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Identifying adverse drug events: development of a computer-based monitor and comparison with chart review and stimulated voluntary report.

BACKGROUND: Adverse drug events (ADEs) are both common and costly. Most hospitals identify ADEs using spontaneous reporting, but this approach lacks sensitivity; chart review identifies more events but is expensive. Computer-based approaches to ADE identification appear promising, but they have not been directly compared with chart review and they are not widely used. OBJECTIVES: To develop a computer-based ADE monitor, and to compare the rate and type of ADEs found with the monitor with those discovered by chart review and by stimulated voluntary report. 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 eight-month period. MAIN OUTCOME MEASURE: Adverse drug events identified by the computer-based monitor, by chart review, and by stimulated voluntary report. METHODS: A computer-based monitoring program identified alerts, which were situations suggesting that an ADE might be present (e.g., an order for an antidote such as naloxone). A trained reviewer then examined patients' hospital records to determine whether an ADE had occurred. The results of the computer-based monitoring strategy were compared with two other ADE detection strategies: intensive chart review and stimulated voluntary report by nurses and pharmacists. The monitor and the chart review strategies were independent, and the reviewers were blinded. RESULTS: The computer monitoring strategy identified 2,620 alerts, of which 275 were determined to be ADEs. The chart review found 398 ADEs, whereas voluntary report detected 23. Of the 617 ADEs detected by at least one method, 76 ADEs were detected by both computer monitor and chart review. The computer monitor identified 45 percent; chart review, 65 percent; and voluntary report, 4 percent. The ADEs identified by computer monitor were more likely to be classified as "severe" than were those identified by chart review (51 versus 42 percent, p = .04). The positive predictive value of computer-generated alerts was 16 percent during the first eight weeks of the study; rule modifications increased this to 23 percent in the final eight weeks. The computer strategy required 11 person-hours per week to execute, whereas chart review required 55 person-hours per week and voluntary report strategy required 5. CONCLUSIONS: The computer-based monitor identified fewer ADEs than did chart review but many more ADEs than did stimulated voluntary report. The overlap among the ADEs identified using different methods was small, suggesting that the incidence of ADEs may be higher than previously reported and that different detection methods capture different events. The computer-based monitoring system represents an efficient approach for measuring ADE frequency and gauging the effectiveness of ADE prevention programs.

Adverse Drug Reaction Reporting Systems↗

Prevention of adverse drug events through computerized surveillance.

Adverse drug events (ADEs) are a serious health problem and are the leading adverse event experienced by hospitalized patients. Numerous hospitals have used different methods to improve the reporting of ADEs but few have undertaken studies aimed at the prevention of ADEs. We found that computerized ADE surveillance identified significantly more ADEs than our previous voluntary reporting method. Moreover, the computerized ADE surveillance system created a database of ADEs which allowed us to analyze the ADEs and design methods for prevention. We found that computer alerts of previously known drug allergies generated when drugs were ordered significantly reduced the number of type B ADEs, 56 vs 8 (p < 0.001). In addition, we found that the timely surveillance of ADEs combined with physician notification reduced the number of severe ADEs, 41 vs 12 (p < 0.001). Initial analysis of the ADE database has shown that on average patients with type B ADEs are hospitalized longer (17 vs 14 days) and have larger hospitalization costs ($30,617 vs $23,256) than patients with type A ADEs. Patients with severe ADEs also are hospitalized longer (20 vs 13 days) and have larger hospitalization costs ($38,007 vs $22,474) than patients with moderate ADEs. This indicates that the prevention and early treatment of ADEs can reduce the length of hospitalization and result in a considerable cost savings to the hospital.

Clinical Pharmacy Information Systems↗

Analysis of medication-related malpractice claims: causes, preventability, and costs.

