Successful deployment of drug-disease interaction clinical decision support across multiple Kaiser Permanente regions.

OBJECTIVE: The study sought to develop a criteria-based scoring tool for assessing drug-disease knowledge base content and creation of a subset and to implement the subset across multiple Kaiser Permanente (KP) regions. MATERIALS AND METHODS: In Phase I, the scoring tool was developed, used to create a drug-disease alert subset, and validated by surveying physicians and pharmacists from KP Northern California. In Phase II, KP enabled the alert subset in July 2015 in silent mode to collect alert firing rates and confirmed that alert burden was adequately reduced. The alert subset was subsequently rolled out to users in KP Northern California. Alert data was collected September 2015 to August 2016 to monitor relevancy and override rates. RESULTS: Drug-disease alert scoring identified 1211 of 4111 contraindicated drug-disease pairs for inclusion in the subset. The survey results showed clinician agreement with subset examples 92.3%-98.5% of the time. Postsurvey adjustments to the subset resulted in KP implementation of 1189 drug-disease alerts. The subset resulted in a decrease in monthly alerts from 32 045 to 1168. Postimplementation monthly physician alert acceptance rates ranged from 20.2% to 29.8%. DISCUSSION: Our study shows that drug-disease alert scoring resulted in an alert subset that generated acceptable interruptive alerts while decreasing overall potential alert burden. Following the initial testing and implementation in its Northern California region, KP successfully implemented the disease interaction subset in 4 regions with additional regions planned. CONCLUSIONS: Our approach could prevent undue alert burden when new alert categories are implemented, circumventing the need for trial live activations of full alert category knowledge bases.

Variation in Generic Drug Manufacturers' Product Characteristics.

OBJECTIVES: Studies suggest appearance may be an important factor in medication nonadherence. This study was undertaken to characterize the range of appearances and costs of 16 oral solid generic medications in four major chronic diseases/conditions. METHODS: We identified frequently prescribed medications in four therapeutic classes-antidiabetics, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), beta blockers, and heart failure drugs-and verified that each had at least three generic manufacturer sources in 2016. The color, shape, scoring, and size for each formulation were compared. Prices were determined based on manufacturers' self-reported wholesale acquisition costs effective December 31, 2016. RESULTS: We identified 40 unique manufacturers for the antidiabetics, 35 for the statins, 38 for the beta blockers, and 71 for the heart failure agents. For all 16 drugs across all four disease states, there was an average of three colors, two shapes, 11 manufacturers, and four appearances when color and shape together are considered. The cost variance per drug ranged from 2% to more than 62,253%. CONCLUSION: Substantial appearance variation among generically equivalent products raises the strong possibility that patients may experience product switches that could increase the likelihood of nonadherence. Our data support the need to further study drug appearance changes and interventions as a potential factor affecting chronic disease adherence outcomes.

Depression screening for prescribed medications with mental health risk: Considerations for clinical decision support, workflow redesign, and health information exchange arrangements.

OBJECTIVE: Depression screening should be increased when prevailing knowledge underscoring medication-associated mental health risk is highest. Depression screening in primary care practices when medications with mental health risk were prescribed was estimated while considering the absence and presence of clinical decision support systems. MATERIALS AND METHODS: A cross-sectional, descriptive study using the National Ambulatory Medical Care Survey (NAMCS) data from 2008 to 2010 was conducted. Primary care physician visits were classified based on whether a medication prescribed had a contraindication, severe warning, moderate warning, adverse event only, or no documented mental health risk. Adjusted odds of depression screening for each risk warning level were estimated while controlling for important sociodemographic factors and presence of computerized systems for medication warnings and guideline recommendations. RESULTS: Depression screening at primary care practice visits when medications were prescribed was 2.1% and increased to 2.8% or higher when medications had a moderate or severe mental health risk warning or medication-disease contraindication. Depression screening was increased at visits when at least one medication was prescribed that had a contraindication (AOR = 6.31, P < 0.001), severe warning (AOR = 2.04, P = 0.003), or moderate warning (AOR = 2.50, P = 0.012) for mental health risk, but not for mental health adverse event only warnings alone (AOR = 1.54, P = 0.074). DISCUSSION: Depression screening is increased when medications were prescribed with a documented mental health risk. Presence of clinical decision support systems may help discern between minor and major medication-associated mental health risks. CONCLUSIONS: Appropriately, positioned warning systems with targeted content, workflow redesign, and health information exchange may improve depression screening in at-risk patients.

