohort study utilizing the National Poison Data System from 2000 to 2017. A total of 4110 exposures met inclusion criteria: 847 from before (2000-2003) and 3263 after removal of unit-dose package regulations (2004-2017). The incidence of any marker of severity (7.2% vs 3.8%; odds ratio = 0.51, 95% confidence interval = 0.37-0.69) and frequency of deferoxamine use were both higher in the early time period (2.6% vs 1.0%; odds ratio = 0.38, 95% confidence interval = 0.22-0.66). There was no difference in the frequency of key serious effects (acidosis, elevated transaminases, hypotension). Despite removal of iron packaging regulations in the United States, there continues to be a decrease in the incidence of severe iron exposures in children.

Background: Prepacked naloxone kits (PNKs) are frequently used to reverse opioid intoxication. It is unknown if the presence of illicitly manufactured fentanyl and its analogs (IMFs) in heroin supply is affecting the PNK doses given by laypersons. We investigated the trend of PNK dose administered to reverse opioid toxicity in suspected/undifferentiated opioid intoxication. Methods: We retrospectively reviewed PNK administrations reported to the Maryland Poison Center between 1 January 2015 and 15 October 2017. Primary outcome was the mean PNK dose administered to reverse opioid-induced central nervous system and ventilatory depression. Secondary outcomes included the reversal rate of opioid toxicity, patient disposition, and survival rate. Results: Our analysis involved 1139 PNK administrations. The mean age of subjects was 34.3 years; 68.8% ( n  = 781) were male. Ventilatory depression was present in 98.2% ( n  = 958) of cases, and 97% ( n  = 1097) were unresponsive. Law enforcement administered the majority of PNK (91.0%; n  = 1035); the primary route was intranasal (97.9%; n  = 1051). Toxicity was reversed in 79.2% ( n  = 886) of overdose victims after a mean PNK dose of 3.12 mg. EMS personnel gave 291 subjects additional naloxone (mean: 2.2 mg), reversing opioid toxicity in 94.2% ( n  = 254). Between 2015 and 2017, the mean PNK dose increased from 2.12 to 3.63 mg ( p  < .0001) while the reversal rate decreased from 82.1% to 76.4% ( p  = .04). One hundred and eighty-two patients (15.9%) refused transport; of those transported to a hospital, 73.4% ( n  = 569) were treated and released and 12.4% ( n  = 96) required hospitalization. Ninety-six percent ( n  = 1092) of the subjects survived. Forty subjects were pronounced dead at the scene. Fentanyl or its analog was detected in 36 of 55 opioid-related deaths (65.5%). Conclusions: PNK administration reversed toxicity in the majority of patients with undifferentiated opioid intoxication. Between 2015 and 2017, increasing doses of PNK were administered but the reversal rate decreased. These trends are likely multifactorial, including increasing availability of IMFs.

Background: Widespread use of the Internet has increased availability of numerous products. Multiple published cases highlight that toxic xenobiotics are available for purchase online. Most cases describe purchase from the deep web. We sought to identify extremely hazardous substances available from an online retailer. Methods: Over a 10-month period, the online retailer Amazon.com ® was searched for each of the products listed by the Environmental Protection Agency's "List of Extremely Hazardous Substances." Product names, availability on Amazon Prime ® , need for a business account, price, and quantity were collated. Results: We identified 79/340 (23.2%) of these substances were available on Amazon.com ® . Almost one-third of the available substances were eligible for Amazon Prime ® . Approximately one-third of the products were available in an amount that could be toxic by purchasing a single unit (31/79). Of these 31 products, only four required a business account, 18 were eligible for Amazon Prime ® , and nine were neither eligible for Prime nor required a business account. Notable products include sodium azide, acrylamide, mercuric acetate, and hydrazine. Conclusions: The ease of purchase and ready availability of such highly toxic substances is concerning. Online retailers like Amazon.com ® should consult with toxicologists or other qualified experts and governmental agencies to identify which products should be removed or restricted to business accounts.

