Interventions, Barriers, and Proposed Solutions Associated With the Implementation of a Protocol That Uses Clinical Decision Support and a Stress Biomarker Test to Identify ICU Patients at High-Risk for Drug Associated Acute Kidney Injury.

BACKGROUND: Damage biomarkers are helpful in early identification of patients who are at risk of developing acute kidney injury (AKI). Investigations are ongoing to identify the optimal role of stress/damage biomarkers in clinical practice regarding AKI risk prediction, surveillance, diagnosis, and prognosis. OBJECTIVE: To determine the impact of utilizing a clinical decision support system (CDSS) to guide stress biomarker testing in intensive care unit (ICU) patients at risk for drug-induced acute kidney injury (D-AKI). METHODS: A protocol was designed utilizing a clinical decision support system (CDSS) alert to identify patients that were ordered 3 or more potentially nephrotoxic medications, suggesting risk for progressing to AKI from nephrotoxic burden. Once alerted to these high-risk patients, the pharmacist determined if action was needed by ordering a stress biomarker test, tissue inhibitor of metalloproteinase-2-insulin-like growth factor-binding protein 7 (TIMP-2•IGFBP7). If the biomarker test result was elevated, the pharmacist provided nephrotoxin stewardship recommendations to the team. Pharmacists recorded the response to the clinical decision support alert, ordering, and interpreting the TIMP-2•IGFBP7, and information regarding clinical interventions. An alert in conjunction with TIMP-2•IGFBP7 as a strategy for AKI risk prediction and stimulant for patient care management was assessed. In addition, barriers and solutions to protocol implementation were evaluated. RESULTS: There were 394 total activities recorded by pharmacists for 345 unique patients. Ninety-three (93/394; 23.6%) actionable alerts resulted in a TIMP-2•IGFBP7 test being ordered. Thirty-one TIMP-2•IGFBP7 results were >0.3 (31/81; 38.3%), suggesting a high-risk of progression to AKI, which prompted 191 pharmacist/team interventions. On average, there were 1.64 interventions per patient in the low-risk patients, 3.43 in high-risk patients, and 3.75 in the highest-risk patients. CONCLUSION AND RELEVANCE: Stress biomarkers can be used in conjunction with CDSS alerts to affect therapeutic decisions in ICU patients at high-risk for D-AKI.

Patient-Reported Outcomes Associated With Sedation and Agitation Intensity in the Critically Ill.

BACKGROUND: Patient-reported outcomes are essential to understand the relationship between patients' perception of sedation and clinicians' assessments of sedation. OBJECTIVES: To evaluate the association between sedation and agitation indexes and patient-reported outcomes of sedation and analgesia. METHODS: This prospective, single-center, observational study included adult patients who were continuously sedated for at least 24 hours in a medical or surgical/ trauma intensive care unit. Patients were interviewed after sedation was discontinued regarding their satisfaction with the quality of sedation and potentially related factors. The primary outcome was the correlation between sedation and agitation indexes and patient-reported outcomes. RESULTS: A total of 68 patients were interviewed after sedation. Of these, 29 (42.6%) described their overall feelings about their experience while receiving mechanical ventilation in the intensive care unit as "pleasant". When asked about their desires if they were to experience the situation again, 29 patients (42.6%) reported that they would want more sedation. Agitation index was statistically significantly correlated with several patient-reported outcomes. Receiving mechanical ventilation (r = 0.41, P = .002), the amount of noise (r = 0.34, P = .01), suctioning (r = 0.32, P = .02), difficulty resting or sleeping (r = 0.39, P = .003), inability to communicate by talking (r = 0.36, P = .008), anxiety (r = 0.29, P = .03), panic (r = 0.3, P = .02), and frustration (r = 0.47, P < .001) were associated with a higher agitation index. CONCLUSION: Agitation index was significantly associated with several patient-reported outcomes and thus seems to be a promising descriptor of patients' experience.

A Pharmacotherapy Scholars Program to Provide Intensive Training to Enhance Pharmacy Students' Postgraduate Readiness.

