Performance of trigger tools in identifying adverse drug events in emergency department patients: a validation study.

AIMS: Trigger tools are retrospective surveillance methods that can be used to identify adverse drug events (ADEs), unintended and harmful effects of medications, in medical records. Trigger tools are used in quality improvement, public health surveillance and research activities. The objective of the study was to evaluate the performance of trigger tools in identifying ADEs. METHODS: This study was a sub-study of a prospective cohort study which enrolled adults presenting to one tertiary care emergency department. Clinical pharmacists evaluated patients for ADEs at the point-of-care. Twelve months after the prospective study's completion, the patients' medical records were reviewed using eight different trigger tools. ADEs identified using each trigger tool were compared with events identified at the point-of-care. The primary outcome was the sensitivity of each trigger tool for ADEs. RESULTS: Among 1151 patients, 152 (13.2%, 95% confidence intervals (CI) 11.4, 15.3%) were diagnosed with one or more ADEs at the point-of-care. The sensitivity of the trigger tools for detecting ADEs ranged from 2.6% (95% CI 0.7, 6.6%) to 15.8% (95% CI 10.6, 22.8%). Their specificity varied from 99.3% (95% CI 98.6, 99.7) to 100% (95% CI 99.6, 100%). CONCLUSION: The trigger tools examined had poor sensitivity for identifying ADEs in emergency department patients, when applied manually and in retrospect. Reliance on these methods to detect ADEs for quality improvement, surveillance, and research activities is likely to underestimate their occurrence, and may lead to biased estimates.

Development and validation of a prediction rule for early discharge of low-risk emergency department patients with potential ischemic chest pain.

OBJECTIVES: Current guidelines emphasize that emergency department (ED) patients at low risk for potential ischemic chest pain cannot be discharged without extensive investigations or hospitalization to minimize the risk of missing acute coronary syndrome (ACS). We sought to derive and validate a prediction rule that permitted 20 to 30% of ED patients without ACS safely to be discharged within 2 hours without further provocative cardiac testing. METHODS: This prospective cohort study enrolled 1,669 chest pain patients in two blocks in 2000-2003 (development cohort) and 2006 (validation cohort). The primary outcome was 30-day ACS diagnosis. A recursive partitioning model incorporated reliable and predictive cardiac risk factors, pain characteristics, electrocardiographic findings, and cardiac biomarker results. RESULTS: In the derivation cohort, 165 of 763 patients (21.6%) had a 30-day ACS diagnosis. The derived prediction rule was 100.0% sensitive and 18.6% specific. In the validation cohort, 119 of 906 patients (13.1%) had ACS, and the prediction rule was 99.2% sensitive (95% CI 95.4-100.0) and 23.4% specific (95% CI 20.6-26.5). Patients have a very low ACS risk if arrival and 2-hour troponin levels are normal, the initial electrocardiogram is nonischemic, there is no history of ACS or nitrate use, age is < 50 years, and defined pain characteristics are met. The validation of the rule was limited by the lack of consistency in data capture, incomplete follow-up, and lack of evaluation of the accuracy, comfort, and clinical sensibility of this clinical decision rule. CONCLUSION: The Vancouver Chest Pain Rule may identify a cohort of ED chest pain patients who can be safely discharged within 2 hours without provocative cardiac testing. Further validation across other centres with consistent application and comprehensive and uniform follow-up of all eligible and enrolled patients, in addition to measuring and reporting the accuracy of and comfort level with applying the rule and the clinical sensibility, should be completed prior to adoption and implementation.

Evaluating adverse drug event reporting in administrative data from emergency departments: a validation study.

BACKGROUND: Adverse drug events are a frequent cause of emergency department presentations. Administrative data could be used to identify patients presenting with adverse drug events for post-market surveillance, and to conduct research in patient safety and in drug safety and effectiveness. However, such data sources have not been evaluated for their completeness with regard to adverse drug event reporting. Our objective was to determine the proportion of adverse drug events to outpatient medications diagnosed at the point-of-care in emergency departments that were documented in administrative data. METHODS: We linked the records of patients enrolled in a prospective observational cohort study on adverse drug events conducted in two Canadian tertiary care emergency departments to their administrative data. We compared the number of adverse drug events diagnosed and recorded at the point-of-care in the prospective study with the number of adverse drug events recorded in the administrative data. RESULTS: Among 1574 emergency department visits, 221 were identified as adverse drug event-related in the prospective database. We found 15 adverse drug events documented in administrative records with ICD-10 codes clearly indicating an adverse drug event, indicating a sensitivity of 6.8% (95% CI 4.0-11.2%) of this code set. When the ICD-10 code categories were broadened to include codes indicating a very likely, likely or possible adverse event to a medication, 62 of 221 events were identifiable in administrative data, corresponding to a sensitivity of 28.1% (95% CI 22.3-34.6%). CONCLUSIONS: Adverse drug events to outpatient medications were underreported in emergency department administrative data compared to the number of adverse drug events diagnosed and recorded at the point-of-care.

