Ioana Danciu

A Computerized Provider Order Entry Intervention for Medication Safety During Acute Kidney Injury: A Quality Improvement Report

BACKGROUND Frequently, prescribers fail to account for changing kidney function when prescribing medications. We evaluated the use of a computerized provider order entry intervention to improve medication management during acute kidney injury. STUDY DESIGN Quality improvement report with time series analyses. SETTING & PARTICIPANTS 1,598 adult inpatients with a minimum 0.5-mg/dL increase in serum creatinine level over 48 hours after an order for at least one of 122 nephrotoxic or renally cleared medications. QUALITY IMPROVEMENT PLAN Passive noninteractive warnings about increasing serum creatinine level appeared within the computerized provider order entry interface and on printed rounding reports. For contraindicated or high-toxicity medications that should be avoided or adjusted, an interruptive alert within the system asked providers to modify or discontinue the targeted orders, mark the current dosing as correct and to remain unchanged, or defer the alert to reappear in the next session. OUTCOMES & MEASUREMENTS Intervention effect on drug modification or discontinuation, time to modification or discontinuation, and provider interactions with alerts. RESULTS The modification or discontinuation rate per 100 events for medications included in the interruptive alert within 24 hours of increasing creatinine level improved from 35.2 preintervention to 52.6 postintervention (P < 0.001); orders were modified or discontinued more quickly (P < 0.001). During the postintervention period, providers initially deferred 78.1% of interruptive alerts, although 54% of these eventually were modified or discontinued before patient death, discharge, or transfer. The response to passive alerts about medications requiring review did not significantly change compared with baseline. LIMITATIONS Single tertiary-care academic medical center; provider actions were not independently adjudicated for appropriateness. CONCLUSIONS A computerized provider order entry-based alerting system to support medication management after acute kidney injury significantly increased the rate and timeliness of modification or discontinuation of targeted medications.

Estimating Baseline Kidney Function in Hospitalized Patients with Impaired Kidney Function

BACKGROUND AND OBJECTIVES Inaccurate determination of baseline kidney function can misclassify acute kidney injury (AKI) and affect the study of AKI-related outcomes. No consensus exists on how to optimally determine baseline kidney function when multiple preadmission creatinine measurements are available. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The accuracy of commonly used methods for estimating baseline serum creatinine was compared with that of a reference standard adjudicated by a panel of board-certified nephrologists in 379 patients with AKI or CKD admitted to a tertiary referral center. RESULTS Agreement between estimating methods and the reference standard was highest when using creatinine values measured 7-365 days before admission. During this interval, the intraclass correlation coefficient (ICC) for the mean outpatient serum creatinine level (0.91 [95% confidence interval (CI), 0.88-0.92]) was higher than the most recent outpatient (ICC, 0.84 [95% CI, 0.80-0.88]; P<0.001) and the nadir outpatient (ICC, 0.83 [95% CI, 0.76-0.87; P<0.001) serum creatinine. Using the final creatinine value from a prior inpatient admission increased the ICC of the most recent outpatient creatinine method (0.88 [95% CI, 0.85-0.91]). Performance of all methods declined or was unchanged when the time interval was broadened to 2 years or included serum creatinine measured within a week of admission. CONCLUSIONS The mean outpatient serum creatinine measured within a year of hospitalization most closely approximates nephrologist-adjudicated serum creatinine values.

Secondary use of clinical data

The last decade has seen an exponential growth in the quantity of clinical data collected nationwide, triggering an increase in opportunities to reuse the data for biomedical research. The Vanderbilt research data warehouse framework consists of identified and de-identified clinical data repositories, fee-for-service custom services, and tools built atop the data layer to assist researchers across the enterprise. Providing resources dedicated to research initiatives benefits not only the research community, but also clinicians, patients and institutional leadership. This work provides a summary of our approach in the secondary use of clinical data for research domain, including a description of key components and a list of lessons learned, designed to assist others assembling similar services and infrastructure.