Background : Therapeutic errors are costly and result in unplanned hospital visits. Recent poison center studies on therapeutic errors have focused on coded data from either the National Poison Data System (NPDS) or individual poison centers. Approximately 21% of therapeutic errors reported to NPDS are coded as "other incorrect dose" (OI) or "other/unknown therapeutic error" (OU). The purpose of this study was to characterize errors coded as OI or OU reported to a single poison center. Methods : Retrospective, single poison center chart review was conducted of therapeutic error exposures with at least one scenario coded as OI or OU seen in or referred to hospitals from 1/1/2000 to 9/30/2017. Cases were reviewed and re-coded to predefined or newly created scenarios. Results : A total of 3413 cases were identified. There were 726 cases assessed as not therapeutic errors and re-coded as either intentional misuse (430), adverse reaction drug (204), or other non-therapeutic errors (82). Of the remaining cases, 1726 cases were re-coded to one of the 16 existing therapeutic error scenarios. After re-coding, there remained 971 coded as OI or OU. Most were due to double, triple, quadruple, or higher than recommended dose (477/971); an additional common error was mistaken strength (81/971). The remaining scenarios occurred in fewer than 50 cases each with greater than 40 different scenarios such that additional coded scenarios would not be feasible. Conclusions : Most cases coded as OI or OU could be recoded as one of the NPDS predefined therapeutic error scenarios or non-error reasons for exposure. Considering the large proportion of double dose cases and the unique errors associated with mistaken strengths of tablets, these scenarios could be appropriate to add as new predefined coding scenarios, which would aid in future research and patient counseling.

Background : Venlafaxine use to achieve an amphetamine-like high has been described but data regarding the epidemiology and clinical effects are sparse. Objectives : Describe the prevalence and toxicity of venlafaxine abuse reported to US poison control centers. Methods : This was a retrospective review of venlafaxine exposures reported to the National Poison Data System (NPDS) from 2000 to 2016. Inclusion criteria were: age 12 years and older, reason for exposure intentional-abuse, and either single-substance exposure or venlafaxine was the first substance. The primary outcome was prevalence of intentional-abuse of venlafaxine. Secondary outcomes characterized demographics, geographic distribution, toxicity, and outcomes. Results : Intentional-abuse accounted for 752 of 85,621 venlafaxine exposures. Overall prevalence was 87.8 intentional-abuse exposures/10,000 venlafaxine exposures reported to NPDS (range, 59.3-117.6/10,000). Prevalence decreased from 107/10,000 in 2000 to 59.3/10,000 in 2016. Median age was 23 years and 50% were female. Primary route was ingestion (90.8%) with 4.7% using venlafaxine via inhalation/intranasal insufflation, and 3.7% both routes. There were 227 venlafaxine-only exposures; 54.0% were treated/released from the emergency department, 20% were admitted for medical management, 9.0% to a psychiatric facility, and 17.0% managed at home. Known medical outcomes for single-substance exposures were: no effect (24.0%), minor (39.0%), moderate (33.0%), and major (4.0%); no deaths occurred. Most frequent clinical effects were tachycardia (33.9%), drowsiness (20.7%), and agitation (11.5%). Conclusion : The prevalence of venlafaxine abuse reported to poison control centers has decreased. Medical outcomes are usually not serious. Clinicians should be aware that non-medical use is possible but infrequently reported to poison control centers.

Background: Lysergic acid diethylamide (LSD) and psilocybin are serotonergic hallucinogens that are used primarily for recreational abuse. Small studies evaluated the efficacy of LSD and psilocybin for several psychiatric conditions. There are limited safety or toxicity data for either of these substances, especially in large populations., Methods: This was a retrospective analysis of single-substance exposures of LSD or psilocybin-containing mushrooms (PcMs) reported to United States poison centers from 1 January 2000 to 31 December 2016. The study describes the most frequent toxicities, management sites, and medical outcomes., Results: A total of 5883 PcM and 3554 LSD exposures were included. Most patients were between 13 and 29 years of age (83.9% PcM, 88.9% LSD) and primarily male (77.9% PcM, 74.1% LSD). Most common clinical effects were hallucinations (45.8% PcM, 37.4% LSD), agitation (24.1% PcM, 42.4% LSD), and tachycardia (18.0% PcM, 38.6% LSD). Serious clinical effects were infrequent, but included hyperthermia, seizures, coma, increased serum creatinine, and cardiac arrest. Most patients were treated and released from the emergency department. More LSD patients were admitted to critical care and non-critical care units than PcM patients. Moderate effect was the most frequent outcome for both substances (61.0% PcM, 62.3% LSD)., Conclusion: These data find that LSD and PcM use occurs primarily in adolescents and young adults, who experience mild to moderate adverse effects. Serious effects are infrequent but can occur. While most LSD and PcM users require only emergency department management, LSD use is more likely to require medical admission.