Objective. To design, integrate the curriculum for, and evaluate an innovative program to facilitate placement of students into postgraduate pharmacy residency training programs involving direct patient care. Methods. The Pharmacotherapy Scholars Program (PSP) was designed to prepare fourth-professional year students to become highly proficient in a direct patient care role and to successfully match with postgraduate residency training programs. The following elements were included in the year-long curriculum: integrated synchronous advanced pharmacy practice experiences with personal advising, team-based mentoring, peer-to-peer learning, longitudinal research, and professional development. Program goals were modeled after the accreditation standards for postgraduate year one (PGY1) pharmacy residency programs. Program faculty members ensured that the PSP had a broad scope, included rigorous student assessments, had a strong research focus, and provided scholarship opportunities. Results. Sixty-eight students completed the program from fall 2013 through spring 2019. The overall residency match rate was 93%. Students' performance on both knowledge and clinical skills assessments significantly improved after completing the program. There was an approximately 15% increase in knowledge and a 30% improvement in clinical skills based on comprehensive readiness assessments and an intermittent clinical examination that used patient simulation, respectively. Conclusion. The Pharmacotherapy Scholars Program is an innovative training program designed to enhance PharmD students' preparation for advanced clinical training. Students who completed the PSP achieved a high PGY1 residency placement rate while demonstrating significant improvements in pharmacotherapy knowledge and clinical skills in direct patient care activities.

Clinical outcomes with unfractionated heparin monitored by anti-factor Xa vs. activated partial Thromboplastin time.

Anti-factor Xa (anti-Xa) monitoring of unfractionated heparin (UFH) is associated with less time to achieve therapeutic anticoagulation compared to the activated partial thromboplastin time (aPTT). However, it is unknown whether clinical outcomes differ between these methods of monitoring. The aim of this research was to compare the rate of venous thrombosis and bleeding events in patients that received UFH monitored by anti-Xa compared to the aPTT. A retrospective review of electronic health records identified adult patients that received UFH given intravenously (IV) for ≥2 days, with either anti-Xa or aPTT monitoring at an academic tertiary care hospital. This was a pre/post study design conducted between January 1 to December 30, 2014 (aPTT), and January 1 to December 30, 2016 (anti-Xa). All UFH adjustments were based on institutional nomograms. The primary outcome was venous thrombosis and the secondary outcome was bleeding, both of which occurred between UFH administration and discharge from the index hospitalization. A total of 2500 patients were in the anti-Xa group and 2847 patients aPTT group. Venous thrombosis occurred in 10.2% vs 10.8% of patients in the anti-Xa and aPTT groups, respectively (P = .49). Bleeding occurred in 33.7% vs 33.6% of patients in the anti-Xa and aPTT groups, respectively (P = .94). Anti-Xa monitoring was not an independent predictor of either outcome in multivariate logistic regression analyses. Our study found no difference in clinical outcomes between anti-Xa and aPTT-based monitoring of UFH IV.

Predictors of resistant alcohol withdrawal (RAW): A retrospective case-control study.

BACKGROUND: Benzodiazepine-resistant alcohol withdrawal (RAW), defined by a requirement of ≥ 40 mg of diazepam in 1 h, represents a severe form of withdrawal without predictive parameters. This study was designed to identify risk factors associated with RAW versus withdrawal without benzodiazepine resistance (nRAW). METHODS: A retrospective cohort of adults with severe alcohol withdrawal were screened. Demographic and clinical variables, collected through chart review, underwent logistic regression to select the subset that predicst RAW. RESULTS: 736 patients (515 nRAW, 221 RAW) were analyzed. RAW patients were younger (P < 0.001), male (P = 0.008) Caucasians (P = 0.037) with histories of psychiatric illness (P < 0.001), higher serum ethanol concentrations (P < 0.007), and abnormal liver enzymes (P = 0.01). RAW patients had significantly lower platelets (P < 0.001), chloride (P = 0.02), and potassium (P = 0.01) levels; severity of illness (SAPSII) (P < 0.001) and comorbidity scores (P < 0.001). Caucasian race and male gender were found to be 3.6 and 2.6 times more likely to be RAW. For every 1-unit increase in comorbidity and severity of illness scores, patients were 22% [OR(95% CI) 0.78 (0.66-0.90)] and 4% [0.96 (0.93-0.98)] less likely to be RAW. Patients with a psychiatric history or thrombocytopenia were 2 times more likely [2.02 (1.24-3.30); 2.13 (1.31-3.50), respectively] to be RAW. CONCLUSION: These data demonstrate the predictive ability of a history of psychiatric illness, thrombocytopenia, gender, race, baseline severity of illness and comorbidity scores for developing RAW. Considering these characteristics in early withdrawal management may prevent progression to RAW outcomes.