BACKGROUND: Adverse drug events (ADEs) may lead to serious injury and may result in malpractice claims. While ADEs resulting in claims are not representative of all ADEs, such data provide a useful resource for studying ADEs. Therefore, we conducted a review of medication-related malpractice claims to study their frequency, nature, and costs and to assess the human factor failures associated with preventable ADEs. We also assessed the potential benefits of proved effective ADE prevention strategies on ADE claims prevention. METHODS: We conducted a retrospective analysis of a New England malpractice insurance company claims records from January 1, 1990, to December 31, 1999. Cases were electronically screened for possible ADEs and followed up by independent review of abstracts by 2 physician reviewers (T.K.G. and R.K.). Additional in-depth claims file reviews identified potential human factor failures associated with ADEs. RESULTS: Adverse drug events represented 6.3% (129/2040) of claims. Adverse drug events were judged preventable in 73% (n = 94) of the cases and were nearly evenly divided between outpatient and inpatient settings. The most frequently involved medication classes were antibiotics, antidepressants or antipsychotics, cardiovascular drugs, and anticoagulants. Among these ADEs, 46% were life threatening or fatal. System deficiencies and performance errors were the most frequent cause of preventable ADEs. The mean costs of defending malpractice claims due to ADEs were comparable for nonpreventable inpatient and outpatient ADEs and preventable outpatient ADEs (mean, $64,700-74,200), but costs were considerably greater for preventable inpatient ADEs (mean, $376,500). CONCLUSIONS: Adverse drug events associated with malpractice claims were often severe, costly, and preventable, and about half occurred in outpatients. Many interventions could potentially have prevented ADEs, with error proofing and process standardization covering the greatest proportion of events.

Health Care Costs↗

Conformational preferences of anticodon 3'-adjacent hypermodified nucleic acid base cis-or trans-zeatin and its 2-methylthio derivative, cis-or trans- ms(2)zeatin.

Conformational preferences of the hypermodified nucleic acid bases N6-(Delta(2)-cis-hydroxyisopentenyl)adenine, cis-io(6)Ade also known as cis-zeatin, and N(6)-(Delta(2)-trans-hydroxyisopentenyl)adenine, trans-io(6)ade or trans-zeatin, and 2-methylthio derivatives of these cis-ms(2)io(6)Ade or cis-ms(2)zeatin, and trans-ms(2)io6Ade or trans-ms(2)zeatin have been investigated theoretically by the quantum chemical Perturbative Configuration Interaction with Localized Orbitals (PCILO) method. Automated geometry optimization using quantum chemical MNDO, AM1 and PM3 methods has also been made to compare the salient features. The predicted most stable conformation of cis-io(6)Ade, trans-io(6)Ade, cis-ms(2)io(6)Ade and trans-ms(2)io(6)Ade are such that in each of these molecules the isopentenyl substituent spreads away (has "dista" conformation) from the five membered ring imidazole moiety of the adenine. The atoms N(6), C(10) and C(11) remain coplanar with the adenine ring in the predicted preferred conformation for each of these molecules. In cis-io(6)Ade as well as cis-ms(2)io(6)Ade the hydroxyl oxygen may participate in intramolecular hydrogen bonding with the H-C(10)-H group. In trans-io(6)Ade the hydroxyl group is oriented towards the H-C(2) instead. This orientation is retained in trans-ms(2)io(6)Ade, possible O-H...S hydrogen bonding may be a stabilizing factor. In all these four modified adenines C(11)-H is favourably placed to participate in intramolecular hydrogen bonding with N(1). In cis-ms(2)io(6)Ade as well as trans-ms(2)io(6)Ade the 2-methylthio group preferentially orients on the same side as C(2)-N(3) bond, due to this non-obstrusive placing, orientation of the hydroxyisopentenyl substituent remains unaffected by 2-methylthiolation. Thus the N(1) site remains shielded irrespective of the 2-methylthiolation status in these various cis-and trans-zeatin analogs alike. Firmly held orientation of hydroxyisopentenyl substituent in zeatin isomers and derivatives, in contrast to adaptable orientation of isopentenyl substituent in i(6)Ade and ms(2)i(6)Ade, may account for the increased efficiency of suppressor tRNA and reduced codon context sensitivity accompanied with the occurrence of ms(2)-zeatin (ms(2)io(6)Ade) modification.

Anticodon↗

Adverse drug events in hospitalized elderly.

