Opioid Prescribing Rate for Nonoperative Distal Radius Fractures and Clinician Response to a Clinical Decision Support Alert.

BACKGROUND: Opioids are commonly prescribed for the management of acute orthopedic trauma pain, including nonoperative distal radius fractures. OBJECTIVES: This prospective study aimed to determine if a clinical decision support intervention influenced prescribing decisions for patients with known risk factors. We sought to quantify frequency of opioid prescriptions for acute nonoperative distal radius fractures treated. METHODS: We performed a prospective study at one large health care system. Utilizing umbrella code S52.5, we identified all distal radius fractures treated nonoperatively, and the encounters were merged with the Prescription Reporting with Immediate Medication Mapping (PRIMUM) database to identify encounters with opioid prescriptions and patients with risk factors for opioid use disorder. We used multivariable logistic regression to determine patient characteristics associated with the prescription of an opioid. Among encounters that triggered the PRIMUM alert, we calculated the percentage of encounters where the PRIMUM alert influenced the prescribing decision. RESULTS: Of 2984 encounters, 1244 (41.7%) included an opioid prescription. Age increment is a significant factor to more likely receive opioid prescriptions (p < 0.0001) after adjusting for other factors. Among encounters where the physician received an alert, those that triggered the alert for early refill were more likely to influence physicians' opioid prescribing when compared with other risk factors (p = 0.0088). CONCLUSION: Over 90% of patients (106/118) continued to receive an opioid medication despite having a known risk factor for abuse. Additionally, we found older patients were more likely to be prescribed opioids for nonoperatively managed distal radius fractures.

Opioid Prescribing Risk Factors in Nonoperative Ankle Fractures: The Impact of a Prospective Clinical Decision Support Intervention.

Opioids are frequently used for acute pain management of musculoskeletal injuries, which can lead to misuse and abuse. This study aimed to identify the opioid prescribing rate for ankle fractures treated nonoperatively in the ambulatory and emergency department setting across a single healthcare system and to identify patients considered at high risk for abuse, misuse, or diversion of prescription opioids that received an opioid. A retrospective cohort study was performed at a large healthcare system. The case list included nonoperatively treated emergency department, urgent care and outpatient clinic visits for ankle fracture and was merged with the Prescription Reporting With Immediate Medication Mapping (PRIMUM) database to identify encounters with prescription for opioids. Descriptive statistics characterize patient demographics, treatment location and prescriber type. Rates of prescribing among subgroups were calculated. There were 1,324 patient encounters identified, of which, 630 (47.6%) received a prescription opioid. The majority of patients were 18-64 years old (60.3%). Patients within this age range were more likely to receive an opioid prescription compared to other age groups (p < .0001). Patients treated in the emergency department were significantly more likely to receive an opioid medication (68.3%) compared to patients treated at urgent care (33.7%) or in the ambulatory setting (16.4%) (p < .0001). Utilizing the PRIMUM tool, 14.2% of prescriptions were provided to patients with at least one risk factor. Despite the recent emphasis on opioid stewardship, 14.2% of patients with risk factors for misuse, abuse, or diversion received opioid analgesics in this study, identifying an area of improvement for prescribers.

Fomepizole as an Adjunctive Treatment in Severe Acetaminophen Toxicity.

A 33-year-old male presented to the emergency department with a chief complaint of abdominal pain after taking #50 500 mg acetaminophen tablets over the preceding two days. He was tachycardic and tachypneic, and the initial labs were notable for acetaminophen level, 337 mg/L; AST, 137 IU/L; ALT, 194 IU/L; ABG pH, 7.24; and lactate, 4.1 mmol/L. The patient was started on IV N-Acetylcysteine (NAC) as well as given a single dose of 15 mg/kg fomepizole. The patient did remarkably well, with a peak AST of 198 IU/L, peak ALT of 301 IU/L, and peak INR of 3.1. Biochemical and animal data support fomepizole having hepatoprotective effects in acetaminophen poisoning. To our knowledge, this is the first human case of an intentional dual NAC/fomepizole regimen for severe acetaminophen toxicity.

Exploratory Ingestions of Novel Anticoagulants and Antiplatelets: What Is the Risk?