Clinical decision rules to improve the detection of adverse drug events in emergency department patients.

OBJECTIVES: Adverse drug events (ADEs) are unintended and harmful consequences of medication use. They are associated with high health resource use and cost. Yet, high levels of inaccuracy exist in their identification in clinical practice, with over one-third remaining unidentified in the emergency department (ED). The study objective was to derive clinical decision rules (CDRs) that are sensitive for the detection of ADEs, allowing their systematic identification early in a patient's hospital course. METHODS: This was a prospective observational cohort study carried out in two Canadian tertiary care hospitals. Participants were adults presenting to the ED having ingested at least one prescription or over-the-counter medication within 2 weeks. Nurses and physicians evaluated patients for standardized clinical findings. A second evaluator performed interobserver assessments of predictor variables in a subset of patients. Pharmacists, who were blinded to the predictor variables, evaluated all patients for ADEs. An independent committee reviewed and adjudicated cases where the ADE assessment was uncertain or the pharmacist's diagnosis differed from the physician's working diagnosis. The primary outcome was an ADE that required a change in medical therapy, diagnostic testing, consultation, or hospital admission. CDRs were derived using kappa coefficients, chi-square statistics, and recursive partitioning. RESULTS: Among 1,591 patients, 131 (8.2%, 95% confidence interval [CI] = 7.0% to 9.7%) were diagnosed with the primary outcome. The following variables were associated with ADEs and were used to derive two CDRs: 1) presence of comorbid conditions, 2) antibiotic use within 7 days, 3) medication changes within 28 days, 4) age ≥ 80 years, 5) arrival by ambulance, 6) triage acuity, 7) recent hospital admission, 8) renal failure, and 9) use of three or more prescription medications. The more sensitive rule had a sensitivity of 96.7% (95% CI = 91.8% to 98.6%) and required 40.8% (95% CI = 37.7% to 42.9%) of patients to have medication review. The more specific rule had a sensitivity 90.8% (95% CI = 81.4% to 95.7%) and required 28.3% of patients to proceed to medication review. CONCLUSIONS: The authors derived CDRs that identified patients with ADEs with high sensitivity. These rules may improve the identification of ADEs early in a patient's hospital course while limiting the number of patients requiring a detailed medication review.

Safety and efficiency of a chest pain diagnostic algorithm with selective outpatient stress testing for emergency department patients with potential ischemic chest pain.

STUDY OBJECTIVE: Chest pain units have been used to monitor and investigate emergency department (ED) patients with potential ischemic chest pain to reduce the possibility of missed acute coronary syndrome. We seek to optimize the use of hospital resources by implementing a chest pain diagnostic algorithm. METHODS: This was a prospective cohort study of ED patients with potential ischemic chest pain. High-risk patients were referred to cardiology, and patients without ECG or biomarker evidence of ischemia were discharged home after 2 to 6 hours of observation. Emergency physicians scheduled discharged patients for outpatient stress ECGs or radionuclide scans at the hospital within 48 hours. Patients with positive provocative test results were immediately referred back to the ED. The primary outcome was the rate of missed diagnosis of acute coronary syndrome at 30 days. RESULTS: We prospectively followed 1,116 consecutive patients who went through the chest pain diagnostic algorithm, of whom 197 (17.7%) were admitted at the index visit and 254 (22.8%) received outpatient testing on discharge. The 30-day acute coronary syndrome event rate was 10.8%, and the 30-day missed acute coronary syndrome rate was 0% (95% confidence interval 0% to 2.4%). Of the 120 acute coronary syndrome cases, 99 (82.5%) were diagnosed at the index ED visit, and 21 patients (17.5%) received the diagnosis during outpatient stress testing. CONCLUSION: In ED patients with chest pain, a structured diagnostic approach with time-focused ED decision points, brief observation, and selective application of early outpatient provocative testing appears both safe and diagnostically efficient, even though some patients with acute coronary syndrome may be discharged for outpatient stress testing on the index ED visit.

Safety of assessment of patients with potential ischemic chest pain in an emergency department waiting room: a prospective comparative cohort study.

