Scott R. Kegler

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

Context Emergency department visits by older adults are often due to adverse drug events, but the proportion of these visits that are the result of drugs designated as inappropriate for use in this population is unknown. Contribution Analyses of a national surveillance study of adverse drug events and a national outpatient survey estimate that Americans age 65 years or older have more than 175000 emergency department visits for adverse drug events yearly. Three commonly prescribed drugs accounted for more than one third of visits: warfarin, insulin, and digoxin. Caution The study was limited to adverse events in the emergency department. Implication Strategies to decrease adverse drug events among older adults should focus on warfarin, insulin, and digoxin. The Editors Adverse drug events cause clinically significant morbidity and mortality and are associated with large economic costs (15). They are common in older adults, regardless of whether they live in the community, reside in long-term care facilities, or are hospitalized (59). Most physicians recognize that prescribing medications to older patients requires special considerations, but nongeriatricians are typically unfamiliar with the most commonly used measure of medication appropriateness for older patients: the Beers criteria (1012). The Beers criteria are a consensus-based list of medications identified as potentially inappropriate for use in older adults. The criteria were introduced in 1991 to help researchers evaluate prescription quality in nursing homes (10). The Beers criteria were updated in 1997 and 2003 to apply to all persons age 65 years or older, to include new medications judged to be ineffective or to pose unnecessarily high risk, and to rate the severity of adverse outcomes (11, 12). Prescription rates of Beers criteria medications have become a widely used measure of quality of care for older adults in research studies in the United States and elsewhere (1326). The application of the Beers criteria as a measure of health care quality and safety has expanded beyond research studies. The Centers for Medicare & Medicaid Services incorporated the Beers criteria into federal safety regulations for long-term care facilities in 1999 (27). The prescription rate of potentially inappropriate medications is one of the few medication safety measures in the National Healthcare Quality Report (28) and has been introduced as a Health Plan and Employer Data and Information Set quality measure for managed care plans (29). Despite widespread adoption of the Beers criteria to measure prescription quality and safety, as well as proposals to apply these measures to additional settings, such as medication therapy management services under Medicare Part D (30), population-based data on the effect of adverse events from potentially inappropriate medications are sparse and do not compare the risks for adverse events from Beers criteria medications against those from other medications (31, 32). Adverse drug events that lead to emergency department visits are clinically significant adverse events (5) and result in increased health care resource utilization and expense (6). We used nationally representative public health surveillance data to estimate the number of emergency department visits for adverse drug events involving Beers criteria medications and compared the number with that for adverse drug events involving other medications. We also estimated the frequency of outpatient prescription of Beers criteria medications and other medications to calculate and compare the risks for emergency department visits for adverse drug events per outpatient prescription visit. Methods Data Sources National estimates of emergency department visits for adverse drug events were based on data from the 58 nonpediatric hospitals participating in the National Electronic Injury Surveillance SystemCooperative Adverse Drug Event Surveillance (NEISS-CADES) System, a nationally representative, size-stratified probability sample of hospitals (excluding psychiatric and penal institutions) in the United States and its territories with a minimum of 6 beds and a 24-hour emergency department (Figure 1) (3335). As described elsewhere (5, 34), trained coders at each hospital reviewed clinical records of every emergency department visit to report physician-diagnosed adverse drug events. Coders reported clinical diagnosis, medication implicated in the adverse event, and narrative descriptions of preceding circumstances. Data collection, management, quality assurance, and analyses were determined to be public health surveillance activities by the Centers for Disease Control and Prevention (CDC) and U.S. Food and Drug Administration human subjects oversight bodies and, therefore, did not require human subject review or institutional review board approval. Figure 1. Data sources and descriptions. NAMCS= National Ambulatory Medical Care Survey (36); NEISS-CADES= National Electronic Injury Surveillance SystemCooperative Adverse Drug Event Surveillance System (5, 3335); NHAMCS = National Hospital Ambulatory Medical Care Survey (37). *The NEISS-CADES is a 63-hospital national probability sample, but 5 pediatric hospitals were not included in this analysis. National estimates of outpatient prescription were based on 2 cross-sectional surveys, the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS), designed to provide information on outpatient office visits and visits to hospital outpatient clinics and emergency departments (Figure 1) (36, 37). These surveys have been previously used to document the prescription rates of inappropriate medications (17, 3840). Definition of Potentially Inappropriate Medications The most recent iteration of the Beers criteria (12) categorizes 41 medications or medication classes as potentially inappropriate under any circumstances (always potentially inappropriate) and 7 medications or medication classes as potentially inappropriate when used in certain doses, frequencies, or durations (potentially inappropriate in certain circumstances). For example, ferrous sulfate is considered to be potentially inappropriate only when used at dosages greater than 325 mg/d, but not potentially inappropriate if used at lower dosages. For this investigation, we included the Beers criteria medications listed in Table 1. Because medication dose, duration, and frequency were not always available in NEISS-CADES and are not reported in NAMCS and NHAMCS, we included medications regardless of dose, duration, or frequency of use. We excluded 3 medications considered to be potentially inappropriate when used in specific formulations (short-acting nifedipine, short-acting oxybutynin, and desiccated thyroid) because NEISS-CADES, NAMCS, and NHAMCS do not reliably identify these formulations. Table 1. Potentially Inappropriate Medications for Individuals Age 65 Years or Older The updated Beers criteria identify additional medications as potentially inappropriate if they are prescribed to patients who have certain preexisting conditions. We did not include these medications because they have rarely been used in previous studies or safety measures and NEISS-CADES, NAMCS, and NHAMCS do not reliably identify preexisting conditions. Identification of Emergency Department Visits for Adverse Drug Events We defined an adverse drug event case as an incident emergency department visit by a patient age 65 years or older, from 1 January 2004 to 31 December 2005, for a condition that the treating physician explicitly attributed to the use of a drug or for a drug-specific effect (5). Adverse events include allergic reactions (immunologically mediated effects) (41), adverse effects (undesirable pharmacologic or idiosyncratic effects at recommended doses) (41), unintentional overdoses (toxic effects linked to excess dose or impaired excretion) (41), or secondary effects (such as falls and choking). We excluded cases of intentional self-harm, therapeutic failures, therapy withdrawal, drug abuse, adverse drug events that occurred as a result of medical treatment received during the emergency department visit, and follow-up visits for a previously diagnosed adverse drug event. We defined an adverse drug event from Beers criteria medications as an emergency department visit in which a medication from Table 1 was implicated. Identification of Outpatient Prescription Visits We used the NAMCS and NHAMCS public use data files for the most recent year available (2004) to identify outpatient prescription visits. We defined an outpatient prescription visit as any outpatient office, hospital clinic, or emergency department visit at which treatment with a medication of interest was either started or continued. We identified medications by generic name for those with a single active ingredient and by individual active ingredients for combination products. We categorized visits with at least 1 medication identified in Table 1 as involving Beers criteria medications. Statistical Analysis Each NEISS-CADES, NAMCS, and NHAMCS case is assigned a sample weight on the basis of the inverse probability of selection (33, 4244). We calculated national estimates of emergency department visits and prescription visits by summing the corresponding sample weights, and we calculated 95% CIs by using the SURVEYMEANS procedure in SAS, version 9.1 (SAS Institute, Cary, North Carolina), to account for the sampling strata and clustering by site. To obtain annual estimates of visits for adverse events, we divided NEISS-CADES estimates for 20042005 and corresponding 95% CI end points by 2. Estimates based on small numbers of cases (<20 cases for NEISS-CADES and <30 cases for NAMCS and NHAMCS) or with a coefficient of variation greater than 30% are considered statistically unstable and are identified in the tables. To estimate the risk for adverse events relative to outpatient prescription