BACKGROUND: Historically, anticoagulants and antiplatelet agents included warfarin and aspirin, respectively. In recent years, numerous novel anticoagulants (eg, direct thrombin inhibitors and factor Xa inhibitors) as well as the adenosine diphosphate receptor antagonists have increased significantly. Little information on the bleeding risk after exploratory ingestion of these agents is available. The primary purpose of this study is to evaluate the bleeding risk of these agents after an exploratory ingestion in children 6 years or younger. METHODS: This retrospective multicenter poison control center study was conducted on calls between 2005 and 2014. The following agents were included: apixaban, clopidogrel, dabigatran, edoxaban, prasugrel, rivaroxaban, or ticagrelor. Bleeding characteristics and treatment rendered were recorded. RESULTS: A total of 638 cases were identified. Most cases involved antiplatelet agents. No patient developed any bleeding complication. The administration of charcoal was independent of the amount of drug ingested. CONCLUSION: Accidental, exploratory ingestions of these agents seem well tolerated, with no patient developing bleeding complications.

Opioid Prescribing and Patient Satisfaction Scores Across Practice Types.

US physicians prescribe opioids at a high rate relative to other countries. Of the US physicians surveyed, almost half report having prescribed an inappropriate opioid due to concerns about patient satisfaction scores. We investigated patterns in controlled substance prescribing practices, patient risk factors, and associated Press Ganey patient satisfaction scores at a sample of orthopaedic surgery and primary care clinics over a 6month time period. Primary care practices had higher proportions of prescriptions, and patient risk profiles varied across sites. However, overall satisfaction was high, with little variation between sites (78.3 81.3%). Satisfaction with pain control was lower and more varied (67.1 78.0%). A total of 4,229 Press Ganey survey responses were received, including 7,232 comments, of which only 10 (0.1%) expressed frustration for not receiving opioids. Opioid prescriptions had minimal association with Press Ganey scores among varied practices and patient populations. Prescribers should prescribe opioids appropriately without fear that this will negatively impact their satisfaction scores. (Journal of Surgical Orthopaedic Advances 29(1):59, 2020).

Assessing Bleeding Risk in Patients With Intentional Overdoses of Novel Antiplatelet and Anticoagulant Medications.

STUDY OBJECTIVE: In recent years, the use of novel anticoagulants and antiplatelet agents has become widespread. Little is known about the toxicity and bleeding risk of these agents after acute overdose. The primary objective of this study is to evaluate the relative risk of all bleeding and major bleeding in patients with acute overdose of novel antiplatelet and anticoagulant medications. METHODS: This study is a retrospective study of acute ingestion of apixaban, clopidogrel, ticlopidine, dabigatran, edoxaban, prasugrel, rivaroxaban, and ticagrelor reported to 7 poison control centers in 4 states during a 10-year span. The prevalence of bleeding for each agent was calculated, and hemorrhage was classified as trivial, minor, or major. RESULTS: A total of 322 acute overdoses were identified, with the majority of cases involving clopidogrel (260; 80.7%). Hemorrhage occurred in 16 cases (4.9%), including 7 cases of clopidogrel, 6 cases of rivaroxaban, 2 cases of dabigatran, and 1 case of apixaban. Most cases of hemorrhage were classified as major (n=9). Comparing the novel anticoagulants with the P2Y12 receptor inhibitors, the relative risk for any bleeding with novel anticoagulant was 6.68 (95% confidence interval 2.63 to 17.1); the relative risk of major bleeding was 18.1 (95% confidence interval 3.85 to 85.0). CONCLUSION: Acute overdose of novel anticoagulants or antiplatelet agents is associated with a small risk of significant hemorrhage. The risk is greater with the factor Xa inhibitors and direct thrombin inhibitors than with the P2Y12 receptor antagonists.

Photokeratitis among restaurant workers: A case series.

This case report highlights the challenges associated with the diagnosis and workplace evaluation of occupationally acquired ultraviolet (UV) radiation-induced photokeratitis and associated skin burns in a group of restaurant workers. UV-C spectrum bulbs were inadvertently shipped and installed in insect light traps. Ocular and dermal symptoms were reported in 18 of 85 restaurant employees to varying degrees of severity over a 2-day period. One patient was formally diagnosed with a chemical burn/irritation of the cornea. More severe symptoms were reported by individuals working in close proximity to the lights. This clinical picture can resemble mass chemical or irritant exposure when multiple individuals are affected, and a multidisciplinary approach was required for rapid identification of the source to limit morbidity. Prevention strategies for similar events should be considered which can include limiting hardware compatibility and improving warning labels.

