National Electronic Injury Surveillance System-Cooperative Research Articles

US‐based emergency department visits for fluoroquinolone‐associated hypersensitivity reactions

To estimate the rate of hypersensitivity reactions per 100,000 prescription dispensings of fluoroquinolones based on care rendered in a nationally representative sample of US hospital emergency departments (ED). We analyzed the frequency of fluoroquinolone-associated hypersensitivity reactions using the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance system (2004-2010) in conjunction with US retail outpatient prescription data from IMS Health (2004-2010). We further categorized reaction severity into three subgroups (mild, moderate, and severe). Based on 1422 cases of fluoroquinolone-associated hypersensitivity reactions and national drug utilization projections, we estimated risk of hypersensitivity reactions for moxifloxacin, ciprofloxacin, and levofloxacin. The absolute risk of a fluoroquinolone-related hypersensitivity reaction of any severity was low (44.0 (95% CI 34.8-53.3) ED visits/100,000 prescriptions); however, we identified a statistically significant difference in the relative risk (rate ratios) of seeking care in an ED attributed to moxifloxacin hypersensitivity compared to either levofloxacin or ciprofloxacin. For all reaction severities, the estimated ED visits/100,000 prescriptions were 141.3 (95% CI 99.9-182.7) for moxifloxacin, 40.8 (95% CI 31.5-50.0) for levofloxacin, and 26.3 (95% CI 20.8-31.9) for ciprofloxacin. When the rates were stratified by reaction severity category (mild or moderate-severe), moxifloxacin continued to be implicated in more ED visits per 100,000 prescriptions dispensed than either levofloxacin or ciprofloxacin. Fluoroquinolones may cause hypersensitivity reactions requiring care in an ED, and relative to use, the rate of moxifloxacin-related hypersensitivity reactions is higher compared to levofloxacin or ciprofloxacin.

OTC eye drop, nasal spray dangers in kids

Ingestion by young children of OTC eye drops and nasal sprays that contain tetrahydrozoline, oxymetazoline, or naphazoline can result in serious harm, according to a safety communication released by FDA last October. The accidental ingestion of these products by children 5 years and younger has resulted in serious adverse events, the agency reported, with some children requiring hospitalization. Parents and caregivers need to be educated on these risks and on the measures they can take to prevent accidental exposure.

Analysis of Benzonatate Overdoses Among Adults and Children from 1969–2010 by the United States Food and Drug Administration

To augment the December 2010 United States Food and Drug Administration (FDA) Drug Safety Communication on accidental ingestion of benzonatate in children less than 10years old by summarizing data on emergency department visits, benzonatate exposure, and reports of benzonatate overdoses from several data sources. Retrospective review of adverse-event reports and drug utilization data of benzonatate. The FDA Adverse Event Reporting System (AERS) database (1969-2010), the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance Project (NEISS-CADES, 2004-2009), and the IMS commercial data vendor (2004-2009). Any patient who reported an adverse event with benzonatate captured in the AERS or NEISS-CADES database or received a prescription for benzonatate according to the IMS commercial data vendor. Postmarketing adverse events with benzonatate were collected from the AERS database, emergency department visits due to adverse events with benzonatate were collected from the NEISS-CADES database, and outpatient drug utilization data were collected from the IMS commercial data vendor. Of 31 overdose cases involving benzonatate reported in the AERS database, 20 had a fatal outcome, and five of these fatalities occurred from accidental ingestions in children 2 years of age and younger. The NEISS-CADES database captured emergency department visits involving 12 cases of overdose from accidental benzonatate ingestions in children aged 1-3years. Signs and symptoms of overdose included seizures, cardiac arrest, coma, brain edema or anoxic encephalopathy, apnea, tachycardia, and respiratory arrest and occurred in some patients within 15minutes of ingestion. Dispensed benzonatate prescriptions increased by approximately 52% from 2004 to 2009. Although benzonatate has a long history of safe use, accumulating cases of fatal overdose, especially in children, prompted the FDA to notify health care professionals about the risks of benzonatate overdose. Pharmacists may have a role in preventing benzonatate overdoses by counseling patients on signs and symptoms of benzonatate overdose, the need for immediate medical care, and safe storage and disposal of benzonatate.

