Disparate Utilization of Urine Drug Screen Nationwide in the Evaluation of Acute Chest Pain.

INTRODUCTION: Urine drug screens (UDS) have unproven clinical utility in emergency department (ED) chest pain presentations. A test with such limited clinical utility may exponentiate biases in care, but little is known about the epidemiology of UDS use for this indication. We hypothesized that UDS utilization varies nationally across race and gender. METHODS: This was a retrospective observational analysis of adult ED visits for chest pain in the 2011-2019 National Hospital Ambulatory Medical Care Survey. We calculated the utilization of UDS across race/ethnicity and gender and then characterized predictors of use via adjusted logistic regression models. RESULTS: We analyzed 13,567 adult chest pain visits, representative of 85.8 million visits nationally. Use of UDS occurred for 4.6% of visits (95% CI 3.9%-5.4%). White females underwent UDS at 3.3% of visits (95% CI 2.5%-4.2%), and Black females at 4.1% (95% CI 2.9%-5.2%). White males were tested at 5.8% of visits (95% CI 4.4%-7.2%), while Black males were tested at 9.3% of visits (95% CI 6.4%-12.2%). A multivariate logistic regression model including race, gender, and time period shows significantly increased odds of ordering UDS for Black patients (odds ratio [OR] 1.45 (95% CI 1.11-1.90, p = 0.007)) and male patients (OR 2.0 (95% CI 1.55-2.58, p < 0.001) as compared to White patients and female patients. CONCLUSION: We identified wide disparities in the utilization of UDS for the evaluation of chest pain. If UDS were used at the rate observed for White women, Black men would undergo nearly 50,000 fewer tests annually. Future research should weigh the potential of the UDS to magnify biases in care against the unproven clinical utility of the test.

Treatment of Toxin-Related Status Epilepticus With Levetiracetam, Fosphenytoin, or Valproate in Patients Enrolled in the Established Status Epilepticus Treatment Trial.

STUDY OBJECTIVE: We describe a subset of patients with toxin-related precipitants of seizures/status epilepticus enrolled in the Established Status Epilepticus Treatment Trial (ESETT). METHODS: The ESETT was a prospective, double-blinded, adaptive trial evaluating levetiracetam, valproate, and fosphenytoin as second-line agents in benzodiazepine-refractory status epilepticus in adults and children. The primary outcome was the absence of seizures and improvement in the level of consciousness 1 hour after study drug administration. In this post hoc analysis, the safety and efficacy of second-line agents in a subset of patients with toxin-related seizures are described. RESULTS: A total of 249 adults and 229 children were enrolled in the ESETT. Toxin-related seizures occurred in 29 (11.6%) adults and 1 child (0.4%). In adults, men were more likely to have toxin-related seizures than women (25 of 145, 17.2% versus 4 of 104, 3.9%). The most common toxin-related precipitants were alcohol withdrawal and cocaine, 11(37%) of 30 patients each. Cocaine was used with other substances by most patients 10 (91%) of 11, most commonly with an opioid 7 (64%) of 11. For alcohol withdrawal-related seizures, treatment successes with levetiracetam, valproate, and fosphenytoin were 3 (100%) of 3, 3 (50%) of 6, and 1 (50%) of 2, respectively. For cocaine-related seizures, treatment success was 1 (14%) of 7 for levetiracetam, 0 (0%) of 1 for valproate, and 1 (33%) of 3 for fosphenytoin. One patient who used cocaine and an opioid received fosphenytoin and developed life-threatening hypotension. CONCLUSION: In the ESETT, approximately 1 in 10 adult patients with status epilepticus presented with a toxin-related seizure. Alcohol withdrawal and cocaine/opioid use were the most common toxin-related precipitants. Toxin-related benzodiazepine-refractory status epilepticus was successfully treated with a single dose of second-line antiseizure medication in 42% of the patients.

Thiocyanate toxicity: a teaching case.

