Evaluation of an electronic health record Drug Interaction Customization Editor (DICE).

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Due to the low specificity of drug-drug interaction (DDI) warnings, hospitals and healthcare systems would benefit from the ability to customize alerts, thereby reducing the burden of alerts while simultaneously preventing harm. We developed a tool, called the Drug Interaction Customization Editor (DICE), as a prototype to identify features and functionality that could assist healthcare organizations in customizing DDI alerts. METHODS: A team of pharmacists, physicians, and DDI experts identified attributes expected to be useful for filtering DDI warnings. A survey was sent to pharmacists with informatics responsibilities and other medication safety committee members to obtain their opinions about the tool. The survey asked participants to evaluate the 4 sections of the DICE tool (General, Medication, Patient, and Visit) on a scale ranging from 0 (not useful) to 100 (very useful). The survey provided an opportunity for participants to express their opinions on the overall usefulness of the DICE tool and to provide other comments. RESULTS: The 50 survey respondents were mainly pharmacists (n = 47, 94%) with almost half (n = 23, 47%) having health information technology/informatics training. Most respondents (n = 33, 80%) were employed by organizations with over 350 beds. Respondents indicated the most useful features of the DICE tool were the ability to filter DDI warnings based on routes of administrations (mean [SD] rating scale score, 86.5 [21.6]), primary drug properties (85.7 [20.5]) patient attributes (85.6 [16.7]) and laboratory attributes (88.8 [18.0]). The overall impression of the DICE tool was rated at 82.8 (19.0), and when asked about the potential to reduce DDI alerts, respondents rated the tool at 83.7 (21.8). CONCLUSION: The ability to customize DDI alerts using data elements currently within the EHR has the potential to decrease alert fatigue and override rates. This prototype DICE tool could be used by end users and vendors as a template for developing a more advanced DDI filtering tool within EHR systems.

Hand Surgeon Posture: An Evaluation and Factors That Affect It.

Objective: Approximately 68% of orthopaedic surgeons report occupational related musculoskeletal pain, with back pain being the most common. Poor posture while operating has been proven to contribute to these high rates of musculoskeletal pain. There is little research regarding intraoperative surgeon posture within the field of hand and upper extremity surgery. This prospective study aims to investigate and analyze hand surgeon posture in the operating room. Methods: Posture of three hand surgeons was recorded using the UPRIGHT GO posture tracking device while performing a prospective series of 223 hand and upper extremity surgeries. This device reports posture in terms of overall percentage of time spent slouched versus upright. For this cohort of 223 cases, data were collected including surgical procedure, whether the surgery was performed in a seated or standing position, whether or not loupes were worn during the procedure, and if the surgeon was the primary or assistant surgeon. These data were then analyzed to look for any contributing factors to poor posture. Results: The three hand surgeons in this study spent an average of 40.3% of their time slouched while operating. The average percentage of time slouched was significantly greater with the use of loupes versus no loupes. Additionally, mean time slouching was slightly increased when the surgeon was seated and also when the surgeon was acting as the assistant surgeon. Conclusion: The three orthopaedic hand surgeons in our study spent a significant portion of their operative time slouched. The main variable associated with a significant risk of poor surgical posture was wearing loupes. Slight increases in slouching were seen with operating while seated and as the assistant surgeon. Surgeon awareness of these variables, as well as techniques to improve surgeon posture, should be developed in order to help contribute to better surgeon posture within the field of hand surgery.

MRI order appropriateness for chronic neck pain: Comparison of ordering practices and treatment outcomes for primary care physicians and specialists.