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.

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

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.

Adverse Events From Cough and Cold Medications After a Market Withdrawal of Products Labeled for Infants

OBJECTIVE: A voluntary market withdrawal of orally administered, over-the-counter, infant cough and cold medications (CCMs) was announced in October 2007. The goal of this study was to assess CCM-related adverse events (AEs) among children after the withdrawal. METHODS: Emergency department (ED) visits for CCM-related AEs among children <12 years of age were identified from a nationally representative, stratified, probability sample of 63 US EDs, for the 14 months before and after announcement of withdrawal. RESULTS: After withdrawal, the number and proportion of estimated ED visits for CCM-related AEs involving children <2 years of age were less than one-half of those in the prewithdrawal period (1248 visits [13.3%] vs 2790 visits [28.7%]; difference: −15.4% [95% confidence interval [CI]: −25.9% to −5.0%]), whereas the overall number of estimated ED visits for CCM-related AEs for children <12 years of age remained unchanged (9408 visits [95% CI: 6874–11 941 visits] vs 9727 visits [95% CI: 6649–12 805 visits]). During both periods, two-thirds of estimated ED visits involved unsupervised ingestions (ie, children finding and ingesting medications). CONCLUSIONS: ED visits for CCM-related AEs among children <2 years of age were substantially reduced after withdrawal of over-the-counter infant CCMs. Further reductions likely will require packaging improvements to reduce harm from unsupervised ingestions and continued education about avoiding CCM use for young children. Monitoring of CCM-related harm should continue because recommendations were updated in October 2008 to avoid the use of CCMs for children <4 years of age.

