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Relationship between medication errors and adverse drug events.

OBJECTIVE: To evaluate the frequency of medication errors using a multidisciplinary approach, to classify these errors by type, and to determine how often medication errors are associated with adverse drug events (ADEs) and potential ADEs. DESIGN: Medication errors were detected using self-report by pharmacists, nurse review of all patient charts, and review of all medication sheets. Incidents that were thought to represent ADEs or potential ADEs were identified through spontaneous reporting from nursing or pharmacy personnel, solicited reporting from nurses, and daily chart review by the study nurse. Incidents were subsequently classified by two independent reviewers as ADEs or potential ADEs. SETTING: Three medical units at an urban tertiary care hospital. PATIENTS: A cohort of 379 consecutive admissions during a 51-day period (1,704 patient-days). INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Over the study period, 10,070 medication orders were written, and 530 medications errors were identified (5.3 errors/100 orders), for a mean of 0.3 medication errors per patient-day, or 1.4 per admission. Of the medication errors, 53% involved at least one missing dose of a medication; 15% involved other dose errors, 8% frequency errors, and 5% route errors. During the same period, 25 ADEs and 35 potential ADEs were found. Of the 25 ADEs, five (20%) were associated with medication errors; all were judged preventable. Thus, five of 530 medication errors (0.9%) resulted in ADEs. Physician computer order entry could have prevented 84% of non-missing dose medication errors, 86% of potential ADEs, and 60% of preventable ADEs. CONCLUSIONS: Medication errors are common, although relatively few result in ADEs. However, those that do are preventable, many through physician computer order entry.

Boston↗

Practical approach to determining costs and frequency of adverse drug events in a health care network.

The frequency, preventability, severity, root causes, and projected costs of adverse drug events (ADEs) occurring after or causing admission to a four-hospital integrated academic health network were studied. The sample included all admissions during a 53-day study period. Events were identified through daily record review of a random patient sample, computerized flags, and self-reporting. A case review committee validated the occurrence, classification, and root causes of the events. Additional length of stay and costs associated with ADEs were analyzed by using a case-control, multiple linear regression model. The estimated ADE rate during hospitalization was 4.2 events per 100 admissions, with a cost of $2162 per ADE. In addition, 3.2% of admissions were caused by ADEs, with an associated cost of $6685 per event. Fifteen percent of hospital ADEs and 76% of ADEs causing admission were judged preventable. The annual cost to the organization for events occurring during hospitalization was $1.7 million, and the cost of preventable ADEs was $260,000, while the projected costs of preventable ADEs causing admission were $3.8 million. The rate of admissions to the mental health center caused by ADEs was higher than for other settings at 13.6%, with a cost of preventable ADEs of $1.3 million. Patient noncompliance was judged to be the cause of the 69% of the ADEs causing admission. Seventy-one percent of the serious medication errors occurred at the prescribing stage of the medication-use process. ADEs were frequent, costly, and often preventable and resulted in many admissions to a mental health center.

Costs and Cost Analysis↗

Medication errors and adverse drug events in pediatric inpatients.

CONTEXT: Iatrogenic injuries, including medication errors, are an important problem in all hospitalized populations. However, few epidemiological data are available regarding medication errors in the pediatric inpatient setting. OBJECTIVES: To assess the rates of medication errors, adverse drug events (ADEs), and potential ADEs; to compare pediatric rates with previously reported adult rates; to analyze the major types of errors; and to evaluate the potential impact of prevention strategies. DESIGN, SETTING, AND PATIENTS: Prospective cohort study of 1120 patients admitted to 2 academic institutions during 6 weeks in April and May of 1999. MAIN OUTCOME MEASURES: Medication errors, potential ADEs, and ADEs were identified by clinical staff reports and review of medication order sheets, medication administration records, and patient charts. RESULTS: We reviewed 10 778 medication orders and found 616 medication errors (5.7%), 115 potential ADEs (1.1%), and 26 ADEs (0.24%). Of the 26 ADEs, 5 (19%) were preventable. While the preventable ADE rate was similar to that of a previous adult hospital study, the potential ADE rate was 3 times higher. The rate of potential ADEs was significantly higher in neonates in the neonatal intensive care unit. Most potential ADEs occurred at the stage of drug ordering (79%) and involved incorrect dosing (34%), anti-infective drugs (28%), and intravenous medications (54%). Physician reviewers judged that computerized physician order entry could potentially have prevented 93% and ward-based clinical pharmacists 94% of potential ADEs. CONCLUSIONS: Medication errors are common in pediatric inpatient settings, and further efforts are needed to reduce them.