Opioid Prescribing in the Pediatric Orthopaedic Trauma Population.

The purpose of this article is to describe opioid prescribing patterns for children with orthopaedic injuries. A retrospective chart review was conducted on pediatric orthopaedic trauma patients (n = 124) who were discharged from the hospital or emergency department or had a clinic visit during a 1-month period. Patient demographics, prescription specifics, injury details, and fracture fixation information were collected. Results show that most children received opioids after injury (82.3%). While children undergoing operative fixation typically received opioids, only 39.5% with closed reduction did. Hydrocodone- acetaminophen accounted for 93% of prescriptions, but adolescents were more likely to receive other drugs. There was a significant trend of increasing daily dosage with increased age; 36.73% of adolescents received > 50 morphine milligram equivalents per day. Children with orthopaedic injuries are typically prescribed opioids; older children more commonly receive higher dosages. Further study is needed to define prescribing trends across facility and specialty types to aid in development of standardized prescribing guidelines. (Journal of Surgical Orthopaedic Advances 27(4):269-273, 2018).

Laundry detergent "pod" ingestions: a case series and discussion of recent literature.

OBJECTIVES: The objectives of this study were to present and explore the clinical presentation of the increasingly common pediatric exposure to the widely available single-use laundry packets or "laundry pods." METHODS: This is a case report of 4 pediatric patients with significant toxicity due to laundry pod detergent exposure and a review of the available literature including abstract-only publications. RESULTS: An unexpectedly severe clinical pattern was noted; 3 of the 4 children required intubation for management, airway injury was noted in 1 of them, and 2 of them had hospital courses of at least 1 week. The literature suggests that laundry pod exposures are associated with increased morbidity compared to traditional laundry detergent exposures. To date, no specific contaminant or component has been identified as being responsible for the injury, although some evidence points to the surfactant component. CONCLUSIONS: A different approach to the triage and management of pediatric exposures to laundry detergent pod ingestions is required compared with nonpod ingestions. Although the exact cause is not known, practitioners should be vigilant for rapid onset of neurological impairment and inability to protect the airway in addition to its caustic effects.

Evaluation of changes in poisoning in young children: 2000 to 2010.

OBJECTIVE: The nature of pediatric poisonings is dynamic, with changes occurring over time. We evaluated poisoning in children younger than 6 years for trends during an 11-year period regarding the substances involved in the poisoning, medical outcomes, and health care use. METHODS: This was retrospective study of poisoning in children younger than 6 years reported to 12 poison centers in 5 U.S. states for the years 2000 through 2010. Data abstracted included substance category involved in the exposure, age of patient, year of occurrence, location of patient management, and medical outcome. RESULTS: There were 2,577,036 poison exposures in children younger than 6 years, with a 12.4% increase from 210,270 poison exposures in 2000 to 236,425 poison exposures in 2010. There was a 33% increase (P < 0.05) in pharmaceutical related exposures in children younger than 6 years and a 2.8% decline in the number of nonpharmaceutical related exposures. Among those substance categories representing more than 1% of exposures, the only pharmaceutical showing decline was cough/cold preparations. There was a 53% increase in serious medical outcomes, including 119 deaths and a significant increase in health care facility use, primarily owing to pharmaceutical exposures. CONCLUSIONS: Poisoning in young children increasingly involves pharmaceuticals and is associated with an increased number of serious outcomes and children treated in a health care facility. We believe that these changes are related to increased availability of medications in the home and poison prevention education efforts should include a focus on the availability of these products to small children.

