A clinician's guide to drug-drug interactions with direct-acting antiviral agents for the treatment of hepatitis C viral infection.

UNLABELLED: The US Food and Drug Administration has recently approved a number of new direct-acting antiviral agents for the treatment of chronic hepatitis C virus that have significantly increased the likelihood of a virological cure. These agents are highly effective but present a substantial risk for a host of clinically relevant drug-drug interactions. These interactions must be considered both when starting and stopping any medication, including over-the-counter medications and herbal supplements. These drug-drug interactions can increase the risk of toxicity or decrease the likelihood of treatment response. Knowledge of these interactions is paramount in optimizing the success of antiviral therapy. CONCLUSION: In this review we summarize the available data regarding drug-drug interactions for direct-acting antiviral agents, the interactions being the most clinically relevant that are currently known; this review is intended to serve as a clinician's guide to understanding and managing these complex interactions. (Hepatology 2016;63:634-643).

Multicenter evaluation of efficacy and safety of low-dose versus high-dose valganciclovir for prevention of cytomegalovirus disease in donor and recipient positive (D+/R+) renal transplant recipients.

BACKGROUND: The cytomegalovirus (CMV) donor-positive/recipient-positive (D+/R+) population is the largest proportion of renal transplant recipients (RTR). Guidelines for prevention of CMV in the intermediate-risk D+/R+ population include prophylaxis with valganciclovir (VGCV) 900 mg/day for 3 months. This study is the first head-to-head analysis, to our knowledge, comparing the efficacy and safety CMV prophylaxis of VGCV 450 vs 900 mg/day for 3 months in D+/R+ RTR. METHODS: A multicenter, retrospective analysis evaluated 478 adult RTR between January 2008 and October 2011. Study participants received VGCV 450 mg/day (Group 1; n=398) or 900 mg/day (Group 2; n=89)×3 months for CMV prophylaxis. All VGCV was adjusted for renal function. All groups included in this study received study-approved induction and maintenance immunosuppression regimens. The primary endpoint was incidence of CMV disease at 12 months. RESULTS: The rates of graft loss, patient survival, T-cell and/or antibody-mediated rejection, hematological adverse events, opportunistic infections, and early VGCV discontinuation were evaluated. Patient demographics were comparable, but had significant differences in ethnicity and donor type between the groups. CONCLUSION: The occurrence of CMV disease at 12 months was similar between the groups (3.5% vs 3.4%; P=1.000). Log-rank test found no statistically significant difference in the time to development of CMV between the 2 groups (P=.939).

Development and implementation of pharmacy department and pharmacy resident well-being programs.

PURPOSE: Burnout in healthcare can have serious consequences, as it decreases patient care quality. Recent studies have found pharmacy employees have high rates of burnout, but formalized pharmacy well-being programs are not reported in the literature. METHODS: We developed a departmental pharmacy well-being program and focused residency well-being program in October and July 2020, respectively. The program committees sent anonymous surveys to all pharmacy employees to identify opportunities to improve well-being. The feasibility and impact of ideas were assessed by committee members and presented to pharmacy leadership who endorsed and supported all proposed initiatives prior to implementation. Pharmacist distress scores were measured using the Well-Being Index (WBI). RESULTS: The WBI was completed by 49% of invited pharmacists (137 of 278) in November 2020 and 41% (116 of 283) in June 2021. There was a numerical improvement in mean (SD) WBI scores from 2.06 (2.47) in November 2020 to 1.52 (2.49) in June 2021 (P = 0.09). Pharmacy residents had significantly higher distress scores than nonresident pharmacists (P = 0.01). However, pharmacy resident scores improved by almost 50% between the 2 time points, from 4.43 (2.13) to 2.40 (2.42); P = 0.03. CONCLUSION: The development of a system-wide pharmacy well-being program creates a structure to collect ideas from employees, implement well-being initiatives, measure burnout using a validated tool such as the WBI, and continue to build, evaluate, and adapt new interventions. Importantly, the program went beyond addressing individual needs and addressed institutional opportunities that impact well-being. This can serve as a model for other pharmacy departments looking to implement similar programs.