Introduction: Thiocyanate can cause gastrointestinal, neurologic, and cardiovascular toxicity. Additionally, it interferes with multiple laboratory assays. We present a case of acute thiocyanate toxicity. Case: A 17-year-old female presented with an intentional thiocyanate ingestion. Her course was notable for delirium, wide complex tachycardia, and presumed seizure activity with concurrent lactatemia, acidemia, and narrowing of her arterio-venous oxygen gradient. She received lipid emulsion therapy (LET). While hemodialysis was considered, she recovered without additional treatment. After resolution of her critical illness, a serum cyanide concentration was 0.21 mcg/mL. She had laboratory testing notable for hyperchloremia, hypocalcemia, hypokalemia, and an elevated salicylate concentration attributed to interference by thiocyanate. The thiocyanate was eliminated via first-order kinetics with a half-life of 61.6 hours. Discussion: Thiocyanate poisoning may cause cardiac and neurologic toxicity. Laboratory evidence of impaired cellular respiration in this case suggests possible in vivo conversion to cyanide, however this is not proven. Cyanide antidotal treatment was not administered for this patient, however LET was given based on thiocyanate's lipophilicity. Hemodialysis is known to effectively remove thiocyanate from the blood, however the patient improved without it. The patient's laboratory derangements were due to thiocyanate interference with ion selective electrode and colorimetric analyzer technology. Conclusions: Thiocyanate can cause cardiac and neurologic toxicity, and interferes with several laboratory assays. Theoretically, LET and cyanide antidotal treatment may be useful, but this requires further investigation. Thiocyanate toxicity should be managed supportively, and hemodialysis may be used in severe cases.

Performance-enhancing drugs and the Olympics.

The rules of fair play in sport generally prohibit the use of performance-enhancing drugs (PEDs). The World Anti-Doping Agency (WADA) oversees global antidoping regulations and testing for elite athletes participating in Olympic sports. Efforts to enforce antidoping policies are complicated by the diverse and evolving compounds and strategies employed by athletes to gain a competitive edge. Now between the uniquely proximate 2021 Tokyo and 2022 Beijing Olympic Games, we discuss WADA's efforts to prevent PED use during the modern Olympic Games. Then, we review the major PED classes with a focus on pathophysiology, complexities of antidoping testing, and relevant toxicities. Providers from diverse practice environments are likely to care for patients using PEDs for a variety of reasons and levels of sport; these providers should be aware of common PED classes and their risks.

A Geographically Distinct Case of Fatal Methanol Toxicity from Ingestion of a Contaminated Hand Sanitizer Product During the COVID-19 Pandemic.

The COVID-19 pandemic has triggered outbreaks of unanticipated toxicities, including methanol toxicity. Multiple methanol outbreaks have been described, including contaminated hand sanitizer in the southwest USA. In this case, we describe a fatal case of methanol toxicity from hand sanitizer ingestion, geographically separated from the outbreak in the southwest USA and prior to the announcement of nationwide warnings by the Food and Drug Administration (FDA). The product was identified as one later recalled by the FDA for methanol contamination. Additionally, the consumption in this case was related to a desire to conceal alcohol consumption from family members. This case of methanol toxicity should increase awareness of the ease of which contaminated products can be widely distributed and of the use of alternative ethanol-containing products to obscure relapse in alcohol use disorder.

Geospatial correlation between COVID-19 health misinformation and poisoning with household cleaners in the Greater Boston Area.

INTRODUCTION: Calls to poison control about exposure to household cleaners have increased during the COVID-19 pandemic. This dynamic may reflect increased exposure from public health efforts as well as health misinformation shared on social media. METHODS: We analyzed the dynamics of calls to the Regional Center for Poison Control and Prevention serving Massachusetts and Rhode Island (MARI PCC) and tweets discussing treating COVID-19 with house cleaners from January 20, 2020 to May 5, 2020. We obtained publicly available tweets discussing the use of household cleaners to "cure COVID" from the same time period with geographic co-ordinates indicating that they were emitted from the Greater Boston Area. RESULTS: Our main finding is that public health efforts were followed by a sustained increase in calls after March 15, 2020 (10 ± 2 calls per day before to 15 ± 2.5 after) while misinformation on social media was associated with intermittent spikes in calls. Overall, calls significantly increased during the study period by 34% as compared to the previous 8 years, mostly reporting unintentional ingestions with no serious effects. The daily volume of tweets and retweets was significantly correlated with daily call rates to MARI PCC for the surrounding 7-10 days. CONCLUSIONS: Health misinformation on social media about using household cleaning agents to treat COVID-19 and public health efforts lead to different dynamics in PCC calls. Public health efforts were followed by a sustained increase in calls after March 15, 2020 while misinformation on social media was followed by intermittent spikes in calls. This analysis is the first to link the geospatial dynamics of social media and public health interventions to poison center calls about exposure to household cleaners.

A review of toxic effects of electronic cigarettes/vaping in adolescents and young adults.

