Maribeth C. Lovegrove

Emergency Hospitalizations for Adverse Drug Events in Older Americans

BACKGROUND Adverse drug events are important preventable causes of hospitalization in older adults. However, nationally representative data on adverse drug events that result in hospitalization in this population have been limited. METHODS We used adverse-event data from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project (2007 through 2009) to estimate the frequency and rates of hospitalization after emergency department visits for adverse drug events in older adults and to assess the contribution of specific medications, including those identified as high-risk or potentially inappropriate by national quality measures. RESULTS On the basis of 5077 cases identified in our sample, there were an estimated 99,628 emergency hospitalizations (95% confidence interval [CI], 55,531 to 143,724) for adverse drug events in U.S. adults 65 years of age or older each year from 2007 through 2009. Nearly half of these hospitalizations were among adults 80 years of age or older (48.1%; 95% CI, 44.6 to 51.6). Nearly two thirds of hospitalizations were due to unintentional overdoses (65.7%; 95% CI, 60.1 to 71.3). Four medications or medication classes were implicated alone or in combination in 67.0% (95% CI, 60.0 to 74.1) of hospitalizations: warfarin (33.3%), insulins (13.9%), oral antiplatelet agents (13.3%), and oral hypoglycemic agents (10.7%). High-risk medications were implicated in only 1.2% (95% CI, 0.7 to 1.7) of hospitalizations. CONCLUSIONS Most emergency hospitalizations for recognized adverse drug events in older adults resulted from a few commonly used medications, and relatively few resulted from medications typically designated as high-risk or inappropriate. Improved management of antithrombotic and antidiabetic drugs has the potential to reduce hospitalizations for adverse drug events in older adults.

Emergency Department Visits for Adverse Events Related to Dietary Supplements

BACKGROUND Dietary supplements, such as herbal or complementary nutritional products and micronutrients (vitamins and minerals), are commonly used in the United States, yet national data on adverse effects are limited. METHODS We used nationally representative surveillance data from 63 emergency departments obtained from 2004 through 2013 to describe visits to U.S. emergency departments because of adverse events related to dietary supplements. RESULTS On the basis of 3667 cases, we estimated that 23,005 (95% confidence interval [CI], 18,611 to 27,398) emergency department visits per year were attributed to adverse events related to dietary supplements. These visits resulted in an estimated 2154 hospitalizations (95% CI, 1342 to 2967) annually. Such visits frequently involved young adults between the ages of 20 and 34 years (28.0% of visits; 95% CI, 25.1 to 30.8) and unsupervised children (21.2% of visits; 95% CI, 18.4 to 24.0). After the exclusion of unsupervised ingestion of dietary supplements by children, 65.9% (95% CI, 63.2 to 68.5) of emergency department visits for single-supplement-related adverse events involved herbal or complementary nutritional products; 31.8% (95% CI, 29.2 to 34.3) involved micronutrients. Herbal or complementary nutritional products for weight loss (25.5%; 95% CI, 23.1 to 27.9) and increased energy (10.0%; 95% CI, 8.0 to 11.9) were commonly implicated. Weight-loss or energy products caused 71.8% (95% CI, 67.6 to 76.1) of supplement-related adverse events involving palpitations, chest pain, or tachycardia, and 58.0% (95% CI, 52.2 to 63.7) involved persons 20 to 34 years of age. Among adults 65 years of age or older, choking or pill-induced dysphagia or globus caused 37.6% (95% CI, 29.1 to 46.2) of all emergency department visits for supplement-related adverse events; micronutrients were implicated in 83.1% (95% CI, 73.3 to 92.9) of these visits. CONCLUSIONS An estimated 23,000 emergency department visits in the United States every year are attributed to adverse events related to dietary supplements. Such visits commonly involve cardiovascular manifestations from weight-loss or energy products among young adults and swallowing problems, often associated with micronutrients, among older adults. (Funded by the Department of Health and Human Services.).