Adolescent↗

Identifying hospital admissions due to adverse drug events using a computer-based monitor.

BACKGROUND: Hospital admissions due to adverse drug events (ADEs) are expensive, and many may be preventable, yet few institutions have ongoing surveillance for these events. OBJECTIVE: To evaluate the use of a computer-based ADE monitor to identify admissions due to ADEs and to measure the associated costs. DESIGN: Prospective cohort study in one tertiary care hospital. PARTICIPANTS: All patients admitted to nine medical and surgical units in a tertiary care hospital over an 8-month period. MAIN OUTCOME MEASURE: Admissions to the hospital due to an adverse drug event. METHODS: A computer-based monitoring program generated alerts suggesting that an ADE might be present. A trained reviewer then evaluated the record. RESULTS: Among the 3238 admissions, 76 (2.3%, 1.4% after adjusting for sampling) were found to be caused by an ADE. Of these ADEs, 78% were severe and 28% were preventable. Estimated costs were $16,177 per ADE, and $10,375 per preventable ADE; annualized costs to the hospital were $6.3 million per year for all ADEs, and $1.2 million for preventable ADEs. CONCLUSIONS: Many admissions were caused by ADEs, although our point estimate undoubtedly represents a lower bound. These events were mostly severe, often preventable, and expensive. The computer-based monitoring system represents a practical approach for identifying ADEs that occur in outpatients and cause admission to the hospital.

Adult↗

[Adverse drug effects: a prospective study by Apnet performed in seven emergency care units in France: propositions for preventive measures].

Various studies have shown that adverse drug effects (ADEs) are a substantial cause of hospital admissions. However, little is known about the incidence and severity of ADEs resulting in hospital visits. To address this issue, we conducted a prospective survey in primary care and emergency departments of French public hospitals. This study was performed over two periods of one week, one in January, February and one in June 2003, in primary care and emergengy departments of four university hospitals and three general hospitals throughout France. Out of a total of 1826 patients consulting, 1663 were taking at least one drug during the previous week and were included for analysis according to the protocol. Altogether, 370 (22.2%; IC 95: 20.2-24.3%) of these patients receiving at least one drug consulted because of an ADE. From these 370 patients, 263 (15.8%) where considered as touched by a probably (12), likely (13) or very likely (14) ADE. The sex ratio was the same in both groups with or without ADE (0.88%; P=0.95). Patients with ADE were older than those without (62.4 vs 53.8 years, P=0.0016). Furthermore, ADE patients were more likely to have a higher severity score than no-ADE group (P=0.0003). The outcome seemed to be worse in patients with an ADE. The percentage of patients treated with 2 or more drugs and the number of drug exposures were significantly higher in patients with ADE than in those without (93.2% vs 84.2%, P<0.0001, and 5.8 vs 4.5 P<0.0001, respectively). The most frequent causes of visits for ADE-patients were digestive (n=38: 14.4%), neurological (n=23: 10.6%), malaise (n=48: 18,2%) events. The most frequently incriminated drug classes were (1) psychotropic agents, (including anxiolytics, hypnotics, antidepressants and antipsychotics), (2) diuretics (3) anticoagulants, (4) other cardiovascular drugs and (5) analgesics, including non steroidal anti-inflammatory agents. In 150 cases (40.8%; IC 95: 33.7% - 45%), the ADE was considered to be preventable because a contra-indication or a warning about drug use had not been respected.