2022 Annual Report of the National Poison Data System® (NPDS) from America's Poison Centers®: 40th Annual Report.

INTRODUCTION: This is the 40th Annual Report of America's Poison Centers National Poison Data System (NPDS). As of 1 January, 2022, all 55 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 4.72 [4.40, 9.27] (median [25%, 75%]) minutes, effectuating a near real-time national exposure and information database and surveillance system. METHODS: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure. RESULTS: In 2022, 2,483,183 closed encounters were logged by NPDS: 2,064,875 human exposures, 50,381 animal exposures, 363,099 information requests, 4,790 human confirmed nonexposures, and 38 animal confirmed nonexposures. Total encounters showed a 12.9% decrease from 2021, and human exposure cases decreased by 0.771%, while health care facility (HCF) human exposure cases increased by 0.214%. All information requests decreased by 48.4%, medication identification (Drug ID) requests decreased by 21.2%, and medical information requests showed a 76.92% decrease, although these remain twice the median number before the COVID-19 pandemic. Drug Information requests showed a 52.4% decrease, due to declining COVID-19 vaccine calls to PCs but still comprised 5.55% of all information contacts. Human exposures with less serious outcomes have decreased 1.70% per year since 2008, while those with more serious outcomes (moderate, major or death) have increased 4.41% per year since 2000.Consistent with the previous year, the top 4 substance classes most frequently involved in all human exposures were analgesics (11.5%), household cleaning substances (7.23%), antidepressants (5.61%), and cosmetics/personal care products (5.23%). Antihistamines (4.81%) replaced sedatives/hypnotics/antipsychotics as the 5th substance class. As a class, analgesic exposures increased most rapidly, by 1,514 cases/year (3.26%/year) over the past 10 years for cases with more serious outcomes.The top 5 most common exposures in children age 5 years or less were household cleaning substances (10.3%), analgesics (9.54%), cosmetics/personal care products (9.49%), dietary supplements/herbals/homeopathic (6.65%), and foreign bodies/toys/miscellaneous (6.61%). NPDS documented 3,255 human exposures resulting in death; 2,622 (80.6%) of these were judged as related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory). CONCLUSIONS: These data support the continued value of PC expertise and the need for specialized medical toxicology information to manage the increasing number of more serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time status of NPDS represents a national public health resource to collect and monitor US exposure cases and information requests. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, infectious, venomous, chemical agent, or commercial product), and the identification and tracking of significant public health events. NPDS is a model system for the near real-time surveillance of national and global public health.

Adherence to legislation limiting opioid prescription duration following musculoskeletal injury.

OBJECTIVES: North Carolina had implemented legislation (Strengthen Opioid Misuse Prevention (STOP) Act) limiting opioid prescriptions to 5 days for acute pain and 7 days for post-operative pain. This study aimed to identify patient, prescriber, and facility characteristics associated with STOP Act adherence for patients with acute or post-surgical musculoskeletal (MSK) conditions. DESIGN: A three-level hierarchical logistic regression model was used to predict odds of adherence with STOP Act duration limits, accounting for fixed and random effects at the patient, prescriber, and facility levels. SETTING: A large healthcare system in North Carolina. PATIENTS AND PARTICIPANTS: Patients (N = 6,849) presenting from 2018 to 2020 with a diagnosis of an acute MSK injury. INTERVENTIONS: The STOP Act limited the duration of opioid prescriptions in North Carolina. MAIN OUTCOME MEASURE: Prescriptions adhering to the STOP Act duration limits of 5 days (nonoperative) or 7 days (operative) were the primary outcome. RESULTS: Opioids were compliant with STOP Act duration limits in 69.3 percent of encounters, with 33 percent of variation accounted for by clinician and 29 percent by facility. Patients prescribed >1 opioid (odds ratio (OR) 0.46, 95 percent confidence interval (CI): 0.36, 0.58) had reduced odds of a compliant prescription; surgical patients had increased odds of a compliant prescription (outpatient surgery: OR 5.89, 95 percent CI: 2.43-14.29; inpatient surgery: OR 7.71, 95 percent CI: 3.04-19.56). Primary care sports medicine clinicians adhered to legislation less frequently than orthopedic surgeons (OR 0.38, 95 percent CI: 0.15, 0.97). CONCLUSIONS: Most prescriptions adhered to STOP Act legislation. Tailored interventions to improve adherence among targeted groups of prescribers, eg, those treating nonoperative injuries and sport medicine clinicians, could be useful.

Patients with glenohumeral arthritis are more likely to be prescribed opioids in the emergency department or urgent care setting.