Adjunct Ketamine Use in the Management of Severe Ethanol Withdrawal.

OBJECTIVES: Ketamine offers a plausible mechanism with favorable kinetics in treatment of severe ethanol withdrawal. The purpose of this study is to determine if a treatment guideline using an adjunctive ketamine infusion improves outcomes in patients suffering from severe ethanol withdrawal. DESIGN: Retrospective observational cohort study. SETTING: Academic tertiary care hospital. PATIENTS: Patients admitted to the ICU and diagnosed with delirium tremens by Diagnostic and Statistical Manual of Mental Disorders V criteria. INTERVENTIONS: Pre and post guideline, all patients were treated in a symptom-triggered fashion with benzodiazepines and/or phenobarbital. Postguideline, standard symptom-triggered dosing continued as preguideline, plus, the patient was initiated on an IV ketamine infusion at 0.15-0.3 mg/kg/hr continuously until delirium resolved. Based upon withdrawal severity and degree of agitation, a ketamine bolus (0.3 mg/kg) was provided prior to continuous infusion in some patients. MEASUREMENTS AND MAIN RESULTS: A total of 63 patients were included (29 preguideline; 34 postguideline). Patients treated with ketamine were less likely to be intubated (odds ratio, 0.14; p < 0.01; 95% CI, 0.04-0.49) and had a decreased ICU stay by 2.83 days (95% CI, -5.58 to -0.089; p = 0.043). For ICU days outcome, correlation coefficients were significant for alcohol level and total benzodiazepine dosing. For hospital days outcome, correlation coefficients were significant for patient age, aspartate aminotransferase, and alanine aminotransferase level. Regression revealed the use of ketamine was associated with a nonsignificant decrease in hospital stay by 3.66 days (95% CI, -8.40 to 1.08; p = 0.13). CONCLUSIONS: Mechanistically, adjunctive therapy with ketamine may attenuate the demonstrated neuroexcitatory contribution of N-methyl-D-aspartate receptor stimulation in severe ethanol withdrawal, reduce the need for excessive gamma-aminobutyric acid agonist mediated-sedation, and limit associated morbidity. A ketamine infusion in patients with delirium tremens was associated with reduced gamma-aminobutyric acid agonist requirements, shorter ICU length of stay, lower likelihood of intubation, and a trend toward a shorter hospitalization.

Blended Simulation Progress Testing for Assessment of Practice Readiness.

Objective. To design an assessment of practice readiness using blended-simulation progress testing. Design. A five-station, blended simulation assessment was developed to evaluate patient care outcomes in first- and third-year pharmacy (P1 and P3) students, as well as first-year postgraduate (PGY1) pharmacy residents. This assessment of practice readiness included knowledge and performance evaluations administered as a progress test. Assessment. Eighteen PGY1 residents, 108 P3 students, and 106 P1 students completed the assessment. P3 students scored significantly higher than P1 students across all evaluations. Third-year pharmacy students scored significantly lower than PGY1 residents in interprofessional communications and attitudes of ownership in a standardized colleague/mannequin model station, and in patient communication in a standardized patient station. Conclusion. Learners demonstrated evolving skills as they progressed through the curriculum. A blended simulation integrated progress test provides data for improvement of individual student clinical skills, informs curricular advancement, and aligns curricular content, process, and outcomes with accreditation standards.

Evaluation of Branched-Narrative Virtual Patients for Interprofessional Education of Psychiatry Residents.

