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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. 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. 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). 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. 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. [ABSTRACT FROM AUTHOR]

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. 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). 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). 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. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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 FROM AUTHOR]

"Time and a Hall's the American Way": A History of the Exclusion of White-Collar Workers from Overtime Regulation, 1868-2004. By Marc Linder, Fanpihua Press, Iowa City, Iowa, 2004, 1,342 pp., [...]

This is a descriptive study evaluating fatal iatrogenic and in-hospital medication errors reported to United States poison centers. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.