OBJECTIVE: The objective is to quantify the rate of opioid and benzodiazepine prescribing for the diagnosis of shoulder osteoarthritis across a large healthcare system and to describe the impact of a clinical decision support intervention on prescribing patterns. DESIGN: A prospective observational study. SETTING: One large healthcare system. PATIENTS AND PARTICIPANTS: Adult patients presenting with shoulder osteoarthritis. INTERVENTIONS: A clinical decision support intervention that presents an alert to prescribers when patients meet criteria for increased risk of opioid use disorder. MAIN OUTCOME MEASURE: The percentage of patients receiving an opioid or benzodiazepine, the percentage who had at least one risk factor for misuse, and the percent of encounters in which the prescribing decision was influenced by the alert were the main outcome measures. RESULTS: A total of 5,380 outpatient encounters with a diagnosis of shoulder osteoarthritis were included. Twenty-nine percent (n = 1,548) of these encounters resulted in an opioid or benzodiazepine prescription. One-third of those who received a prescription had at least one risk factor for prescription misuse. Patients were more likely to receive opioids from the emergency department or urgent care facilities (40 percent of encounters) compared to outpatient facilities (28 percent) (p < .0001). Forty-four percent of the opioid prescriptions were for "potent opioids" (morphine milliequivalent conversion factor > 1). Of the 612 encounters triggering an alert, the prescribing decision was influenced (modified or not prescribed) in 53 encounters (8.7 percent). All but four (0.65 percent) of these encounters resulted in an opioid prescription. CONCLUSION: Despite evidence against routine opioid use for osteoarthritis, one-third of patients with a primary diagnosis of glenohumeral osteoarthritis received an opioid prescription. Of those who received a prescription, over one-third had a risk factor for opioid misuse. An electronic clinic decision support tool influenced the prescription in less than 10 percent of encounters.

Management of Acetaminophen Poisoning in the US and Canada: A Consensus Statement.

Importance: The US and Canada currently have no formal published nationwide guidelines for specialists in poison information or emergency departments for the management of acetaminophen poisoning, resulting in significant variability in management. Objective: To develop consensus guidelines for the management of acetaminophen poisoning in the US and Canada. Evidence Review: Four clinical toxicology societies (America's Poison Centers, American Academy of Clinical Toxicology, American College of Medical Toxicology, and Canadian Association of Poison Control Centers) selected participants (n = 21). Led by a nonvoting chairperson using a modified Delphi method, the panel created a decision framework and determined the appropriate clinical management of a patient with acetaminophen poisoning. Unique to this effort was the collection of guidelines from most poison centers in addition to systematic collection and review of the medical literature. Comments from review by external organizations were incorporated before the guideline was finalized. The project began in March 2021 and ended in March 2023. Findings: The search retrieved 84 guidelines and 278 publications. The panel developed guidelines for emergency department management of single or repeated ingestion of acetaminophen. In addition, the panel addressed extended-release formulation, high-risk ingestion, coingestion of anticholinergics or opioids, age younger than 6 years, pregnancy, weight greater than 100 kg, and intravenous acetaminophen use. Differences from current US practice include defining acute ingestion as an ingestion presentation from 4 to 24 hours after overdose was initiated. A revised form of the Rumack-Matthew nomogram was developed. The term massive ingestion was replaced with the term high-risk ingestion and denoted by a specific nomogram line. Other recommendations include specific criteria for emergency department triage, laboratory evaluation and monitoring parameters, defining the role of gastrointestinal decontamination, detailed management of acetylcysteine treatment, associated adverse effects, and stopping criteria for acetylcysteine treatment, as well as criteria for consultation with a clinical toxicologist. Finally, specific treatment considerations, including acetylcysteine dosing, fomepizole administration, and considerations for extracorporeal elimination and transplant evaluation, were addressed. Conclusions and Relevance: This qualitative study provides a consensus statement on consistent evidence-based recommendations for medical, pharmacy, and nursing education and practice to optimize care of patients with acetaminophen poisoning.

Lipid emulsion therapy during management of the critically-ill poisoned patient: a prospective cohort study.

BACKGROUND: Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The "lipid sink" theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant's degree of lipophilicity. METHODS: We reviewed all cases in the Toxicology Investigators Consortium's lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant's octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration. RESULTS: We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis (P = 0.89) or polynomial model (P = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration. CONCLUSION: Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion.

Single bag high dose intravenous N-acetylcysteine associated with decreased hepatotoxicity compared to triple bag intravenous N-acetylcysteine in high-risk acetaminophen ingestions.

