Neonatal and Maternal Ichthyosiform Dermopathy in Association with Kava Use during Pregnancy.

INTRODUCTION: Kava, a substance derived from the Piper methysticum plant, is enjoying a surge in popularity in the United States due to its purported anxiolytic and analgesic effects. Though ichthyosiform dermopathy is a known adverse effect associated with chronic kava exposure in adults, dermopathy in a newborn due to maternal kava use has not yet been described. CASE REPORT: This is a case of a 41-year-old woman who was taking a combination kava/kratom product throughout her pregnancy. She developed an ichthyosiform dermopathy that resolved after she stopped using the product postpartum. Her male infant had a neonatal course complicated by both neonatal opioid withdrawal syndrome, attributed to maternal kratom and buprenorphine use, as well as a diffuse ichthyosiform rash similar to descriptions of kava ichthyosiform dermopathy in adults. His neonatal course was complicated by Group B streptococcus and Serratia marscecens bacteremia (treated with antibiotics) and seizures (treated with lorazepam and phenobarbital). His rash resolved completely by day of life 22. At 9-month outpatient follow-up, he had no dermatologic abnormalities or rash recurrence. DISCUSSION: Maternal kava use during pregnancy may cause fetal dermopathy presenting as an acquired ichthyosis. More public education is needed about the potential consequences of kava use, particularly during pregnancy.

The Toxicology Investigators Consortium 2022 Annual Report.

Since 2010, medical toxicology physicians from the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) have provided reports on their in-hospital and clinic patient consultations to a national case registry, known as the ToxIC Core Registry. De-identified patient data entered into the registry includes patient demographics, reason for medical toxicology evaluation, exposure agents, clinical signs and symptoms, treatments and antidotes administered, and mortality. This thirteenth annual report provides data from 7206 patients entered into the Core Registry in 2022 by 35 participating sites comprising 52 distinct healthcare facilities, bringing the total case count to 94,939. Opioid analgesics were the most commonly reported exposure agent class (15.9%), followed by ethanol (14.9%), non-opioid analgesic (12.8%), and antidepressants (8.0%). Opioids were the leading agent of exposure for the first time in 2022 since the Core Registry started. There were 118 fatalities (case fatality rate of 1.6%). Additional descriptive analyses in this annual report were conducted to describe the location of the patient during hospitalization, telemedicine consultations, and addiction medicine treatments.

The Toxicology Investigators Consortium Case Registry-the 2021 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Core Registry was established by the American College of Medical Toxicology in 2010. The Core Registry collects data from participating sites with the agreement that all bedside and telehealth medical toxicology consultations will be entered. This twelfth annual report summarizes the registry's 2021 data and activity with its additional 8552 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from January 1 to December 31, 2021. Detailed data was collected from these cases and aggregated to provide information, which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. Gender distribution included 50.4% of cases in females, 48.2% of cases in males, and 1.4% of cases in transgender or gender non-conforming individuals. Non-opioid analgesics were the most commonly reported agent class (14.9%), followed by opioids (13.1%). Acetaminophen was the most common agent reported. Fentanyl was the most common opioid reported and was responsible for the greatest number of fatalities. There were 120 fatalities, comprising 1.4% of all cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe new demographic characteristics, including marital status, housing status and military service, the continued COVID-19 pandemic and related toxicologic exposures, and novel substances of exposure.

The Toxicology Investigators Consortium 2020 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology in 2010. The registry collects data from participating sites with the agreement that all bedside and telehealth medical toxicology consultation will be entered. This eleventh annual report summarizes the Registry's 2020 data and activity with its additional 6668 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from January 1 to December 31, 2020. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. Gender distribution included 50.6% cases in females, 48.4% in males, and 1.0% identifying as transgender. Non-opioid analgesics were the most commonly reported agent class, followed by opioid and antidepressant classes. Acetaminophen was once again the most common agent reported. There were 80 fatalities, comprising 1.2% of all registry cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe race and ethnicity demographics and exposures in the registry, telemedicine encounters, and cases related to the COVID-19 pandemic.

