Hands-Free Analytical Urine Testing Technology Validated for Drug-Facilitated Crime Investigations.

Forensic laboratories need quick and simple technology to improve turnaround times, while delivering reliable results. The goal of this study is first to create a simplified workflow to meet new Academy Standards Board requirements for urine testing in drug-facilitated crime investigations and, second, to create "ready-to-go", "hands-free" testing technology to further streamline analytical procedures. A first of its kind, the ToxBox forensic test kit is used to validate a single analytical procedure for opioids, benzodiazepines, cannabinoids, antidepressants, and several other drug classes. Method performance indicators follow accreditation requirements and include accuracy, precision, measurement uncertainty, calibration models, reportable range, sensitivity, specificity, carryover, interference, ion suppression/enhancement, and analyte stability. "Hands-free" testing platforms require the use of new suspended-state technology to stabilize NIST-traceable standards premanufactured at precise concentrations in the presence of sample preparation reagents. By suspending all reaction components in the solid state, with air gaps between the phases, reference standards and process controls are built in a "ready-to-go" format and stabilized for long-term storage in the presence of a sample matrix, ß-d-glucuronidase, and enzymatic buffers. "Hands-free" test kits are removed from storage, incubated at either ambient temperature or 60 °C, and assayed using validated methods. This is the first example of how complex forensic testing workflows can be streamlined with new "hands-free" testing strategies to meet analytical challenges associated with quantitative and confirmatory analyses.

Suspected Suicidal Cannabis Exposures Reported to US Poison Centers, 2009-2021.

This cross-sectional study examines case characteristics of suicidal cannabis exposures reported to US poison centers before vs during the COVID-19 pandemic.

Pharmacogenomic Profiling of Pediatric Patients on Psychotropic Medications in an Emergency Department.

OBJECTIVE: The aim of the study was to evaluate the ability of a combinatorial pharmacogenomic test to predict medication blood levels and relative clinical improvements in a selected pediatric population. METHODS: This study enrolled patients between ages 3 to 18 years who presented to a pediatric emergency department with acute psychiatric, behavioral, or mental health crisis and/or concerns, and had previously been prescribed psychotropic medications. Patients received combinatorial pharmacogenomic testing with medications categorized according to gene-drug interactions (GDIs); medications with a GDI were considered "incongruent," and medications without a GDI were considered "congruent." Blood levels for escitalopram, fluoxetine, aripiprazole, and clonidine were evaluated according to level of GDI. Relative clinical improvements in response to the prescribed psychotropic medications were measured using a parent-rated Clinical Global Impression of Improvement (CGI-I) assessment, where lower scores corresponded with greater improvement. RESULTS: Of the 100 patients enrolled, 73% reported taking ≥1 incongruent medication. There was no significant difference in CGI-I scores between patients prescribed congruent versus incongruent medications (3.37 vs 3.68, P = 0.343). Among patients who presented for depression or suicidal ideation, those prescribed congruent medications had significantly lower CGI-I scores compared with those taking incongruent medications ( P = 0.036 for depression, P = 0.018 for suicidal ideation). There was a significant association between medication GDI and blood levels for aripiprazole (n = 15, P = 0.01) and escitalopram (n = 10, P = 0.01). CONCLUSIONS: Our preliminary findings suggest that combinatorial pharmacogenomic testing can predict medication blood levels and relative outcomes based on medication congruency in children presenting to an emergency department with acute psychiatric/behavioral crises. Additional studies will be needed to confirm these findings.

Synthetic cannabinoid poisonings and access to the legal cannabis market: findings from US national poison centre data 2016-2019.