Chronic neck pain is a common reason for doctor visits in the United States. This diagnosis can be evaluated through patient history, physical examination, and judicious use of radiographs. However, possible inappropriate magnetic resonance imaging (MRI) ordering persists. We hypothesized that no difference in ordering practices, ordering appropriateness, and subsequent intervention would be appreciated regarding physician specialty, location, patient characteristics, and history and physical exam findings. A multisite retrospective review of cervical spine MRI between 2014 and 2018 was performed. A total of 332 patients were included. Statistical analysis was used to assess MRI order appropriateness, detail of history and physical exam findings, and intervention decision-making among different specialties. If significant differences were found, multiple linear regression was performed to evaluate the association of MRI order appropriateness regarding physician specialty, location, patient characteristics and history, and physical exam findings. The significance level for all tests was set at <0.05 Orthopedic surgeons ordered MRIs most appropriately with an average American College of Radiology (ACR) score of 8.4 (p < 0.005). Orthopedic surgeons had more comprehensive physical exams as compared to the remaining specialties. The decision for intervention did not vary by physician specialty or ACR score, except for patients of pain medicine physicians who received pain management (p = 0.000). Orthopedic surgeons utilize MRI most appropriately and have more comprehensive physical exams. These findings suggest a need for increased physician education on what indicates an appropriate MRI order to improve the use of resources and further protect patient risk-benefit profiles. Further research elucidating factors to minimize negative findings in "appropriate" MRIs is indicated. Clinical significance: More detailed physical exams may lead to more appropriately ordered MRIs, subsequently resulting in surgery or procedures being performed when appropriately indicated. This suggests the need for increased physician education on when MRI ordering is appropriate for chronic neck pain to improve the use of resources and further protect patient risk-benefit profiles.

Barriers to Adoption of Tailored Drug-Drug Interaction Clinical Decision Support.

OBJECTIVE: Despite the benefits of the tailored drug-drug interaction (DDI) alerts and the broad dissemination strategy, the uptake of our tailored DDI alert algorithms that are enhanced with patient-specific and context-specific factors has been limited. The goal of the study was to examine barriers and health care system dynamics related to implementing tailored DDI alerts and identify the factors that would drive optimization and improvement of DDI alerts. METHODS: We employed a qualitative research approach, conducting interviews with a participant interview guide framed based on Proctor's taxonomy of implementation outcomes and informed by the Theoretical Domains Framework. Participants included pharmacists with informatics roles within hospitals, chief medical informatics officers, and associate medical informatics directors/officers. Our data analysis was informed by the technique used in grounded theory analysis, and the reporting of open coding results was based on a modified version of the Safety-Related Electronic Health Record Research Reporting Framework. RESULTS: Our analysis generated 15 barriers, and we mapped the interconnections of these barriers, which clustered around three entities (i.e., users, organizations, and technical stakeholders). Our findings revealed that misaligned interests regarding DDI alert performance and misaligned expectations regarding DDI alert optimizations among these entities within health care organizations could result in system inertia in implementing tailored DDI alerts. CONCLUSION: Health care organizations primarily determine the implementation and optimization of DDI alerts, and it is essential to identify and demonstrate value metrics that health care organizations prioritize to enable tailored DDI alert implementation. This could be achieved via a multifaceted approach, such as partnering with health care organizations that have the capacity to adopt tailored DDI alerts and identifying specialists who know users' needs, liaise with organizations and vendors, and facilitate technical stakeholders' work. In the future, researchers can adopt the systematic approach to study tailored DDI implementation problems from other system perspectives (e.g., the vendors' system).

Colchicine Drug Interaction Errors and Misunderstandings: Recommendations for Improved Evidence-Based Management.

Colchicine is useful for the prevention and treatment of gout and a variety of other disorders. It is a substrate for CYP3A4 and P-glycoprotein (P-gp), and concomitant administration with CYP3A4/P-gp inhibitors can cause life-threatening drug-drug interactions (DDIs) such as pancytopenia, multiorgan failure, and cardiac arrhythmias. Colchicine can also cause myotoxicity, and coadministration with other myotoxic drugs may increase the risk of myopathy and rhabdomyolysis. Many sources of DDI information including journal publications, product labels, and online sources have errors or misleading statements regarding which drugs interact with colchicine, as well as suboptimal recommendations for managing the DDIs to minimize patient harm. Furthermore, assessment of the clinical importance of specific colchicine DDIs can vary dramatically from one source to another. In this paper we provide an evidence-based evaluation of which drugs can be expected to interact with colchicine, and which drugs have been stated to interact with colchicine but are unlikely to do so. Based on these evaluations we suggest management options for reducing the risk of potentially severe adverse outcomes from colchicine DDIs. The common recommendation to reduce the dose of colchicine when given with CYP3A4/P-gp inhibitors is likely to result in colchicine toxicity in some patients and therapeutic failure in others. A comprehensive evaluation of the almost 100 reported cases of colchicine DDIs is included in table form in the electronic supplementary material. Colchicine is a valuable drug, but improvements in the information about colchicine DDIs are needed in order to minimize the risk of serious adverse outcomes.