Recommendations for selecting drug-drug interactions for clinical decision support.

PURPOSE: Recommendations for including drug-drug interactions (DDIs) in clinical decision support (CDS) are presented. SUMMARY: A conference series was conducted to improve CDS for DDIs. A work group consisting of 20 experts in pharmacology, drug information, and CDS from academia, government agencies, health information vendors, and healthcare organizations was convened to address (1) the process to use for developing and maintaining a standard set of DDIs, (2) the information that should be included in a knowledge base of standard DDIs, (3) whether a list of contraindicated drug pairs can or should be established, and (4) how to more intelligently filter DDI alerts. We recommend a transparent, systematic, and evidence-driven process with graded recommendations by a consensus panel of experts and oversight by a national organization. We outline key DDI information needed to help guide clinician decision-making. We recommend judicious classification of DDIs as contraindicated and more research to identify methods to safely reduce repetitive and less-relevant alerts. CONCLUSION: An expert panel with a centralized organizer or convener should be established to develop and maintain a standard set of DDIs for CDS in the United States. The process should be evidence driven, transparent, and systematic, with feedback from multiple stakeholders for continuous improvement. The scope of the expert panel's work should be carefully managed to ensure that the process is sustainable. Support for research to improve DDI alerting in the future is also needed. Adoption of these steps may lead to consistent and clinically relevant content for interruptive DDIs, thus reducing alert fatigue and improving patient safety.

Caring for Glucose-6-Phosphate Dehydrogenase (G6PD)-Deficient Patients: Implications for Pharmacy.

This article explores the basis of glucose-6-phosphate dehydrogenase deficiency and defines the role that health care informatics can play in optimal treatment.

Identifying knowledge gaps in the labeling of medications for geriatric patients.

The authors found that two-thirds of drugs approved by the FDA in recent years lacked adequate efficacy and safety information for use in older patients. With an expected doubling of the elderly population by 2040, it is time for pharmaceutical manufacturers to incorporate more robust prescribing information into their product labels of drugs used in this patient population.

Sulfonamide cross-reactivity: is there evidence to support broad cross-allergenicity?

PURPOSE: Published and manufacturer-provided data regarding potential cross-reactivity between antibacterial and nonantibacterial sulfonamide agents are reviewed. SUMMARY: An estimated 3-6% of the general population is allergic to sulfonamides and thus at risk for type I and other hypersensitivity reactions to sulfamethoxazole and other sulfonamide antibacterial agents. Concerns have been raised that a history of sulfa allergy may be associated with an increased risk of adverse reactions to a wide range of nonantibacterial sulfonamides, including certain antivirals, carbonic anhydrase inhibitors, cyclooxygenase-2- selective nonsteroidal antiinflammatory drugs, loop and thiazide diuretics, and sulfonylureas; concerns have also been raised that patients who have experienced an allergic reaction to one nonantibacterial sulfonamide may be at risk for an adverse reaction to others. Structurally, none of the nonantibiotic sulfonamides exhibit both of the features shown to be responsible for sulfonamide reactions (i.e., an N-containing ring attached to the N1 nitrogen of the sulfonamide group and an arylamine group at the N4 position), and only two agents (amprenavir and fosamprenavir) have the latter characteristic. A comprehensive literature search (1966-December 2011) identified nine case reports indicating possible cross-reactivity to sulfonamide medications; however, in most cases, adequate patient testing was not conducted to firmly establish either sulfa allergy or sulfonamide cross-sensitivity. The weight of evidence suggests that withholding nonantibacterial sulfonamides from patients with prior reactions to antibacterial sulfonamides or other nonantibacterial sulfonamides is not clinically justified. CONCLUSION: A review of the professional literature and manufacturer-provided data did not find convincing evidence of broad cross-reactivity between antibacterial and nonantibacterial sulfonamide agents.