AIM: To investigate trends in synthetic cannabinoid exposures reported to United States (US) poison control centres, and their association with status of state cannabis legalisation. METHODS: A retrospective study of National Poison Data System (NPDS) data from 2016 to 2019 identified and associated synthetic poisoning reports with annual state cannabis law and market status. State status was categorised as restrictive (cannabis illegal or limited medical legalisation), medical (allowing THC-containing medical cannabis use) and permissive (allowing non-medical use of THC-containing cannabis by adults). We categorised a subset of states with permissive policies by their implementation of legal adult possession/use and opening retail markets, on a quarterly basis. Mixed-effects Poisson regression models assessed synthetic exposures associated with legal status, first among all states using annual counts, and then among states that implemented permissive law alone using quarterly counts. RESULTS: A total of 7600 exposures were reported during the study period. Overall, reported synthetic exposures declined over time. Most reported exposures (64.8%) required medical attention, and 61 deaths were documented. State implementation of medical cannabis law was associated with 13% fewer reported annual exposures. Adoption of permissive state cannabis policy was independently and significantly associated with 37% lower reported annual synthetic exposures, relative to restrictive policies (IRR: 0.63, 95% CI: 0.50-0.79). Among states with permissive law during the period, implementation of legal adult possession/use was associated with 22% fewer reported quarterly exposures. Opening of retail markets was associated with 36% fewer reported exposures, relative to states with medical cannabis only. CONCLUSIONS: Adoption of permissive cannabis law was associated with significant reductions in reported synthetic cannabinoid exposures. More permissive cannabis law may have the unintended benefit of reducing both motivation and harms associated with use of synthetic cannabis products.

Methylene Blue: An Antidote for Methemoglobinemia and Beyond.

ABSTRACT: Methylene blue has been in medicinal use for centuries and is best known as an antidotal treatment for acquired methemoglobinemia (MetHB). More recently, methylene blue has gained recognition for its efficacious use in the treatment of ifosfamide neurotoxicity and refractory vasoplegic shock in both the pediatric and adult critical care literature, extending its use beyond MetHB. Methylene blue's mechanism of action is somewhat complex and based partly on its oxidizing capabilities, ironically the same mechanism that causes MetHB. This review will examine methylene blue's use in the treatment of acquired MetHB and ifosfamide neurotoxicity and review the current literature regarding its role in critically ill pediatric and adult patients with refractory vasoplegic shock. Methylene blue's pharmacologic actions, dosing, and adverse effects will also be discussed.

Kratom exposures among older adults reported to U.S. poison centers, 2014-2019.

BACKGROUND: In recent years, use of the herbal supplement kratom has increased in the United States. The reasons for use include pain relief, particularly as a substitute for opioids. OBJECTIVES: To describe epidemiologic trends in kratom-related exposures among older adults reported to U.S. poison centers. DESIGN: Retrospective analysis of American Association of Poison Control Center's National Poison Data System (NPDS). SETTING: Data from all U.S. poison centers from 2014 to 2019 were examined. PARTICIPANTS: Kratom exposure cases involving adults aged 18 and older. Kratom cases were identified by product and NPDS generic codes. Non-human and information-only calls were excluded. Data were examined for all calls for exposures among adults, with a focus on older adults aged 60-69 years and above 70 years. MEASUREMENTS: Descriptive analyses were used to characterize individual demographic, exposure information, clinical effects, and medical outcomes associated with kratom exposures among older adults. Comparisons across age groups (18-59, 60-69, and 70+ years) were made using Fisher's exact tests. RESULTS: Among 3484 kratom-related exposures reported between 2014 and 2019, 4.6% (n = 162) were among adults over 60 years. The number of kratom-related exposures increased over time. Most cases originated with calls from healthcare facilities (81.1%) and involved kratom as a single ingestant (63.0%). The reason for most ingestions was intentional (74.5%). One in five exposures among adults aged 70 and older involved an adverse reaction (e.g., drug interaction; 21.9%), compared with 12.3% among ages 60-69 and 9.6% among ages 18-59 years. Neurological and cardiovascular clinical effects were observed. Twenty-three deaths were observed among older adults. CONCLUSION: Healthcare providers and older adult patients should be aware of the potential risks of kratom use, including medication interactions and falls. When reviewing medication lists, providers should query this population for all medications and substances being used, especially in people being treated for pain.

