Results of a multicenter cluster-randomized controlled clinical trial testing the effectiveness of a bioinformatics-enabled pharmacist intervention in transplant recipients.

An ambulatory medication safety dashboard was developed to identify missing labs, concerning labs, drug interactions, nonadherence, and transitions in care. This system was tested in a 2-year, prospective, cluster-randomized, controlled multicenter study. Pharmacists at 5 intervention sites used the dashboard to address medication safety issues, compared with usual care provided at 5 control sites. A total of 2196 transplant events were included (1300 intervention vs 896 control). During the 2-year study, the intervention arm had a 11.3% (95% confidence interval, 7.1%-15.5%) absolute risk reduction of having ≥1 emergency department (ED) visit (44.2% vs 55.5%, respectively; P < .001, respectively) and a 12.3% (95% confidence interval, 8.2%-16.4%) absolute risk reduction of having ≥1 hospitalization (30.1% vs 42.4%, respectively; P < .001). In those with ≥1 event, the median ED visit rate (2 [interquartile range (IQR) 1, 5] vs 2 [IQR 1, 4]; P = .510) and hospitalization rate (2 [IQR 1, 3] vs 2 [IQR 1, 3]; P = .380) were similar. Treatment effect varied by comorbidity burden, previous ED visits or hospitalizations, and heart or lung recipients. A bioinformatics dashboard-enabled, pharmacist-led intervention reduced the risk of having at least one ED visit or hospitalization, predominantly demonstrated in lower risk patients.

A Randomized Control Trial Testing a Medication Safety Dashboard in Veteran Transplant Recipients.

INTRODUCTION: Medication errors, adverse events, and nonadherence in organ transplant recipients are common and can lead to suboptimal outcomes. A medication safety dashboard was developed to identify issues in medication therapy. RESEARCH QUESTIONS: Can a multicenter bioinformatics dashboard accurately identify clinically relevant medication safety issues in US military Veteran transplant recipients? DESIGN: The dashboard was tested through a 24-month, prospective, cluster-randomized controlled multicenter study. Pharmacists used the dashboard to identify and address potential medication safety issues, which was compared with usual care. RESULTS: Across the 10 sites (5 control sites and 5 intervention sites), 2012 patients were enrolled (1197 intervention vs 831 control). The mean age was 65 (10) years, 95% male, and 27% Black. The dashboard produced 18 132 alerts at a rate of 0.61(0.32) alerts per patient-month, ranging from 0.44 to 0.72 across the 5 intervention sites. Lab-based issues were most common (83.4%), followed by nonadherence (9.4%) and transitions in care (6.4%); 56% of alerts were addressed, taking an average of 43 (29) days. Common responses to alerts included those already resolved by another provider (N = 4431, 44%), the alert not clinically relevant (N = 3131, 31%), scheduling of follow-up labs (N = 591, 6%), and providing medication reconciliation/education (N = 99, 1%). Inaccurate flags significantly decreased over the study by a mean of -0.6% per month (95% CI -0.1 to -1.0; P = .0265), starting at 13.4% and ending at 2.6%. CONCLUSION: This multicenter cluster-randomized controlled trial demonstrated that a medication safety dashboard was feasibly deployable across the VA healthcare system, creating valid alerts.

Exercising empathy: Pharmacists possess skills to increase coronavirus vaccine confidence.

The coronavirus disease 2019 (COVID-19) vaccines are the essential public health intervention to confer immunity against severe acute respiratory syndrome coronavirus 2, while decreasing the risks of severe COVID-19 disease, hospitalizations, and death associated with natural infection. Public health experts agree that the public health interventions of social distancing and face coverings will only be able to successfully curtail the COVID-19 pandemic in the United States when combined with the highly effective COVID-19 vaccines. The risk for severe COVID-19 is higher in Americans with highly prevalent metabolic and cardiovascular chronic conditions as well as vulnerable demographics, such as minorities and pregnant women. Unfortunately, experience with past unethical health practices can influence current vaccine confidence in people of color and women of childbearing age. Pharmacists are well-positioned in myriad health care settings across the nation to listen to these concerns and have the conversations necessary to increase vaccine confidence. Similar to effective roles that pharmacists have had in other health prevention efforts such as smoking cessation, pharmacists possess the motivational interviewing skills to guide patients from the "precontemplation" to the "action" stages of health behavior change. This nonjudgmental, mutual understanding will help identify the individual factors influencing vaccine decision-making and bring us closer to achieving "community immunity."

Treating Hepatitis C Virus Reinfection With 8 Weeks of Ledipasvir/Sofosbuvir Achieves Sustained Virologic Response.

Three patients reinfected with hepatitis C virus after a sustained virologic response were considered treatment naïve and treated with a short-course direct acting antiviral regimen.

Improving Transplant Medication Safety Through a Technology and Pharmacist Intervention (ISTEP): Protocol for a Cluster Randomized Controlled Trial.