National Estimates of Insulin-related Hypoglycemia and Errors Leading to Emergency Department Visits and Hospitalizations

IMPORTANCE Detailed, nationally representative data describing high-risk populations and circumstances involved in insulin-related hypoglycemia and errors (IHEs) can inform approaches to individualizing glycemic targets. OBJECTIVE To describe the US burden, rates, and characteristics of emergency department (ED) visits and emergency hospitalizations for IHEs. DESIGN, SETTING, AND PARTICIPANTS Nationally representative public health surveillance of adverse drug events among insulin-treated patients seeking ED care (National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project) and a national household survey of insulin use (the National Health Interview Survey) were used to obtain data from January 1, 2007, through December 31, 2011. MAIN OUTCOMES AND MEASURES Estimated annual numbers and estimated annual rates of ED visits and hospitalizations for IHEs among insulin-treated patients with diabetes mellitus. RESULTS Based on 8100 National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance cases, an estimated 97,648 (95% CI, 64,410-130,887) ED visits for IHEs occurred annually; almost one-third (29.3%; 95% CI, 21.8%-36.8%) resulted in hospitalization. Severe neurologic sequelae were documented in an estimated 60.6% (95% CI, 51.3%-69.9%) of ED visits for IHEs, and blood glucose levels of 50 mg/dL (to convert to millimoles per liter, multiply by 0.0555) or less were recorded in more than half of cases (53.4%). Insulin-treated patients 80 years or older were more than twice as likely to visit the ED (rate ratio, 2.5; 95% CI, 1.5-4.3) and nearly 5 times as likely to be subsequently hospitalized (rate ratio, 4.9; 95% CI, 2.6-9.1) for IHEs than those 45 to 64 years. The most commonly identified IHE precipitants were reduced food intake and administration of the wrong insulin product. CONCLUSIONS AND RELEVANCE Rates of ED visits and subsequent hospitalizations for IHEs were highest in patients 80 years or older; the risks of hypoglycemic sequelae in this age group should be considered in decisions to prescribe and intensify insulin. Meal-planning misadventures and insulin product mix-ups are important targets for hypoglycemia prevention efforts.

US Emergency Department Visits for Outpatient Adverse Drug Events, 2013-2014

Importance The Patient Protection and Affordable Care Act of 2010 brought attention to adverse drug events in national patient safety efforts. Updated, detailed, nationally representative data describing adverse drug events can help focus these efforts. Objective To describe the characteristics of emergency department (ED) visits for adverse drug events in the United States in 2013-2014 and describe changes in ED visits for adverse drug events since 2005-2006. Design, Setting, and Participants Active, nationally representative, public health surveillance in 58 EDs located in the United States and participating in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project. Exposures Drugs implicated in ED visits. Main Outcomes and Measures National weighted estimates of ED visits and subsequent hospitalizations for adverse drug events. Results Based on data from 42 585 cases, an estimated 4.0 (95% CI, 3.1-5.0) ED visits for adverse drug events occurred per 1000 individuals annually in 2013 and 2014 and 27.3% (95% CI, 22.2%-32.4%) of ED visits for adverse drug events resulted in hospitalization. An estimated 34.5% (95% CI, 30.3%-38.8%) of ED visits for adverse drug events occurred among adults aged 65 years or older in 2013-2014 compared with an estimated 25.6% (95% CI, 21.1%-30.0%) in 2005-2006; older adults experienced the highest hospitalization rates (43.6%; 95% CI, 36.6%-50.5%). Anticoagulants, antibiotics, and diabetes agents were implicated in an estimated 46.9% (95% CI, 44.2%-49.7%) of ED visits for adverse drug events, which included clinically significant adverse events, such as hemorrhage (anticoagulants), moderate to severe allergic reactions (antibiotics), and hypoglycemia with moderate to severe neurological effects (diabetes agents). Since 2005-2006, the proportions of ED visits for adverse drug events from anticoagulants and diabetes agents have increased, whereas the proportion from antibiotics has decreased. Among children aged 5 years or younger, antibiotics were the most common drug class implicated (56.4%; 95% CI, 51.8%-61.0%). Among children and adolescents aged 6 to 19 years, antibiotics also were the most common drug class implicated (31.8%; 95% CI, 28.7%-34.9%) in ED visits for adverse drug events, followed by antipsychotics (4.5%; 95% CI, 3.3%-5.6%). Among older adults (aged ≥65 years), 3 drug classes (anticoagulants, diabetes agents, and opioid analgesics) were implicated in an estimated 59.9% (95% CI, 56.8%-62.9%) of ED visits for adverse drug events; 4 anticoagulants (warfarin, rivaroxaban, dabigatran, and enoxaparin) and 5 diabetes agents (insulin and 4 oral agents) were among the 15 most common drugs implicated. Medications to always avoid in older adults according to Beers criteria were implicated in 1.8% (95% CI, 1.5%-2.1%) of ED visits for adverse drug events. Conclusions and Relevance The prevalence of emergency department visits for adverse drug events in the United States was estimated to be 4 per 1000 individuals in 2013 and 2014. The most common drug classes implicated were anticoagulants, antibiotics, diabetes agents, and opioid analgesics.