Don’t get burned by OTC topical analgesics

Some consumers have reported receiving serious skin injuries while using certain OTC topical pain relievers to relieve mild muscle and joint pain, FDA has warned. When these products are applied to the skin, they should produce a local sensation of warmth or coolness; they should not cause pain or skin damage. The reported cases of skin injuries ranged from first- to third-degree burns, often following one application of the product.

Adverse Events in Elderly Mostly From Common Drugs

Nearly 100,000 Americans aged 65 years and older are hospitalized each year after adverse drug events, and most of these emergencies result from a few commonly used medications, according to a study from the Centers for Disease Control and Prevention. Of an estimated 99,628 hospitalizations—about half coming among people aged 80 years and older—66% were the result of unintentional overdoses, Dr. Daniel S. Budnitz, director of the CDC's Medication Safety Program, and his colleagues reported in the New England Journal of Medicine. The medications most often implicated were warfarin, insulins, oral anti-platelet agents, and oral hypoglycemic agents, which either alone or in combination accounted for 33%, 14%, 13%, and 11% of the hospitalizations, respectively, the investigators reported (N. Engl. J. Med. 2011;365:2002-12). Emergency department visits resulting in hospitalization were more likely than those not resulting in hospitalization to involve unintentional overdoses (66% vs. 46%) and to involve at least five medications (55% vs. 40%). The researchers noted that medications typically deemed high risk or inappropriate for elderly patients resulted in relatively few emergency hospitalizations, accounting for only about 1% and 7% of the 65-and-over emergency admissions, respectively. The findings have important implications for reducing harm and health care costs among older adults, said Dr. Budnitz and his colleagues. Such detailed and drug-specific data can help focus current patient-safety efforts, such as the Partnership for Patients, they said. That $1 billion federal initiative has the goal of decreasing preventable hospitalizations 20% by the end of 2013. The investigators used adverse-event data for 2007 through 2009 from the National Electronic Injury Surveillance System—Cooperative Adverse Drug Event Surveillance Project. They based their national estimates on an analysis of 5,077 emergency hospitalizations in older adults at 58 nonpediatric hospitals that participate in the surveillance system. The numbers probably represent underestimates of emergency hospitalizations, the investigators said. They explained that some patient groups—such as those admitted for diagnostic evaluation or transferred from other hospitals—were not represented in the analysis. “Our findings suggest that efforts to improve medication safety for older adults should focus on areas in which improvements are most likely to have sizable, clinically significant, and measurable effects, such as improving the management of antithrombotic and antidiabetic drugs,” the investigators concluded. In a press statement, Dr. Budnitz acknowledged that blood thinners and diabetes medications are critical medicines for many older adults. “Doctors and patients should continue to use them but remember to work together to safely manage them,” he said. Neither Dr. Budnitz nor any of the other investigators disclosed any conflict of interest.

Emergency Hospitalizations for Adverse Drug Events in Older Americans

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. 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. 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. 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.

Preventing Medication Overdoses in Young Children: An Opportunity for Harm Elimination

Medication overdoses in young children are an increasingly common public health problem, but it is a preventable problem that can be addressed by combining strategies. The introduction of child-resistant packaging (CRP), product reformulations, heightened parental awareness, and poison control professionals and systems have made deaths from pediatric poisonings uncommon. However, the morbidity rate from medication overdoses, measured by emergency department (ED) visits and from calls to poison control centers, has been rising.1,2 Medications have surpassed household products (eg, cleaning agents) as the predominant cause of pediatric poisonings.3 More than 70 000 children are brought to EDs for unintentional medication overdoses annually; the peak incidence is in 2-year-olds (Fig 1). Between 2005 and 2009, ED visits for medication overdoses among children younger than 5 years rose 20%. In 2009, 1 of every 151 2-year-olds was assessed in an ED for a medication overdose. Among children younger than 5 years, 95% of these ED visits for medication overdoses were a result of unsupervised (accidental) ingestions. Fewer than 5% of ED visits were a result of errors made by a caregiver; such visits primarily involve incorrect dosing. Recognizing the significance of this problem, a new Healthy People 2020 objective calls for reversal of these morbidity trends and a reduction in ED visits by 10% by 2020.4 FIGURE 1 Rate of ED visits for unintentional medication overdoses in young children: United States, 2006–2009. Population rate estimates were based on the National Electronic Injury Surveillance System–Cooperative … Address correspondence to DanielS. Budnitz, MD, MPH, Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Rd, NE, Mail Stop A-24, Atlanta, GA 30333. E-mail: dbudnitz{at}cdc.gov