Increased rates of diphenhydramine overdose, abuse, and misuse in the United States, 2005-2016.

OBJECTIVES: To describe trends in abuse, misuse, and suicide attempts involving diphenhydramine (DPH). METHODS: We analyzed intentional DPH exposures of individuals ≥10 years old reported to U.S. Poison Control Centers using data from the National Poison Data System, 2005-2016. RESULTS: There were 158,774 intentional DPH exposures in our dataset. The rate of intentional exposures increased 63% over the 12-year study period for all ages combined. Suicide attempts involving DPH showed a bimodal distribution-increasing 263% among children 10-14 years of age, and 126 and 143% among those 55-64 and ≥65 years of age, respectively. Older adults in both the 55-64 and ≥65-year-old age groups had about a 230% increase in rates of misuse. Major adverse clinical effects increased by 91%. There were 745 total reported deaths with a 3.6% increase across all age groups. CONCLUSIONS: Intentional DPH exposures among individuals ≥10 years old have been increasing since 2005. Increasing rates of suicide attempts among children ages 10-14 and increasing misuse among individuals ≥65, coupled with a trend toward greater severity of overdoses, highlight the significant public health impact of this commonly available over-the-counter drug.

Lead Pellet Ingestion in 3 Children: Another Source for Lead Toxicity.

Acute ingestions of spherical lead ammunition foreign bodies such as bullets and lead shot can cause acute blood lead level elevations and clinical symptoms necessitating emergency department evaluations and sometimes treatment. This article presents 3 cases of children ingesting lead ammunition, all receiving gastrointestinal (GI) decontamination and chelation therapy for significantly elevated blood lead level. Case-specific exposures and treatments for the lead ammunitions are presented. Radiographs documented lead pellet ingestion in all 3 cases. Pediatric patients absorb lead from the GI tract more quickly than adults and may necessitate more urgent evaluation and treatment than adolescents/adults. More rapid GI absorption has the potential to result in possible irreversible neurotoxicity and neurocognitive deficits as well as behavioral changes. Failure of lead foreign bodies to pass from the GI tract may require more aggressive interventions for their removal to prevent ongoing absorption. Emergency health care providers should be aware of alternative lead sources besides the most common source of paint, as these lead foreign bodies also need urgent evaluation and possibly treatment.

Appropriate use of vancomycin in a pediatric emergency department through the use of a standardized electronic guideline.

OBJECTIVES: (a) Compare utilization of vancomycin in the ED prior to and after implementation of standardized treatment guideline and order template (STGOT); (b) assess the appropriate use as initial therapy based on indication versus admitting diagnosis. METHODS: Chart audits on all patients who received vancomycin and were admitted. Overall utilization and appropriateness of starting therapy were compared pre-and post-STGOT implementation. RESULTS: Overall utilization of vancomycin was 4% pre-STGOT compared to 3% post-STGOT; 98% of patients pre-STGOT compared to 99% post-STGOT received vancomycin appropriately. CONCLUSION: There was no difference in vancomycin utilization and appropriateness of initiating therapy after STGOT implementation.

Common ocular effects reported to a poison control center after systemic absorption of drugs in therapeutic and toxic doses.

PURPOSE OF REVIEW: Ocular effects resulting from medications assist toxicologists in determining substances involved when treating a poisoned patient. The intention of this review is to discuss the most common ocular effects, the medications that cause them, and the mechanisms by which they occur. RECENT FINDINGS: According to National Poison Data System, the most common reported ocular effects following a drug ingestion/injection/inhalation are mydriasis, miosis, and nystagmus. The most common drug/drug classes reported to a regional poison control center causing these ocular effects include the following: first, mydriasis - amphetamines and diphenhydramine; second, miosis - clonidine and opioids; third, nystagmus - dextromethorphan. However, many other drugs/substances can cause these effects along with other systemic effects. SUMMARY: Ocular findings are a pertinent component of any patient assessment involving therapeutic and/or toxic exposure to medications and other substances.