STUDY OBJECTIVE: Emergency department (ED) crowding has been associated with a variety of adverse outcomes. Current guidelines suggest that patients with potentially ischemic chest pain should undergo rapid assessment and treatment in a monitored setting to optimize the diagnosis of acute coronary syndrome. These patients may be at high risk of incorrect diagnosis and adverse events when their evaluation is delayed because of crowding. To mitigate crowding-related delays, we developed processes that enabled emergency physicians to evaluate potentially sick patients in the waiting room when all nurse-staffed stretchers are occupied. The objective of this study was to investigate the safety of waiting room chest pain evaluation. METHODS: This prospective comparative cohort study was conducted in a busy urban, tertiary care ED. Explicit triage and waiting room evaluation processes were introduced. One thousand one hundred seven patients with chest pain of potential cardiac origin were triaged either to a monitored bed or a waiting room chair, depending on bed availability and triage judgment. After diagnostic evaluation, patients were followed for 30 days to identify the proportion of missed cases of acute coronary syndrome (primary outcome) and other prespecified adverse events. Analysis was based on intention to treat. RESULTS: Eight hundred four patients were triaged to monitored bed and 303 to waiting room evaluation. Initial vital signs were similar, but the waiting room group was younger and had lower rates of some cardiovascular risk factors. The rate of acute coronary syndrome, defined as acute myocardial infarction or objective unstable angina, was 11.7% in the monitored bed group and 7.6% in waiting room patients. There were no missed acute coronary syndrome cases in either the monitored bed group (0%; 95% confidence interval [CI] 0% to 0.4%) or the waiting room group (0%; 95% CI 0% to 1.0%). There were 32 adverse events in the monitored bed group (4.0%; 95% CI 2.6% to 5.3%) and 2 in the waiting room group (0.7%; 95% CI 0% to 1.6%). CONCLUSION: Our organized approach to triage and waiting room evaluation for stable chest pain patients was safe and efficient. Although waiting room evaluation is not ideal, it may be a feasible contingency strategy for periods when ED crowding compromises access to monitored, nurse-staffed ED beds.

Low Prevalence of Elevated ApoB Levels in Patients with Type 2 Diabetes Not Receiving Lipid-Lowering Therapy.

OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of death in people with type 2 diabetes. Apolipoprotein B (apoB) is known to be a better marker of CVD risk than low-density lipoprotein cholesterol (LDL-C). This study investigated apoB levels in people with type 2 diabetes. METHODS: We obtained blood samples from 507 consenting people with type 2 diabetes who were not receiving lipid-lowering medication and who had no previous history of CVD. Subjects were divided into 3 groups: men (M), women <50 years old (W1) and women ≥50 years old (W2). Primary analysis examined lipid parameters, specifically apoB. Secondary analysis involved classifying patients according to the Canadian Diabetes Association's apoB, LDL-C and triglyceride (TG) targets. RESULTS: We found a total mean apoB level of 0.92 g/L. Among patients who failed to achieve the LDL-C target, 28% of M, 39% of W1 and 30% of W2 met the apoB target. The proportions of individuals categorized as being above the LDL-C and apoB targets were significantly different in all 3 groups (p<0.01). When LDL-C was below target and TG was <1.5 mmol/L, 100% of M and W1 and 93% of W2 met the apoB target. CONCLUSIONS: The discordance between the proportions of patients meeting LDL-C and apoB targets may lead to patients being erroneously classified. ApoB and LDL-C correlate very well when TG is <1.5 mmol/L, but not when ≥1.5 mmol/L. Approximately one-third of patients met both LDL-C and apoB goals. Thus, not all patients with type 2 diabetes should be considered to be at a high risk of CVD.

Sulfonylurea therapy is associated with increased NT-proBNP levels in the treatment of type 2 diabetes.

BACKGROUND: We sought to determine N-terminal pro-Brain Natriuretic Peptide (NTproBNP) levels among a population of individuals with type 2 diabetes, and to correlate these levels with diabetes medications and patient demographics. METHODS: We analyzed data from 506 patients with type 2 diabetes. We compared NT-proBNP levels of these patients with those from the general population. We also sought to determine whether patients' NT-proBNP levels were correlated with diabetes medications, age, gender, creatinine, hemoglobin A1C levels, BMI, blood pressure, and lipid levels. RESULTS: Increasing doses of sulfonylureas were associated with increasing levels of NT-proBNP. However, patients on combined sulfonylurea and metformin therapy had lower NT-proBNP levels than those on sulfonylureas alone. Neither thiazolidinediones nor insulin were associated with NT-proBNP levels. The majority of patients with type 2 diabetes had similar NT-proBNP levels compared to a reference group from the general population. In no age category did NT-proBNP levels differ significantly between men and women. Levels of NT-proBNP were positively associated with age (p<0.0001), systolic blood pressure (p<0.01) and creatinine levels (p<0.0001), and negatively associated with diastolic blood pressure (p<0.001). Levels of NT-proBNP were not associated with A1C, BMI, triglycerides, and high density lipoprotein (p=NS). CONCLUSIONS: Levels of NT-proBNP are associated with increasing sulfonylurea dosage, age, blood pressure, and creatinine levels. There is unlikely to be clinically significant differences in NT-proBNP levels between patients with type 2 diabetes and a normal population.

