An observational study of adverse drug reactions to COVID-19 vaccines reported to the New Mexico poison center hotline.

INTRODUCTION: Post-marketing data on coronavirus vaccines are limited. This study evaluated adverse reactions reported to a statewide hotline after the administration of a coronavirus disease-2019 (COVID-19) vaccine. METHODS: We collected reports between 1 December 2020 through 30 August 2021 of any individual 12 years of age and older who received an FDA EUA-approved vaccine and experienced an adverse reaction. For each case, we collected vaccine brand, demographics, adverse reaction type, severity, onset of reaction, duration, and outcome. Relative risk analyses were conducted to investigate factors associated with vaccine adverse reactions. RESULTS: 638 adverse drug reaction cases were recorded. The majority identified as female (70.8%) and the median age was 56. Implicated brands were Pfizer BNT162b2 (46.6%), Moderna mRNA-1273 (43.41%), and Janssen Ad26.COV2.S (8.78%). Although the lowest number of cases was with Janssen, this vaccine had the highest incident rate based on reactions per 100,000 doses. Adverse reactions with the highest incidence were systemic reactions (92.7%), injection-site reactions (8.5%), and local non-injection-site reactions (10.4%), with most judged as minor severity. Relative risk was higher for Moderna compared to Pfizer for injection-site non-severe (RR 2.01) and injection-site severe (RR 1.94) reactions. Janssen had a higher risk of headache, dyspnea, and vision changes compared to Pfizer, and a higher risk of headache compared to Moderna. The relative risk for fever, chills, and lymphadenopathy was higher for the second dose than the first dose for all patients. CONCLUSION: This observational study analyzing adverse drug reactions of the COVID-19 vaccine found that most complaints concerned systemic reactions. We found reaction differences among vaccine brands, between first and second doses for some effects, and selected recurrent events. Poison control centers are uniquely positioned to conduct post-marketing surveillance for the new vaccines as they are available 24/7 to the public and are healthcare providers. Further post-marketing studies are essential to provide a holistic safety profile of COVID-19 vaccines.

2020 webPOISONCONTROL data summary.

INTRODUCTION: Increasing use of the internet for health information has decreased utilization of traditional telephone-based poison centers in the United States. webPOISONCONTROL®, a browser-based tool and app was launched to meet the growing demand for online, personalized recommendations for human poison exposures. This study was conducted to characterize webPOISONCONTROL cases and highlight its potential for real-time monitoring of poisoning. METHODS: Case data for all completed, nonduplicated public cases entered in 2020 were analyzed using a custom Qlik Sense dashboard. RESULTS: Of the 156,202 cases, 52.9% occurred in children younger than 4 years. Most cases (109,057, 69.8%) were initially triaged to home, 28.4% were advised to call Poison Control, and 1.7% were referred to the ED. Follow-up was available for 33.3% of home-triaged cases; 1.7% of those had a change in triage recommendation. Pharmaceuticals were implicated in 41.5% of cases (nonpharmaceuticals in 58.5%). Ingestion was the most common route (88.4%, 138,012). One-time double dose therapeutic error cases were implicated in 17,901 cases (27.6% of pharmaceutical cases). Cosmetics (13.9%) and cleaning substances (12.9%) were the most frequent substance categories. Melatonin was the most frequently implicated generic substance (4.5% of cases). Most (72.0%) cases had no effect (21.4%), a minor effect (3.9%) or were minimally toxic with unknown outcome (46.7%). There were no deaths, 17 major outcomes (0.01%), and 26.7% of cases had potentially toxic exposures with no outcome determination. In 2020, webPOISONCONTROL handled 7.3% as many human poison exposure cases as were reported to U.S. phone-based poison centers. Online cases are skewed towards younger ages (53% in children younger than 4 years vs 37% of phone-based cases) and towards nonpharmaceuticals (58.5% vs 43.5%). Near real-time data visualizations enabled detection of COVID-19-related increases in exposures to hand sanitizers and cleaners, illustrating the public health surveillance and hazard detection capabilities of webPOISONCONTROL. CONCLUSION: The webPOISONCONTROL tool provides a safe, quick and fully-automated alternative to those who are unable or unwilling to use the telephone to call a traditional poison center.

