Upper Extremity Crotalid Envenomation: A Review of Incidence and Recent Trends in Management of Snakebites.

PURPOSE: The goal of this study was to evaluate the recent trends in the management of upper extremity Crotalid envenomation in the state of Georgia, United States. METHODS: A retrospective review of the Georgia Poison Center database looking at the reported snakebites to the upper extremity between 2015 and 2020 was performed. Patient demographics, timing and location of injury, severity of envenomation, treatment, including use of antivenin and surgical intervention, and reported complications related to the use of antivenin was extracted. RESULTS: A retrospective review of snakebites between 2015 and 2020 showed 2408 snakebite cases with a mean patient age of 37.4 years. Males incurred 62.8% of all bites. The highest incidence was in summer 52.5%, and between the hours of 5 PM to midnight 57.2%. Overall, 1010 (41.9%) of all bites were categorized as venomous snakebites (55.6% copperhead, 20% rattlesnake, 2.4% cottonmouth, and 22% miscellaneous [including 3 Elapid envenomations] or unidentified. The total number of venomous bites to the upper extremity was 575 (56.9%) and 567 patients received antivenin. Envenomation severity was mild in 29%, moderate in 45%, severe in 10%, and undetermined in 16% of cases. Crotalidae polyvalent immune Fab (Ovine) was the main antivenin used, with overall mean initial therapy dose of 6.2 vials and 59% of patients receiving maintenance therapy. Three patients (0.5%) had a severe anaphylactic reaction to antivenin requiring cessation of therapy. Seven patients had acute compartment syndrome of the upper extremity requiring fasciotomy (3 copperhead, 2 rattlesnake, and 2 unidentified). There was no reported mortality during this period. CONCLUSIONS: Hand surgeons should be familiar with the management of upper extremity Crotalid envenomation. Antivenin remains the main treatment for symptomatic patients. Crotalid snakebites rarely require operative intervention. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Disproportionate Burden of COVID-19 Infection Among Hispanic Patients During the First COVID-19 Surge in South Texas.

Introduction: The morbidity and mortality of the COVID-19 pandemic have disproportionately burdened Hispanic populations in the United States. While health equity research is typically conducted in populations where Hispanics are the minority, this project analyzes COVID-19 racioethnic transmission trends over the first 6 months of the pandemic within a large majority-minority city in South Texas. Methods: Patients diagnosed with COVID-19 across inpatient, emergency department, and outpatient settings of a large county health system were included in a clinical registry. For 4644 COVID-19-positive patients between March 16 and August 31, 2020, demographic and clinical data were abstracted from the registry. Race/ethnicity trends over time were compared for patients with and without COVID-19 diagnoses. Logistic regressions identified predictors of inpatient diagnosis by age, race/ethnicity, and testing delay. Results: The proportion of patients with COVID-19 identifying as Hispanic increased rapidly during the pandemic's first months: from 55.6% in March to 85.7% in June. A significantly greater proportion of patients identified as Hispanic within the COVID-19 cohort compared to other diagnoses cohort. Testing delay was 11.6% longer for Hispanic patients, with each day of testing delay associated with 7% increased odds of inpatient COVID-19 diagnosis. Conclusion: These findings highlight the disproportionate impact of COVID-19 on Hispanic populations even within a majority-minority community. In the United States, Hispanic persons are more likely to work frontline jobs, live in multigenerational homes in poverty, and be uninsured. The burden of COVID-19 cases within Bexar County's largest hospital system reflects this systemic inequity. Identifying racioethnic health disparities supports efforts toward mitigating structural factors that predispose minority groups to illness and death.

Pegfilgrastim Biosimilars in US Supportive Oncology: A Narrative Review of Administration Options and Economic Considerations to Maximize Patient Benefit.

