Correspondence

Emergency Hospitalizations for Adverse Drug Events

N Engl J Med 2012; 366:858-860March 1, 2012DOI: 10.1056/NEJMc1114768

Article

To the Editor:

We commend Budnitz and colleagues (Nov. 24 issue)1 for their contribution to our understanding of emergency hospitalizations caused by adverse drug events. However, as a result of detection bias, it is likely that the relative contribution of bleeding and hypoglycemic manifestations of adverse drug events have been overestimated and that the overall burden of disease has been underestimated. This is because the case-finding methods at institutions participating in the National Electronic Injury Surveillance System–Cooperative Adverse Drug Event Surveillance (NEISS-CADES) project rely on coders who use a short list of symptoms that include “bleeding” and “hypoglycemia” to identify adverse drug events.2 Other commonly found manifestations of adverse drug events, such as neuropsychiatric, gastrointestinal, and cardiovascular symptoms, are not listed as triggers and therefore are less likely to be identified.3 In addition, emergency physicians frequently do not attribute emergency department presentations to adverse drug events, which leads to a lack of documentation in hospital records.4 Validation of the triggers in the NEISS-CADES project against a prospective criterion standard would enable a better estimate of the sensitivity of such measures. Prospective case-finding methods may yield more accurate data on the frequency and causes of adverse drug events and on the relative contribution of various adverse drug events to the overall disease burden.

Corinne M. Hohl, M.D., M.H.Sc.
University of British Columbia, Vancouver, BC, Canada
chohl@mail.ubc.ca

Jane de Lemos, Pharm.D.
Richmond Hospital, Richmond, BC, Canada

Riyad B. Abu Laban, M.D., M.H.Sc.
University of British Columbia, Vancouver, BC, Canada

No potential conflict of interest relevant to this letter was reported.

4 References

1. 1

   Budnitz DS, Lovegrove MC, Shehab N, Richards CL. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med 2011;365:2002-2012
   Free Full Text | Web of Science | Medline

2. 2

   Budnitz DS, Pollock DA, Mendelsohn AB, Weidenbach KN, McDonald AK, Annest JL. Emergency department visits for outpatient adverse drug events: demonstration for a national surveillance system. Ann Emerg Med 2005;45:197-206
   CrossRef | Web of Science | Medline

3. 3

   Zed PJ, Abu-Laban RB, Balen RM, et al. Incidence, severity and preventability of medication-related visits to the emergency department: a prospective study. CMAJ 2008;178:1563-1569
   CrossRef | Web of Science

4. 4

   Hohl CM, Zed PJ, Brubacher JR, Abu-Laban RB, Loewen PS, Purssell RA. Do emergency physicians attribute drug-related emergency department visits to medication-related problems? Ann Emerg Med 2010;55:493-502
   CrossRef | Web of Science

To the Editor:

Budnitz et al. report the proportions of adverse drug events resulting in emergency hospitalizations for various types of medications, including 33.3% for warfarin, 13.9% for insulins, 13.3% for oral antiplatelet agents, and 10.7% for oral hypoglycemic agents. It is interesting that only 1.2% of hospitalizations for adverse drug events were attributed to the use of high-risk medicines, as defined in the Healthcare Effectiveness Data and Information Set,1 and that 6.6% were attributed to potentially inappropriate medicines, as defined in the 2002 Beers criteria.2

However, it is important to note that various high-risk medicines have been linked to functional impairment and geriatric syndromes (e.g., cognitive impairment and falls), which may not be recognized as adverse drug events.3 Nevertheless, geriatric syndromes are common and have substantial negative implications for functioning, quality of life, and mortality in older adults in the community and in the hospital.4 Better recognition of functional impairment and geriatric syndromes as adverse drug events is required to accurately identify high-risk medicines in older adults.

Danijela Gnjidic, Ph.D., M.P.H.
Sarah N. Hilmer, M.D., Ph.D.
University of Sydney, Sydney, NSW, Australia
danijela.gnjidic@sydney.edu.au

No potential conflict of interest relevant to this letter was reported.