Adult↗

Using computerized data to identify adverse drug events in outpatients.

OBJECTIVE: To evaluate the use of a computer program to identify adverse drug events (ADEs) in the ambulatory setting and to evaluate the relative contribution of four computer search methods for identifying ADEs, including diagnosis codes, allergy rules, computer event monitoring rules, and text searching. DESIGN: Retrospective analysis of one year of data from an electronic medical record, including records for 23,064 patients with a primary care physician, of whom 15,665 actually came for care. MEASUREMENT: Presence of an ADE; sensitivity and specificity of computer searches for ADE. RESULTS: The computer program identified 25,056 incidents, which were associated with an estimated 864 (95 percent confidence interval [CI], 750-978) ADES. Thus, the ADE rate was 5.5 (CI, 5.2-5.9) per 100 patients coming for care. Furthermore, in 79 (CI, 68-89) ADEs, the patient required hospitalization, resulting in an estimated rate of 3.4 (CI, 2.7-4.3) admissions per 1,000 patients. The sensitivity of the search methods for identifying ADEs was estimated to be 58 (CI, 18-98) percent, and the estimated specificity was 88 (CI, 87-88) percent. The positive predictive value was 7.5 (CI, 6.5-8.5) percent, and the negative predictive value was 99.2 (CI, 95.5-99.98) percent. Compared with age and gender-matched controls with no positive screen, patients with ADEs had twice as many outpatient visits and were taking nearly three times as many drugs. Antihypertensives, ACE-inhibitors, antibiotics, and diuretics were associated with 56 (CI, 47-65) percent of ADES. Among ADEs, 23 (CI, 16-32) percent were life-threatening or serious, and 38 (CI, 29-47) percent were judged preventable. CONCLUSION: Computerized search programs can detect ADEs, and free-text searches were especially useful. Adverse drug events were frequent, and admissions were not rare, although most hospitals today do not identify them. Thus, such detection programs demonstrate "value-added" for the electronic record and may be useful for directing and assessing the impact of quality improvement efforts.

Adverse Drug Reaction Reporting Systems↗

Adverse Drug Events Involving COX-2 Inhibitors.

OBJECTIVE: To describe the types and severity of adverse drug-related events (ADEs) observed in patients receiving cyclooxygenase-2 (COX-2) inhibitors and to increase the awareness of risk factors that predispose patients to ADEs associated with COX-2 inhibitors. METHODS: A review of ADEs reported at the University of Pittsburgh Medical Center Presbyterian Hospital (UPMC-P) revealed significant events related to use of celecoxib or rofecoxib. A query of the internal ADE database was performed to identify ADEs involving COX-2 inhibitors from January 1999 to June 2002. A similar query was performed to identify ADEs involving nonselective nonsteroidal antiinflammatory drugs (NSAIDs) reported during this same time period. Utilization data were also collected. RESULTS: Forty-eight ADEs involving 24 patients receiving COX-2 inhibitors were reported and validated via the UPMC-P ADE review process compared with 38 events in 33 patients receiving nonselective NSAIDs. The types of ADEs reported as related to COX-2 inhibitors were similar to those reported in association with nonselective NSAIDs. Forty-two percent of ADEs (n = 20) involving COX-2 inhibitors and 45% of events (n = 17) involving nonselective NSAIDs were classified as severe. All patients receiving COX-2 inhibitors and 91% of patients receiving nonselective NSAIDs exhibited risk factors that increased their risk to experience an ADE; all but 1 of these patients were receiving outpatient COX-2 inhibitor therapy. CONCLUSIONS: The observed ADEs involving COX-2 inhibitors were similar to those associated with nonselective NSAIDs. Most events may have been preventable, highlighting the need for education regarding the appropriate use of COX-2 inhibitors.