Granulocyte colony-stimulating factor (G-CSF) biologics, such as pegfilgrastim, are a standard of care in supportive cancer treatment that are administered once per chemotherapy cycle to reduce the incidence of febrile neutropenia. The high cost of these biologics in the United States can be a limiting factor to accessing care; however, lower-cost pegfilgrastim biosimilars have been available for several years for patients requiring prophylaxis of febrile neutropenia. Different options for pegfilgrastim administration are also now available to accommodate specific patient preferences. As patients may want to minimize the risk of both neutropenia and SARS-CoV-2 infection, same-day administration is a pertinent option during the present COVID-19 pandemic. Therefore, individualized, patient-centered approaches and risk-management strategies should be considered when selecting the treatment and administration method for prophylaxis of febrile neutropenia. Three methods of administration would minimize hospital or clinic visits while also providing the prophylactic effect of G-CSF: same-day administration after chemotherapy, use of the US Food and Drug Administration-approved on-body injector delivering pegfilgrastim approximately 27 h after chemotherapy, or self-administration by the patient or caregiver > 24 h after chemotherapy. Choice of the specific administration option should be based on the patient's specific needs, while also considering mitigating factors, such as the economic burden associated with biologic medications and the risk of COVID-19. Pegfilgrastim biosimilars can minimize the additional financial burden on patients and the health care system during this pandemic and beyond.

Developing and implementing core competencies in children's environmental health for students, trainees and healthcare providers: a narrative review.

Knowledge of the health impacts of environmental exposures (such as pollution disasters, poor air quality, water contamination, climate change) on children's health has dramatically increased in the past 40 years. The World Health Organization (WHO) estimated that 23% of all deaths worldwide were attributable to the environment, and 26% of deaths in children less than 5 years old could be prevented with removal of environmental risks factors. Yet, little has permeated medical education, leaving pediatric providers ill equipped to address these issues. To address this gap, members from the Pediatric Environmental Health Specialty Units, a United States nationwide network of academically affiliated experts who have created numerous environmental health educational materials and programs, have identified fifteen core environmental health (EH) competencies needed by health care providers to enable them to effectively address environmental health concerns. These competencies can serve as the foundation for the development and implementation of relevant educational programs. The core EH competencies are based upon these foundational elements: 1) Definition of "children's environmental health" that describes how environmental exposures (positive and negative) in early life influence the health and development in childhood and across the entire human life span 2) Children are not "little adults" and so have unique vulnerabilities to environmental hazards; 3) Environmental health inequities exist, causing some children to have a disproportionate amount of unhealthy exposures and consequently a greater risk of adverse effects; 4) Climate change will translate to numerous adverse health effects that will particularly affect children worldwide. In this article, the authors describe the core environmental health competencies and provide resources, online tools, strategies, and examples targeted to all levels of training and practice to better enable leaders and educators to bring this important content to the forefront.

Adult opioid poisonings by drug, intent, and resource use from the United States National Poison Data System from 2005-2018.

INTRODUCTION: Deaths due to an opioid overdose nearly doubled from 2013 to 2017. Our objective is to describe the trends in intent, healthcare resource use, and clinical outcomes among adults with opioid exposures. MATERIALS AND METHODS: This study is a retrospective analysis of data from the 55 U.S. poison control centers. Adults, >19 years, with an opioid as the primary poisoning agent between 2005 and 2018 were included. These years were divided into three epochs (2005-2009, 2010-2014, and 2015-2018) to describe the trends in frequency, intent, severity, healthcare resource use, and regional differences in U.S. adults affected by prescription and illicit opioid exposures. RESULTS: A total of 546,049 (54.4%) of the 1,002,947 opioid-related cases reported to the U.S. poison centers met inclusion criteria. The percentage of patients with a moderate/major clinical effect increased in each epoch (24.4, 29.13, and 35.3%) as did the proportion of patients with illicit opioids (coded as heroin) as their primary substance (2.89, 5.47, and 13.95%). Illicit opioid use was associated with increased frequency of moderate/major clinical effects (54.2 vs. 27.4%), need for an ICU procedure (11.4 vs. 6.8%), and death (3.9 vs. 1.2%) compared with prescription opioid use. Suicidal intent (34.88%) followed by misuse/abuse (26.26%) were the most frequent intents. Misuse/abuse increased in frequency over each epoch in the study period (23.1 vs. 26.12 vs. 30.3%). Discussion and conclusions: The severity of clinical effects and death following acute opioid poisonings increased over the study period, driven by suicidal intent and an increasing proportion of illicit opioid cases. This study highlights the importance of developing strategies to address suicide prevention in addition to the continued focus on opioid use disorder.