Laundry detergent pod ingestions: is there a need for endoscopy?

INTRODUCTION: Laundry detergent pod (LDP) exposures in children have resulted in several referrals to the emergency department. Signs and symptoms can include gastrointestinal symptoms (vomiting, drooling), neurological symptoms (depressed sensorium), or metabolic changes (lactic acidosis). There is limited literature on esophageal injury following LDP ingestions. CASE SERIES: We reviewed three cases of pediatric LDP ingestions that underwent an upper endoscopy in a tertiary care pediatric hospital. All of our patients were younger than 3 years old. The upper endoscopies revealed superficial esophageal erosions in two patients and erythema in the other. None of the patients had oral burns. Two of them developed swallowing dysfunction. Follow-up upper GI studies were normal. CASE DISCUSSION: Our three patients ingested laundry detergent pods and all of them developed some degree of esophageal injury despite the absence of oral erythema, ulcers, or swelling. A review of literature suggests LDP exposures are more severe than non-pod detergents. Reasons as to why this may be remain unclear, although investigation into the ingredients and mode of delivery may help us to better understand. In a literature review, no esophageal strictures have been reported after LDP ingestion. We reviewed esophageal injury classification systems in an attempt to predict who may be at greatest risk for stricture based on initial findings. CONCLUSION: Our case series demonstrates it is hard to predict esophageal injury based on signs and symptoms. Based on a literature review, long-term esophageal stricture is unlikely, but if gastrointestinal symptoms persist, it is reasonable to evaluate with an upper endoscopy. Larger studies are needed.

Recognizing serotonin toxicity in the pediatric emergency department.

The use of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in treating depression, mood disorders, and behavioral disorders has escalated dramatically in the last 20 years, resulting in increased risk and clinical presentation of serotonin toxicity. Health care providers must also be aware of other medications and substances with proserotonergic activity that can cause serotonin toxicity when used in combination with these medications. There are many adverse effects of selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, although their toxicity profile compared to older antidepressants seems to be safer. Serotonin syndrome is described as a clinical triad of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. It encompasses a spectrum of clinical findings ranging from a few nonspecific symptoms to significant clinical toxicity that can result in death. The objectives of this article are to review specific serotonergic medications including their adverse effects and toxicity in overdose, to describe other medications/substances that have proserotonergic effects, which could result in serotonin excess in combination with traditional serotonergic agents, and to define the criteria for serotonin syndrome/toxicity and its treatment.

Adverse Effects and Toxicity of the Atypical Antipsychotics: What is Important for the Pediatric Emergency Medicine Practitioner.

Medications are being used with greater frequency to address pediatric mental health problems, and in recent years atypical antipsychotic (AAP) prescriptions have increased more than any other class. Acute care practitioners must be aware of the pharmacology of AAPs and the conditions, on- and off-label, for which they are prescribed. This involves identifying and managing side effects that manifest both mentally and physically. Although "atypicality" confers a lower risk of movement side effects compared to conventional agents, children are more sensitive than adults to extrapyramidal reactions. Like adults, they also may present with toxic sedation, confusion, cardiovascular dysfunction, and metabolic derangements. Evaluation and management of these toxicities requires an index of suspicion, a careful symptom and medication history, physical examination, and targeted interventions. This review is designed to orient the emergency practitioner to the challenging task of recognizing and treating adverse effects related to acute and chronic atypical antipsychotic exposure in children.

Clinical experience with intravenous lipid emulsion for drug-induced cardiovascular collapse.