Emergency department visits for overdoses of acetaminophen-containing products.

BACKGROUND Limited national data on the circumstances of acetaminophen overdoses have hindered identification and implementation of prevention strategies. PURPOSE To estimate the frequency of and characterize risks for emergency department visits for acetaminophen overdoses that were not related to abuse in the U.S. METHODS Data were collected from two components of the National Electronic Injury Surveillance System from January 1, 2006, through December 31, 2007, and analyzed from 2009 to 2010 to estimate the annual number of emergency department visits for non-abuse-related acetaminophen overdose by patient demographics, treatments, and type and amount of acetaminophen-containing product ingested. RESULTS There were an estimated 78,414 emergency department visits (95% CI=63655, 93172) annually for non-abuse-related overdoses of acetaminophen-containing products. Most emergency department visits for acetaminophen overdose were for self-directed violence (69.8%, 95% CI=66.4%, 73.2%), with the highest rate among patients aged 15-24 years (46.4 per 100,000 individuals per year). Unsupervised ingestions by children aged <6 years accounted for 13.4% (95% CI=11.0%, 15.9%) of visits for acetaminophen overdoses (42.5 per 100,000 individuals per year). Therapeutic misadventures accounted for 16.7% (95% CI=14.0%, 19.5%) of visits and most involved overuse for medicinal effects (56.1%, 95% CI=50.6%, 61.6%) rather than use of multiple acetaminophen-containing products or dose confusion. CONCLUSIONS Non-abuse-related overdoses of acetaminophen products lead to many emergency department visits each year, particularly emergency department visits for self-directed violence. Acetaminophen overdose prevention efforts will likely need to be multidimensional.

Characterization of acetaminophen overdose-related emergency department visits and hospitalizations in the United States.

To estimate the number of acetaminophen overdose‐related emergency department (ED) visits and hospitalizations in the United States, characterize these by intentionality, age, and gender, and compare the strengths and limitations of the utilized databases.

Emergency Hospitalizations for Unsupervised Prescription Medication Ingestions by Young Children

BACKGROUND: Emergency department visits and subsequent hospitalizations of young children after unsupervised ingestions of prescription medications are increasing despite widespread use of child-resistant packaging and caregiver education efforts. Data on the medications implicated in ingestions are limited but could help identify prevention priorities and intervention strategies. METHODS: We used nationally representative adverse drug event data from the National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance project and national retail pharmacy prescription data from IMS Health to estimate the frequency and rates of emergency hospitalizations for unsupervised prescription medication ingestions by young children (2007–2011). RESULTS: On the basis of 1513 surveillance cases, 9490 estimated emergency hospitalizations (95% confidence interval: 6420–12 560) occurred annually in the United States for unsupervised prescription medication ingestions among children aged <6 years from 2007 through 2011; 75.4% involved 1- or 2-year old children. Opioids (17.6%) and benzodiazepines (10.1%) were the most commonly implicated medication classes. The most commonly implicated active ingredients were buprenorphine (7.7%) and clonidine (7.4%). The top 12 active ingredients, alone or in combination with others, were implicated in nearly half (45.0%) of hospitalizations. Accounting for the number of unique patients who received dispensed prescriptions, the hospitalization rate for unsupervised ingestion of buprenorphine products was significantly higher than rates for all other commonly implicated medications and 97-fold higher than the rate for oxycodone products (200.1 vs 2.1 hospitalizations per 100 000 unique patients). CONCLUSIONS: Focusing unsupervised ingestion prevention efforts on medications with the highest hospitalization rates may efficiently achieve large public health impact.

Spatial clustering of filarial transmission before and after a Mass Drug Administration in a setting of low infection prevalence