OBJECTIVE: This pilot study evaluated the utility of branched-narrative virtual patients in an interprofessional education series for psychiatry residents. METHODS: Third-year psychiatry residents attended four interprofessional education advanced psychopharmacology sessions that involved completion of a branched-narrative virtual patient and a debriefing session with a psychiatric pharmacist. Pre- and post-assessments analyzed resident learning and were administered around each virtual patient. Simulation 4 served as a comprehensive review. The primary outcome was differences in pre- and post-assessment scores. Secondary outcomes included resident satisfaction with the virtual patient format and psychiatric pharmacist involvement. RESULTS: Post-test scores for simulations 1, 2, and 3 demonstrated significant improvement (p < 0.05) from pre-test scores. Scores for simulation 4 did not retain significance. Resident satisfaction with the branched-narrative virtual patient format and psychiatric pharmacist involvement was high throughout the series (100 %; n = 18). CONCLUSIONS: Although there are important methodological limitations to this study including a small sample size and absence of a comparator group, this pilot study supports the use of branched-narrative virtual patients in an interprofessional education series for advanced learners.

Recommendations for Aligning PGY2 Pharmacy Residency Training and Pharmacy Specialist Board Certification.

With the increased focus and anticipated growth in specialty training and certification within the profession of pharmacy, it is important for the profession to step back and evaluate the manner in which its adopted education and certification systems interface. As a result of specialty practice development, significant growth is occurring in both postgraduate year two (PGY2) pharmacy residency programs and individuals seeking certification by the Board of Pharmacy Specialties. As the profession continues to evolve its specialty training and credentialing systems, it is important to consider the inherent relationship between these systems. This paper considers the current landscape of specialty training and certification, including issues related to the quality of PGY2 training, consistent application of standards across and within PGY2 programs, credentialing of preceptors and program directors, and alignment of training with specialty certification examination content domains. We outline recommendations across three areas: (1) creating consistency between specialty training and certification, (2) aligning qualifications of PGY2 residency program directors and preceptors with the designated specialty area, and (3) assessing program quality in the context of the expectations of specialists established by the profession. The goal of this paper is to stimulate professional dialogue on these issues. Establishing both formal and informal connections between specialty training and certification can serve as the foundation for a rational approach to professional development and the credentialing that will be recognized by stakeholders outside the pharmacy profession. Establishing these connections will also support and advance the profession's mission of meeting the medication needs of patients.

Illustrating idiographic methods for translation research: moderation effects, natural clinical experiments, and complex treatment-by-subgroup interactions.

A critical juncture in translation research involves the preliminary studies of intervention tools, provider training programs, policies, and other mechanisms used to leverage knowledge garnered at one translation stage into another stage. Potentially useful for such studies are rigorous techniques for conducting within-subject clinical trials, which have advanced incrementally over the last decade. However, these methods have largely not been utilized within prevention or translation contexts. The purpose of this manuscript is to demonstrate the flexibility, wide applicability, and rigor of idiographic clinical trials for preliminary testing of intervention mechanisms. Specifically demonstrated are novel uses of state-space modeling for testing intervention mechanisms of short-term outcomes, identifying heterogeneity in and moderation of within-person treatment mechanisms, a horizontal line plot to refine sampling design during the course of a clinic-based experimental study, and the need to test a treatment's efficacy as treatment is administered along with (e.g., traditional 12-month outcomes).

Combination of a Flipped Classroom Format and a Virtual Patient Case to Enhance Active Learning in a Required Therapeutics Course.

Objective. To design and evaluate the integration of a virtual patient activity in a required therapeutics course already using a flipped-classroom teaching format. Design. A narrative-branched, dynamic virtual-patient case was designed to replace the static written cases that students worked through during the class, which was dedicated to teaching the complications of liver disease. Students completed pre- and posttests before and after completing the virtual patient case. Examination scores were compared to those in the previous year. Assessment. Students' posttest scores were higher compared to pretest scores (33% vs 50%). Overall median examination scores were higher compared to the historical control group (70% vs 80%), as well as scores on questions assessing higher-level learning (67% vs 83%). A majority of students (68%) felt the virtual patient helped them apply knowledge gained in the pre-class video lecture. Students preferred this strategy to usual in-class activities (33%) or indicated it was of equal value (37%). Conclusion. The combination of a pre-class video lecture with an in-class virtual patient case is an effective active-learning strategy.

Virtual Patient Case Sharing Across Two Schools of Pharmacy.