QTc Prolongation with the Use of Hydroxychloroquine and Concomitant Arrhythmogenic Medications: A Retrospective Study Using Electronic Health Records Data.

INTRODUCTION: Hydroxychloroquine can induce QT/QTc interval prolongation for some patients; however, little is known about its interactions with other QT-prolonging drugs. OBJECTIVE: The purpose of this retrospective electronic health records study was to evaluate changes in the QTc interval in patients taking hydroxychloroquine with or without concomitant QT-prolonging medications. METHODS: De-identified health records were obtained from the Cerner Health Facts® database. Variables of interest included demographics, diagnoses, clinical procedures, laboratory tests, and medications. Patients were categorized into six cohorts based on exposure to hydroxychloroquine, methotrexate, or sulfasalazine alone, or the combination of any those drugs with any concomitant drug known to prolong the QT interval. Tisdale QTc risk score was calculated for each patient cohort. Two-sample paired t-tests were used to test differences between the mean before and after QTc measurements within each group and ANOVA was used to test for significant differences across the cohort means. RESULTS: A statistically significant increase in QTc interval from the last measurement prior to concomitant exposure of 18.0 ms (95% CI 3.5-32.5; p < 0.05) was found in the hydroxychloroquine monotherapy cohort. QTc changes varied considerably across cohorts, with standard deviations ranging from 40.9 (hydroxychloroquine monotherapy) to 57.8 (hydroxychloroquine + sulfasalazine). There was no difference in QTc measurements among cohorts. The hydroxychloroquine + QTc-prolonging agent cohort had the highest average Tisdale Risk Score compared with those without concomitant exposure (p < 0.05). CONCLUSION: Our analysis of retrospective electronic health records found hydroxychloroquine to be associated with a moderate increase in the QTc interval compared with sulfasalazine or methotrexate. However, the QTc was not significantly increased with concomitant exposure to other drugs known to increase QTc interval.

Overriding Drug-Drug Interaction Alerts in Clinical Decision Support Systems: A Scoping Review.

Ineffective computerized alerts for potential Drug-Drug Interactions (DDI) is a longstanding informatics issue. Prescribing clinicians often ignore or override such alerts due to lack of context and clinical relevance, among various other reasons. In this study, we reveiwed published data on the rate of DDI alert overrides and medications involved in the overrides. We identified 34 eligible studies from sites across Asia, Europe, the United States, and the United Kingdom. The override rate of DDI alerts ranged from 55% to 98%, with more than half of the studies reporting the most common drug pairs or medications involved in acceptance or overriding of alerts. The high prevalance of alert overrides highlights the need for decision support systems that take user, drug, and institutional factors into consideration, as well as actionable metrics to better characterize harm associated with overrides.

Improving the specificity of drug-drug interaction alerts: Can it be done?

PURPOSE: Inaccurate and nonspecific medication alerts contribute to high override rates, alert fatigue, and ultimately patient harm. Drug-drug interaction (DDI) alerts often fail to account for factors that could reduce risk; further, drugs that trigger alerts are often inconsistently grouped into value sets. Toward improving the specificity of DDI alerts, the objectives of this study were to (1) highlight the inconsistency of drug value sets for triggering DDI alerts and (2) demonstrate a method of classifying factors that can be used to modify the risk of harm from a DDI. METHODS: This was a proof-of-concept study focused on 15 well-known DDIs. Using 3 drug interaction references, we extracted 2 drug value sets and any available order- and patient-related factors for each DDI. Fleiss' kappa was used to measure the consistency of value sets among references. Risk-modifying factors were classified as order parameters (eg, route and dose) or patient characteristics (eg, comorbidities and laboratory results). RESULTS: Seventeen value sets (56%) had nonsignificant agreement. Agreement among the remaining 13 value sets was on average moderate. Thirty-three factors that could reduce risk in 14 of 15 DDIs (93%) were identified. Most risk-modifying factors (67%) were classified as order parameters. CONCLUSION: This study demonstrates the importance of increasing the consistency of drug value sets that trigger DDI alerts and how alert specificity and usefulness can be improved with risk-modifying factors obtained from drug references. It may be difficult to operationalize certain factors to reduce unnecessary alerts; however, factors can be used to support decisions by providing contextual information.