The Toxicology Investigators Consortium Case Registry-the 2019 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology (ACMT) in 2010. The Registry collects data from participating sites with the agreement that all bedside medical toxicology consultation will be entered. This tenth annual report summarizes the Registry's 2019 data and activity with its additional 7177 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2019. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. 50.7% of cases were female, 48.5% were male, and 0.8% were transgender. Non-opioid analgesics was the most commonly reported agent class, followed by opioid and antidepressant classes. Acetaminophen was once again the most common agent reported. There were 91 fatalities, comprising 1.3% of all Registry cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe exposures in cases of self-harm, gender differences in substance use disorder, and trends in addiction medicine and pain management consultations.

Thromboelastography with Platelet Studies (TEG® with PlateletMapping®) After Rattlesnake Envenomation in the Southwestern United States Demonstrates Inhibition of ADP-Induced Platelet Activation As Well As Clot Lysis.

INTRODUCTION: Hematologic effects of North American rattlesnake envenomation can include fibrinogenolysis and thrombocytopenia, depending on species, geography, and other variables. During treatment, these effects are routinely monitored through assessment of fibrinogen concentrations and platelet counts. However, these tests provide no information about fibrinolysis or platelet dysfunction, both of which can also occur with venom from some species. METHODS: This was a retrospective chart review of patients admitted to a quaternary care academic hospital (Banner - University Medical Center Phoenix) in the southwestern United States for treatment of rattlesnake envenomation, over an approximately 1-year period from March 2017 through April 2018. Patients who had thromboelastography with platelet studies (TEG® with PlateletMapping®) during their care were included. RESULTS: Twelve patients were identified for this study. Four patients exhibited inhibition of ADP-induced platelet activation: one had normal fibrinogen and platelet count, two had concurrent hypofibrinogenemia, and one had concurrent thrombocytopenia. Crotalidae polyvalent immune Fab (ovine) reversed platelet inhibition in the single patient for whom serial thromboelastographs were available. Fibrinolysis was present in seven patients and resolved in the two patients with serial thromboelastographs. CONCLUSIONS: Inhibition of ADP-induced platelet aggregation and fibrinolysis occurred independent of hypofibrinogenemia and thrombocytopenia, indicating fibrinogen concentration (or protime) and platelet count monitoring alone is insufficient to assess the extent of hematologic toxicity in rattlesnake envenomation. Crotalidae polyvalent immune Fab (ovine) reversed platelet inhibition in one case, suggesting platelet inhibition could also be used in treatment decisions. Fibrinolysis could also be reversed, although the timing to antivenom administration was less clear.

The Effect of 4-Methylpyrazole on Oxidative Metabolism of Acetaminophen in Human Volunteers.

INTRODUCTION: Acetaminophen (APAP) is commonly ingested in both accidental and suicidal overdose. Oxidative metabolism by cytochrome P450 2E1 (CYP2E1) produces the hepatotoxic metabolite, N-acetyl-p-benzoquinone imine. CYP2E1 inhibition using 4-methylpyrazole (4-MP) has been shown to prevent APAP-induced liver injury in mice and human hepatocytes. This study was conducted to assess the effect of 4-MP on APAP metabolism in humans. METHODS: This crossover trial examined the ability of 4-MP to inhibit CYP2E1 metabolism of APAP in five human volunteers. Participants received a single oral dose of APAP 80 mg/kg, both with and without intravenous 4-MP, after which urinary and plasma oxidative APAP metabolites were measured. The primary outcome was the fraction of ingested APAP excreted as total oxidative metabolites (APAP-CYS, APAP-NAC, APAP-GSH). RESULTS: Compared with APAP alone, co-treatment with 4-MP decreased the percentage of ingested APAP recovered as oxidative metabolites in 24-hour urine from 4.48 to 0.51% (95% CI = 2.31-5.63%, p = 0.003). Plasma concentrations of these oxidative metabolites also decreased. CONCLUSIONS: These results show 4-MP effectively reduced oxidative metabolism of APAP in human volunteers ingesting a supratherapeutic APAP dose. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03878693.

Triptan and ergotamine overdoses in the United States: Analysis of the National Poison Data System.

