Report from the American Society of Transplantation Psychosocial Community of Practice Adherence Task Force: Real-world options for promoting adherence in adult recipients.

Starting in 2015, the American Society of Transplantation Psychosocial Community of Practice, with representatives of the Transplant Pharmacy Community of Practice, convened a taskforce to develop a white paper that focused on clinically practical, evidenced-based interventions that transplant centers could implement to increase adherence to medication and behavioral recommendations in adult solid organ transplant recipients. The group focused on what centers could do in their daily routines to implement best practices to increase adherence in adult transplant recipients. We developed a list of strategies using available resources, clinically feasible methods of screening and tracking adherence, and activities that ultimately empower patients to improve their own self-management. We limited the target population to adults because they predominate the research, and because adherence issues differ in pediatric patients, given the necessary involvement of parents/guardians. We also examined broader multilevel areas for intervention including provider and transplant program practices. Ultimately, the task force aims to foster greater recognition, discussion, and solutions required for implementing practical interventions targeted at improving adherence.

KidneyCare Guided Immuno-Optimization in Renal Allografts: The KIRA Protocol.

Immunosuppressant agents are essential in every transplant recipient's care yet walking the fine line of over- or under-immunosuppression is a constant struggle for both patients and transplant providers alike. Optimization and personalization of immunosuppression has been limited by the need for non-invasive graft surveillance methods that are specific enough to identify organ injury in real time. With this in mind, we propose a pilot study protocol utilizing both donor derived cell free DNA (dd-cfDNA, gene expression profiling (GEP), and machine learning (iBox), called KidneyCare, to assess the feasibility and safety in reducing immunosuppressant exposure without increasing the risk of clinical rejection, graft injury, or allograft loss. Patients randomized to the immunominimization arm will be enrolled in one of two protocols designed to eliminate one immunosuppressant and optimize the dose of the Calcineurin Inhibitors (CNIs) using the KidneyCare platform. All patients will be maintained on dual therapy of either steroids and a low dose CNI, or mycophenolate mofetil (MMF) and low dose CNI. Their outcomes will be compared to patients who have their immunosuppressants managed using standard clinical assessment and treatment protocols to determine the impact of immuno-optimization on graft function, complications, and patient reported outcomes.

Grazoprevir/elbasvir for the treatment of adults with chronic hepatitis C: a short review on the clinical evidence and place in therapy.

Chronic hepatitis C virus (HCV) infection impacts approximately 71 million people and approximately 400,000 deaths are attributed to HCV-related liver disease annually worldwide. Mainstay of treatment for over 25 years has been pegylated interferon until the advent of protease inhibitors, which has led to all-oral HCV treatment regimens that have changed the outlook of hepatitis C treatment. Grazoprevir/elbasvir provides high rates of efficacy and tolerability and is an all-oral once daily treatment option for HCV infection. Efficacy of grazoprevir/elbasvir has been proven in patients with cirrhosis, patients who have previously failed treatment with peginterferon and ribavirin (RBV), patients with end-stage renal disease and patients with HIV co-infection. Data have shown a high barrier to resistance despite the presence of resistance-associated substitutions. Grazoprevir/elbasvir represents a very promising regimen for treatment of HCV infection. This review provides a summary of pharmacology, efficacy, and safety of grazoprevir/elbasvir for the treatment of HCV infection.

Brincidofovir as Salvage Therapy for Adenovirus Disease in Intestinal Transplant Recipients.