Outcomes of a pharmacist-managed glucose collaborative practice agreement.

PURPOSE: The impact of a pharmacist-managed glucose collaborative practice agreement (CPA) on glycemic control at a tertiary medical center was investigated. METHODS: A retrospective data analysis was performed on hospitalized, noncritically ill patients admitted between December 2012 and June 2014 who received at least one dose of subcutaneous insulin and experienced at least one blood glucose concentration of 140 mg/dL or higher. The study population was divided into cohorts based on admittance before versus after implementation of the CPA, as well as glucose management by pharmacist versus nonpharmacist provider. The primary endpoint of the study was glycemic control, defined as the percentage of total admitted days spent within a goal blood glucose range of 70-180 mg/dL. Secondary endpoints included the rate of hypoglycemia (less than 70 mg/dL), the rate of severe hypoglycemia (less than 40 mg/dL), the rate of severe hyperglycemia (greater than 300 mg/dL), the length of stay, and workload metrics. RESULTS: A total of 5146 patients were included in the study. There was no statistically significant difference in glycemic control across all cohorts (p > 0.05). Secondary outcomes showed no statistically significant differences in the rates of hypoglycemia, severe hypoglycemia, and severe hyperglycemia across all cohorts. There was a significantly longer length of stay in the pharmacist-managed cohort (p < 0.001). Workload metrics indicated a 25.8% increase in the number of pharmacist-managed glucose consults post-CPA implementation. CONCLUSION: Pharmacists at a tertiary medical center were able to provide an inpatient glucose management service that maintained similar glycemic control for patients with diabetes as nonpharmacist providers.

Nonalcoholic Fatty Liver Disease and Liver Transplantation.

Nonalcoholic fatty liver disease (NAFLD) is prevalent in the general population and a growing indication for liver transplant. Longer wait times and challenges with pretransplant survivorship are expected, underscoring the need for improved management of attendant comorbidities. Recognition with potential modification of obesity, sarcopenia, chronic kidney disease, and cardiovascular disease in patients with NAFLD may have important implications in the pretransplant and posttransplant periods. Although patients with NAFLD have generally favorable postoperative outcomes, they are at risk for developing recurrent disease in their allograft, driving the need for pharmacotherapies and dietary innovations appropriate for use in the posttransplant period.

Defining and implementing a model for pharmacy resident research projects.

OBJECTIVE: To describe a standard approach to provide a support structure for pharmacy resident research that emphasizes self-identification of a residency research project. METHODS: A subcommittee of the residency advisory committee was formed at our institution. The committee was initially comprised of 2 clinical pharmacy specialists, 1 drug information pharmacist, and 2 pharmacy administrators. The committee developed research guidelines that are distributed to residents prior to the residency start that detail the research process, important deadlines, and available resources. Instructions for institutional review board (IRB) training and deadlines for various assignments and presentations throughout the residency year are clearly defined. Residents conceive their own research project and emphasis is placed on completing assignments early in the residency year. RESULTS: In the 4 years this research process has been in place, 15 of 16 (94%) residents successfully identified their own research question. All 15 residents submitted a complete research protocol to the IRB by the August deadline. Four residents have presented the results of their research at multi-disciplinary national professional meetings and 1 has published a manuscript. Feedback from outgoing residents has been positive overall and their perceptions of their research projects and the process are positive. CONCLUSION: Pharmacy residents selecting their own research projects for their residency year is a feasible alternative to assigning or providing lists of research projects from which to select a project.

Real-time prediction learning for the simultaneous actuation of multiple prosthetic joints.

Integrating learned predictions into a prosthetic control system promises to enhance multi-joint prosthesis use by amputees. In this article, we present a preliminary study of different cases where it may be beneficial to use a set of temporally extended predictions--learned and maintained in real time--within an engineered or learned prosthesis controller. Our study demonstrates the first successful combination of actor-critic reinforcement learning with real-time prediction learning. We evaluate this new approach to control learning during the myoelectric operation of a robot limb. Our results suggest that the integration of real-time prediction and control learning may speed control policy acquisition, allow unsupervised adaptation in myoelectric controllers, and facilitate synergies in highly actuated limbs. These experiments also show that temporally extended prediction learning enables anticipatory actuation, opening the way for coordinated motion in assistive robotic devices. Our work therefore provides initial evidence that realtime prediction learning is a practical way to support intuitive joint control in increasingly complex prosthetic systems.