A systematic review of second line therapies in toxic seizures.

BACKGROUND: Seizures are a common manifestation of toxic exposures requiring immediate and possibly ongoing management. Guidelines recommend benzodiazepines as first-line therapy for toxic seizures; however, there is a paucity of literature regarding optimal secondary treatment. We systematically evaluated the available literature for second-line treatment of toxic seizures. METHODS: We searched PubMed, Embase, PsychINFO, Cochrane Library, Web of Science, Google Scholar, and International Pharmaceutical Abstracts from inception through August of 2018, following PRISMA Guideline. The MESH terms focused on identifying treatments for seizures induced by drugs or other potentially toxic substances. We excluded the articles if they involved animals, had seizures resulting from alcohol withdrawal, were case reports, or not peer-reviewed. Our primary outcome was seizure termination and/or suppression by the second-line agent as agreed upon by two authors. We used descriptive statistics for analysis. RESULTS: We identified six case series that met inclusion and exclusion criteria. Included case series contained nine to 235 patient cases each. The most common xenobiotic exposures were bupropion, isoniazid, and anti-psychotics. The description of seizure type and duration was diverse. First-line treatments were primarily benzodiazepines. Secondary treatments included propofol, barbiturates, phenytoin, valproic acid, and levetiracetam. Patient outcomes differed, attributable to any of the following: mixed toxic substances, drug-drug interactions, inability to control seizures, or toxicity of the anti-epileptic drugs (AED) themselves. Few cases specifically discussed the success of secondary treatment administration to suppress or terminate seizures. CONCLUSIONS: Available literature discussing second-line treatment for toxic seizures is of poor quality with high heterogeneity. Although the majority of articles used similar second-line agents, it is difficult to compare the efficacy of the regimens. Additional studies are necessary to identify the most efficacious second-line therapies in toxic seizures.

Stoned on spices: a mini-review of three commonly abused household spices.

INTRODUCTION: Although spices are widely used as food products and are generally regarded as safe, intentional abuse of household spices may occur and is likely underreported in the medical literature. Spices are inexpensive and widely available for purchase by individuals of all ages and may be perceived as being safer than traditional drugs of abuse. DISCUSSION: Nutmeg, cinnamon, and vanilla are commonly abused spices. The major component of nutmeg is myristicin; myristicin has activity at serotonergic receptors and may result in psychomimetic symptoms after exposure. Cinnamon oils contain local irritants which may cause dermatitis or ulcerations after topical application. Ground cinnamon contains cellulose fibers; these are biopersistent and bioresistant, and inhalational exposure to cinnamon powder can result in chronic pulmonary inflammation and fibrosis. Pure vanilla extract contains a minimum of 35% ethanol according to the United States Food and Drug Administration standards, and abuse of vanilla extract may occur among individuals seeking ethanol intoxication. CONCLUSIONS: Overall, misuse or abuse of these spices frequently results in mild to moderate symptoms that do not require medical intervention, although more serious intoxications may require hospitalization. Clinicians should be aware of the potential dangers of household spice abuse and understand management strategies for these exposures.

Serious Adverse Health Events, Including Death, Associated with Ingesting Alcohol-Based Hand Sanitizers Containing Methanol - Arizona and New Mexico, May-June 2020.