Characteristics of fatal abusive head trauma among children in the USA: 2003–2007: an application of the CDC operational case definition to national vital statistics data

Objective In March of 2008, an expert panel was convened at the Centers for Disease Control and Prevention to develop code-based case definitions for abusive head trauma (AHT) in children under 5 years of age based on the International Classification of Diseases, 10th Revision (ICD-10) nature and cause of injury codes. This study presents the operational case definition and applies it to US death data. Methods National Center for Health Statistics National Vital Statistics System data on multiple cause-of-death from 2003 to 2007 were examined. Results Inspection of records with at least one ICD-10 injury/disease code and at least one ICD-10 cause code from the AHT case definition resulted in the identification of 780 fatal AHT cases, with 699 classified as definite/presumptive AHT and 81 classified as probable AHT. The fatal AHT rate was highest among children age <1 year with a peak in incidence that occurred at 1–2 months of age. Fatal AHT incidence rates were higher for men than women and were higher for non-Hispanic African–Americans compared to other racial/ethnic groups. Fatal AHT incidence was relatively constant across seasons. Conclusions This report demonstrates that the definition can help to identify population subgroups at higher risk for AHT defined by year and month of death, age, sex and race/ethnicity. This type of definition may be useful for various epidemiological applications including research and surveillance. These activities can in turn inform further development of prevention activities, including educating parents about the dangers of shaking and strategies for managing infant crying.

Ecological level analysis of the relationship between smoking and residential-fire mortality

Objectives: To examine the association between tobacco smoking and residential-fire mortality and to investigate whether this association is explained by the confounding effects of selected socioeconomic factors (ie, educational attainment and median household income). Design: An ecological analysis relating state-level residential-fire mortality to state-level percentages of adults who smoke was conducted. Negative binomial rate regression was used to model this relationship, simultaneously controlling for the selected socioeconomic factors. Results: After educational attainment and median household income had been controlled for, smoking percentages among adults correlated significantly with state-level, population-based residential-fire mortality (estimated relative rate for a 1% decrease in smoking = 0.93; 95% CI 0.89 to 0.97). Conclusions: Mortality from residential fires is high in states with high smoking rates. This relationship cannot be explained solely by the socioeconomic factors examined in this study.

Applying the compound Poisson process model to the reporting of injury-related mortality rates

Injury-related mortality rate estimates are often analyzed under the assumption that case counts follow a Poisson distribution. Certain types of injury incidents occasionally involve multiple fatalities, however, resulting in dependencies between cases that are not reflected in the simple Poisson model and which can affect even basic statistical analyses. This paper explores the compound Poisson process model as an alternative, emphasizing adjustments to some commonly used interval estimators for population-based rates and rate ratios. The adjusted estimators involve relatively simple closed-form computations, which in the absence of multiple-case incidents reduce to familiar estimators based on the simpler Poisson model. Summary data from the National Violent Death Reporting System are referenced in several examples demonstrating application of the proposed methodology.

Violence-related injury in emergency departments in Brazil

OBJECTIVE This article describes the characteristics of violence-related injury (VRI) cases presenting at emergency departments (EDs) in Brazil and compares circumstances for assault-related and self-inflicted cases. METHODS The study is cross-sectional. The data describe cases seen in September 2006 in 62 EDs, representing all 26 states and the Federal District. A total of 4 835 case records were analyzed. Basic statistical tabulations were complemented by logistic regression analysis to assess potential associations between type of violence (assault or self-harm) and multiple factors. RESULTS Males comprised 72.8% of cases while those aged 20 to 29 comprised 35.4%. Alcohol use was reported or suspected in 42.7% of cases, more commonly among males. Assault victims comprised 91.4% of cases versus self-inflicted injuries, which accounted for 8.6%. Three-fourths of the assault victims were male, while over half of the self-inflicted injury victims were female. The leading mechanism for assaults was physical force/blunt objects (46.2%), whereas poisoning was the predominant mechanism for self-inflicted injuries (71.4%). Younger females were significantly more likely to have been victims of self-inflicted injuries than younger males, while younger males were more likely to have been victims of assault; this finding is more pronounced in cases where alcohol use was reported. Self-inflicted injuries were significantly more likely to occur in residences, while assaults were more likely to occur away from home. CONCLUSION These results can improve understanding of the scope and characteristics of VRIs in Brazil (and thus contribute to national injury prevention efforts), and help identify areas for future research.