Objective. To expand the use of virtual patients at 2 schools of pharmacy through virtual patient case sharing. Design. Faculty members at two schools of pharmacy collaborated to expand the use of virtual patients. Two simulation programs, vpSim and DecisionSim (Decision Simulation, LLC, Chadsford, PA), were used to create interactive patient cases for a required course and an elective course at the different schools. Each school developed cases for their own use and then shared the cases with the other school. Assessment. The development, sharing, and subsequent modification of cases were examined using a standardized data collection form completed by both schools. Survey instruments were used to gather data regarding faculty perception and student satisfaction. Pre- and post-tests were administered to assess student learning. Five cases were developed and shared between the institutions. The time spent constructing new cases (22 hours/case) was significantly longer than the time spent modifying the shared cases (1.2 hours/case). Faculty members and students were largely satisfied with case sharing and the use of virtual patient cases, respectively. Virtual patients significantly enhanced student learning of material (mean score: 3.2 vs 3.6 on a 5-point scale). Conclusions. The sharing of virtual patient cases may allow institutions to overcome barriers to implementation of virtual patient programs, namely faculty resources, while improving student learning and satisfaction.

Effect of critical care pharmacist's intervention on medication errors: A systematic review and meta-analysis of observational studies.

Pharmacists are integral members of the multidisciplinary team for critically ill patients. Multiple nonrandomized controlled studies have evaluated the outcomes of pharmacist interventions in the intensive care unit (ICU). This systematic review focuses on controlled clinical trials evaluating the effect of pharmacist intervention on medication errors (MEs) in ICU settings. Two independent reviewers searched Medline, Embase, and Cochrane databases. The inclusion criteria were nonrandomized controlled studies that evaluated the effect of pharmacist services vs no intervention on ME rates in ICU settings. Four studies were included in the meta-analysis. Results suggest that pharmacist intervention has no significant contribution to reducing general MEs, although pharmacist intervention may significantly reduce preventable adverse drug events and prescribing errors. This meta-analysis highlights the need for high-quality studies to examine the effect of the critical care pharmacist.

Management of benzodiazepine-resistant alcohol withdrawal across a healthcare system: Benzodiazepine dose-escalation with or without propofol.

BACKGROUND: Severe cases of alcohol withdrawal syndrome (AWS) may not resolve despite escalating doses of benzodiazepines (BZDs). Benzodiazepine-resistant alcohol withdrawal (RAW) is a subset of severe alcohol withdrawal defined by the requirement of ≥40mg of diazepam administered within one hour. Use of adjunct agents, such as propofol, may be beneficial to minimize BZD adverse effects and improve symptom control. While limited evidence suggests propofol as an effective adjunct in AWS through improved sedation, evidence is currently lacking for the addition of only propofol to BZDs for management of RAW. METHODS: Retrospective review of adult patients from January, 2009 to March, 2012 with RAW. Patients were categorized into BZD dose-escalation only or BZD plus propofol. The primary endpoint was time to resolution of AWS. Secondary endpoints included safety outcomes associated with medication use. RESULTS: Of 1083 patients with severe AWS, 66 RAW patients (n=33 BZD only, n=33 BZD plus propofol) met inclusion. Median time to AWS resolution was 5.0 and 7.0 days for BZD only vs. BZD plus propofol (p=0.025). Duration of mechanical ventilation, ICU and hospital length of stay were significantly higher with propofol (p=0.017, <0.001 and <0.001, respectively). Ten patients required intervention for management of propofol-induced adverse reactions. CONCLUSIONS: The addition of propofol for RAW treatment is associated with significant increases in clinical care. While randomized, prospective evaluations are necessary to determine the cause of this association, our data suggests use of adjunctive propofol therapy in RAW is associated with longer and more complicated hospital admissions.

Effectiveness of educational technology to improve patient care in pharmacy curricula.

A review of the literature on the effectiveness of educational technologies to teach patient care skills to pharmacy students was conducted. Nineteen articles met inclusion criteria for the review. Seven of the articles included computer-aided instruction, 4 utilized human-patient simulation, 1 used both computer-aided instruction and human-patient simulation, and 7 utilized virtual patients. Educational technology was employed with more than 2700 students at 12 colleges and schools of pharmacy in courses including pharmacotherapeutics, skills and patient care laboratories, drug diversion, and advanced pharmacy practice experience (APPE) orientation. Students who learned by means of human-patient simulation and virtual patients reported enjoying the learning activity, whereas the results with computer-aided instruction were mixed. Moreover, the effect on learning was significant in the human-patient simulation and virtual patient studies, while conflicting data emerged on the effectiveness of computer-aided instruction.