BACKGROUND: The study objectives were (a) to describe the occurrence, types, and preventability of adverse drug events (ADEs) in hospitalized patients 70 years of age and older; (b) to examine the association between potential risk factors and ADEs; and (c) to examine the relationship of an ADE occurrence and hospital length of stay (LOS) and functional decline. METHOD: Consecutive general medical admissions (n = 157) of community-dwelling persons were prospectively monitored daily for ADE occurrence. Admission assessment included demographic factors, cognition, preadmission medication use, and functional status. Discharge assessment included functional status. LOS, discharge diagnoses, and medication use during the hospitalization. RESULTS: Twenty-three patients (14.6%) experienced 28 probable ADEs, of which 54.2% (13/24) were judged to be potentially preventable. Patients experiencing an ADE had a significantly lower mean Mini-Mental State Examination score (23.6 +/- 4.3 vs 25.5 +/- 3.6, p = .039) and were prescribed significantly more new inpatient medications (4.0 +/- 2.3 vs 2.6 +/- 1.7, p = .01) compared to non-ADE patients. Age, gender, functional status prior to admission, percent with more than four active diagnoses, or number of preadmission medications were not associated with ADE status. Upon discharge, 50.0% of ADE patients experienced a decline in one or more activities of daily living (ADLs), compared with 24.1% of non-ADE patients (p = .017). ADE patients had a longer LOS (8.7 +/- 4.9 vs 6.6 +/- 3.0 days, p = .022) compared to non-ADE patients. CONCLUSIONS: ADEs were associated with number of new inpatient medications and admission cognitive status, but not demographic, disease, or physical function variables. Patients experiencing an ADE were more likely to experience a longer LOS and to decline in ADL function. ADEs may be one factor contributing to functional decline during hospitalization. Future research in this area should include larger samples and multivariable analyses controlling for potential confounders.

Activities of Daily Living↗

The costs of adverse drug events in hospitalized patients. Adverse Drug Events Prevention Study Group.

OBJECTIVE: To assess the additional resource utilization associated with an adverse drug event (ADE). DESIGN: Nested case-control study within a prospective cohort study. PARTICIPANTS: The cohort included 4108 admissions to a stratified random sample of 11 medical and surgical units in 2 tertiary-care hospitals over a 6-month period. Cases were patients with an ADE, and the control for each case was the patient on the same unit as the case with the most similar pre-event length of stay. MAIN OUTCOME MEASURES: Postevent length of stay and total costs. METHODS: Incidents were detected by self-report stimulated by nurses and pharmacists and by daily chart review, and were classified as to whether they represented ADEs. Information on length of stay and charges was obtained from billing data, and costs were estimated by multiplying components of charges times hospital-specific ratios of costs to charges. RESULTS: During the study period, there were 247 ADEs among 207 admissions. After outliers and multiple episodes were excluded, there were 190 ADEs, of which 60 were preventable. In paired regression analyses adjusting for multiple factors, including severity, comorbidity, and case mix, the additional length of stay associated with an ADE was 2.2 days (P=.04), and the increase in cost associated with an ADE was $3244 (P=.04). For preventable ADEs, the increases were 4.6 days in length of stay (P=.03) and $5857 in total cost (P=.07). After adjusting for our sampling strategy, the estimated postevent costs attributable to an ADE were $2595 for all ADEs and $4685 for preventable ADEs. Based on these costs and data about the incidence of ADEs, we estimate that the annual costs attributable to all ADEs and preventable ADEs for a 700-bed teaching hospital are $5.6 million and $2.8 million, respectively. CONCLUSIONS: The substantial costs of ADEs to hospitals justify investment in efforts to prevent these events. Moreover, these estimates are conservative because they do not include the costs of injuries to patients or malpractice costs.

Boston↗

Optimal myocardial preconditioning in a human model of ischemia and reperfusion.