OBJECTIVE: To examine the clinical outcomes of intentional overdoses involving triptans and ergotamines with a retrospective review of the National Poison Data System (NPDS). METHODS: This was a 5-year retrospective cross-sectional study (2014-2018) using the NPDS. Demographics, exposure characteristics, and outcomes were described. Univariate logistic regression was used to estimate the odds ratio (OR) for major effect or death. A multivariable logistic regression model with inclusion criteria of p < 0.1 in univariate analysis was implemented with backwards selection. RESULTS: In this population (n = 1,489), multiple exposure was most common (n = 1,145). The mean age was 31.2 years and 1,197 (80.4%) participants were female. Major effects from a single exposure were seen in <1% with no recorded deaths. Triptan ingestion (n = 328) resulted in hypertension (14%), tachycardia (10.7%), drowsiness (11%), nausea (6.4%), vomiting (4.6%), vertigo (4%), chest pain (3.7%), and diaphoresis (2.4%). Ergotamine ingestion (n = 16) resulted in abdominal pain (16%), vomiting (12.5%), numbness (12.5%), nausea (6.3%), diarrhea (6.3%), and vertigo (6.3%). No clinical effect was seen in 90 (26.2%). No cases met Hunter criteria for serotonin syndrome. There is risk of major event or death due to age (OR 1.02; 95% confidence interval [CI] 1.01-1.04; p = 0.004), multiple product exposure (OR 9.50; 95% CI 2.29-39.48; p = 0.002), and concomitant overdose with benzodiazepines (OR 1.71; 95% CI 1.05-2.78; p = 0.032) or tricyclic antidepressants (OR 3.16; 95% CI 1.88-5.31; p < 0.001). CONCLUSION: The risk of major effect or death was low and predicted by age, multiple product exposure, and concomitant benzodiazepine or tricyclic antidepressant. The triptan toxidrome consists of hypertension, tachycardia, and drowsiness. The toxic effects of ergotamine are acute gastrointestinal syndrome with vertigo and numbness. No cases of serotonin syndrome were seen.

The Toxicology Investigators Consortium Case Registry-the 2018 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology (ACMT) in 2010. The Registry collects data from participating sites with the agreement that all bedside medical toxicology consultation will be entered. The objective of this ninth annual report is to summarize the Registry's 2018 data and activity with its additional 7043 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2018. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. A total of 51.5% of cases were female, 48% were male, and 0.6% transgender. Non-opioid analgesics were the most commonly reported agent class, followed by antidepressants and opioids. Acetaminophen was once again the most common agent reported. There were 106 fatalities, comprising 1.5% of all registry cases. Major trends in demographics and exposure characteristics remained similar to past years' reports. Sub-analyses were conducted to describe exposures in elderly patients, addiction consultation practices, and risk factors for bupropion-induced seizures. The launch of the ToxIC Qualified Clinical Data Registry (TQCDR) is also described.

The Relationship Between Circulating Acetaminophen-Protein Adduct Concentrations and Alanine Aminotransferase Activities in Patients With and Without Acetaminophen Overdose and Toxicity.

INTRODUCTION: Measurement of serum acetaminophen-protein adducts (APAP-CYS) has been suggested to support or refute a diagnosis of acetaminophen (APAP)-induced hepatotoxicity when ingestion histories are unreliable or unavailable and when circulating APAP concentrations are low or undetectable. Non-APAP overdose patients commonly have used APAP products in non-toxic quantities and, thus, will have measurable APAP-CYS concentrations, even when hepatic injury results from other causes, such as ischemic hepatitis. The relationship between alanine aminotransferase (ALT) activity and APAP-CYS concentration might assist in distinguishing between toxic and non-toxic APAP doses in patients suspected of drug overdose. METHODS: We measured serial levels of serum APAP-CYS and ALT activities in 500 overdose patients in whom APAP toxicity was suspected on inpatient admission, but who were then classified at time of discharge and before results of APAP-CYS concentrations were available into three groups: 1) definite APAP group; 2) definitely not APAP group; and 3) indeterminate group. Subjects in the definite and definitely not APAP groups were selected in whom a plasma ALT activity was measured within ± 4 h of a serum APAP-CYS concentration. Regressions with correlation coefficients between APAP-CYS and ALT were calculated for repeat measures in the 335 subjects (908 blood samples) in the definite APAP group and 79 subjects (231 samples) in the definitely not APAP group, with an emphasis on APAP-CYS concentrations and calculation of 95% prediction intervals when ALT was ≥ 1000 IU/L. RESULTS: A strong correlation was found between APAP-CYS and ALT in the definite APAP group over all ALT activities (r = 0.93, p < 0.001; N = 335), and when ALT was > 1000 IU/L (r = 0.82, p < 0.001, N = 144). In the 79 definitely not APAP subjects, no significant correlation was found when ALT exceeded 1000 IU/L (r = 0.04; p = 0.84, N = 32). All subjects in the definitely not APAP group displayed APAP-CYS concentrations < 3 µM. In definitely not APAP subjects, the great majority of APAP-CYS levels were below the 95% prediction interval for APAP-CYS concentrations in definite APAP group subjects when ALT was ≥ 1000 IU/L. However, some definitely not APAP group subjects who had ingested non-toxic doses of APAP displayed APAP-CYS concentrations as high as 2.8 µM in the face of ALT elevation from ischemic hepatitis. CONCLUSION: The interpretation of serum APAP-CYS concentrations must always be made in light of detailed clinical information and the population being tested, especially because of some overlap in APAP-CYS levels in subjects with and without APAP toxicity.