Poisonings due to storage in a secondary container reported to the National Poison Data System, 2007-2017.

BACKGROUND: Transfer of xenobiotics from their original container to an unlabeled or secondary container is a well-identified risk factor for poisoning. Nonetheless, recent large-scale data on the practice are unavailable. The objective of this study is to describe the incidence and features of poisonings in the United States due to xenobiotics stored in a secondary container. METHODS: This was a retrospective review of the National Poison Data System (NPDS) from 2007 to 2017. Non-suicidal exposures associated with the scenario "container transfer involved (product transferred from original container to unlabeled container, incorrectly labeled container, or food container for use or storage and patient accessed product from second container)" were included. RESULTS: Forty-five thousand five hundred and twelve cases were included. The median age of subjects was 30 years (interquartile range: 6-53); 52% were female. Cleaning products (38.2%), disinfectants (17.3%), and hydrocarbons (5.0%) were the most common xenobiotics reported. The annual incidence of cases increased over the study period. There were 9369 (20.6%) ED visits and 1856 (4.1%) hospital admissions. Most cases (72%) were deemed nontoxic or resulted in no effects; 4.4% resulted in serious outcomes (moderate effects, major effects, or death), including 23 deaths. Morbidity was highest for pesticides, prescription medications, and herbicides, with 10.3%, 9.8%, and 7.6% of cases resulting in serious outcomes, respectively. Hydrofluoric acid and herbicides were associated with the most deaths (13/23 [57%]). CONCLUSIONS: Transfer of xenobiotics to a secondary container is a scenario increasingly reported to U.S. poison centers. Although most exposures do not result in significant toxicity, ED visits are common and substantial morbidity can occur. This represents an opportunity for public health intervention to curb the practice.

Toward global standardization of conducting fair investigations of allegations of research misconduct.

In the United States, through nation-wide discussions, the procedures for handling allegations of research misconduct are now well established. Procedures are geared toward carefully treating both complainants and respondents fairly in accordance with the US framework. Other countries, which have their own cultural and legal framework, also need fair and legally compatible procedures for conducting investigations of allegations of research misconduct. Given the rapid growth of international collaboration in research, it is desirable to have a global standard, or common ground, for misconduct investigations. Institutions need clear guidance on important subjects such as what information should be included in the investigation reports, how the investigation committee should be organized once research misconduct allegation has been received, how to conduct the investigation, how the data and information obtained should be taken as evidence for vs. against misconduct, and what policies the investigation committee should follow. We explore these issues from the viewpoint of members of committees investigating accusations of research misconduct (hereafter referred to as "investigation committees") as well as persons overseeing the committees in Japan. We hope to engender productive discussions among experts in misconduct investigations, leading to a formulation of international standards for such investigation.

All that glitters is not gold: Mercury poisoning in a family mimicking an infectious illness.

Three siblings with inhalational elemental mercury toxicity presented with fever, rash, and upper respiratory tract symptoms. The patients were heavily exposed to elemental mercury that was spilled in their home and then vacuumed. Initial whole blood mercury levels were elevated at >200 µg/L, 153 µg/L and 130 µg/L (Mayo Clinic Laboratories lab reference range <9 µg/L) for Cases 1, 2, and 3, respectively. All three required chelation with succimer. Clinically significant elemental mercury toxicity can resemble an infectious illness. Severe morbidity and mortality can be prevented if heavy metal poisoning is considered early, through a detailed history including an environmental exposure history. For elemental mercury spills in the home, safe and effective clean-up steps are needed. Improved public health education is needed to prevent similar household exposures.

Circumstances Involved in Unsupervised Solid Dose Medication Exposures among Young Children.