BACKGROUND: Adenosine (ADE) may mediate the protective effects of preconditioning (PC). However, human data are lacking, and the optimal method of ADE administration and the mechanism of protection remain unresolved. METHODS AND RESULTS: We have developed a model of simulated "ischemia" (I) and "reperfusion" (R) in quiescent human ventricular cardiomyocytes. Cellular injury and metabolic parameters were assessed after various interventions: Cells were preconditioned with anoxia (PC0), hypoxia (PC16), anoxic supernatant (SUP0), or hypoxic supernatant (SUP16) with or without the ADE receptor antagonist (SPT) or ADE deaminase (ADA). ADE was applied before, during, or after I or continuously with and without SPT. Cells were treated with the PKC agonist PMA. PC cells were incubated with the protein kinase-C (PKC) antagonist Calphostin-C (Cal-C). PKC translocation and PKC activity were assessed. PC0 was most protective. Protection was transferable via SUP0, which produced the highest concentrations of ADE. Protection was lost with SPT or ADA. Intracellular ATP fell after PC and prolonged I and R. Exogenous ADE was most protective when administered before I at 50 mumol. ADE during I was partially protective. No additional protection was provided with continuous ADE treatment. ADE prevented ATP degradation but increased lactate immediately after its administration. SPT abolished the protective effects of ADE. PMA conferred protection, which was abolished with Cal-C. ADE stimulated PKC translocation and PKC activity in the absence of SPT. CONCLUSIONS: Maximal I confers maximal PC. The degree of I is reflected in supernatant ADE concentrations. The initial ATP fall with PC may account for a lack of ATP preservation after I and R. ADE reproduces the protective effects of PC, preserves ATP, and increases lactate production, perhaps by stimulating glycolysis. Clinical trials of ADE administered during cardiac surgery are necessary to further define its beneficial effects in humans.

Adenosine↗

Incidence and impact of adverse drug events in pediatric inpatients.

OBJECTIVES: To determine the incidence and causes of adverse drug events (ADEs) and potential ADEs in hospitalized children, and to examine the consequences of these events. DESIGN: Prospective review of medical records and staff interviews were performed. The ADEs were defined as injuries from medications or lack of an intended medication, and potential ADEs, as errors with the potential to result in injury. SETTING: A general pediatric unit and a pediatric intensive care unit in a metropolitan medical center. PATIENTS: A total of 1197 consecutive patient admissions were studied from September 15, 2000, to May 10, 2001. The admissions represented a total of 922 patients and 10,164 patient-days. RESULTS: The ADEs (6/100 admissions, 7.5/1000 patient-days) and potential ADEs (8/100 admissions, 9.3/1000 patient-days) were common in hospitalized children. Demographic variables associated with the occurrence of these events were the length of hospital stay, case-mix index, and amount of medication exposure. After adjusting for length of stay, medication exposure continued to have a significant influence on ADEs and potential ADEs. For ADEs, 18 (24%) were judged to be serious or life threatening. Most ADEs were not associated with major or permanent disability. Patients with both ADEs and potential ADEs were less likely to be routinely discharged and more likely to be discharged with home health care or to another institution, suggesting that patient disposition was not related to the adverse event. CONCLUSIONS: Both ADEs and potential ADEs are common among hospitalized children with greater disease burden and medication exposure. These findings suggest that these events were a consequence, rather than a cause, of more severe illness.

Child↗

Adverse drug events in hospitalized patients treated with cardiovascular drugs and anticoagulants.

PURPOSE: To evaluate the incidence of serious adverse drug events (ADEs) caused by cardiovascular drugs during hospitalization in a department of internal medicine, and to identify patients at highest risk. PATIENTS AND METHODS: All the patients treated with cardiovascular drugs and/or anticoagulants in the department between November 1999 and January 2000 were recruited into the study. During hospitalization the patients' charts were reviewed by a pharmacist and a clinician, and the occurrence of serious ADEs was assessed using the Naranjo algorithm. 'Possible' and 'doubtful' ADEs were not counted. RESULTS: Of 496 patients who were enrolled in the study, 20 (4%) had serious ADEs. Compared to patients without ADEs, patients in the ADE group were older (72 +/- 12.6 years (mean +/- SD) vs. 65 +/- 13 years, p = 0.048), their average stay in hospital was longer (7.3 +/- 5.5 days vs. 5.2 +/- 3.7 days, p = 0.018) and their mean urea levels were higher (10.8 +/- 9.3 mmol/l vs. 7.8 +/- 5.3 mmol/l, p = 0.027). The most frequent background pathologies of the 20 patients with ADEs were hypertension (in 18 (90%)) and atrial fibrillation (in nine (45%)). In 50% of the the ADE group there was a history of drug allergies. The ADEs recorded were bleeding in four (20%), arrhythmias in six (30%), orthostatic hypotension in six (30%) and skin necrosis, paranoid reaction, acute hepatitis and acute renal failure in four (20%). The causative drugs were warfarin (which accounted for 25% of the ADEs), beta-blockers (15%), propafenone (5%), amiodarone (5%), and Ca(2+)-channel blockers, nitrates and diuretics (together accounting for 50% of ADEs). Drug combinations were implicated in 50% of ADE. CONCLUSIONS: Serious ADEs were developed by 4% of hospitalized patients taking cardiovascular drugs. Those at highest risk were older, were receiving multiple drug therapy and had higher urea levels. Warfarin and beta-blockers were the drugs causing the largest number of adverse effects. ADEs are an important cause of preventable morbidity, often with serious economic implications and special attention should be given to their prevention.