Study of Factors Contributing to Scorpion Envenomation in Arizona.

INTRODUCTION: Arizona has the highest incidence of scorpion envenomation reported to US poison control centers (PCCs). Most cases reported are from a residence, but specific details are limited. METHODS: Specialists at Arizona's two PCCs prospectively completed the Factors of Envenomation in Arizona Residences Survey (FEARS) for residential scorpion exposures reported during 4-week periods in the summer and winter. Based on these results, a second questionnaire, FEARS-2, targeting indoor residential exposures was then administered. RESULTS: Among 382 FEARS responses, no significant differences were found between summer and winter exposures, except for rainfall in the previous 24 hours. Scorpions had previously been seen in 81.8% of exposures, and 29.4% reported a previous envenomation at the residence. Most exposures occurred indoors (86.5%) and in a bedroom (42.5%), where the scorpion was in the bed in 54.7% of cases. Among all stings in a bed, 72.7% occurred while sleeping. Children were stung more often in a family room (38.6% vs. 14.5%; p < .00001) and by a scorpion on the floor (53.5% vs. 35.0%; p = .0014). Distal extremities were stung most often, particularly the foot (34.5%), with most being while barefoot (81.9%). CONCLUSION: A variety of characteristics and associations involving residential scorpion envenomations were identified. These details can be used to guide public education and primary prevention efforts to help decrease residential scorpion exposures.

Geographic Distribution of Scorpion Exposures in the United States, 2010-2015.

OBJECTIVES: To determine the geographic distribution of scorpion envenomations in the United States by zip code, with particular attention to the neurotoxic Centruroides sculpturatus (Arizona bark scorpion), for which an antivenom is available. METHODS: We obtained scorpion exposure cases for 2010 to 2015 from the National Poison Data System. Using geographic information systems software, we mapped total exposures and incidence rates for 9 states that reported more than 100 annual calls. We also mapped cases that reported fasciculations and nystagmus (unique to C. sculpturatus among native scorpions). RESULTS: The highest exposure incidences occurred in Phoenix (up to 677 per 100 000 population) and Tucson (584), both in Arizona. Elsewhere, high incidences were found in El Paso, Texas (213); Oklahoma City (209) and Tulsa (178), Oklahoma; and Las Vegas, Nevada (170). Fasciculations and nystagmus were reported in Arizona and southeastern Nevada, with small numbers in surrounding states, including Utah. CONCLUSIONS: Scorpion exposures occurred at baseline rates throughout many of the southern states, whereas several states reported effects indicative of Arizona bark scorpion envenomation. Public Health Implications. Public and health care provider education, as well as the stocking of antivenom, should be targeted based on these findings.

Nationwide Scorpion Exposures Reported to US Poison Control Centers from 2005 to 2015.

INTRODUCTION: Previous studies of scorpion envenomation in the United States (US) have focused on Arizona and the bark scorpion, Centruroides sculpturatus. Although many other scorpion species live in the US, information about envenomations in other states is lacking. METHODS: Nationwide scorpion exposures from 2005 to 2015 were analyzed using the National Poison Data System. RESULTS: Of the 185,402 total exposures, Arizona (68.2%), Texas (10.3%), and Nevada (4.2%) were the top contributors. However, six other southern states reported greater than 100 cases annually, primarily during the warmer months and evening hours. Envenomations occurred most often in a home (97.8%) and were typically managed on-site (90.1%). Pain was the most common effect nationwide (88.7%). Arizona had the highest frequencies of sensory, neuromuscular, and respiratory effects along with higher hospitalization and ICU admission rates, although the latter appeared to drop over the study period. In contrast, local skin effects such as erythema and edema were more common outside of Arizona. Children under 10 years of age in Arizona and Nevada had the highest rates of systemic effects, hospitalization, and ICU admission. CONCLUSIONS: Scorpion envenomations occurred throughout the southern US with similar seasonal and daily variations. Common clinical effects included pain, local edema, and erythema, except in Arizona and Nevada where severe systemic symptoms were more common. Systemic effects correlated with high rates of ICU admissions and intubations, especially in children under 10 years of age.