BACKGROUND: Medication errors, adverse drug events, and nonadherence lead to increased health care utilization and increased risk of adverse clinical outcomes, including graft loss, in solid organ transplant recipients. Veterans living with organ transplants represent a population that is at substantial risk for medication safety events and fragmented care coordination issues. To improve medication safety and long-term clinical outcomes in veteran transplant patients, interventions should address interorganizational system failures and provider-level and patient-level factors. OBJECTIVE: This study aims to measure the clinical and economic effectiveness of a pharmacist-led, technology-enabled intervention, compared with usual care, in veteran organ transplant recipients. METHODS: This is a 24-month prospective, parallel-arm, cluster-randomized, controlled multicenter study. The pharmacist-led intervention uses an innovative dashboard system to improve medication safety and health outcomes, compared with usual posttransplant care. Pharmacists at 10 study sites will be consented into this study before undergoing randomization, and 5 sites will then be randomized to each study arm. Approximately, 1600 veteran transplant patients will be included in the assessment of the primary outcome across the 10 sites. RESULTS: This study is ongoing. Institutional review board approval was received in October 2018 and the study opened in March 2019. To date there are no findings from this study, as the delivery of the intervention is scheduled to occur over a 24-month period. The first results are expected to be submitted for publication in August 2021. CONCLUSIONS: With this report, we describe the study design, methods, and outcome measures that will be used in this ongoing clinical trial. Successful completion of the Improving Transplant Medication Safety through a Technology and Pharmacist Intervention study will provide empirical evidence of the effectiveness of a feasible and scalable technology-enabled intervention on improving medication safety and costs. CLINICAL TRIAL: ClinicalTrials.gov NCT03860818; https://clinicaltrials.gov/ct2/show/NCT03860818. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/13821.

Significant HbA1c Lowering in Patients Achieving a Hepatitis C Virus Cure.

The immediate clinically significant reduction in hemoglobin A1c following HCV treatment observed in this study contrasts with the expected rise seen with normal disease progression.

Soluble Markers of Immune Activation Differentially Normalize and Selectively Associate with Improvement in AST, ALT, Albumin, and Transient Elastography During IFN-Free HCV Therapy.

BACKGROUND: During chronic hepatitis C virus (HCV) infection, Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels mark active liver inflammation and tissue damage, while albumin reflects synthetic liver function and nutritional status. Transient Elastography (TE) is a clinical measure of liver stiffness that facilitates evaluation of liver damage stage. While a portion of the TE score is attributable to liver fibrosis and relatively irreversible damage, another component of the TE score is attributable to liver inflammation or edema. Markers of inflammation during chronic HCV infection include soluble markers of immune activation, which are also associated with morbid outcome (including cardiovascular disease and liver-disease progression). Whether soluble markers of immune activation or changes in their level during HCV therapy relate to normalization of AST, ALT, Albumin, or TE score, is not clear. METHODS: We evaluated soluble markers of immune activation (plasma sCD14, IL-6, sCD163, autotaxin [ATX], and Mac2BP) and TE score, and their relationship in 20 HCV-infected patients before, during, and after HCV-directed IFN-free direct-acting antiviral (DAA) therapy. We evaluated normalization of parameters and the relationship between each over a 6-month window. RESULTS: Before therapy, serum AST levels positively correlated with plasma levels of sCD14, sCD163, and Mac2BP, while ALT levels positively correlated with Mac2BP. Serum albumin level negatively correlated with plasma IL-6 and ATX levels. IFN-free therapy uniformly resulted in sustained virological response at 12 and 24 weeks after therapy completion. After initiation of therapy AST and ALT normalized, while levels of ATX, Mac2BP, sCD163, and TE score partially normalized over 6 months. Additionally, change in AST level and APRI score correlated with change in sCD163, IL-6, and Mac2BP levels, and change in ALT correlated with change in IL-6 and Mac2BP levels. Improvement in TE score correlated with a decrease in the level of sCD14 at week 4, and almost statistically significant with decrease in sCD14 at weeks 20-24 after initiation of IFN-free HCV therapy. CONCLUSIONS: Soluble markers of immune activation normalize or partially normalize at different rates after initiation of curative HCV DAA therapy, and TE scores improve, with wide variability in the degree of absolute improvement in liver stiffness from patient to patient. Decline magnitude of sCD14 was associated with improvement in TE score, while magnitude of improvement in AST correlated with reduction in sCD163 levels. These data provide support for a model where monocyte/Kupffer cell activation may account for a portion of the liver inflammation and edema, which is at least partially reversible following initiation of HCV DAA therapy.

During Hepatitis C Virus (HCV) Infection and HCV-HIV Coinfection, an Elevated Plasma Level of Autotaxin Is Associated With Lysophosphatidic Acid and Markers of Immune Activation That Normalize During Interferon-Free HCV Therapy.

BACKGROUND: Immune activation predicts morbidity during hepatitis C virus (HCV) infection and human immunodeficiency virus (HIV) infection, although mechanisms underlying immune activation are unclear. Plasma levels of autotaxin and its enzymatic product, lysophosphatidic acid (LPA), are elevated during HCV infection, and LPA activates immunocytes, but whether this contributes to immune activation is unknown. METHODS: We evaluated plasma levels of autotaxin, interleukin 6 (IL-6), soluble CD14 (sCD14), soluble CD163 (sCD163), and Mac2 binding protein (Mac2BP) during HCV infection, HIV infection, and HCV-HIV coinfection, as well as in uninfected controls, before and after HIV antiretroviral therapy (ART) initiation and during interferon-free HCV therapy. RESULTS: We observed greater plasma autotaxin levels in HCV-infected and HCV-HIV-coinfected participants, compared with uninfected participants, primarily those with a higher ratio of aspartate aminotransferase level to platelet count. Autotaxin levels correlated with IL-6, sCD14, sCD163, Mac2BP, and LPA levels in HCV-infected participants and with Mac2BP levels in HCV-HIV-coinfected participants, while in HIV-infected individuals, sCD14 levels correlated with Mac2BP levels. Autotaxin, LPA, and sCD14 levels normalized, while sCD163 and Mac2BP levels partially normalized within 6 months of starting interferon-free HCV therapy. sCD163 and IL-6 levels normalized within 6 months of starting ART for HIV infection. In vitro, LPA activated monocytes. CONCLUSIONS: These data indicate that elevated levels of autotaxin and soluble markers of immune activation during HCV infection are partially reversible within 6 months of initiating interferon-free HCV treatment and that autotaxin may be causally linked to immune activation during HCV infection and HCV-HIV coinfection.