Adopting Real-Time Surveillance Dashboards as a Component of an Enterprisewide Medication Safety Strategy

BACKGROUND High-alert medications are frequently responsible for adverse drug events and present significant hazards to inpatients, despite technical improvements in the way they are ordered, dispensed, and administered. METHODS A real-time surveillance application was designed and implemented to enable pharmacy review of high-alert medication orders to complement existing computerized provider order entry and integrated clinical decision support systems in a tertiary care hospital. The surveillance tool integrated real-time data from multiple clinical systems and applied logical criteria to highlight potentially high-risk scenarios. Use of the surveillance system for adult inpatients was analyzed for warfarin, heparin and enoxaparin, and aminoglycoside antibiotics. RESULTS Among 28,929 hospitalizations during the study period, patients eligible to appear on a dashboard included 2224 exposed to warfarin, 8383 to heparin or enoxaparin, and 893 to aminoglycosides. Clinical pharmacists reviewed the warfarin and aminoglycoside dashboards during 100% of the days in the study period-and the heparinlenoxaparin dashboard during 71% of the days. Displayed alert conditions ranged from common events, such as 55% of patients receiving aminoglycosides were missing a baseline creatinine, to rare events, such as 0.1% of patients exposed to heparin were given a bolus greater than 10,000 units. On the basis of interpharmacist communication and electronic medical record notes recorded within the dashboards, interventions to prevent further patient harm were frequent. CONCLUSIONS Even in an environment with sophisticated computerized provider order entry and clinical decision support systems, real-time pharmacy surveillance of high-alert medications provides an important platform for intercepting medication errors and optimizing therapy.

Adverse Drug Events during AKI and Its Recovery

BACKGROUND AND OBJECTIVES The impact of AKI on adverse drug events and therapeutic failures and the medication errors leading to these events have not been well described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A single-center observational study of 396 hospitalized patients with a minimum 0.5 mg/dl change in serum creatinine who were prescribed a nephrotoxic or renally eliminated medication was conducted. The population was stratified into two groups by the direction of their initial serum creatinine change: AKI and AKI recovery. Adverse drug events, potential adverse drug events, therapeutic failures, and potential therapeutic failures for 148 drugs and 46 outcomes were retrospectively measured. Events were classified for preventability and severity by expert adjudication. Multivariable analysis identified medication classes predisposing AKI patients to adverse drug events. RESULTS Forty-three percent of patients experienced a potential adverse drug event, adverse drug event, therapeutic failure, or potential therapeutic failure; 66% of study events were preventable. Failure to adjust for kidney function (63%) and use of nephrotoxic medications during AKI (28%) were the most common potential adverse drug events. Worsening AKI and hypotension were the most common preventable adverse drug events. Most adverse drug events were considered serious (63%) or life-threatening (31%), with one fatal adverse drug event. Among AKI patients, administration of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, antibiotics, and antithrombotics was most strongly associated with the development of an adverse drug event or potential adverse drug event. CONCLUSIONS Adverse drug events and potential therapeutic failures are common and frequently severe in patients with AKI exposed to nephrotoxic or renally eliminated medications.

Acute Kidney Injury Incidence in Noncritically Ill Hospitalized Children, Adolescents, and Young Adults: A Retrospective Observational Study

BACKGROUND Acute kidney injury (AKI) has been characterized in high-risk pediatric hospital inpatients, in whom AKI is frequent and associated with increased mortality, morbidity, and length of stay. The incidence of AKI among patients not requiring intensive care is unknown. STUDY DESIGN Retrospective cohort study. SETTING & PARTICIPANTS 13,914 noncritical admissions during 2011 and 2012 at our tertiary referral pediatric hospital were evaluated. Patients younger than 28 days or older than 21 years of age or with chronic kidney disease (CKD) were excluded. Admissions with 2 or more serum creatinine measurements were evaluated. FACTORS Demographic features, laboratory measurements, medication exposures, and length of stay. OUTCOME AKI defined as increased serum creatinine level in accordance with KDIGO (Kidney Disease: Improving Global Outcomes) criteria. Based on time of admission, time interval requirements were met in 97% of cases, but KDIGO time window criteria were not strictly enforced to allow implementation using clinically obtained data. RESULTS 2 or more creatinine measurements (one baseline before or during admission and a second during admission) in 2,374 of 13,914 (17%) patients allowed for AKI evaluation. A serum creatinine difference ≥0.3mg/dL or ≥1.5 times baseline was seen in 722 of 2,374 (30%) patients. A minimum of 5% of all noncritical inpatients without CKD in pediatric wards have an episode of AKI during routine hospital admission. LIMITATIONS Urine output, glomerular filtration rate, and time interval criteria for AKI were not applied secondary to study design and available data. The evaluated cohort was restricted to patients with 2 or more clinically obtained serum creatinine measurements, and baseline creatinine level may have been measured after the AKI episode. CONCLUSIONS AKI occurs in at least 5% of all noncritically ill hospitalized children, adolescents, and young adults without known CKD. Physicians should increase their awareness of AKI and improve surveillance strategies with serum creatinine measurements in this population so that exacerbating factors such as nephrotoxic medication exposures may be modified as indicated.