Multicenter evaluation of pharmacologic management and outcomes associated with severe resistant alcohol withdrawal.

INTRODUCTION: A subset of patients with alcohol withdrawal syndrome does not respond to benzodiazepine treatment despite escalating doses. Resistant alcohol withdrawal (RAW) is associated with higher incidences of mechanical ventilation and nosocomial pneumonia and longer intensive care unit (ICU) stay. The objective of this study is to characterize pharmacologic management of RAW and outcomes. METHODS: Adult patients were identified retrospectively via International Classification of Diseases, Ninth Revision codes for severe alcohol withdrawal from 2009 to 2012 at 3 hospitals. Data collected included pharmacologic management and clinical outcomes. RESULTS: A total of 184 patients met inclusion criteria. Sixteen medications and 74 combinations of medications were used for management. Propofol was the most common adjunct agent, with dexmedetomidine and antipsychotics also used. One hundred seventy-five patients (96.2%) were admitted to the ICU, with 149 patients (81.9%) requiring ventilator support. Median time to resolution of alcohol withdrawal syndrome from RAW designation was 6.0 days. Median ICU and hospital length of stay were 9.0 and 12.7 days, respectively. CONCLUSION: Diverse patterns exist in the management of patients meeting RAW criteria, indicating lack of refined approach to treatment. High doses of sedatives used for these patients may result in a high level of care, illustrating a need for evidence-based clinical guidelines to optimize outcomes.

Evaluation of adjunctive ketamine to benzodiazepines for management of alcohol withdrawal syndrome.

BACKGROUND: Adjunctive medications to manage alcohol withdrawal syndrome (AWS) in patients not adequately responding to escalating doses of benzodiazepines (BZDs) are limited. The use of the N-methyl-d-aspartate antagonist ketamine, may serve as an effective adjunct agent; however, no published data currently exist for this practice. OBJECTIVE: To determine the safety and efficacy of adjunct ketamine for management of AWS. METHODS: The study was a retrospective review of adult patients from April 2011 to March 2014 who were administered ketamine specifically for management of AWS. Outcomes included changes in BZD requirements and ketamine-related adverse reactions. RESULTS: Of 235 patients screened, 23 patients met study eligibility. Ketamine was initiated primarily with toxicology consultation for significant BZD requirements or delirium tremens. The mean time to initiation of ketamine from first treatment of AWS, and total duration of therapy were 33.6 and 55.8 hours, respectively. Mean initial infusion dose and median total infusion rate during therapy were 0.21 and 0.20 mg/kg/h, respectively. There was no change in sedation or alcohol withdrawal scores in patients within 6 hours of ketamine initiation. The median change in BZD requirements at 12 and 24 hours post-ketamine initiation were -40.0 and -13.3 mg, respectively. The mean time to AWS resolution was 5.6 days. There was one documented adverse reaction of oversedation, requiring dose reduction. CONCLUSIONS: Ketamine appears to reduce BZD requirements and is well tolerated at low doses. Prospective dose range evaluations in the management of AWS would be helpful in determining its place as an adjunctive agent.

Use of virtual patients in an advanced therapeutics pharmacy course to promote active, patient-centered learning.

OBJECTIVE: To assess student satisfaction and learning of course objectives following the integration of virtual patient cases designed to promote active, patient-centered learning in an advanced therapeutics pharmacy course. DESIGN: A dynamic virtual patient platform that incorporated a branched-narrative, decision-making teaching model was used in an advanced therapeutics course to supplement lecture content. ASSESSMENT: Presimulation and postsimulation tests were used to assess student learning. The use of virtual patients significantly enhanced student learning for both higher- and lower-level test questions (p<0.001 and p=0.01, respectively). Students agreed or strongly agreed that the virtual patient cases provided an effective way to learn (72%), were enjoyable (69%), and were appropriate in content (80%), and that more should be incorporated (59%). CONCLUSION: The use of virtual patients in an advanced therapeutics practicum effectively promoted active, patient-centered learning; engaged students in an interactive and dynamic educational technology; encouraged teamwork; enhanced higher-level student learning; and improved student satisfaction in the course.