Alcohol-based hand sanitizer is a liquid, gel, or foam that contains ethanol or isopropanol used to disinfect hands. Hand hygiene is an important component of the U.S. response to the emergence of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). If soap and water are not readily available, CDC recommends the use of alcohol-based hand sanitizer products that contain at least 60% ethyl alcohol (ethanol) or 70% isopropyl alcohol (isopropanol) in community settings (1); in health care settings, CDC recommendations specify that alcohol-based hand sanitizer products should contain 60%-95% alcohol (≥60% ethanol or ≥70% isopropanol) (2). According to the Food and Drug Administration (FDA), which regulates alcohol-based hand sanitizers as an over-the-counter drug, methanol (methyl alcohol) is not an acceptable ingredient. Cases of ethanol toxicity following ingestion of alcohol-based hand sanitizer products have been reported in persons with alcohol use disorder (3,4). On June 30, 2020, CDC received notification from public health partners in Arizona and New Mexico of cases of methanol poisoning associated with ingestion of alcohol-based hand sanitizers. The case reports followed an FDA consumer alert issued on June 19, 2020, warning about specific hand sanitizers that contain methanol. Whereas early clinical effects of methanol and ethanol poisoning are similar (e.g., headache, blurred vision, nausea, vomiting, abdominal pain, loss of coordination, and decreased level of consciousness), persons with methanol poisoning might develop severe anion-gap metabolic acidosis, seizures, and blindness. If left untreated methanol poisoning can be fatal (5). Survivors of methanol poisoning might have permanent visual impairment, including complete vision loss; data suggest that vision loss results from the direct toxic effect of formate, a toxic anion metabolite of methanol, on the optic nerve (6). CDC and state partners established a case definition of alcohol-based hand sanitizer-associated methanol poisoning and reviewed 62 poison center call records from May 1 through June 30, 2020, to characterize reported cases. Medical records were reviewed to abstract details missing from poison center call records. During this period, 15 adult patients met the case definition, including persons who were American Indian/Alaska Native (AI/AN). All had ingested an alcohol-based hand sanitizer and were subsequently admitted to a hospital. Four patients died and three were discharged with vision impairment. Persons should never ingest alcohol-based hand sanitizer, avoid use of specific imported products found to contain methanol, and continue to monitor FDA guidance (7). Clinicians should maintain a high index of suspicion for methanol poisoning when evaluating adult or pediatric patients with reported swallowing of an alcohol-based hand sanitizer product or with symptoms, signs, and laboratory findings (e.g., elevated anion-gap metabolic acidosis) compatible with methanol poisoning. Treatment of methanol poisoning includes supportive care, correction of acidosis, administration of an alcohol dehydrogenase inhibitor (e.g., fomepizole), and frequently, hemodialysis.

Utilization of lipid emulsion therapy in fatal overdose cases: an observational study.

OBJECTIVE: Although anecdotal reports suggest that intravenous lipid emulsion (ILE) therapy is effective in a large variety of overdoses, the few controlled human trials published to date yielded disappointing results. Because of potential publication biases, there are few reports concerning the failure of ILE. The primary aim of this study was to identify fatal poisoning cases in the American Association of Poison Control Centers (AAPCC) National Poison Data System (NPDS) in which ILE was administered. METHODS: We obtained an approved release of data from NPDS for years 2010-2015 in which the words "lipid," "ILE," or "fat" appeared in the narrative. Duplicate cases were excluded as were cases in which ILE was not clearly given. Case data were extracted by one author using a predetermined tool, and the information was confirmed by a second author. The timing of ILE administration was characterized into one of four categories: cardiac arrest, first line, last resort, or part of multiple therapies given simultaneously. Response to ILE and adverse events was recorded. RESULTS: Of the 826 cases retrieved from NPDS, 459 met final inclusion criteria. Over 50% of included cases involved either a calcium channel blocker or a beta-adrenergic antagonist. Of note, less than 25% of cases involved a substance for which the Lipid Emulsion Working Group found evidence to support its use. Most often, ILE was given along with multiple therapies (277 cases) or as a last resort (137 cases). In 127 cases, ILE was given during cardiac arrest. ILE was used as first line therapy in 34 cases. Response rates were reported as follows: no response (45%), unknown response (38%), transient/minimal response (7%), ROSC (7%), and immediate worsening (3%). Possible adverse reactions included: ARDS in 39 patients, lipemia causing a delay in laboratory evaluation in three cases, lipemia causing failure of a CRRT filter in two cases, worsening or new onset seizure in two cases, asystole immediately after administration in two cases, and fat embolism in one case. CONCLUSION: Within the Association of Poison Control Centers (AAPCC) National Poison Data System (NPDS), hundreds of cases exist in which ILE therapy was given and death occurred. In many of these cases, ILE was given prior to cardiovascular collapse. Although there is some suggestion of transient improvement in a small subset of cases, adverse effects are also reported. When taken in totality, the number of published cases of failed lipid emulsion therapy outnumbers the published instances of ILE success. Given all the uncertainty generated by case reports, the evaluation of the role and efficacy of ILE therapy in non-local anesthetic poisoning needs robust controlled clinical trials.

A 29-year analysis of acute peak salicylate concentrations in fatalities reported to United States poison centers.