In this review, we examine the known and suspected toxicity of electronic cigarettes (e-cigarettes) in adolescents and young adults, to improve awareness of risks and identification of complications of their use. The use of e-cigarettes, or "vaping," is exploding among the pediatric population. E-cigarettes heat a solution containing a psychoactive compound, most commonly nicotine or tetrahydrocannabinol (THC), along with flavorings and other additives to a vapor, which users inhale. Since their introduction in the early 2000s, e-cigarette use is now prolific among youth, per the Monitoring the Future survey, with over 40% of high school seniors reporting use within the past year. Adolescents are vulnerable to the risks of e-cigarettes, as they are targeted as new consumers with advertisements and flavoring compounds, and are not utilizing them as a means to smoking cessation. The pulmonary risks of vaping are rapidly emerging, with the most immediately alarming being the condition electronic-cigarette/vaping associated lung injury (EVALI). Additionally, there have been more recent studies showing extrapulmonary effects including cardiovascular, immunologic and neuro-developmental effects. Many of these effects are likely dose-dependent. Public health efforts are urgently needed to decrease or eliminate new e-cigarette initiation, and support should be established to assist current e-cigarette users with cessation. We strongly advocate for the elimination of e-cigarette flavorings and advertising directed at adolescents, and call for physicians to be cognizant of this expanding epidemic.

Case series: Adolescent victims of the vaping public health crisis with pulmonary complications.

Alongside the epidemic use of electronic cigarettes (e-cigarettes) across the country, evidence of multiple pulmonary complications has emerged, with the most immediately life-threatening being the new clinical condition of e-cigarette/vaping-associated lung injury (EVALI), with investigation actively underway to further define this entity and determine the cause or causes. We present a series of cases of respiratory illnesses associated with e-cigarette use, many of which meet criteria for suspected or confirmed EVALI, managed at a pediatric tertiary care center, demonstrating notable variation in presenting symptoms and severity. Most cases improved with supportive respiratory care and the administration of corticosteroids and antibiotics, although generally no infection was found. The cases also tend to show improvement with discontinuation of the use of e-cigarettes. We discuss challenges in determining the contribution of e-cigarettes to the case pathology and review possible diagnostic and treatment options. In patients suffering from e-cigarette-related respiratory illness including EVALI, the primary treatment goal should be the cessation of e-cigarette use and avoidance of other possible pulmonary toxins, including conventional cigarettes. Prevention of e-cigarette use is critical in the youth population, as these patients are typically nicotine naïve and do not engage in smoking conventional cigarettes before initiation of vaping.

A unique case of bradycardia recognized by wearable technology as first presentation of complete heart block.

Wearable technology has advanced significantly, and the proposed health benefits have been widely touted. Most of the discussion has been surrounding the identification and diagnosis of asymptomatic atrial fibrillation. However, the heart monitoring functions of the wearable technology can also identify other abnormalities as well. We present the first case of wearable technology identified bradycardia diagnosed as the primary presentation of complete heart block. Wearable technology has advanced significantly, but still poses questions regarding its use in screening for rare conditions. One remaining challenge is balancing the desire to screen for rare asymptomatic conditions without overburdening emergency departments with patients responding to alarms on their devices.

Kratom (Mitragynine) Ingestion Requiring Naloxone Reversal.

Kratom (mitragynine) is a naturally occurring opioid agonist whose use has been escalating. Its suppliers advertise it as a safe alternative for opioids and a safe treatment for opioid-withdrawal symptoms. There has been controversy in the past two years regarding the legal status and lack of regulation surrounding kratom. Currently, kratom is legal and unregulated, leaving users at risk from unpredictable potencies and effects. We present the first case of successful naloxone reversal of opioid toxidrome from recreationally used kratom. We advocate further research and regulation to ensure standardized dosing to protect patients.

#DidacticsRevolution: Applying Kotter's 8-Step Change Management Model to Residency Didactics.