National Estimates of Emergency Department Visits for Hemorrhage-Related Adverse Events From Clopidogrel Plus Aspirin and From Warfarin

Dual antiplatelet therapy (DAT) with clopidogrel plus aspirin is a well-established antithrombotic strategy, with hemorrhage being the chief adverse event (AE) of concern. Outside of clinical trials, few published data describe the magnitude and nature of hemorrhage-related AEs from DAT. To estimate the numbers and rates of emergency department (ED) visits for hemorrhage-related AEs (hemorrhage or evaluation for potential hemorrhage) from DAT in the United States and put them in the context of those from warfarin, we analyzed AEs from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project, 2006-2008, and outpatient prescribing from the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, 2006-2007. Based on 384 cases, there were an estimated 7654 (95% confidence interval [CI], 3325-11 983) ED visits annually for hemorrhage-related AEs from DAT compared with 2926 cases and an estimated 60 575 (36 117-85 033) ED visits from warfarin. Approximately 60% of ED visits for DAT consisted of epistaxis or other minor hemorrhages (eg, bleeding from small cuts). The risk of hospitalization for ED visits involving acute hemorrhages was not significantly different between DAT and warfarin (risk ratio, 0.73; 95% CI, 0.38-1.08). The estimated rate of ED visits involving acute hemorrhages from DAT was 1.2 per 1000 outpatient prescription visits vs 2.5 per 1000 outpatient prescription visits for warfarin (risk ratio, 0.49; 95% CI, 0.15-0.83). These findings indicate that the acute hemorrhagic risk with DAT is clinically significant and reinforce the importance of practitioners and patients recognizing and anticipating this risk.

Emergency Department Visits for Antibiotic‐Associated Adverse Events

Drug-related adverse events are an under-appreciated consequence of antibiotic use, and the national magnitude and scope of these events have not been studied. Our objective was to estimate and compare the numbers and rates of emergency department (ED) visits for drug-related adverse events associated with systemic antibiotics in the United States by drug class, individual drug, and event type. We analyzed drug-related adverse events from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project (2004-2006) and outpatient prescriptions from national sample surveys of ambulatory care practices, the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey (2004-2005). On the basis of 6614 cases, an estimated 142,505 visits (95% confidence interval [CI], 116,506-168,504 visits) annually were made to US EDs for drug-related adverse events attributable to systemic antibiotics. Antibiotics were implicated in 19.3% of all ED visits for drug-related adverse events. Most ED visits for antibiotic-associated adverse events were for allergic reactions (78.7% of visits; 95% CI, 75.3%-82.1% of visits). One-half of the estimated ED visits were attributable to penicillins (36.9% of visits; 95% CI, 34.7%-39.2% of visits) and cephalosporins (12.2%; 95% CI, 10.9%-13.5%). Among commonly prescribed antibiotics, sulfonamides and clindamycin were associated with the highest rate of ED visits (18.9 ED visits per 10,000 outpatient prescription visits [95% CI, 13.1-24.7 ED visits per 10,000 outpatient prescription visits] and 18.5 ED visits per 10,000 outpatient prescription visits [95% CI, 12.1-25.0 ED visits per 10,000 outpatient prescription visits], respectively). Compared with all other antibiotic classes, sulfonamides were associated with a significantly higher rate of moderate-to-severe allergic reactions (4.3% [95% CI, 2.9%-5.8%] vs. 1.9 % [95% CI, 1.5%-2.3%]), and sulfonamides and fluoroquinolones were associated with a significantly higher rate of neurologic or psychiatric disturbances (1.4% [95% CI, 1.0%-1.7%] vs. 0.5% [95% CI, 0.4%-0.6%]). Antibiotic-associated adverse events lead to many ED visits, and allergic reactions are the most common events. Minimizing unnecessary antibiotic use by even a small percentage could significantly reduce the immediate and direct risks of drug-related adverse events in individual patients.