BACKGROUND/OBJECTIVES: The threshold salicylate concentration commonly recommended to initiate extracorporeal elimination, in the absence of significant end-organ toxicity, is 100 mg/dL. Unfortunately, the grade of evidence to support this decision is low. Our primary aim is to describe highest reported salicylate concentrations in patients who died from acute salicylate ingestions. Our secondary aim is to determine if age or coingestants varied with highest reported salicylate concentration. METHODS: We analyzed acute salicylate fatalities reported to the National Poison Data System (NPDS) between 1 January 1986 and 31 December 2014. Included were patients who died during the index hospitalization and for which acute salicylate toxicity was the primary cause of death. We used descriptive statistics with standard deviations (SD) or 95% confidence intervals (CI) where appropriate. We created a general linear model that evaluated the association of age and coingestions with salicylate concentrations. We divided the patients into age quartiles to assess a possible interaction between age and salicylate concentration. RESULTS: We identified 602 acute salicylate fatalities that fit inclusion criteria. The mean peak reported fatal salicylate concentration across all age groups was 99.19 mg/dL (± 50.2 mg/dL). The median peak fatal salicylate concentration was 97.0 mg/dL. The oldest quartile had a lower mean concentration (age >57 years; 90.4 mg/dL) than the youngest quartile (age <30 years; 111.6 mg/dL, mean difference 21.2 mg/dL, 95%CI 6.1-36.3). Fatalities with a coingestant had a lower mean concentration of 91.5 mg/dL compared to 104.8 mg/dL among those ingesting salicylates alone (mean difference 13.4 mg/dL, 95%CI 21.4-5.3). Increasing age and the presence of any coingestions were negatively associated with fatal concentrations (estimates; 95%CI 0.41; 0.61-0.021 and -14.43; 22.45-6.42, respectively). When opioids were a coingestant, mean concentration was 72.8 (mean difference 32.1 95%CI 23.1-41.1). CONCLUSIONS: Using the current recommended hemodialysis threshold of 100 mg/dL, more than half of the patients would be deprived of this critical life-saving therapy. Additionally, increasing age and ingestion of other substances, especially opioids, are associated with lower peak fatal salicylate concentrations. A prospective, randomized controlled trial considering salicylate concentrations and other clinical factors may provide further guidance for hemodialysis.

Levetiracetam in toxic seizures.

BACKGROUND/OBJECTIVES: The use of levetiracetam (LEV) in the management of drug-induced seizures has not been systematically investigated. Repetitive and continuous seizures that do not respond to benzodiazepines require second line therapy. Levetiracetam has a unique receptor binding site, rapid absorption, no known cardiac effects at therapeutic doses, and is theoretically a good candidate for use in drug-induced seizures. We evaluate the safety of LEV and its association with seizure cessation in this retrospective chart review of patients who received LEV as a control agent in drug-induced seizures. METHODS: We identified the medical records of patients presenting to an urban, level 1 trauma center between 1 January 2010 and 31 May 2015 by ICD-9 codes based on the following: (1) a poisoning diagnosis, (2) a seizure diagnosis, and (3) administration of LEV. We included patients with a drug-induced seizure based on history, electroencephalogram results, blood alcohol concentrations, urine drug screens, and adequate documentation. We excluded patients with alcohol withdrawal, anoxic brain injury, subtherapeutic concentrations of other antiepileptics, hypoglycemia, and pseudoseizures. Primary outcomes of interest included cessation of active seizures or the prevention of seizure recurrence. We assessed safety by the presence or absence of adverse drug effects (ADE) attributed to the administration of LEV. RESULTS: Thirty-four patients met inclusion and exclusion criteria. Half of the study cohort (17) presented with generalized tonic-clonic seizures (TCS); half (17) presented in generalized convulsive status epilepticus (GCSE). Six patients in GCSE received LEV during their seizures; 2 also received fosphenytoin. One improved immediately following LEV administration, and the remaining 5 had seizure control. Eleven GCSE patients (65%) remained seizure free after LEV therapy. The patients with TCS (17) received LEV after seizure(s) control. Sixteen (94%) were seizure-free during their hospital course. We found no adverse drug effects. In total, 27 of 34 patients (79%) had a return to baseline neurological and physical health. Six had long-term sequelae; none of which are known LEV side-effects. We identified 46 toxic substances and 22 known seizurogenic agents (48%). The median length of stay was 3.7 days (0.4-96), and the median duration of in-hospital LEV therapy was 1.6 days (0-49). CONCLUSIONS: Levetiracetam used as a second-line agent was associated with control of drug-induced seizures and prevention of seizure recurrence without obvious adverse effects. A prospective study is needed to confirm these results.