Adult↗

The quality of published adverse drug event reports.

BACKGROUND: Case reports of adverse drug events (ADEs) are an important source of information. OBJECTIVE: To determine what variables are reported in ADE case reports, how causality was assessed for each report, and what criteria are specified for publishing ADE case reports. METHODS: A descriptive analysis of highly significant ADE case reports published in English over a 20-year period was performed. Main outcome measures included frequency distributions for the types of variables reported. The presence of causality assessment and the criteria for submitting an ADE report to practitioner journals were also examined. RESULTS: A highly significant ADE was described in 1520 published case reports during the study period. Three patient variables were reported >90% of the time, while 12 others were reported <25% of the time. Only 1 drug variable was reported >90% of the time; 6 others were reported 14-74% of the time. Most of the relevant ADE variables were reported most often. Added information for drug interactions, medication errors, and allergic drug reactions were reported 61-99% of the time. Less than 1% of ADE reporters objectively assessed the probability of the ADE. All but one journal publishing the most ADE reports did not require such assessment. CONCLUSIONS: Professional journals might consider stricter requirements for publishing ADE reports. As a minimum, requirements should include an objective assessment of ADE causality, with explicit recognition in the published text and abstract of the report.

Adverse Drug Reaction Reporting Systems↗

Adverse-drug-event rates for high-cost and high-use drugs in the intensive care unit.

PURPOSE: The rates of adverse drug events (ADEs) associated with high-cost and high-use drugs in the intensive care unit (ICU) were studied. METHODS: This retrospective analysis was conducted from October 1997 through June 2001 in a 647-bed academic medical center with over 120 ICU beds. Adult patients with a documented ADE occurring in the ICU were included in the analysis. ADE information, including suspected medication, causality, preventability, and severity, was extracted from the institutional ADE database. Published definitions of ADEs and published scales for causality and severity assessments were used. High-cost medications were those in the top 50% of cumulative ICU medication costs, and high-use medications accounted for the upper 50% of all medications used in the ICU. Between-group comparisons of ADE rates, preventability, and severity associated with high-cost and high-use medications were conducted. RESULTS: Of the 17 medications that were considered high cost, 9 (53%) were associated with ADEs. Of the 15 medications that met the criteria for high-use drugs, 12 (80%) were associated with ADEs. The rates of ADEs associated with high-cost and high-use drugs did not significantly differ (43% versus 75%, respectively; p = 0.098). ADEs associated with high-cost and high-use medications were categorized as mild (15% versus 10%, respectively), moderate (52% versus 50%, respectively), and severe (33% versus 40%, respectively) (p > 0.05). CONCLUSION: The frequency, severity, and preventability of ADEs in the ICU were not associated with a drug's cost or frequency of use. Monitoring priorities of the critical care pharmacist should not be dictated by cost alone but should include frequency of use and the potential for causing an ADE.

Drug Costs↗

[Adverse drug effects observed at French admissions departments and emergency services (Prospective study of the National Educational Association for Teaching Therapeutics and proposals for preventive measures].