Fatal wrong-way collisions on New Mexico's interstate highways, 1990-2004.

Medical examiner files from 1990 through 2004 were reviewed to identify fatalities caused by drivers traveling the wrong direction on interstate highways and identify risk factors and prevention strategies. Other fatal nonpedestrian interstate motor vehicle crashes served as a comparison group. Data abstracted included decedent demographics, driver/passenger status, seatbelt use, blood alcohol concentration, weather and light at time of occurrence and types of vehicles involved. Of 1171, 79 (6.7%) interstate motor vehicle fatalities were because of drivers traveling against the posted direction in 49 crashes, with one to five fatalities per crash. Wrong-way collisions were significantly more likely to occur during darkness (p < 0.0001) and involve legally intoxicated drivers (p < 0.0001). In 29/49 (60%) wrong-way crashes, alcohol was a factor. Prevention strategies aimed at reducing the incidence of driving while intoxicated, as well as improved lighting and signage at ramps, could help reduce the occurrence of fatal wrong-way collisions on interstates.

Definign and implementing a model for pharmacy resident research projects / Definición e implantación de un modelo de proyectos de investigación para residentes en farmacia

Objective: To describe a standard approach to provide a support structure for pharmacy resident research that emphasizes self-identification of a residency research project. Methods: A subcommittee of the residency advisory committee was formed at our institution. The committee was initially comprised of 2 clinical pharmacy specialists, 1 drug information pharmacist, and 2 pharmacy administrators. The committee developed research guidelines that are distributed to residents prior to the residency start that detail the research process, important deadlines, and available resources. Instructions for institutional review board (IRB) training and deadlines for various assignments and presentations throughout the residency year are clearly defined. Residents conceive their own research project and emphasis is placed on completing assignments early in the residency year. Results: In the 4 years this research process has been in place, 15 of 16 (94%) residents successfully identified their own research question. All 15 residents submitted a complete research protocol to the IRB by the August deadline. Four residents have presented the results of their research at multi-disciplinary national professional meetings and 1 has published a manuscript. Feedback from outgoing residents has been positive overall and their perceptions of their research projects and the process are positive. Conclusion: Pharmacy residents selecting their own research projects for their residency year is a feasible alternative to assigning or providing lists of research projects from which to select a project (AU)

Objetivo: Describir un abordaje estándar para proporcionar una estructura de apoyo a los residentes de investigación en farmacia que enfatice la autoidentificación de un proyecto de investigación en la residencia. Métodos: En nuestra institución se creó un subcomité del comité asesor de la residencia. Inicialmente el comité se componía de 2 especialistas en farmacia clínica, un farmacéutico de información sobre medicamentos, y dos administradores de farmacia. El comité desarrolló guías que detallaban el proceso de investigación, fechas límite importantes, y recursos disponibles, y que se distribuyeron entre los residentes antes de comenzase la residencia. Se definieron claramente instrucciones para la junta de investigación de la institución (IRB) con entrenamiento y fechas límite para varias tareas y presentaciones a lo largo del año de residencia. Los residentes concebían su propio proyecto de investigación y se colocaba énfasis en completar las tareas de la parte inicial del año de residencia. Resultados: En los 4 años que este procedimiento de investigación lleva en vigor, 15 de los 16 (94%) residentes identificaron con éxito sus propias preguntas de investigación. Todos los 15 residentes enviaron un protocolo de investigación completo al IRB en la fecha límite de agosto. Cuatro residentes presentaron resultados de su investigación en reuniones profesionales nacionales multidisciplinarias y uno publicó un artículo. El retorno de los residentes salientes ha sido en general positivo y sus percepciones sobre sus proyectos de investigación y el proceso son positivas. Conclusión: Residentes de farmacia seleccionando su propio proyecto de investigación es una alternativa factible a asignar oa proporcionar listas de proyectos para que elijan uno (AU)