OBJECTIVE: To identify types of containers from which young children accessed solid dose medications (SDMs) during unsupervised medication exposures and the intended recipients of the medications to advance prevention. STUDY DESIGN: From February to September 2017, 5 US poison centers enrolled individuals calling about unsupervised solid dose medication exposures by children ≤5 years. Study participants answered contextually directed questions about exposure circumstances. RESULTS: Sixty-two percent of eligible callers participated. Among 4496 participants, 71.6% of SDM exposures involved children aged ≤2 years; 33.8% involved only prescription medications, 32.8% involved only over-the-counter (OTC) products that require child-resistant packaging, and 29.9% involved ≥1 OTC product that does not require child-resistant packaging. More than one-half of exposures (51.5%) involving prescription medications involved children accessing medications that had previously been removed from original packaging, compared with 20.8% of exposures involving OTC products (aOR, 3.39; 95% CI, 2.87-4.00). Attention deficit hyperactivity disorder medications (49.3%) and opioids (42.6%) were often not in any container when accessed; anticonvulsants (41.1%), hypoglycemic agents (33.8%), and cardiovascular/antithrombotic agents (30.8%) were often transferred to alternate containers. Grandparents' medications were involved in 30.7% of prescription medication exposures, but only 7.8% of OTC product exposures (aOR, 3.99; 95% CI, 3.26-4.87). CONCLUSIONS: Efforts to reduce pediatric SDM exposures should also address exposures in which adults, rather than children, remove medications from child-resistant packaging. Packaging/storage innovations designed to encourage adults to keep products within child-resistant packaging and specific educational messages could be targeted based on common exposure circumstances, medication classes, and medication intended recipients.

Analysis of 207,543 children with acute opioid poisonings from the United States National Poison Data System.

Introduction: Previous studies using administrative data have demonstrated that the United States opioid epidemic is harming both adults and children, and is straining health care systems. Our objective is to describe the outcomes and trends in resource use among children with acute opioid ingestions using patient-level case report data.Materials and Methods: This study was a retrospective analysis of prospectively collected data from the 55 poison control centers in the United States which comprise the National Poison Data System (NPDS). Children under 19 years of age with a primary opioid ingestion between 1 January 2005 and 31 December 2018 were included in the analysis. Trends over three eras (2005-2009, 2010-2014, 2015-2018) were assessed using a Cochran-Armitage Trend Test. Yearly trends in the proportion of cases were calculated using generalized linear models. Multi-variable logistic regression analysis was used to calculate the adjusted odds of variables associated with having at least one Pediatric Intensive Care Unit (PICU) level intervention.Results: Children were involved in 207,543 (27.54%) of a total of 1,002,947 primary exposure-related opioid poisoning cases reported to US poison centers. The percentage of patients admitted to a critical care unit from these exposures increased in each era (6.6%, 8.5%, 9.6%). Suicidal intent increased in each era (14.0%, 15.3%, 21.2%), and was associated with increased adjusted odds of receiving a PICU procedure (OR 9.68, CI 7.97-11.76). Fentanyl (OR 12, CI 9.2-15.7), heroin (OR 11.1, CI 9.4-13.1), and methadone (OR 15, CI 13-17.3) were the opioids most associated with having a PICU procedure.Discussion and Conclusions: The severity of admissions for acute opioid ingestions, especially following attempted suicide, has increased over the studied time frame. Efforts focused on reducing access, especially to synthetic and illicit opioids, and addressing adolescent suicidality are needed to reduce these serious consequences of the opioid epidemic on children in the United States.

Real-world effectiveness of palonosetron-based antiemetic regimens: preventing chemotherapy-induced nausea and vomiting.

Aim: To evaluate real-world effectiveness of guideline-recommended palonosetron-containing antiemetic regimens in patients receiving highly (HEC) or moderately emetogenic (MEC) chemotherapy. Patients & methods: This retrospective analysis used records of adults receiving first-line chemotherapy and a three-drug palonosetron-containing antiemetic regimen for HEC or palonosetron-containing antiemetic regimen for MEC (carboplatin). Results: A total of 1587 records were evaluated. For HEC and MEC, respectively, chemotherapy-induced nausea and vomiting (CINV) occurred in 40 versus 44% of patient cycles (p = 0.01), and unscheduled iv. antiemetics in 41 versus 35% (p < 0.05). A total of 48% of HEC patients versus 42% of MEC patients had CINV-related clinic visits (p = 0.05). Conclusion: Palonosetron-containing antiemetic regimens may provide insufficient CINV control. Alternative regimens may improve patient quality of life and reduce healthcare resource utilization.

Prospective evaluation of a clinical decision tool to reduce childhood admissions to PICUs for poisoning: ReCAP2.