Unlabeled uses of intravenous immune globulin.

PURPOSE: The unlabeled uses of intravenous immune globulin (IVIG) were reviewed. SUMMARY: A literature review was conducted to identify studies examining the unlabeled uses of IVIG. A review of 138 clinical trial abstracts identified 10 trials examining 2 labeled uses (635 patients) and 128 trials examining 61 different off-label uses (6781 patients). The most common off-label indications included multiple sclerosis, graft-versus-host disease in transplant patients, prevention of antiphospholipid syndrome in miscarriage, Guillain-Barré syndrome, and progression of human immunodeficiency virus after delivery. The studies appeared to support many of the acceptable off-label uses cited by various guideline groups. A total of 276 case reports were identified, with 268 reports representing 156 different off-label uses (362 patients). Seven meta-analyses were identified, evaluating recurrent miscarriage, in vitro fertilization failure, infection in preterm infants, multiple sclerosis, immune thrombocytopenic purpura, and pemphigoid. With the exception of recurrent miscarriage and infection in preterm infants, the off-label use of IVIG for these indications was associated with positive outcomes. An examination of IVIG guidelines by specialty society, payer, and other review organizations revealed that the biomedical evidence supporting off-label uses is being interpreted in different ways. Health care institutions are strongly urged to approve and closely monitor specific uses of IVIG to reserve dwindling supplies for the "best-evidence" uses. Clinicians should be aware of the limits of knowledge in many off-label uses and exercise restraint in prescribing for unproven indications. CONCLUSION: A literature review identified more than 150 unlabeled uses of IVIG. The evidence for these uses is being interpreted in different ways by various reviewing organizations.

Use and outcomes of antifibrinolytic therapy in patients undergoing cardiothoracic surgery at 20 academic medical centers in the United States.

BACKGROUND: Several clinical trials have shown an association between the use of aprotinin in cardiothoracic surgery (CTS) patients and an increased risk of adverse renal, cardiovascular, and cerebrovascular events. Other antifibrinolytic agents-aminocaproic acid (AA) and tranexamic acid (TA)-have not shown elevated risks. Using a large administrative data set, we sought to examine these findings. METHODS: In our observational database study of CTS patients who were discharged from 20 academic medical centers from October 2002 through September 2005, we assessed the use of antifibrinolytic therapy on select patient outcomes using descriptive and inferential statistics to compare the various groups. RESULTS: For the CTS patients, AA was used in 9,751 (15.5% of patients) and aprotinin was used in 6,855 (10.9% of patients). Only 17 patients from four hospitals received TA; therefore, TA was excluded from further analysis. A quarterly analysis showed a slow decline in the use of AA, with a gradual increase in the use of aprotinin over the study time period. Variation by hospital using each option was considerable (range, 0%-50%). Statistically significant differences in mortality rates (P < 0.001) occurred with AA (2.6%), aprotinin (5.2%), and control patients (n = 46,123), who did not use any antifibrinolytic agents (3.9%). Rates of acute renal failure were 6.2% with AA, 10.9% with aprotinin, and 6.1% in controls; hemodialysis rates were 2.8%, 6.4%, and 2.6%, respectively. Postoperative acute myocardial infarction occurred in only two cases of patients receiving AA, in none of those using aprotinin, and in 63 controls. CONCLUSION: Although the use of aprotinin has been increasing, compared with AA, the overall use of antifibrinolytic agents in patients undergoing CTS has remained relatively stable over a three-year period, at under 30%. Significant differences in patient outcomes were observed between the two treatment groups. Given the growing body of evidence for the use of antifibrinolytic therapy, hospitals might be best served by examining existing patterns of use and by instituting restrictions of aprotinin for patients facing an increased risk for bleeding during CTS.