Metoclopramide (MCP) is a commonly used anti-emetic in the emergency department (ED). Its use is generally well tolerated; although infrequent adverse reactions such as extrapyramidal reactions or tardive dyskinesia are reported. However, many ED providers are not familiar with the potentially life-threatening hypertensive emergency that can be precipitated by MCP administration in patients with pheochromocytoma. A previously healthy 36-year-old woman presented to the ED with headache and nausea. She developed acute hypertensive emergency (acute agitation, worsening headache, chest pain and wide complex tachycardia) when her blood pressure (BP) increased to 223/102mmHg (initial BP, 134/86mmHg) after receiving intravenous MCP. Her hospital course was complicated by multi-organ injury, including acute respiratory distress syndrome requiring venous-venous extracorporeal membrane oxygenation, non-ST elevation myocardial infarction, cardiogenic shock, acute liver failure, and oliguric kidney injury requiring continuous renal replacement therapy. CT scan showed previously undiagnosed large right adrenal mass (5.9cm). The diagnosis of pheochromocytoma was confirmed after adrenalectomy. Drug-induced acute pheochromocytoma crisis is a rare event. Early recognition and appropriate blood pressure management with clevidipine, nicardipine, or phentolamine is essential., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Low dose naltrexone (LDN) has been evaluated in several small studies for the treatment of inflammatory conditions. It is thought to work through modulation of inflammatory mediators and upregulation of endogenous opioid receptors. This may hypersensitize patients to exogenous opioids. Drug-drug interaction screening tools built into electronic health records and other services identify the interaction as risk of opioid withdrawal rather than hypersensitivity. We present a case of a drug-drug interaction in a patient who was receiving LDN treatment of multiple sclerosis. The patient received a single dose of oxycodone 5mg that resulted in obtundation unresponsive to painful stimuli necessitating the administration of naloxone boluses and infusion along with admission to the intensive care unit for 1 night. The patient responded well to naloxone therapy. He was discharged in satisfactory condition., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Glucagon-like peptide 1 is a compound known to cause reduced food intake in mammals, though its action on feed intake in fish is unknown. The clear differences in the effects of GLP-1 on mammalian and teleostean glucose homeostasis suggest that we cannot assume a similar action of GLP-1 on feeding in mammals and fish. In this study the effects and specificity of centrally administered GLP-1 on feed intake were examined. It was demonstrated that intracerebroventricular (ICV) injection of glucagon-like peptide 1 (GLP-1) in the channel catfish (Ictalurus punctatus) is a potent inhibitor of feed intake with a dose of 0.25 ng g(-1) body wt. reducing feed intake by 50%. The weak response to intraperitoneal (i.p.) and intravenous (i.v.) injection treatments with GLP-1 suggests the major effects on feed intake are centrally mediated. GLP-1 action on feed intake was not antagonized by ICV injection of exendin(9-39). Immunoneutralization of GLP-1 by ICV injection of antisalmon GLP-1 antisera did not affect feed intake over 48 h, while ICV injection of GLP-1 at a dose of 30 ng g(-1) body wt. reduced feed intake for over 20 h. Additionally, there is some evidence that GLP-1 caused gastric evacuation. We conclude that GLP-1 is a potent inhibitor of feeding in fish, but its involvement in feed intake regulation under physiological conditions remains to be clarified.

The action of neuropeptide Y (NPY) on food intake is of interest for the enhancement of growth of channel catfish (Ictalurus punctatus) for aquaculture. We sequenced 795 bp of complementary DNA (including 288 bp of open reading frame that encompassed the signal peptide, mature peptide, and carboxy-terminal peptide) from catfish brain NPY (GenBank accession number AF267164) and identified untranslated regions of the gene. We found high identity (88%-91%) of the amino acid sequence of the translated, mature protein with other fish NPYs. Using Northern blotting and reverse transcriptase polymerase chain reaction, we found NPY gene expression in the hypothalamus, myelencephalon, telencephalon, and optic tectum of the brain, but not the cerebellum or the pituitary gland. NPY expression was also found in immature ovary. Our results highlight the conserved nature of NPY in vertebrate systems, and the probes developed in this work will facilitate physiological and genetic studies of feeding and growth in channel catfish.

Rapid and reproducible fixation of brain and peripheral nerve tissue for light and electron microscopy studies can be done in a microwave oven. In this review we report a standardized nomenclature for diverse fixation techniques that use microwave heating: (1) microwave stabilization, (2) fast and ultrafast primary microwave-chemical fixation, (3) microwave irradiation followed by chemical fixation, (4) primary chemical fixation followed by microwave irradiation, and (5) microwave fixation used in various combinations with freeze fixation. All of these methods are well suited to fix brain tissue for light microscopy. Fast primary microwave-chemical fixation is best for immunoelectron microscopy studies. We also review how the physical characteristics of the microwave frequency and the dimensions of microwave oven cavities can compromise microwave fixation results. A microwave oven can be calibrated for fixation when the following parameters are standardized: irradiation time; water load volume, initial temperature, and placement within the oven; fixative composition, volume, and initial temperature; and specimen container shape and placement within the oven. Using two recently developed calibration tools, the neon bulb array and the agar-saline-Giemsa tissue phantom, we report a simple calibration protocol that identifies regions within a microwave oven for uniform microwave fixation., (Copyright 1998 Academic Press.)