Various studies have shown that adverse drug events (ADE) are a substantial cause of hospital admissions. However, little is known about the incidence and severity of ADE resulting in hospital visits. To address this issue, we conducted a prospective survey in 10 primary care and emergency departments of French public hospitals. This study was performed over two periods of one week, one in June 1999 and one in December 1999, in primary care and emergency departments of five university hospitals and five general hospitals throughout France. Out of a total of 1,937 patients consulting, 1,562 were taking at least one drug during the previous week and were included for analysis according to the protocol. Altogether, 328 (21%; 95% confidence interval 19% to 23%) of these patients receiving at least one drug consulted because of an ADE. The sex ratio (M/F) was the same in both groups with or without ADE (1.04 vs 1.02, respectively, P = 0.83). Patients with ADE were older than those without (63.5 vs 54.8 years, P < 0.0001). Furthermore, ADR patients were more likely to have a higher severity score than no-ADE group (P = 0.019). The outcome seemed to be worse in patients with an ADE. The percentage of patients treated with 2 or more drugs and the number of drug exposures were significantly higher in patients with ADE than in those without (90.9% vs 75.0%, P < 0.0001, and 5.17 vs 3.82, P < 0.0001, respectively). The most frequent causes of visits for ADE-patients were digestive (n = 53, 16.2%), neurological (n = 52, 15.9%), cardiovascular (n = 49, 14.9%) and malaise (n = 49, 14.9%) events. In total, 410 drugs were incriminated in the occurrence of 328 ADE. The most frequently incriminated drug classes were (1) psychotropic agents, including anxiolytics and/or hypnotics, antidepressants and antipsychotics (n = 84, 20.5%), (2) diuretics (n = 48, 11.7%), (3) anticoagulants (n = 38, 9.3%), (4) other cardiovascular drugs (n = 63, 15.4%), and (5) analgesics, including non steroidal antiinflammatory agents (n = 57, 13.9%). The avoidability of ADE could be estimated by an external expert panel in 280 of the 328 cases. In 106 cases (37.9%), ADE was considered to be preventable because a contra-indication or a warning about drug use had not been respected.

Adult↗

Incidence and preventability of adverse drug events in hospitalized adults.

OBJECTIVE: To evaluate the incidence and preventability of adverse drug events (ADEs) and to determine the yield of several strategies for identifying them. DESIGN: Prospective cohort study. SETTING: Seven units, including two medical, two surgical, and two obstetric general care units and a coronary intensive care unit in an urban tertiary care hospital. PATIENTS: All patients on these units over a 37-day period (2,967 patient-days). INTERVENTION: None. METHODS: Events were identified in three ways: 1) logs were placed on each unit and satellite pharmacy for nurses and pharmacists to record incidents; 2) a research nurse solicited reports of incidents twice daily on each unit; and 3) the nurse reviewed all charts at least daily. Incidents were classified by two independent reviewers as ADEs or potential ADEs. RESULTS: The rate of drug-related incidents was 73 in 2,967 patient-days; 27 incidents were judged ADEs, 34 potential ADEs, and 12 problem orders. Fifty different drugs were involved. Physicians were primarily responsible for 72% of the incidents, with the remainder divided evenly between nursing, pharmacy, and clerical personnel. Of the 27 ADEs, five were life-threatening, nine were serious, and 13 were significant. Fifteen (56%) of the 27 were judged definitely or probably preventable. Incidents were discovered about equally often from the logs and by chart review. However, when the incidents in which an ADE was present were compared with the remainder of incidents, the authors found that 67% (18 of 27) of the ADEs were identified only by chart review (p < 0.001), and physicians were more often judged responsible than other personnel (p < 0.001). CONCLUSIONS: The authors conclude that ADEs are not infrequent, often preventable, and usually caused by physician decisions. In this study, solicited reporting by nurses and pharmacists was inferior to chart review for identifying ADEs, but was effective for identifying potential ADEs. Optimal prevention strategies should cover many types of drugs and target physicians' ordering practices.

Adult↗

Comparison of 'sequential' versus 'standard' chemotherapy as re-induction treatment, with or without cyclosporine, in refractory/relapsed acute myeloid leukaemia (AML): results of the UK Medical Research Council AML-R trial.