Intensive care unit telemedicine: review and consensus recommendations.

Intensive care unit telemedicine involves nurses and physicians located at a remote command center providing care to patients in multiple, scattered intensive care units via computer and telecommunication technology. The command center is equipped with a workstation that has multiple monitors displaying real-time patient vital signs, a complete electronic medical record, a clinical decision support tool, a high-resolution radiographic image viewer, and teleconferencing for every patient and intensive care unit room. In addition to communication functions, the video system can be used to view parameters on ventilator screens, infusion pumps, and other bedside equipment, as well as to visually assess patient conditions. The intensivist can conduct virtual rounds, communicate with on-site caregivers, and be alerted to important patient conditions automatically via software-monitored parameters. This article reviews the technology's background, status, significance, clinical literature, financial effect, implementation issues, and future developments. Recommendations from a University HealthSystem Consortium task force are also presented.

Physician factors as an indicator of technological device adoption.

This paper analyzes a sample interventional cardiologist's demographic, academic, and professional characteristics to provide an understanding of their technological device adoption styles. The study sample consisted of 15 physicians from two large Midwestern hospitals, one an academic medical center and the other a medium-sized community hospital. Interventional cardiologists were identified through their online physician profile and respective departments. A questionnaire was developed to assess each physician's self-perceived adoption style, their awareness of the new technology, their participation in clinical trials, organizational support, and how various factors influence their adoption of new technology. Lastly, a database of bare metal and drug eluting stents was examined to document the number of stents used by each physician. Pragmatic and observational findings are presented from the questionnaire, physician profile, to database on stent use. The paper concludes with a discussion of the managerial and forecasting implications and methods to promote technology adoption.

Control mechanisms for guideline implementation.

OBJECTIVES: One approach to reducing health care costs while ensuring high-quality patient care is the use of medical practice guidelines. This study focuses on mechanisms that facilitate the implementation of guidelines primarily intended to reduce cost without increasing patient risk, using a multiinstitutional case study of a single guideline. SUBJECTS AND METHODS: We conducted semistructured interviews with physicians and administrators involved with guideline implementation in 61 academic medical centers. The interviews included questions on both implementation methods and the final success of implementation at each center. RESULTS: We identified 5 factors likely to be of importance to the guideline implementation process: (1) the use of a written form to routinize the process; (2) the acquisition of informed consent; (3) the presence of an active department chair (or section chief) to serve as an opinion leader; (4) the use of individual-level monitoring; and (5) the granting of financial incentives. CONCLUSIONS: This study allowed the identification of four processes for guideline implementation. For hospitals contemplating implementation of guidelines aimed toward cost reduction or selective use of various agents for other purposes, a decision process to identify the control mechanism best suited to an individual institution is a crucial step toward success.

Clinical gene therapy for nonmalignant disease.

Gene therapy is envisioned as a potentially definitive treatment for a variety of diseases that have a genetic etiology. We reviewed trials of clinical gene therapy for nonmalignant, single-gene, and multifactorial disorders and infectious diseases, and found limited evidence suggesting that gene therapy may benefit patients who have severe, combined, immunodeficiency disorder; cystic fibrosis; coronary artery disease or peripheral arterial disease; or hemophilia. Effective gene therapy requires the targeted transfer of exogenous genetic material into human cells and the subsequent regulated expression of the corresponding gene product. Because no phase 3 randomized controlled trials have been completed that fulfill these criteria, it is difficult to correlate signs of clinical benefit with the administration of gene therapy in any disease. Additional clinical and basic research is needed to determine the future role of gene therapy.