INTRODUCTION: Leading change effectively is critical to advancing medical education. Residency didactics often require change in order to meet stakeholder's needs. Kotter's change management model (KCMM) is an 8-step method for implementing change that can be applied to educational initiatives. This innovation improved an emergency medicine residency didactics curriculum through application of KCMM. METHODS: An initiative to improve residency didactics curriculum was titled the "Didactics Revolution" and implemented according to KCMM: establish a sense of urgency, form a powerful guiding coalition, create a vision, communicate the vision, empower others to act on the vision, plan for and create short-term wins, consolidate improvements and produce still more change, and institutionalize new approaches. Data from the Annual Program Review was utilized to assess the impact of the KCMM strategy. RESULTS: The percentage of residents who agreed or strongly agreed that lectures provide a valuable learning experience increased from 39.1% in the year prior to 88.0% in the year during the implementation (p < .001), and remained relatively high at 73.5% in the year following. The percentage of residents who agreed or strongly agreed that they felt well-prepared for the written boards increased from 60.9% in the year prior to 92.0% in the year during the implementation (p = .01) and remained high at 73.5% in the year following. CONCLUSION: Residency didactics can be improved through the use of KCMM, a change management model originally developed in the corporate context.

Exploring the Potential of Predictive Analytics and Big Data in Emergency Care.

Clinical research often focuses on resource-intensive causal inference, whereas the potential of predictive analytics with constantly increasing big data sources remains largely unexplored. Basic prediction, divorced from causal inference, is much easier with big data. Emergency care may benefit from this simpler application of big data. Historically, predictive analytics have played an important role in emergency care as simple heuristics for risk stratification. These tools generally follow a standard approach: parsimonious criteria, easy computability, and independent validation with distinct populations. Simplicity in a prediction tool is valuable, but technological advances make it no longer a necessity. Emergency care could benefit from clinical predictions built using data science tools with abundant potential input variables available in electronic medical records. Patients' risks could be stratified more precisely with large pools of data and lower resource requirements for comparing each clinical encounter to those that came before it, benefiting clinical decisionmaking and health systems operations. The largest value of predictive analytics comes early in the clinical encounter, in which diagnostic and prognostic uncertainty are high and resource-committing decisions need to be made. We propose an agenda for widening the application of predictive analytics in emergency care. Throughout, we express cautious optimism because there are myriad challenges related to database infrastructure, practitioner uptake, and patient acceptance. The quality of routinely compiled clinical data will remain an important limitation. Complementing big data sources with prospective data may be necessary if predictive analytics are to achieve their full potential to improve care quality in the emergency department.

Access to care issues and the role of EDs in the wake of the Affordable Care Act.

CONTEXT: Americans who received public insurance under the Affordable Care Act use the emergency department (ED) more frequently than before they were insured. If newly enrolled patients cannot access primary care and instead rely on the ED, they may not enjoy the full benefits of health care services. OBJECTIVE: The objective of the study is to characterize reasons for ED utilization among American adults by insurance status and usual source of care. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis of adult sample respondents to the 2013 National Health Interview Survey reporting 1 or more ED visits in the preceding 12 months. MAIN OUTCOMES AND MEASURES: Among American ED users that reported no usual source of care and who reported relying on the ED, 27.7% (95% confidence interval [CI], 23.6%-32.2%) and 35.1% (95% CI, 28.0%-43.0%) noted at least 1 issue of access and none of acuity as a reason for their last ED visit, as compared to 17.7% (95% CI, 16.3%-19.2%) among those with a stable usual source of care. CONCLUSIONS AND RELEVANCE: Although past research has shown that those who lack a stable usual source of care use the ED more often, this is the first population-level study to demonstrate their propensity for lack of access-based utilization. In the wake of the Affordable Care Act, EDs will need to evolve into outlets that service a wider range of health care needs rather than function in their current capacity, which is largely to address acute issues in isolation.

Synthesis of orthogonally reactive FK506 derivatives via olefin cross metathesis.

Chemical inducers of dimerization (CIDs) are employed in a wide range of biological applications to control protein localization, modulate protein-protein interactions and improve drug lifetimes. These bifunctional chemical probes are assembled from two synthetic modules, which each provide affinity for a distinct protein target. FK506 and its derivatives are often employed as modules in the syntheses of these bifunctional constructs, owing to the abundance and favorable distribution of their target, FK506-binding protein (FKBP). However, the structural complexity of FK506 necessitates multi-step syntheses and/or multiple protection-deprotection schemes prior to installation into CIDs. In this work, we describe an efficient, one-step synthesis of FK506 derivatives through a selective, microwave-accelerated, cross metathesis diversification step of the C39 terminal alkene. Using this approach, FK506 is modified with an array of functional groups, including primary amines and carboxylic acids, which make the resulting derivatives suitable for the modular assembly of CIDs. To illustrate this idea, we report the synthesis of a heterobifunctional HIV protease inhibitor.