Aim: To prospectively validate a pediatric clinical prediction model to identify children at low risk of clinically significant ingestions to prevent unnecessary pediatric intensive care unit (PICU) admissions.Methods: Calls received by the Georgia Poison Center about children for acute ingestions between May 25, 2017 and May 17, 2018 were scored in real time using the full, age-stratified, and simplified clinical scoring tool to reduce childhood admissions to PICUs for poisoning (RECAP2). Clinically significant ingestions with a poison center recommendation of PICU admission are defined in the simple RECAP2 model as ingestion of clonidine, ethanol, an oral anti-hyperglycemic agent, or exposure to carbon monoxide, as well as the presence of symptoms occurring within 2 h for an immediate release, or 4 h for an extended release, medication exposure. Model statistics and percent reduction in PICU admissions were computed.Results: There were 886 children admitted after ingestions, of which 454 (51.2%) children were admitted to intensive care. At the time of the initial poison center call to report the ingestion, 44 cases (5%) were incomplete using the full, age-stratified model compared to the complete scoring using the simple scoring model. Seventy-two children (8.1%) required monitoring or interventions performed only in a PICU. Real-time application of the full model compared with the simple model would have reduced PICU admissions by 33.3 and 31.7%, respectively.Conclusions: The simple RECAP2 clinical scoring model is a sensitive prediction tool to identify children at very low risk for clinically significant ingestions for whom PICU admission can be avoided. Clinical implementation of the simple RECAP2 model and recommendation for admission to an inpatient unit versus PICU should be further evaluated, to reduce unnecessary PICU admissions following acute ingestions.

Unintentional trazodone overdoses in children ≤6 years of age: data from poison center over a period of 16 years.

CONTEXT: Trazodone is an atypical antidepressant with no established safety in children. Previous case reports showed no complications at doses 50-500 mg in children. Our study objective is to characterize the clinical effects, dose-related toxicity, and establish triage dose for acute trazodone ingestions in children ≤6 years of age. METHODS: Cases with acute trazodone ingestions in children ≤6 years of age between 2000 and 2015 were retrospectively reviewed. Data were analyzed for dose (mg/kg), clinical effects, management site, treatment, and outcome. Cases with coingestions, unknown outcome, or unknown dose were excluded. RESULTS: A total of 84 patients (mean age 26.7 months, 35 females, 49 males) were included. Of those, 52 (61.9%) had no clinical effects; 29 (34.5%) had minor effects (vomiting, dizziness, headache); and three (3.6%) had moderate effects (ataxia, slurred speech, priapism). No major effects or deaths were observed. Moderate effects were manifested at doses ≥6.9 mg/kg. Priapism occurred in a 2-year-old child at a dose of 6.9 mg/kg. Sixteen (19%) patients were managed at home and 68 (81%) patients were referred to a HCF. Among those referred to a HCF, three (4.4%) patients had moderate effects with ingested dose ≥6.9 mg/kg. However, 27 (39.7%) patients of those referred to a HCF had an ingested dose <6 mg/kg and none of them manifested symptoms beyond minor effects. All referred patients had uneventful recovery and no sequela. CONCLUSIONS: Children should be referred for further evaluation in acute unintentional trazodone ingestions with doses ≥6 mg/kg.

Hypersensitivity and infusion-site adverse events with intravenous fosaprepitant after anthracycline-containing chemotherapy: a retrospective study.

AIM: Fosaprepitant, an intravenous neurokinin-1 receptor antagonist for chemotherapy-induced nausea and vomiting, contains polysorbate 80, which is associated with infusion-site adverse events (ISAEs) and hypersensitivity systemic reactions (HSRs). This study investigated ISAEs/HSRs following fosaprepitant with anthracycline-containing chemotherapy. PATIENTS & METHODS: This retrospective chart review noted ISAEs/HSRs following the anthracycline doxorubicin+cyclophosphamide and a three-drug fosaprepitant regimen, via peripheral line. RESULTS: 35/127 patients (28%) developed ISAEs/HSRs with chemotherapy and antiemetic therapy: 32 developed 137 individual ISAEs, primarily erythema, pain and catheter-site swelling; 16 developed 50 individual HSRs, primarily edema/swelling, erythema or dermatitis (no anaphylaxis). CONCLUSION: Fosaprepitant is associated with a significant ISAE/HSR rate following anthracycline-containing chemotherapy via peripheral line. Polysorbate 80-free intravenous neurokinin-1 receptor antagonist may provide a safer chemotherapy-induced nausea and vomiting prophylaxis option.