Adverse Drug Reaction Reporting Systems↗

Extrachromosomal elements in a super-suppression system of yeast. III. Enhanced detection of weak suppressors in certain non-suppressed psi-strains.

Individual colonies of an adenine-requiring strain of the genotype ade 2-1, SUPQ5, [psi minus] exhibit high and uniform frequencies of ADE+ revertants (5-1 times 10-5). The frequencies for strains of the genotypes ade 2-1, SUPQ5+, [psi+] and ade 2-1 SUPQ5+, [psi minus] are by contrast 1-2 times 10-7 and 0-5 times 10-7 respectively. Mutation from [psi minus] to [psi+] can occur. This suggests that the original mutation from [psi+] to [psi minus] is not necessarily a physical loss of, or extensive deletion, the extrachromosomal elements. Although mutation from [psi minus] to [psi+] occurs, the majority of ADE+ revertants from ade 2-1, SUPQ5, [psi minus] strains contain other types of mutation. Crosses between most ADE+ revertants and ade 2-1, SUPO5+, [psi minus] strains yield adenine-requiring diploids and tetrad segregations of 0:4, 1:3 and 2:2 ADE+ :ade minus. It is argued that most mutations give rise to weak recessive suppressors (SUPX) which are themselves incapable of suppressing the ochre allele ade 2-1, unless the allele SUPQ5 is also present. Tests with two suppressors, S-theta and S-zeta, isolated by Dr R. A. Gilmore, which are themselves incapable of suppressing ade 2-1, show that they do not do so even in the presence of SUPQ5. Thus the set of suppressors isolated by us is a special class which can perhaps only be observed in the genetic background ade 2-1, SUPQ5, [psi minus]. There is evidence that some of the new suppressors are capable, in the absence of SUPQ5, of weakly suppressing trp 5-48 and perhaps can 1-100. All ochre alleles are, however, suppressed by the combination SUPQ5, SUPX. SUPQ5 is able to suppress trp 5-48, his 5-2, lys 1-1 and can 1-100 in a [psi minus] background, although it does so variably. It is incapable of suppressing ade 2-1 in such a background. It is argued that the alteration in the [psi] determinant results in a lowered efficiency of suppression by SUPQ5 rather than a changed specificity.

Adenine↗

Antibody-dependent enhancement of HIV-1 infection in human term syncytiotrophoblast cells cultured in vitro.

We examined if Fc receptor-mediated antibody-dependent enhancement (FcR-ADE) or complement-mediated antibody-dependent enhancement (C'-ADE) of virus infection can contribute to increasing replication of HIV-1 in human syncytiotrophoblast (ST) cells. Here we report that both FcR-ADE and C'-ADE may result in enhanced virus release from HIV-1-infected ST cells. We show that FcR-ADE of HIV-1 infection in ST cells is mediated by FcRIII and other FcR(s) belonging to undetermined Fc classes and does not require CD4 receptors, whereas C'-ADE uses both CD4 and CR2-like receptors. FcR-ADE seems to be more efficient in enhancing HIV-1 replication than C'-ADE. While FcR-ADE leads to increased internalization of HIV-1, C'-ADE does not result in enhanced endocytosis of the virus. In addition, antibodies mediating FcR-ADE are reactive with the gp120 viral envelope antigen, whereas antibodies involved in C'-ADE react with the viral transmembrane glycoprotein gp41. Data suggest that both FcR-ADE and C'-ADE may contribute to the spread of HIV-1 from mother to the fetus.