Background In the global program for the elimination of lymphatic filariasis (LF) longitudinal assessment of the prevalence of microfilaremia and antigenemia is recommended to monitor the effect of mass treatment on transmission. Additional monitoring tools such as entomologic and antibody methods may be useful in identifying residual foci of infection. In this study, we characterized serologic markers of infection and exposure spatially both before and after mass treatment, in an area of initial low Wuchereria bancrofti infection prevalence. Methods Consenting persons in the sentinel community were tested for circulating microfilaria and antigen (by immunochromatographic test) before and after the 1st annual mass drug administration of diethylcarbamazine and albendazole. A cohort of 161 persons provided serum specimens both years that were tested for antifilarial IgG (1 and 4) antibody. Every house was mapped using a differential Global Positioning System; this information was linked to the serologic data. W. bancrofti infection in the mosquito vector was assessed with year-round collection. Multiple linear regression was used to investigate the influence of antigen-positive persons on the antifilarial antibody responses of antigen-negative neighbors. Results After mass treatment, decreases were observed in the sentinel site in the overall prevalence of antigen (10.4% to 6.3%) and microfilaremia (0.9 to 0.4%). Of the persons in the cohort that provided serum specimens both years, 79% received treatment. Antigen prevalence decreased from 15.0% to 8.7%. Among 126 persons who received treatment, antigen and antifilarial IgG1 prevalence decreased significantly (p = 0.002 and 0.001, respectively). Among 34 persons who did not receive treatment, antifilarial IgG1 prevalence increased significantly (p = 0.003). Average antifilarial IgG1 levels decreased in households with high treatment coverage and increased in households that refused treatment. Each 10-meter increase in distance from the residence of a person who was antigen-positive in 2000 was associated a 4.68 unit decrease in antifilarial IgG1 level in 2001, controlling for other factors (p = 0.04). Discussion Antifilarial antibody assays can be used as a measure of filarial exposure. Our results suggest that micro-scale spatial heterogeneity exists in LF exposure and infection. Treatment appeared to be associated with reduced exposure at the sub-community level, suggesting the need to achieve high and homogeneous coverage. Public health messages should note the benefits of having ones neighbors receive treatment with antifilarial drugs.

Trends in Emergency Department Visits for Unsupervised Pediatric Medication Exposures, 2004–2013

BACKGROUND: After reports of increasing emergency department (ED) visits for unsupervised pediatric medication exposures in the 2000s, renewed efforts to improve safety packaging and education were initiated. National data on current trends can help further target interventions. METHODS: We used nationally representative data from the National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance project (2004–2013) to assess trends in ED visits for unsupervised medication exposures in children aged <6 years. For 2010 through 2013, the dosage form and prescription status of implicated medications were identified. RESULTS: Based on 13 268 cases, there were an estimated 640 161 ED visits (95% confidence interval: 512 885 to 767 436) for unsupervised medication exposures from 2004 through 2013. From 2004 through 2010, ED visits for unsupervised exposures increased by an average of 5.7% annually, peaking at 75 842. After 2010, this trend reversed, and visits decreased by an average of 6.7% annually to 59 092 in 2013. From 2010 through 2013, 91.0% of unsupervised exposure visits involved 1 medication, most commonly an oral prescription solid (45.9%), oral over-the-counter (OTC) solid (22.3%), or oral OTC liquid (12.4%). More than 260 different prescription solids were implicated; opioids (13.8%) and benzodiazepines (12.7%) were the most common classes. Four medications were implicated in 91.2% of OTC liquid exposure visits: acetaminophen (32.9%), cough and cold remedies (27.5%), ibuprofen (15.7%), and diphenhydramine (15.6%). CONCLUSIONS: Targeting prevention efforts based on harm frequency and intervention feasibility can lead to continued reductions in ED visits for pediatric medication exposures.

Efficacy of flow restrictors in limiting access of liquid medications by young children.

OBJECTIVE To assess whether adding flow restrictors (FRs) to liquid medicine bottles can provide additional protection against unsupervised medication ingestions by young children, even when the child-resistant closure is not fully secured. STUDY DESIGN In April and May 2012, we conducted a block randomized trial with a convenience sample of 110 3- and 4-year-old children from 5 local preschools. Participants attempted to remove test liquid from an uncapped bottle with an FR and a control bottle without an FR (with either no cap or an incompletely closed cap). RESULTS All but 1 (96%; 25 of 26) of the open control bottles and 82% (68 of 83) of the incompletely closed control bottles were emptied within 2 minutes. Only 6% (7 of 110) of the bottles with FRs were emptied during the 10-minute testing period, none before 6 minutes. Overall, children removed less liquid from the bottles with FRs than from the open or incompletely closed control bottles without FRs (both P < .001). All children assigned open control bottles and 90% of those assigned incompletely closed control bottles removed ≥ 25 mL of liquid. In contrast, 11% of children removed ≥ 25 mL of liquid from uncapped bottles with FRs. Older children (aged 54-59 months) were more successful than younger children at removing ≥ 25 mL of liquid (P = .002) from bottles with FRs. CONCLUSION Our findings suggest that adding FRs to liquid medicine bottles limits the accessibility of their contents to young children and could complement the safety provided by current child-resistant packaging.