This aim of the acute myeloid leukaemia (AML)-R trial was to compare sequential (Seq) ADE (cytarabine, daunorubicin, etoposide) with standard (Std) ADE as remission re-induction treatment and to assess any benefit of cyclosporine (CSA) as a multidrug resistance modulator in refractory/relapsed AML patients. Seq ADE, based on the concept of Timed Sequential Therapy, comprised the same drugs as Std ADE but given at higher doses and in a different sequence. Between 1992 and 1997, 235 patients with relapsed (175) and refractory (60) AML were entered: 170 were randomized between Std versus Seq ADE and 213 between CSA versus no CSA. CSA was initially given at a dose of 5 mg/kg/d and increased to 10 mg/kg/d in the latter part of the trial. Overall, the complete remission (CR) rate was 43%, with Std ADE being significantly better than Seq ADE (54% versus 34%, P = 0.01). CR rates did not differ between the CSA and no CSA arms (41% versus 45%, P = 0.6). Overall, 3 year disease-free survival (DFS) of remitters was 16%, with a relapse risk of 70%. DFS was not significantly different between the chemotherapy or the CSA arms. Overall, 3 year survival was 8%. Survival with Std ADE was significantly better than with Seq ADE (12% versus 6%, P = 0.03). CSA did not affect overall survival, except in patients > or = 60 years, who fared worse on CSA (P = 0.0003). No difference in haematological toxicity between the chemotherapy or CSA arms was seen. Survival was better with longer first CR duration (P < 0.0001). We conclude that Std ADE was superior to Seq ADE for CR achievement and survival, with no benefit with CSA, at the doses used in this study.

Acute Disease↗

Potential risks and prevention, Part 1: Fatal adverse drug events.

Potential risk factors for and the preventability of fatal adverse drug events (ADEs) were studied. Case reports of ADEs published in Clin-Alert during 1976-95 were the source of information on fatal ADEs, Patient, drug, and event variables were identified, and the causality, predictability, and preventability of each case were assessed. Data were entered into a relational database for analysis. The data indicated 447 cases involving a fatal ADE. Ten percent of the fatal ADEs were assessed as definite, 46% as probable, and 44% as possible. Fatal-ADE frequency increased with age. Forty-five percent of the patients were 40-69 years of age, and 40% were healthy. Central-nervous-system agents, antineoplastics, antimicrobials, and cardiovascular agents accounted for 69% of the deaths. Only 33% of patients received more than the usual dosage. Many of the suspected drugs could have been monitored with blood level tests but were not, and baseline testing of critical blood count and liver and renal function was often not performed. The most common causes of death were hepatitis, hepatic failure, cardiopulmonary arrest, overdose, and agranulocytosis. ADE types were distributed as adverse drug reactions (58%), allergic reactions (19%), medication errors (17%), and drug interactions (6%). Sixty-eight percent of the fatal ADEs were judged to have been preventable; of these, a pharmacist could have prevented 57%. Litigation was reported for 14% of the fatal-ADE cases; judgments and settlements averaged $1.1 million. A review of published case reports of ADEs for 1976-95 yielded information on possible risk factors for fatal ADEs and on which events may have been preventable.

Adverse Drug Reaction Reporting Systems↗

Identification and quantitation of DNA adducts from calf thymus DNA exposed to 3,4-epoxy-1-butene.