Dietary Supplements in Children.

High-quality systematic reviews of use of herbal or homeopathic remedies in children often suffer from design flaws, such as not following PRISMA guidelines, inconsistent outcome measurements, and paucity of high-quality studies. Herbal remedies have modest demonstrated benefits with insufficient evidence to recommend any particular supplement. Homeopathic remedies have no role in treatment of pediatric conditions, and have been associated with great harm in infants given homeopathic teething products. Two types of herbal supplements are associated with high risk in adolescents, energy drinks and adulterated weight-loss products. Parents should be counseled about risks of these products.

webPOISONCONTROL: can poison control be automated?

BACKGROUND: A free webPOISONCONTROL app allows the public to determine the appropriate triage of poison ingestions without calling poison control. If accepted and safe, this alternative expands access to reliable poison control services to those who prefer the Internet over the telephone. This study assesses feasibility, safety, and user-acceptance of automated online triage of asymptomatic, nonsuicidal poison ingestion cases. METHODS: The user provides substance name, amount, age, and weight in an automated online tool or downloadable app, and is given a specific triage recommendation to stay home, go to the emergency department, or call poison control for further guidance. Safety was determined by assessing outcomes of consecutive home-triaged cases with follow-up and by confirming the correct application of algorithms. Case completion times and user perceptions of speed and ease of use were measures of user-acceptance. RESULTS: Of 9256 cases, 73.3% were triaged to home, 2.1% to an emergency department, and 24.5% directed to call poison control. Children younger than 6 years were involved in 75.2% of cases. Automated follow-up was done in 31.2% of home-triaged cases; 82.3% of these had no effect. No major or fatal outcomes were reported. More than 91% of survey respondents found the tool quick and easy to use. Median case completion time was 4.1 minutes. CONCLUSION: webPOISONCONTROL augments traditional poison control services by providing automated, accurate online access to case-specific triage and first aid guidance for poison ingestions. It is safe, quick, and easy to use.

A systematic analysis of methylene blue for drug-induced shock.

CONTEXT: Pharmacologically induced shock can be refractory to standard resuscitation. Methylene blue (MB) acts to prevent nitric oxide-mediated vasodilation and may be a potential treatment for refractory shock. OBJECTIVE: A systematic analysis of the literature to evaluate MB in pharmacologically induced shock. Primary outcome was survival and secondary outcome was hemodynamic improvement. MATERIALS AND METHODS: A search of MedLine/PubMed, EMBASE, Cochrane Library, TOXLINE, Google Scholar and Google was performed 10 August 2015 using a combination of text words and keywords related to MB, shock and specific drugs. We included primary literature articles reporting clinical outcomes in humans. RESULTS: The searches yielded 928 citations, with 255 exact duplicates. Of the 673 entries screened, 16 citations met study criteria and comprised 17 cases. Calcium channel blockers (CCBs) represented ten cases (six amlodipine, two verapamil, and two diltiazem), atenolol three cases as coingestant with amlodipine, five metformin, one ibuprofen, and one multidrug (quetiapine, carbamazepine, valproic acid, oxazepam, and fluoxetine). Twelve patients survived and nine had hemodynamic improvement following MB administration. Four did not respond to MB but survived with other advanced resuscitative measures. None of the seven cases had BP improvement and four died when lipid was given prior to MB, compared to one death and nine cases of BP improvement when lipid was not given. In all cases, MB was used after failing several other treatments. Bolus doses ranging from 1 to 3 mg/kg, with repeat boluses or maintenance infusions. Reported adverse events were temporary self-limited blue discolorations. CONCLUSION: While there are compelling cases describing an improved hemodynamic status following MB, there are also several cases without observed change. Currently, there is not enough evidence available to recommend the routine administration of MB in refractory pharmacologically induced shock.