Intravenous lipid emulsion (ILE) is an emerging therapy for refractory cardiotoxicity due to lipid-soluble drugs. The purpose of this study was to assess survival to hospital discharge, effects on hemodynamic parameters, and adverse event occurrence for patients who were treated with ILE as part of the resuscitative effort for drug-induced cardiotoxicity. This is a multicenter retrospective chart review of inpatients at three tertiary referral medical centers receiving ILE for drug-induced cardiotoxicity between November 2007 and March 2009. Nine cases with drug-induced cardiovascular collapse, defined as cardiac arrest or refractory shock, were selected for review if patients received either bolus or infusion of ILE in any combination. No interventions were done. The main outcome measures were survival to hospital discharge, effect on hemodynamic parameters, and adverse event. Hemodynamic vital signs (heart rate, systolic blood pressure, diastolic blood pressure, calculated mean arterial pressure [MAP]) were measured before administration of ILE and up to five measurements (if available) were recorded after administration of ILE. Attribution of adverse events was determined by assignment of Naranjo adverse drug reaction (ADR) likelihood score (3) with adjudication of three medical toxicologists; disagreements were settled by majority consensus. Of nine cases identified based on inclusion criteria (three cardiac arrest, six refractory shock), five (55%) survived to hospital discharge. ILE regimens were bolus alone in five patients and bolus plus infusion in four patients. Hemodynamic trends in response to ILE demonstrated no difference in MAP immediately pre- and post-administration of ILE (p = NS). Administration of infusion (versus boluses alone) did not demonstrate a statistically significant improvement in MAP. Adverse events due to ILE therapy that were categorized as "possible" or "probable" based on Naranjo scores included lipemia, digit amputation, lung injury, renal failure, and deep venous thrombosis. ILE administered to patients with drug-induced cardiovascular collapse was associated with 55% survival but with clinically significant adverse effects. At this time, ILE should be restricted to cardiotoxicity involving cardiac arrest or refractory shock until further prospective studies can better evaluate risks and benefits of ILE therapy.

Enhancing patient safety in the pediatric emergency department: teams, communication, and lessons from crew resource management.

The fast-paced and multifaceted nature of patient care in the emergency department makes our discipline especially prone to errors and adverse events. In recent years, strategies such as formal communication and medical team training have been proposed as potential means to enhance patient safety. In many ways, practice dynamics particular to the emergency department make this setting almost ideal for implementation of these strategies. This article reviews concepts of communication and team training in medicine, including those learned from the aviation industry (known as crew resource management). Recent literature pertaining to teams and communication in medicine is reviewed.

Voluntarily reported unintentional injections from epinephrine auto-injectors.

BACKGROUND: Epinephrine auto-injectors provide life-saving prehospital treatment for individuals experiencing anaphylaxis in community settings. OBJECTIVE: To determine the number, demographics, and associated circumstances and outcomes of unintentional injections from epinephrine auto-injectors. METHODS: We searched the databases of the American Association of Poison Control Centers and the Food and Drug Administration's Safety Information and Adverse Event Report System for these incidents as reported by members of the public and by health care professionals. RESULTS: From 1994 to 2007, a total of 15,190 unintentional injections from epinephrine auto-injectors were reported to US Poison Control Centers, 60% of them from 2003 to 2007. Those unintentionally injected had a median age of 14 years (interquartile range, 8-35), 55% were female, and 85% were injected in a home or other residence. Management was documented in only 4101 cases (27%), of whom 53% were observed without intervention, 29% were treated, 13% were neither held for observation nor treated, and 4% refused treatment. In contrast, from 1969 to 2007, only 105 unintentional injections from epinephrine auto-injectors were reported to MedWatch. Forty percent of these occurred during attempts to treat allergic reactions. Injuries resulting in permanent sequelae were rarely reported to either US Poison Control Centers or to MedWatch. CONCLUSION: The number of reported unintentional injections from epinephrine auto-injectors increased annually from 1994 to 2007. To prevent these unintentional injections, improved epinephrine auto-injector design is needed, along with increased vigilance in training the trainers and in training and coaching the users, as well as efforts to increase public awareness of the role of epinephrine auto-injectors in the first-aid treatment of anaphylaxis in the community.