3,4-Epoxy-1-butene (EB) is the major mutagenic metabolite of butadiene (BD), an important industrial chemical classified as a probable human carcinogen. Although the mechanism of carcinogenicity of EB is not known, its reactions with nucleophilic sites of DNA giving pro-mutagenic lesions are likely to constitute the early crucial step in multistage carcinogenesis. This study was conducted to characterize the adducts formed from reactions of EB with the most nucleophilic DNA nucleobases, adenine (Ade) and guanine (Gua), as free nucleobases, 2'-deoxyribonucleosides and constituents of calf thymus DNA (CT DNA) in order to provide insight into the nature of DNA modification by EB. The adducts were isolated using HPLC separation coupled with diode array detection (DAD) and structurally characterized from their electronic, mass- and nuclear magnetic resonance spectra. Four EB-adenine products were identified as N-1-(2-hydroxy-3-buten-1-yl) adenine (EB-Ade I), N-1-(1-hydroxy-3-buten-2-yl) adenine (EB-Ade II), N-3-(2-hydroxy-3-buten-1-yl) adenine (EB-Ade III) and N-3-(1-hydroxy-3-buten-2-yl) adenine (EB-Ade IV). Two previously reported guanine adducts: N-7-(2-hydroxy-3-buten-1-yl) guanine (EB-Gua I) and N-7-(1-hydroxy-3-buten-2-yl) guanine (EB-Gua II) were also collected. The purified adducts were used as reference compounds to detect and quantitate the corresponding adduct species formed in calf thymus DNA incubated with EB. All six adducts were detected in treated DNA. The N-7 position of guanine was the most reactive in DNA followed by N-3 of adenine and N-1 of adenine. The formation of N-1 and N-3-adenine adducts (EB-Ade I, 1.2 +/- 0.36; EB-Ade II, 0.8 +/- 0.27; EB-Ade III, 2.7 +/- 0.38; EB-Ade IV, 5.9 +/- 0.68 nmol/micromol Ade) in CT DNA was approximately one-tenth that of EB-guanine adducts (50.7 +/- 2.37 and 47.9 +/- 3.6 nmol/micromol Gua, respectively). The N-1-EB-Ade adducts detected in this study are likely to be the precursors of previously reported N6-EB-adenine adducts (Koivisto et al., 1995) through Dimroth rearrangement. Since BD and EB induce significant numbers of point mutations at A:T base pairs, the EB-adenine adducts may represent important lesions involved in BD-induced mutagenesis and carcinogenesis.

Adenine↗

Update on adverse drug events associated with parenteral iron.

BACKGROUND: We previously compared the safety profile of three formulations of intravenous iron used during 1998-2000 and found higher rates of adverse drug events (ADEs) associated with the use of higher molecular weight iron dextran and sodium ferric gluconate complex compared with lower molecular weight iron dextran. Since that time, iron sucrose has become widely available and clinicians have gained additional experience with sodium ferric gluconate complex. METHODS: We obtained data from the United States Food and Drug Administration (FDA) on ADEs attributed to the provision of four formulations of intravenous iron during 2001-2003, including higher and lower molecular weight iron dextran, sodium ferric gluconate complex and iron sucrose. We estimated the odds of intravenous iron-related ADEs using 2 x 2 tables and the chi(2) test. RESULTS: The total number of reported parenteral iron-related ADEs was 1141 among approximately 30,063,800 doses administered, yielding a rate of 3.8 x 10(-5), or roughly 38 per million. Eleven individuals died in association with the ADE. Relative to lower molecular weight iron dextran, total and life-threatening ADEs were significantly more frequent among recipients of higher molecular weight iron dextran and significantly less frequent among recipients of sodium ferric gluconate complex and iron sucrose. The absolute rates of life-threatening ADEs were 0.6, 0.9, 3.3 and 11.3 per million for iron sucrose, sodium ferric gluconate complex, lower molecular weight iron dextran and higher molecular weight iron dextran, respectively. Based on differences in the average wholesale price of iron sucrose and lower molecular weight iron dextran in the US, the cost to prevent one life-threatening ADE related to the use of lower molecular weight iron dextran was estimated to be 5.0-7.8 million dollars. The cost to prevent one lower molecular weight iron dextran-related death was estimated to be 33 million dollars. CONCLUSIONS: The frequency of intravenous iron-related ADEs reported to the FDA has decreased, and overall, the rates are extremely low. This is the fourth report suggesting increased risks associated with the provision of higher molecular weight iron dextran. Life-threatening and other ADEs appear to be lower with the use of non-dextran iron formulations, although the cost per ADE prevented is extremely high.

Adverse Drug Reaction Reporting Systems↗

Adverse drug events in trauma patients.