US Poison Control Center Calls for Infants 6 Months of Age and Younger.

BACKGROUND: Anticipatory guidance and prevention efforts to decrease poisonings in young children have historically focused on restricting access to minimize exploratory ingestions. Because infants through 6 months of age have limited mobility, such exposures are expected to be less frequent and therapeutic (or dosing) errors should be more frequent. Although recent prevention efforts target some types of therapeutic errors, the epidemiology of these exposures is not well characterized in this age group. This could have important implications for the effectiveness of current prevention efforts. METHODS: A 10-year (2004-2013) retrospective review of exposure calls for infants through 6 months of age was conducted on National Poison Data System files. RESULTS: A total of 271 513 exposures were reported, of which 96.7% were unintentional. Of these, the most common reasons were general unintentional (50.7%), which includes exploratory exposures, and therapeutic error (36.7%). Among the latter, 47.0% involved quantitative dosing errors (a different amount than intended) and 42.8% involved nonquantitative dosing errors (a medication given twice or too soon, the wrong medication, or wrong route). Most exposures (97.5%)occurred in the home but only 85.2% of calls came from the home;80.4% ofself-referrals to a healthcare facility were not admitted. CONCLUSIONS: General unintentional (including exploratory) exposures and therapeutic errors both comprise a large proportion of calls in this age group. Among therapeutic errors, quantitative and nonquantitative dosing errors are equally concerning. There areappreciablenumbers of patients presenting to healthcare prior topoison centerconsultation. These data can help target future anticipatory guidance and prevention measures.

Vowel production and perception: hyperarticulation without a hyperspace effect.

The ability of speakers to exaggerate speech sounds ("hyperarticulation") has led to the theory that the targets themselves must be hyperspace hyperarticulated. Johnson, Flemming, and Wright (1993) found that perceptual "best exemplar" choices for vowels were more speech extreme than listeners' own productions. Our first experiment, using their procedure, only partially replicated their results. Low vowels vowel perception showed a higher F1, consistent with hyperspace. Front vowels also showed more frontness in F2, but back vowels were less extreme ("hypoarticulated") on F2. Our second experiment used an identification and rating of each stimulus, yielding similar results of a smaller magnitude. Our results indicate that the perceptual space is calibrated to a particular (synthetic) vowel space, which is not related straightforwardly to the speakers' spaces. The original hyperspace hypothesis can be attributed to the methodology which led to extreme judgments and of the fronting of back vowels in California English. The present results indicate that no such hypothesis is needed. Vowel targets are measurable from an individual's productions, and the individual's perception of other speakers (even synthetic ones) is based on information about the vocal tract and dialect of the speaker.

Posterior pharyngeal wall position in the production of speech.

The posterior pharyngeal wall has been assumed to be stationary during speech. The present study examines this assumption in order to assess whether midsagittal widths in the pharyngeal region can be inferred from measurements of the anterior pharyngeal wall. Midsagittal magnetic resonance images and X-ray images were examined to determine whether the posterior pharyngeal wall from the upper oropharynx to the upper laryngopharynx shows anterior movement that can be attributed to variables in speech: vowel quality in both English and Japanese; vowels versus consonants as classes of speech sounds; sustained versus dynamically produced speech; and isolated words versus sentences. Measurements were made of the distance between the anterior portion of the vertebral body and the pharyngeal wall. The first measurement was on a line traversing the junction between the dens and the body of the second cervical vertebra (C2). The next three measurements were on lines at the inferior borders of the bodies of C2, C3, and C4. The measurements showed very little movement of the posterior pharyngeal wall, none of it attributable to speech variables. Therefore, the position of the posterior pharyngeal wall in this region can be eliminated as a variable, and the anterior portion of the pharynx alone can be used to estimate vocal cavities.