Exploring mitochondrial nephrotoxicity as a potential mechanism of kidney dysfunction among HIV-infected patients on highly active antiretroviral therapy.

BACKGROUND: Tenofovir (TDF) exposure has been associated with renal dysfunction. Mitochondrial nephrotoxicity was investigated as an underlying mechanism. Given the interaction between TDF and didanosine (ddl), their concurrent use was also investigated. DESIGN: Relative kidney biopsy mitochondrial DNA (mtDNA) to nuclear DNA ratios were measured retrospectively. HIV+ individuals on TDF within 6 months preceeding the biopsy (HIV+/TDF+, n=21) were compared to HIV+ individuals who never received TDF (HIV+/TDF-, n=10) and to HIV uninfected controls (HIV-,n=22). Twelve of the HIV+/TDF+ individuals received concurrent ddl, 10 of those once at unadjusted ddl dosage. Tubular mitochondria morphology was also examined by electron microscopy. Statistical analyses were done on log-transformed mtDNA/nDNA, using non-parametric tests. RESULTS: Kidney mtDNA levels were different among the three groups (P=0.046). mtDNA ratios were lower in HIV+/TDF+ subjects (7.5 [2.0-12.1]) than in HIV- ones (14.3 [6.0-16.5], P=0.014), but not lower than HIV+/TDF- controls (6.4 [2.8-11.9], P=0.82). Among HIV+ subjects, there was a difference between TDF-, TDF+/ddl- and TDF+/ddl+ (P=0.005), with concurrent TDF/ddl use associated with lower mtDNA (2.1 [1.9-5.5], n=12) than TDF+/ddl- (13.8 [7.5-16.4], n=9, P=0.003). No TDF-/ddl+ biopsies were available. In regression analyses, only HIV infection (P=0.03), and TDF/ddl use (P=0.003) were associated with lower mtDNA. At the ultrastructural level, abnormal tubular mitochondria was more prevalent in HIV+/TDF+ biopsies than HIV+/TDF- and HIV- ones together (P<0.001) but not more so in TDF+/ddl+ biopsies than TDF+/ddl- ones (P=0.67). CONCLUSIONS: Renal dysfunction in this population may be mediated through mitochondrial nephrotoxicity that involves more than one drug and/or pathogenesis. Kidney mtDNA depletion was associated with HIV infection and concurrent TDF/ddl therapy but not TDF use alone, while kidney ultrastructural mitochondrial abnormalities were seen with TDF use. The interaction between TDF and ddl may be relevant in the kidney where both drugs are cleared. The clinical relevance of our findings needs to be evaluated given the current recommendation for reduced doses of ddl when used in conjunction with TDF.

A clinical prediction rule for early discharge of patients with chest pain.

STUDY OBJECTIVE: Current risk stratification tools do not identify very-low-risk patients who can be safely discharged without prolonged emergency department (ED) observation, expensive rule-out protocols, or provocative testing. We seek to develop a clinical prediction rule applicable within 2 hours of ED arrival that would miss fewer than 2% of acute coronary syndrome patients and allow discharge within 2 to 3 hours for at least 30% of patients without acute coronary syndrome. METHODS: This prospective, cohort study enrolled consenting eligible subjects at least 25 years old at a single site. At 30 days, investigators assigned a diagnosis of acute coronary syndrome or no acute coronary syndrome according to predefined explicit definitions. A recursive partitioning model included risk factors, pain characteristics, physical and ECG findings, and cardiac marker results. RESULTS: Of 769 patients studied, 77 (10.0%) had acute myocardial infarction and 88 (11.4%) definite unstable angina. We derived a clinical prediction rule that was 98.8% sensitive and 32.5% specific. Patients have very low risk of acute coronary syndrome if they have a normal initial ECG, no previous ischemic chest pain, and age younger than 40 years. In addition, patients at least 40 years old and with a normal ECG result, no previous ischemic chest pain, and low-risk pain characteristics have very low risk if they have an initial creatine kinase-MB (CK-MB) less than 3.0 microg/L or an initial CK-MB greater than or equal to 3.0 microg/L but no ECG or serum-marker increase at 2 hours. CONCLUSION: The Vancouver Chest Pain Rule for early discharge defines a group of patients who can be safely discharged after a brief evaluation in the ED. Prospective validation is needed.