BACKGROUND: Adverse drug events (ADEs) are noxious and unintended results of drug therapy. ADEs have been shown to be a risk to hospitalized patients. The purpose of this study was to determine the rate and nature of ADEs in trauma patients and to characterize the population at risk. METHODS: An electronic medical record, a hospital wide computerized surveillance program, and a clinical pharmacist prospectively investigated ADEs in 4,320 trauma patients from 1996 through 1999. RESULTS: The rate of ADEs in trauma patients (98/4320, 2.3%) was twice that of non-trauma hospital patients (1,111/96,218, 1.2%, p < 0.001). Traumatized females had ADEs 1.5 times more often than traumatized males (2.7% versus 1.8%, p = 0.052). The medication class most often associated with ADEs was analgesics with 54% involving morphine and 20% involving meperidine. The most common ADEs were nausea, vomiting, and itching. Only one ADE was directly attributed to a medical error. CONCLUSIONS: Trauma patients are at double the risk for ADEs. Analgesics are particularly associated with ADEs and use should be carefully monitored.

Adolescent↗

Nonfatal adverse reactions to iodinated contrast media: spontaneous reporting to the U.S. Food and Drug Administration, 1978-1994.

PURPOSE: To identify any changes in the frequency of serious, nonfatal adverse drug events (ADEs) reported to the U.S. Food and Drug Administration in 1978-1994 since the introduction of low-osmolality contrast media (LOCM). MATERIALS AND METHODS: Reports of ADEs submitted were reviewed for use of iodinated contrast media. RESULTS: The estimated 170 million contrast medium-enhanced radiologic studies performed in 1978-1994 produced 22,785 reports of mild or moderate ADEs, 2,639 reports of serious but nonfatal ADEs, and 920 reports of death. The most common ADEs (urticaria, dyspnea, vomiting, pruritus, facial edema, and hypotension) ranked similarly for ionic and nonionic contrast media. High-osmolality contrast media were associated with 512 serious, nonfatal ADEs reported in 1978-1986; 1,068 were reported in 1987-1994. Nonionic LOCM were associated with 17 serious, nonfatal ADEs reported in 1978-1986; 609 were reported in 1987-1994. Intrathecal injection of nonionic contrast media was associated with 235 reported serious, nonfatal ADEs; intrathecal ionic [corrected] contrast media were associated with 14 such reported ADEs. CONCLUSION: Reports of serious, nonfatal ADEs are uncommon relative to the use of contrast media. The authors observed no decrease in the number of ADEs reported since the introduction of LOCM but did not consider marketing trends or secular reporting trends.

Adverse Drug Reaction Reporting Systems↗

Strategies for detecting adverse drug events among older persons in the ambulatory setting.

OBJECTIVE: To examine various strategies for the identification of adverse drug events (ADEs) among older persons in the ambulatory clinical setting. DESIGN: A cohort study of Medicare enrollees (n = 31,757 per month) receiving medical care from a large multispecialty group practice during a 12-month observation period (July 1, 1999 through June 30, 2000). MEASUREMENTS: Possible drug-related incidents occurring in the ambulatory clinical setting were detected using signals from multiple sources. RESULTS: During the tracking period, there were 1,523 identified ADEs, of which 421 (28%) were considered preventable. Across all sources, 23,917 signals were found; 12,791 (53%) were potential incidents that led to review of a patient's medical record and 2,266 (9%) were presented to physician reviewers. Although the positive predictive value (PPV) for reports from providers was high compared with other sources (54%), only 11% of the ADEs and 6% of the preventable ADEs were identified through this source. PPVs for other sources ranged from a low of 4% for administrative incident reports to a high of 12% for free-text review of electronic notes. Computer-generated signals were the source for 31% of the ADEs and 37% of the preventable ADEs. Electronic notes were the source for 39% of the ADEs and 29% of the preventable ADEs. There was little overlap in the ADEs identified across all sources. CONCLUSION: Our findings emphasize the limitations of voluntary reporting by health care providers as the principal means for detection of ADEs and suggest that multiple strategies are required to detect ADEs in geriatric ambulatory patients.

Adverse Drug Reaction Reporting Systems↗