Pneumonitis and Respiratory Failure Secondary to Civilian Exposure to a Smoke Bomb in a Partially Enclosed Space.

Smoke grenades are used during drills, police and military exercises, and crowd control. We report on a 25-year-old man who was exposed to a Superior 3C smoke bomb. He was initially stable but developed respiratory distress after 3 days and ultimately developed pulmonary fibrosis with marked loss in pulmonary function. The Superior 3C smoke bomb is similar in composition to the British Military's L83A1/2 and L132A1 and the US M18 smoke grenades, all commonly used as multipurpose smoke-producing devices for combat and training. They are primarily composed of zinc oxide and hexachlorethane, the combustion of which produces zinc chloride. These devices are safe when used properly in open air but can cause significant morbidity in an enclosed space. This case emphasizes the potential hazards of using smoke bombs even in semienclosed spaces and the potential delay in the development of significant pulmonary complications.

Real-world efficacy: intravenous palonosetron three-drug regimen for chemotherapy-induced nausea and vomiting with highly emetogenic chemotherapy.

AIM: Real-world palonosetron effectiveness was evaluated in an antiemetic regimen with highly emetogenic chemotherapy (HEC). PATIENTS & METHODS: In this Phase IV, prospective, multicenter observational study, HEC-treated cancer patients received palonosetron, a neurokinin 1 receptor antagonist, and dexamethasone. Primary objective was to assess complete response (CR) for acute (≤24 h), delayed and overall (≤120 h) chemotherapy-induced nausea and vomiting. RESULTS: Of 159 patients, 65.4% had breast cancer, 64.8% received anthracycline (doxorubicin)-plus-cyclophosphamide-containing chemotherapy; 155 completed one HEC cycle. CR was 60.0% acute, 39.4% delayed and 34.8% overall, and then increased (all phases) in 69 patients completing four HEC cycles. Anthracycline (doxorubicin) plus cyclophosphamide-receiving patients had especially low CR. CONCLUSION: Even within a recommended three-drug antiemetic regimen, palonosetron may provide suboptimal chemotherapy-induced nausea and vomiting control with HEC in real-world settings.

Reducing Childhood Admissions to the PICU for Poisoning (ReCAP2) by Predicting Unnecessary PICU Admissions After Acute Intoxication.

OBJECTIVE: To derive and validate clinical prediction models to identify children at low risk of clinically significant intoxications for whom intensive care admission is unnecessary. DESIGN: Retrospective review of data in the National Poison Data Systems from 2011 to 2014 and Georgia Poison Center cases from July to December 2016. SETTING: United States PICUs and poison centers participating in the American Association of Poison Control Centers from 2011 to 2016. PATIENTS: Children 18 years and younger admitted to a United States PICU following an acute intoxication. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary study outcome was the occurrence of clinically significant intoxications defined a priori as organ system-based clinical effects that require intensive care monitoring and interventions. We analyzed 70,364 cases. Derivation (n = 42,240; 60%) and validation cohorts (n = 28,124; 40%) were randomly selected from the eligible population and had similar distributions of clinical effects and PICU interventions. PICU interventions were performed in 1,835 children (14.1%) younger than 6 years, in 374 children (15.4%) 6-12 years, and in 4,446 children (16.5%) 13 years and older. We developed highly predictive models with an area under the receiver operating characteristic curve of 0.834 (< 6 yr), 0.771 (6-12 yr), and 0.786 (≥13 yr), respectively. For predicted probabilities of less than or equal to 0.10 in the validation cohorts, the negative predictive values were 95.4% (< 6 yr), 94.9% (6-12 yr), and 95.1% (≥ 13 yr). An additional 700 patients from the Georgia Poison Center were used to validate the model and would have reduced PICU admission by 31.4% (n = 110). CONCLUSIONS: These validated models identified children at very low risk of clinically significant intoxications for whom pediatric intensive care admission can be avoided. Application of this model using Georgia Poison Center data could have resulted in a 30% reduction in PICU admissions following intoxication.