Recognizing and treating trigger finger.

This inflammatory condition can leave your patient in pain and with impaired function. Here's what you need to know about the diagnosis and Tx options to provide relief.

Serum potassium changes due to concomitant ACEI/ARB and spironolactone therapy: A systematic review and meta-analysis.

PURPOSE: To provide evidence of serum potassium changes in individuals taking angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) concomitantly with spironolactone compared to ACEI/ARB therapy alone. METHODS: PubMed, Embase, Scopus, and Web of Science were searched for studies including exposure to both spironolactone and ACEI/ARB therapy compared to ACEI/ARB therapy alone. The primary outcome was serum potassium change over time. Main effects were calculated to estimate average treatment effect using random effects models. Heterogeneity was assessed using Cochran's Q and I2. Risk of bias was assessed using the revised Cochrane risk of bias tool. RESULTS: From the total of 1,225 articles identified, 20 randomized controlled studies were included in the meta-analysis. The spironolactone plus ACEI/ARB group included 570 patients, while the ACEI/ARB group included 547 patients. Treatment with spironolactone and ACEI/ARB combination therapy compared to ACEI/ARB therapy alone increased the mean serum potassium concentration by 0.19 mEq/L (95% CI, 0.12-0.26 mEq/L), with intermediate heterogeneity across studies (Q statistic = 46.5, P = 0.004; I2 = 59). Sensitivity analyses showed that the direction and magnitude of this outcome did not change with the exclusion of individual studies, indicating a high level of reliability. Reporting risk of bias was low for 16 studies (80%), unclear for 3 studies (15%) and high for 1 study (5%). CONCLUSION: Treatment with spironolactone in combination with ACEI/ARB therapy increases the mean serum potassium concentration by less than 0.20 mEq/L compared to ACEI/ARB therapy alone. However, serum potassium and renal function must be monitored in patients starting combination therapy to avoid changes in serum potassium that could lead to hyperkalemia.

Designing and evaluating contextualized drug-drug interaction algorithms.

OBJECTIVE: Alert fatigue is a common issue with off-the-shelf clinical decision support. Most warnings for drug-drug interactions (DDIs) are overridden or ignored, likely because they lack relevance to the patient's clinical situation. Existing alerting systems for DDIs are often simplistic in nature or do not take the specific patient context into consideration, leading to overly sensitive alerts. The objective of this study is to develop, validate, and test DDI alert algorithms that take advantage of patient context available in electronic health records (EHRs) data. METHODS: Data on the rate at which DDI alerts were triggered but for which no action was taken over a 3-month period (override rates) from a single tertiary care facility were used to identify DDIs that were considered a high-priority for contextualized alerting. A panel of DDI experts developed algorithms that incorporate drug and patient characteristics that affect the relevance of such warnings. The algorithms were then implemented as computable artifacts, validated using a synthetic health records data, and tested over retrospective data from a single urban hospital. RESULTS: Algorithms and computable knowledge artifacts were developed and validated for a total of 8 high priority DDIs. Testing on retrospective real-world data showed the potential for the algorithms to reduce alerts that interrupt clinician workflow by more than 50%. Two algorithms (citalopram/QT interval prolonging agents, and fluconazole/opioid) showed potential to filter nearly all interruptive alerts for these combinations. CONCLUSION: The 8 DDI algorithms are a step toward addressing a critical need for DDI alerts that are more specific to patient context than current commercial alerting systems. Data commonly available in EHRs can improve DDI alert specificity.

Tophaceous gout of the atlantoaxial joint: a case report.