BACKGROUND: Adenoviruses are double-stranded DNA viruses that typically cause mild self-limiting respiratory, ocular, and gastrointestinal infections. In immunocompromised patients, especially transplant recipients, the infection can be severe, with dissemination and multiorgan failure. In intestinal transplant recipients, the incidence is as high as 57%. To our knowledge, no standardized guidelines or U.S. Food and Drug Administration-approved medications exist for the treatment of adenovirus disease. AIMS: We describe two isolated intestinal transplant recipients who developed adenovirus disease (viremia with viral enteritis) that was managed with a new experimental drug, brincidofovir (an oral lipid conjugate prodrug of cidofovir), as salvage therapy. RESULTS: The first patient was a 44-year-old woman who developed adenoviral enteritis 1 month after transplantation, which resolved with ribavirin therapy. Two weeks later, the infection recurred, and brincidofovir was initiated. While receiving this therapy for 3 months, she developed severe acute rejection, which was managed with rabbit antithymocyte globulin followed by infliximab. Eventually, complete resolution of the rejection and adenoviral enteritis was achieved. At 12 months posttransplantation, the patient was healthy and tolerating enteral feeding. The second patient was a 28-year-old man who had undergone isolated intestinal transplantation 6 years before he presented with generalized weakness and an increased ostomy output; he was diagnosed with adenoviral enteritis. Maintenance immunosuppression was reduced, and brincidofovir was started. The infection resolved with a month of therapy. Six months after the infection, he was healthy and tolerating enteral feeding. CONCLUSION: This is the first publication, to our knowledge, to describe two cases in which brincidofovir was used to successfully treat adenovirus infection in intestinal transplant recipients. Thus, these cases demonstrate that brincidofovir appears to be a safe and effective option in the management of adenoviral enteritis in these patients.

Identifying opportunities to advance practice at a large academic medical center using the ASHP Ambulatory Care Self-Assessment Tool.

PURPOSE: The use of the ASHP Ambulatory Care Self-Assessment Tool to advance pharmacy practice at 8 ambulatory care clinics of a large academic medical center is described. SUMMARY: The ASHP Ambulatory Care Self-Assessment Tool was developed to help ambulatory care pharmacists assess how their current practices align with the ASHP Practice Advancement Initiative. The Henry Ford Hospital Ambulatory Care Advisory Group (ACAG) opted to use the "Practitioner Track" sections of the tool to assess pharmacy practices within each of 8 ambulatory care clinics individually. The responses to self-assessment items were then compiled and discussed by ACAG members. The group identified best practices and ways to implement action items to advance ambulatory care practice throughout the institution. Three recommended action items were common to most clinics: (1) identify and evaluate solutions to deliver financially viable services, (2) develop technology to improve patient care, and (3) optimize the role of pharmacy technicians and support personnel. The ACAG leadership met with pharmacy administrators to discuss how action items that were both feasible and deemed likely to have a medium-to-high impact aligned with departmental goals and used this information to develop an ambulatory care strategic plan. This process informed and enabled initiatives to advance ambulatory care pharmacy practice within the system. CONCLUSION: The ASHP Ambulatory Care Self-Assessment Tool was useful in identifying opportunities for practice advancement in a large academic medical center.

Pharmacodynamics and pharmacokinetics of elbasvir and grazoprevir in the treatment of hepatitis C.

INTRODUCTION: Approximately 130 - 150 million people have chronic hepatitis C virus (HCV) infection and upwards of 500,000 deaths annually are attributed to HCV related liver disease worldwide. Pegylated interferon and ribavirin have been the mainstay of treatment for greater than 25 years until recent advent of protease inhibitors which has led to all oral HCV treatment regimens that have changed the outlook of hepatitis C treatment. AREAS COVERED: This review provides summary of pharmacokinetics, pharmacodynamics, efficacy and safety of grazoprevir/elbasvir therapy for treatment of HCV infection. EXPERT OPINION: Grazoprevir/elbasvir provides an all-oral once daily treatment option for HCV infection with high rates of efficacy and tolerability in a pangenotypic fashion. It highly efficacious in treating patients with cirrhosis, patients who have previously failed treatment with pegylated interferon and ribavirin, and patients with HIV co-infection. Grazoprevir/elbasvir has demonstrated higher barrier to resistance even in the presence of variants associated with resistance such as Q41R, F43S, R155K, V36M, T54S, and D168. It is one of only few HCV treatment regimens evaluated for use in patients with advanced chronic kidney disease and dialysis. It is a very promising regimen for treatment of HCV infection.