INTRODUCTION: There is controversy that the triple bag intravenous (IV) N-acetylcysteine (NAC) regimen may be underdosing the sickest patients in its current, common usage. We hypothesize that a higher dose IV NAC regimen improves some outcomes. METHODS: We conducted a poison center based retrospective observational study from January 1, 2016 to December 31, 2017 comparing a single bag higher dose IV NAC regimen (150 mg/kg over 1 h, 15 mg/kg/hour) to the triple bag IV NAC regimen (150 mg/kg over 1 h, 12.5 mg/kg/hour for 4 h, 6.25 mg/kg/hour). In a high-risk population of patients with acetaminophen ingestion (defined as multiplication product ≥ 10,000 mg/L IU/L, not acute ingestions receiving NAC within 8 h, and not hepatotoxic on first contact), we evaluated the rate of hepatotoxicity, peak transaminase, and rate of laboratory coagulopathy. RESULTS: 89 patients met the inclusion criteria. 12 of the 23 patients (52%) who received triple bag NAC became hepatotoxic and 10 (43%) became coagulopathic, while only 19 of 66 patients (29%) who received single bag NAC became hepatotoxic and 15 (23%) became coagulopathic; p = .043 and .057, resp. Mean peak transaminase was 4481 IU/L vs 2143 IU/L in those receiving triple bag NAC vs single bag NAC, difference of means 2338 IU/L; p = .026. CONCLUSION: In this exploratory study of a high-risk population of patients with acetaminophen ingestions, the single bag IV NAC regimen was associated with lower peak transaminase and fewer patients becoming hepatotoxic as compared to the triple bag IV NAC regimen.

Melatonin Supplementation in Undetermined Pediatric Deaths.

Since 2015, the North Carolina Office of the Chief Medical Examiner has investigated seven deaths of infants and toddlers, aged 2 months to 3 years, with exogenous melatonin detected upon toxicological analysis. Melatonin concentrations ranged from 3 to 1,400 ng/mL in postmortem whole blood. While the cause and the manner of all seven deaths were classified as undetermined, the analytical findings are noteworthy. Melatonin is generally considered a safe, natural product appearing in many over-the-counter supplements geared toward young children to facilitate calmness and improve sleep. Melatonin is a neurohormone, which regulates not only circadian rhythms and natural sleep but also other physiological functions. Endogenous melatonin production, derived from essential amino acid metabolism, does not begin until pineal gland maturation at ∼3 months of age with concentrations in plasma peaking during periods of darkness at ∼0.2 ng/mL. Administering commercially available melatonin supplements to infants results in levels substantially greater than endogenous sources, which should not be assumed to be safe just because of their endogenous nature. The finding of exogenous concentrations in some postmortem pediatric cases warrants attention. Several topics of interest surrounding these postmortem melatonin findings will be considered, such as minimal regulatory control over commercial products as well as the potential impact on hazardous sleeping conditions. This manuscript will outline the physiological effects of melatonin and detail the case studies from the North Carolina medical examiner system. Forensic toxicology laboratories should consider including melatonin at exogenous concentrations in their testing schemes for appropriate postmortem infant and toddler cases.

Adverse effects associated with bupropion therapeutic errors in adults reported to four United States Poison Centers.

CONTEXT: Bupropion is a frequently used medication. Excessive doses may cause altered mental status, seizures, and dysrhythmias. There is a need for accurate estimate of seizure risk with therapeutic errors and determination if minor symptoms are harbingers of more severe effects. METHODS: A retrospective review of adult, acute, unintentional therapeutic error, single substance bupropion ingestions with known outcome reported to four poison centers from January 1, 2004 to December 31, 2016. Data included age, gender, single error dose, total bupropion dose over 18 h, prior history of seizure, management site, observation time, occurrence of an out-of-hospital adverse event, "jittery"/anxious/agitated, tachycardia/palpitations, seizures, and dysrhythmias. We recorded the total bupropion dose over 18 h if known; otherwise, we used the single error dose. We compared means for parametric data. We used Fisher's exact test and Mann-Whitney for nonparametric data. RESULTS: We identified 754 potential cases, of which 637 met inclusion criteria after case review. Median age was 42 years, and 76.1% were female. Cases were predominantly managed at home (56.2%). Outcomes were no effect (50.1%), minor (45.5%) and moderate (4.4%). The reported dose with no effect/minor outcome was 694 (±297) mg, and for moderate outcome was 1250 (±815) mg (p < 0.0001). Seizures occurred in four patients with median onset time of 7 h [range 2-21.5 h]. The median reported dose in patients who seized was 900 mg [range 600-3000 mg]. Of patients who developed a seizure and/or an out-of-hospital adverse event, 83% were "jittery"/anxious/agitated whereas "jittery"/anxious/agitated was present in 27% of cases that did not (p = 0.008). Tachycardia/palpitations was reported in 12% of cases; more serious dysrhythmias were not reported. CONCLUSIONS: Outcomes from single unintentional ingestions of bupropion in adults are overall mild and appear to be dose related. Home management may be an option with doses up to 900 mg in an appropriate patient population.