BACKGROUND: To report the occurrence of tophaceous gout in the cervical spine and to review the literature on spinal gout. CASE PRESENTATION: This report details the occurrence of a large and clinically significant finding of tophaceous gout in the atlantoaxial joint of the cervical spine in an 82-year-old Caucasian man with a 40-year history of crystal-proven gout and a 3-month history of new-onset progressive myelopathy. The patient's American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria score was 15.0. CONCLUSION: Spinal gout is more common than previously thought, and it should be considered in patients who present with symptoms of myelopathy. Diagnosis can be made without a tissue sample of the affected joint(s) with tools like the ACR/EULAR criteria and the use of the "diagnostic clinical rule" for determining the likelihood of gout. Early conservative management with neck immobilization and medical management can avoid the need for surgical intervention.

Risk of Bleeding with Exposure to Warfarin and Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review and Meta-Analysis.

BACKGROUND: Warfarin use can trigger the occurrence of bleeding independently or as a result of a drug-drug interaction when used in combination with nonsteroidal anti-inflammatory drugs (NSAIDs). OBJECTIVES: This article examines the risk of bleeding in individuals exposed to concomitant warfarin and NSAID compared with those taking warfarin alone (Prospero Registry ID 145237). METHODS: PubMed, EMBASE, Scopus, and Web of Science were searched. The primary outcome of interest was gastrointestinal bleeding and general bleeding. Summary effects were calculated to estimate average treatment effect using random effects models. Heterogeneity was assessed using Cochran's Q and I 2. Risk of bias was also assessed using the Agency for Healthcare Research and Quality bias assessment tool. RESULTS: A total of 651 studies were identified, of which 11 studies met inclusion criteria for meta-analysis. The odds ratio (OR) for gastrointestinal bleeding when exposed to warfarin and an NSAID was 1.98 (95% confidence interval [CI]: 1.55-2.53). The risk of gastrointestinal bleeding was also significantly elevated with exposure to a COX-2 inhibitor and warfarin relative to warfarin alone (OR = 1.90, 95% CI: 1.46-2.46). There was an increased risk of general bleeding with the combination of warfarin with NSAIDs (OR = 1.58, 95% CI: 1.18-2.12) or COX-2 inhibitors (OR = 1.54, 95% CI: 0.86-2.78) compared with warfarin alone. CONCLUSION: Risk of bleeding is significantly increased among persons taking warfarin and a NSAID or COX-2 inhibitor together as compared with taking warfarin alone. It is important to caution patients about taking these medications in combination.

Evidence of Clinically Meaningful Drug-Drug Interaction With Concomitant Use of Colchicine and Clarithromycin.

INTRODUCTION: Colchicine is currently approved for the treatment of gout and familial Mediterranean fever, among other conditions. Clarithromycin, a strong inhibitor of CYP3A4 and P-glycoprotein, dramatically increases colchicine's half-life, augmenting the risk of a life-threatening adverse reaction when used inadvertently with colchicine. OBJECTIVES: The aim of this study was to examine the evidence and clinical implications of concomitant use of colchicine and clarithromycin. METHODS: Case reports of colchicine-clarithromycin co-administration were searched using the FDA's Adverse Event Reporting System (FAERS) database. PubMed, EMBASE, and Web of Science electronic databases were also searched from January 2005 through November 2019 for articles reporting colchicine-clarithromycin concomitant use. Individual reports were reviewed to identify consequences of coadministration, dose, days to onset of interaction, symptoms, evidence of renal disease, time to resolution of symptoms, and Drug Interaction Probability Scale (DIPS) rating. RESULTS: The FAERS search identified 58 reported cases, nearly 53% of which were from patients aged between 65 and 85 years. Of 30 reported deaths, 11 occurred in males, and 19 in females. Other frequent complications reported in FAERS included diarrhea (31%), pancytopenia (22%), bone marrow failure (14%), and vomiting (14%). From published literature, we identified 20 case reports of concomitant exposure, 19 of which were rated 'probable' and one 'possible' according to DIPS rating. Of these cases, four 'probable' patients expired. The documented onset of colchicine toxicity occurred within 5 days of starting clarithromycin, and death within 2 weeks of concomitant exposure. CONCLUSION: Clinical manifestations of colchicine-clarithromycin interaction may resemble other systemic diseases and may be life threatening. Understanding this clinically meaningful interaction can help clinicians avoid unsafe medication combinations.

Retrospective Analysis of Low-Molecular-Weight Heparin and Unfractionated Heparin in Pediatric Trauma Patients: A Comparative Analysis.