Recent studies have established that microwave irradiation during aldehyde fixation of electron microscopy specimens can reduce fixation times substantially. Similar reductions in duration of histochemical and light microscopy procedures have been reported. Both thermal and non-thermal effects of microwaves have been proposed to explain these dramatic decreases in processing time. Possible thermal effects include increases in fixative diffusion and reaction rates and increased formation of glutaraldehyde monomers. Proposed non-thermal effects include preferential orientation of fixative molecules by the microwave field and other more speculative direct microwave effects. Several reported attempts to produce rapid fixation without temperature increase by cooling specimens during irradiation have produced conflicting results. If rapid fixation is a thermal effect, other heating modes in addition to microwave exposure should produce similar effects. We show that for mouse liver samples (< or = 1 mm3) comparable fixation can be obtained with microwave irradiation, conductive and convective heating in a waterbath, and resistive heating with a low-frequency (1 kHz) current passed through the fixative solution. We also show that using an efficient convective cooling method to prevent temperature increase during microwave exposure produces unsatisfactory fixation. These results are consistent with thermal mechanisms for rapid fixation.

Thin sections of rumen diliated protozoa of the subclass Holotrichia were observed with a transmission electron microscope. These protozoa had a double layered boundary separating the ectoplasm from the endoplasm. Starch granules were abundant throughout the endoplasm and are probably storage starch. Also in the endoplasm of the holotrichs were the macro- and micronuclei. They were adjacent to one another, apparantly surrounded by a continuous membrane. Many unidentified dense bodies appeared in the endoplasm adjacent to the inner layer of the ectoplasmic-endoplasmic boundary. These inclusions could be precursor material to the boundary. The cuticle contained granular inclusions which might be secreted to facilitate ciliary movement. The holotrichs ingested chloroplasts as these were in vacuoles throughout the cytoplasm. The anal pore appeared to be open to the exterior and lined by a unit membrane.

Flexible implant resection arthroplasty for the finger joints can provide rewarding results. The importance of indications, surgical considerations, and postoperative modalities are reviewed for the MP, PIP, and DIP joints.

A variety of transport properties have been measured for solutions of the water soluble polymer poly(ethylene oxide)(PEO) with molecular weights ranging from 200 to 14,000, and volume fractions ranging from 0-80%. The transport properties are thermal conductivity, electrical conductivity at audio frequencies (in solutions containing dilute electrolyte), and water self-diffusion. These data, together with dielectric relaxation data previously reported, are amenable to analysis by the same mixture theory. The ionic conductivity and water self-diffusion coefficient, but not the thermal conductivity, are substantially smaller than predicted by the Maxwell and Hanai mixture relations, calculated using the known transport properties of pure liquid water. A 25% (by volume) solution of PEO exhibits an average dielectric relaxation frequency of the suspending water of one half that of pure water, with clear evidence of a distribution of relaxation times present. The limits of the cumulative distribution of dielectric relaxation times that are consistent with the data are obtained using a linear programming technique. The application of simple mixture theory, under appropriate limiting conditions, yields hydration values for the more dilute polymer solutions that are somewhat larger than values obtained from thermodynamic measurements.

The morphology and ultrastructure of the lateral body integument of the leptocephalus, glass eel, pigmented elver, and adult stages of the American eel, Anguilla rostrata, were examined with light and electron microscopy. The integument consists of an epidermis separated by a basal lamina from the underlying dermis. Three cell types are present in the epidermis in all stages. Filament-containing cells, which are the principal structural cell type, are increasingly numerous at each stage. Mucous cells, which secrete the mucous that compose the mucous surface coat, are also more numerous in each subsequent stage and are more numerous in the anterior lateral body epidermis than in the posterior lateral body epidermis of the adult. Club cells, whose function is unknown, are most numerous in the glass eel and pigmented elver. Chloride cells are common in the leptocephalus which is marine and infrequent in the glass eel. They are not present in the pigmented elver and adult which inhabit estuaries and freshwater. Lymphocytes and melanocytes are also present in some stages. The dermis comprises two layers: a layer of collagenous lamellae, the stratum compactum, and an underlying layer of loose connective tissue, the stratum spongiosum. There is a progressive increase in epidermal thickness at each stage which is paralleled by an increase in the thickness of the stratum compactum. Rudimentary scales are present in the dermis of the adult. The increase in the number of epidermal filament-containing cells, epidermal thickness and stratum compactum thickness is correlated with an increased need for protection from abrasion and mechanical damage as the eel moves from a pelagic, oceanic habitat to a benthic, freshwater habitat. The increase in mucous cell numbers is likewise correlated with an increased need for the protective and anti-bacterial action of the mucous surface coat in the freshwater environment.