Cells, Cultured↗

Computerized surveillance of adverse drug events in hospital patients.

OBJECTIVE: To develop a new method to improve the detection and characterization of adverse drug events (ADEs) in hospital patients. DESIGN: Prospective study of all patients admitted to our hospital over an 18-month period. SETTING: LDS Hospital, Salt Lake City, Utah, a 520-bed tertiary care center affiliated with the University of Utah School of Medicine, Salt Lake City. PATIENTS: We developed a computerized ADE monitor, and computer programs were written using an integrated hospital information system to allow for multiple source detection of potential ADEs occurring in hospital patients. Signals of potential ADEs, both voluntary and automated, included sudden medication stop orders, antidote ordering, and certain abnormal laboratory values. Each day, a list of all potential ADEs from these sources was generated, and a pharmacist reviewed the medical records of all patients with possible ADEs for accuracy and causality. Verified ADEs were characterized as mild, moderate, or severe and as type A (dose-dependent or predictable) or type B (idiosyncratic or allergic) reactions, and causality was further measured using a standardized scoring method. OUTCOME MEASURE: The number and characterization of ADEs detected. RESULTS: Over 18 months, we monitored 36,653 hospitalized patients. There were 731 verified ADEs identified in 648 patients, 701 ADEs were characterized as moderate or severe, and 664 were classified as type A reactions. During this same period, only nine ADEs were identified using traditional detection methods. Physicians, pharmacists, and nurses voluntarily reported 92 of the 731 ADEs detected using this automated system. The other 631 ADEs were detected from automated signals, the most common of which were diphenhydramine hydrochloride and naloxone hydrochloride use, high serum drug levels, leukopenia, and the use of phytonadione and antidiarrheals. The most common symptoms and signs were pruritus, nausea and/or vomiting, rash, and confusion-lethargy. The most common drug classes involved were analgesics, anti-infectives, and cardiovascular agents. CONCLUSION: We believe that screening for ADEs with a computerized hospital information system offers a potential method for improving the detection and characterization of these events in hospital patients.

Adolescent↗

Drug-related deaths in a department of internal medicine.

BACKGROUND: Drug therapy is associated with adverse effects, and fatal adverse drug events (ADEs) have become major hospital problems. Our study assesses the incidence of fatal ADEs in a major medical department and identifies possible patient characteristics signifying fatal ADE risk. METHODS: During a 2-year period, a multidisciplinary study group examined all 732 patients who died--5.2% of the 13992 patients admitted to the Department of Internal Medicine, Central Hospital of Akershus, Nordbyhagen, Norway. Decisions about the presence or absence of fatal ADEs were based on aggregated clinical records, autopsy results, and findings from premortem and postmortem drug analyses. RESULTS: In 18.2% of the patients (133/732) (95% confidence interval, 15.4%-21.0%), deaths were classified as being directly (64 [48.1%] of 133) or indirectly (69 [51.9%] of 133) associated with 1 or more drugs (this equals 9.5 deaths per 1000 hospitalized patients). Those with fatal ADEs (cases) were older, had more diseases, and used more drugs than those without fatal ADEs (noncases). In 75 of the 133 patients with fatal ADEs, autopsy findings and/or drug analysis data were decisive for recognizing the ADEs; in 62 of the remaining 595 patients, similar data proved necessary to exclude the suspicion of a fatal ADE. Major culprit drugs were cardiovascular, antithrombotic, and sympathomimetic agents. CONCLUSIONS: Fatal ADEs represent a major hospital problem, especially in elderly patients with multiple diseases. A higher number of drugs administered was associated with a higher frequency of fatal ADEs, but whether a high number of drugs is an independent risk factor for fatal ADEs is unsettled. Autopsy results and the findings of premortem and postmortem drug analyses were important for recognizing and excluding suspected fatal ADEs.

Adolescent↗

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↗

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↗