Real-time pharmacy surveillance and clinical decision support to reduce adverse drug events in acute kidney injury: a randomized, controlled trial.

OBJECTIVES: Clinical decision support (CDS), such as computerized alerts, improves prescribing in the setting of acute kidney injury (AKI), but considerable opportunity remains to improve patient safety. The authors sought to determine whether pharmacy surveillance of AKI patients could detect and prevent medication errors that are not corrected by automated interventions. METHODS: The authors conducted a randomized clinical trial among 396 patients admitted to an academic, tertiary care hospital between June 1, 2010 and August 31, 2010 with an acute 0.5 mg/dl change in serum creatinine over 48 hours and a nephrotoxic or renally cleared medication order. Patients randomly assigned to the intervention group received surveillance from a clinical pharmacist using a web-based surveillance tool to monitor drug prescribing and kidney function trends. CDS alerting and standard pharmacy services were active in both study arms. Outcome measures included blinded adjudication of potential adverse drug events (pADEs), adverse drug events (ADEs) and time to provider modification or discontinuation of targeted nephrotoxic or renally cleared medications. RESULTS: Potential ADEs or ADEs occurred for 104 (8.0%) of control and 99 (7.1%) of intervention patient-medication pairs (p=0.4). Additionally, the time to provider modification or discontinuation of targeted nephrotoxic or renally cleared medications did not differ between control and intervention patients (33.4 hrs vs. 30.3 hrs, p=0.3). CONCLUSIONS: Pharmacy surveillance had no incremental benefit over previously implemented CDS alerts.

Physician response to implementation of genotype-tailored antiplatelet therapy.

Physician responses to genomic information are vital to the success of precision medicine initiatives. We prospectively studied a pharmacogenomics implementation program for the propensity of clinicians to select antiplatelet therapy based on CYP2C19 loss‐of‐function variants in stented patients. Among 2,676 patients, 514 (19.2%) were found to have a CYP2C19 variant affecting clopidogrel metabolism. For the majority (93.6%) of the cohort, cardiologists received active and direct notification of CYP2C19 status. Over 12 months, 57.6% of poor metabolizers and 33.2% of intermediate metabolizers received alternatives to clopidogrel. CYP2C19 variant status was the most influential factor impacting the prescribing decision (hazard ratio [HR] in poor metabolizers 8.1, 95% confidence interval [CI] [5.4, 12.2] and HR 5.0, 95% CI [4.0, 6.3] in intermediate metabolizers), followed by patient age and type of stent implanted. We conclude that cardiologists tailored antiplatelet therapy for a minority of patients with a CYP2C19 variant and considered both genomic and nongenomic risks in their clinical decision‐making.

Electronic surveillance and pharmacist intervention for vulnerable older inpatients on high-risk medication regimens.

To develop and evaluate an electronic tool to assist clinical pharmacists with reviewing potentially inappropriate medications (PIMs) in hospitalized elderly adults.

A prognostic model based on readily available clinical data enriched a pre-emptive pharmacogenetic testing program

OBJECTIVES We describe the development, implementation, and evaluation of a model to pre-emptively select patients for genotyping based on medication exposure risk. STUDY DESIGN AND SETTING Using deidentified electronic health records, we derived a prognostic model for the prescription of statins, warfarin, or clopidogrel. The model was implemented into a clinical decision support (CDS) tool to recommend pre-emptive genotyping for patients exceeding a prescription risk threshold. We evaluated the rule on an independent validation cohort and on an implementation cohort, representing the population in which the CDS tool was deployed. RESULTS The model exhibited moderate discrimination with area under the receiver operator characteristic curves ranging from 0.68 to 0.75 at 1 and 2 years after index dates. Risk estimates tended to underestimate true risk. The cumulative incidences of medication prescriptions at 1 and 2 years were 0.35 and 0.48, respectively, among 1,673 patients flagged by the model. The cumulative incidences in the same number of randomly sampled subjects were 0.12 and 0.19, and in patients over 50 years with the highest body mass indices, they were 0.22 and 0.34. CONCLUSION We demonstrate that prognostic algorithms can guide pre-emptive pharmacogenetic testing toward those likely to benefit from it.