Emergency Department Visits and Hospitalizations for Digoxin Toxicity: United States, 2005-2010

Background— Recent data on digoxin prescribing and adverse events are lacking but could help inform the management of digoxin in contemporary heart failure treatment. Methods and Results— We determined nationally representative numbers and rates of emergency department (ED) visits for digoxin toxicity in the United States using 2005 to 2010 reports from the National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance project and the National Ambulatory (and Hospital Ambulatory) Medical Care Surveys. Based on 441 cases, an estimated 5156 (95% confidence interval [CI], 2663–7648) ED visits for digoxin toxicity occurred annually in the United States; more than three fourths (78.8% [95% CI, 73.5%–84.1%]) resulted in hospitalization. Serum digoxin level was ≥2.0 ng/mL for 95.8% (95% CI, 93.2%–98.4%) of estimated ED visits with levels reported (n=251 cases). The rate of ED visits per 10 000 outpatient prescription visits among patients ≥85 years was twice that of patients 40 to 84 years (rate ratio, 2.4 [95% CI, 1.2–5.0]); among women, the rate was twice that of men (rate ratio, 2.3 [95% CI, 1.1–4.7]). Digoxin toxicity accounted for an estimated 1.0% (95% CI, 0.6%–1.4%) of ED visits for all adverse drug events among patients ≥40 years, but an estimated 3.3% (95% CI, 2.3%–4.4%) of ED visits and 5.9% (95% CI, 4.0%–7.9%) of hospitalizations for all adverse drug events among patients ≥85 years. Estimated annual ED visits and hospitalizations remained relatively constant from 2005 to 2010. Conclusions— Digoxin toxicity is not declining; more careful prescribing to high-risk groups and improved monitoring of serum levels might be needed to reduce morbidity from outpatient digoxin use.

Statistical air quality predictions for public health surveillance: evaluation and generation of county level metrics of PM2.5 for the environmental public health tracking network.

BackgroundThe Centers for Disease Control and Prevention (CDC) developed county level metrics for the Environmental Public Health Tracking Network (Tracking Network) to characterize potential population exposure to airborne particles with an aerodynamic diameter of 2.5 μm or less (PM2.5). These metrics are based on Federal Reference Method (FRM) air monitor data in the Environmental Protection Agency (EPA) Air Quality System (AQS); however, monitor data are limited in space and time. In order to understand air quality in all areas and on days without monitor data, the CDC collaborated with the EPA in the development of hierarchical Bayesian (HB) based predictions of PM2.5 concentrations. This paper describes the generation and evaluation of HB-based county level estimates of PM2.5.MethodsWe used three geo-imputation approaches to convert grid-level predictions to county level estimates. We used Pearson (r) and Kendall Tau-B (τ) correlation coefficients to assess the consistency of the relationship, and examined the direct differences (by county) between HB-based estimates and AQS-based concentrations at the daily level. We further compared the annual averages using Tukey mean-difference plots.ResultsDuring the year 2005, fewer than 20% of the counties in the conterminous United States (U.S.) had PM2.5 monitoring and 32% of the conterminous U.S. population resided in counties with no AQS monitors. County level estimates resulting from population-weighted centroid containment approach were correlated more strongly with monitor-based concentrations (r = 0.9; τ = 0.8) than were estimates from other geo-imputation approaches. The median daily difference was −0.2 μg/m3 with an interquartile range (IQR) of 1.9 μg/m3 and the median relative daily difference was −2.2% with an IQR of 17.2%. Under-prediction was more prevalent at higher concentrations and for counties in the western U.S.ConclusionsWhile the relationship between county level HB-based estimates and AQS-based concentrations is generally good, there are clear variations in the strength of this relationship for different regions of the U.S. and at various concentrations of PM2.5. This evaluation suggests that population-weighted county centroid containment method is an appropriate geo-imputation approach, and using the HB-based PM2.5 estimates to augment gaps in AQS data provides a more spatially and temporally consistent basis for calculating the metrics deployed on the Tracking Network.