2021 Annual Report of the National Poison Data System© (NPDS) from America's Poison Centers: 39th Annual Report.

ABSTRACTINTRODUCTION: This is the 39th Annual Report of America's Poison Centers' National Poison Data System (NPDS). As of 1 January, 2021, all 55 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 4.87 [4.38, 8.62] (median [25%, 75%]) minutes, effectuating a near real-time national exposure and information database and surveillance system. METHODS: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure. RESULTS: In 2021, 2,851,166 closed encounters were logged by NPDS: 2,080,917 human exposures, 62,189 animal exposures, 703,086 information requests, 4,920 human confirmed nonexposures, and 54 animal confirmed nonexposures. Total encounters showed a 14.0% decrease from 2020, and human exposure cases decreased by 2.22%, while health care facility (HCF) human exposure cases increased by 7.20%. All information requests decreased by 37.0%, medication identification (Drug ID) requests decreased by 20.8%, and medical information requests showed a 61.1% decrease, although these remain about 13-fold higher than before the COVID-19 pandemic. Drug Information requests showed a 146% increase, reflecting COVID-19 vaccine calls to PCs. Human exposures with less serious outcomes have decreased 1.80% per year since 2008, while those with more serious outcomes (moderate, major or death) have increased 4.56% per year since 2000.Consistent with the previous year, the top 5 substance classes most frequently involved in all human exposures were analgesics (11.2%), household cleaning substances (7.49%), cosmetics/personal care products (5.88%), antidepressants (5.61%), and sedatives/hypnotics/antipsychotics (4.73%). As a class, antidepressant exposures increased most rapidly, by 1,663 cases/year (5.30%/year) over the past 10 years for cases with more serious outcomes.The top 5 most common exposures in children age 5 years or less were cosmetics/personal care products (10.8%), household cleaning substances (10.7%), analgesics (8.16%), dietary supplements/herbals/homeopathic (7.00%), and foreign bodies/toys/miscellaneous (6.51%). Drug identification requests comprised 3.64% of all information contacts. NPDS documented 4,497 human exposures resulting in death; 3,809 (84.7%) of these were judged as related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory). CONCLUSIONS: These data support the continued value of PC expertise and the need for specialized medical toxicology information to manage more serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time status of NPDS represents a national public health resource to collect and monitor US exposure cases and information contacts. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, infectious, venomous, chemical agent, or commercial product), and the identification and tracking of significant public health events. NPDS is a model system for the near real-time surveillance of national and global public health.

Balancing Safety, Comfort, and Fall Risk: An Intervention to Limit Opioid and Benzodiazepine Prescriptions for Geriatric Patients.

Introduction: This study reports on the impact of a clinical decision support tool embedded in the electronic medical record and characterizes the demographics, prescribing patterns, and risk factors associated with opioid and benzodiazepine misuse in the older adult population. Significance: This study reports on prescribing patterns for patients ≥65 years-old who presented to Emergency Departments (ED) or Urgent Care (UC) facilities across a large healthcare system following a fall (n = 34,334 encounters; n = 25,469 patients). This system implemented a clinical decision support intervention which provides an alert when the patient has an evidence-based risk factor for prescription drug misuse; prescribers can continue, amend or cancel the prescription. Results: Of older adults presenting with a fall, 31.4% (N = 7986) received an opioid or benzodiazepine prescription. Women and younger patients (65-74) had a higher likelihood of receiving a prescription (P < .0001). 11% had ≥1 risk factor. Women were more likely to receive an early refill (P = .0002) and younger (65-74) men were more likely to have a past positive toxicology (P < .0001). A prescription was initiated in 8,591 encounters, and 946 (9.0%) triggered an alert. In 58 cases, the alert resulted in a prescription modification, and in 80 the prescription was canceled. Conclusions: Documented risk for opioid misuse in the elderly was 10% among patients presenting to the ED/UC after a fall. The dangers associated with opioid/benzodiazepine use increase with age as does fall risk. Awareness of risk factors is an important first step; more work is needed to address potentially hazardous prescriptions in this population.