4 References

1. 1

   Healthcare Effectiveness Data and Information Set (HEDIS). 2011 Final NDC lists: use of high-risk medications in the elderly (DAE). Washington, DC: National Committee on Quality Assurance (http://www.ncqa.org/tabid/1274/Default.aspx).
   

2. 2

   Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH. Updating the Beers criteria for potentially inappropriate medication use in older adults: results of a US consensus panel of experts. Arch Intern Med 2003;163:2716-2724[Erratum, Arch Intern Med 204;164:298.]
   CrossRef | Web of Science | Medline

3. 3

   Hilmer SN, Gnjidic D. The effects of polypharmacy in older adults. Clin Pharmacol Ther 2009;85:86-88
   CrossRef | Web of Science

4. 4

   Inouye SK, Studenski S, Tinetti ME, Kuchel GA. Geriatric syndromes: clinical, research, and policy implications of a core geriatric concept. J Am Geriatr Soc 2007;55:780-791
   CrossRef | Web of Science

Author/Editor Response

We agree with Hohl and colleagues that validation against a criterion standard is important in evaluating public health surveillance systems. In fact, the evaluation of the NEISS-CADES system against a criterion standard in 2004 identified underreporting (not overreporting) of adverse drug events involving bleeding and hypoglycemia, as compared with other types of adverse drug events.1 The issue underlying the suggestion that bleeding and hypoglycemia may be overrepresented relates to the definition of an adverse drug event. We adopted a definition that is commonly used by clinicians and policymakers for addressing patient safety — “harm caused by the use of a drug” — which generally includes adverse drug reactions, supratherapeutic effects, and administration errors.2 The studies cited by Hohl et al. also include patient nonadherence, improper drug selection, untreated indication, and use of subtherapeutic doses as drug-related adverse events.3 Although patients' nonadherence and clinicians' failure to select optimal drug therapies or doses are certainly important problems, we find it difficult to consider cases in which the patient was not taking the drug or in which the patient's underlying condition worsened to be cases of drug-induced harm.

We agree with Gnjidic and Hilmer that the contribution of medications to geriatric conditions such as cognitive impairment and falls may not be recognized in emergency settings. But even when the use of high-risk medications is identified, because these syndromes typically involve the interaction of multiple factors, decisively determining a causal role for these medications is a diagnostic challenge.4 Nevertheless, we recognize that a public health surveillance system that is based on emergency department documentation is limited to the information charted by the treating physician. We also agree with both correspondents that with improvements in clinical documentation, public health surveillance of adverse drug events could potentially identify additional events. However, the possibility of detection bias (additional events might be detectable by other methods) does not negate the absolute findings of tens of thousands of emergency hospitalizations of older adults that are attributed to antithrombotic and antidiabetic agents every year.

Daniel S. Budnitz, M.D., M.P.H.
Maribeth C. Lovegrove, M.P.H.
Nadine Shehab, Pharm.D., M.P.H.
Centers for Disease Control and Prevention, Atlanta, GA
dbudnitz@cdc.gov

Since publication of their article, the authors report no further potential conflict of interest.

4 References

1. 1

   Assessing the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project -- six sites, United States, January 1-June 15, 2004. MMWR Morb Mortal Wkly Rep 2005;54:380-383
   

2. 2

   Nebeker JR, Barach P, Samore MH. Clarifying adverse drug events: a clinician's guide to terminology, documentation, and reporting. Ann Intern Med 2004;140:795-801
   Web of Science

3. 3

   Zed PJ, Abu-Laban RB, Balen RM, et al. Incidence, severity and preventability of medication-related visits to the emergency department: a prospective study. CMAJ 2008;178:1563-1569
   CrossRef | Web of Science

4. 4

   Inouye SK, Studenski S, Tinetti ME, Kuchel GA. Geriatric syndromes: clinical, research, and policy implications of a core geriatric concept. J Am Geriatr Soc 2007;55:780-791
   CrossRef | Web of Science