Medication Use Leading to Emergency Department Visits for Adverse Drug Events in Older Adults: Budnitz DS, Shehab N, Kegler SR, et al. Ann Intern Med 2007;147:755–65

This study was an analysis of data compiled from the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance (NEISS-CADES), National Ambulatory Medical Care Survey (NAMCS), and the National Hospital Ambulatory Medical Care Survey (NHAMCS). It attempted to estimate the number of Emergency Department (ED) visits for adverse drug events involving medications that by consensus have been deemed potentially inappropriate for use in elderly patients (Beers criteria) compared with other medications.

Medication Use Leading to Emergency Department Visits for Adverse Drug Events in Older Adults

The Beers criteria identify inappropriate use of medications in older adults. The number of and risk for adverse events from these medications are unknown. To estimate the number of and risk for emergency department visits for adverse events involving Beers criteria medications compared with other medications. Nationally representative, public health surveillance of adverse drug events and a cross-sectional survey of outpatient medical visits. National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance System, 2004-2005; National Ambulatory Medical Care Survey, 2004; and National Hospital Ambulatory Medical Care Survey, 2004. Persons 65 years of age or older seeking emergency department and outpatient care. Estimated number of and risks for emergency department visits for adverse drug events involving Beers criteria medications and other medications. Among U.S. patients 65 years of age or older, an estimated 177,504 emergency department visits (95% CI, 100,155 to 254,854 visits) for adverse drug events occurred both years. An estimated 3.6% (CI, 2.8% to 4.5%) of these visits were for adverse events medications considered to be always potentially inappropriate, according to the Beers criteria, and 33.3% (CI, 27.8% to 38.7%) of visits were for adverse events from 3 other medications (warfarin [17.3%], insulin [13.0%], and digoxin [3.2%]). Accounting for outpatient prescription frequency, the risk for emergency department visits for adverse events due to these 3 medications was 35 times (CI, 9.6 to 61) greater than that for medications considered to be always potentially inappropriate. Adverse events were identified only in emergency departments. Compared with other medications, Beers criteria medications caused low numbers of and few risks for emergency department visits for adverse events. Performance measures and interventions targeting warfarin, insulin, and digoxin use could prevent more emergency department visits for adverse events.

Evaluation and Overview of the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance Project (NEISS-CADES)

Adverse drug events (ADEs) are an important cause of patient injury. Although most medications are prescribed and used in the outpatient setting, prevention efforts focus on the inpatient setting, partly because of limited data on outpatient events. We describe and evaluate a new system for surveillance of outpatient ADEs treated in hospital emergency departments (EDs). We used guidelines for evaluating public health surveillance systems, developed by the Centers for Disease Control and Prevention, to assess the performance of the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project (NEISS-CADES) from January 1, 2004 through December 31, 2004. NEISS-CADES is a nationally representative surveillance system that identifies ADEs using ED clinical records. Of 10,383 reports in 2004, 100% listed patient age, sex, and disposition; 98% listed the implicated drugs. A 6-hospital evaluation of data quality, completeness, and other system attributes showed that NEISS-CADES data accurately reflected clinical records with respect to patient age and sex (100%), primary diagnosis (93%), implicated drugs (93%), primary treatments (80%), and diagnostic testing (61%). Sensitivity of case identification was estimated to be at least 0.33; estimated positive predictive value was 0.92. Data collection does not require additional work by clinical staff and has been well accepted by participating institutions. NEISS-CADES provides detailed and timely information on outpatient ADEs treated in EDs and identifies specific drugs and circumstances associated with these injuries. Findings from NEISS-CADES can help design and prioritize patient safety interventions for outpatient ADEs.