BACKGROUND: Chemoprophylaxis with either unfractionated heparin (UFH) or Low-Molecular-Weight Heparin (LMWH) are recommended to prevent Venous Thromboembolism (VTE) after trauma. Experimental work has shown beneficial effects of LMWH in animal models, but it is unknown if similar effects exist in humans. We hypothesized that treatment with LMWH is associated with a survival benefit when compared to UFH. METHODS: We performed a retrospective analysis of our level I trauma center database from January 2009 to June 2018. Pediatric patients (age < 18) were included if they received either LMWH or UFH during their stay. Outcome measures included mortality, VTE complications, and hospital length of stay (HLOS). RESULTS: A total of 354 patients were included. Patients who received LMWH had lower mortality compared to those who received UFH. After multivariate logistic regression, LMWH was still independently associated with improved survival. No association was found between LMWH and UFH regarding deep vein thrombosis (DVT) or pulmonary embolism (PE) rates. No association was found between LMWH with HLOS. CONCLUSIONS: LMWH was associated with improved survival compared to UFH in our pediatric trauma patients. This was independent of injury severity or VTE complications. Further studies are required to understand better the mechanisms by which LMWH improves survival. LEVEL OF EVIDENCE: 3.

Predictors of Oxygenator Exchange in Patients Receiving Extracorporeal Membrane Oxygenation.

Thrombosis within the membrane oxygenator (MO) during extracorporeal membrane oxygenation (ECMO) can lead to sudden oxygenator dysfunction with deleterious effects to the patient. The purpose of this study was to identify predictors of circuit exchange during ECMO. This is a single-center, retrospective study of all patients who received ECMO at our institution from January 2010 to December 2015. Changes in potential markers were compared on Day 3 vs. Day 0 before MO exchange. Of the 150 patients who received ECMO, there were 58 MO exchanges in 35 patients. Mean ECMO duration was 21.1 (±12.7) days. D-dimer (DD) (µg/mL) (mean difference -2.6; 95% confidence interval [CI]: -4.2 to -1.1; p = .001) increased significantly in the 3 days leading up to MO exchange, whereas fibrinogen (mg/dL) (mean difference 90.7; 95% CI: 41.8-139.6; p = .001), platelet (PLT) count (1,000/µL) (mean difference 23.3; 95% CI: 10.2-36.4; p = .001), and heparin dose (units/h) (mean difference 261.7; 95% CI: 46.3-477.1; p = .02) decreased. Increasing DD or decreasing fibrinogen, PLT count, or heparin dose may indicate an impending need for MO exchange in patients receiving ECMO. Early identification of these changes may help prevent sudden MO dysfunction.

Accuracy of adverse-drug-event reports collected using an automated dispensing system.

PURPOSE: The accuracy of adverse-drug-event (ADE) reports collected using an automated dispensing system was evaluated. METHODS: ADE reports were collected by requiring nurses on five units in a tertiary care facility to select a reason for removing two tracer drugs (dextrose injection 50% [D50] and naloxone) from an automated dispensing system (Medstation 2000, Pyxis, San Diego, CA). The accuracy of the ADE reports during a period of 4.5 months was evaluated through retrospective chart review. The sensitivity, specificity, positive predictive value, and negative predictive value of the reports were calculated. RESULTS: A review of 61 D50 transactions found that the appropriate reason for removal was selected by nursing staff 62% of the time. Twenty-seven transactions were recorded as occurring due to an ADE, and 70% of these were confirmed in the medical record. The sensitivity and specificity of the ADE reports for D50 were 55.9% (95% confidence interval [CI], 39.2-72.6%) and 70.4% (95% CI, 53.2-87.6%), respectively. A review of 32 naloxone transactions found that nurses correctly selected the reason for removal 88% of the time. Twenty-three transactions were recorded as occurring due to an ADE, and 87% of these were confirmed in the medical record. The sensitivity and specificity of the ADE reports for naloxone were 95.2% (95% CI, 86.1-104.4%) and 72.7% (95% CI, 46.4-99.1%), respectively. CONCLUSION: A Pyxis ADE reporting mechanism using the tracer drugs D50 and naloxone increased the overall reporting of ADEs.