Utilization of direct‐acting oral anticoagulation in solid organ transplant patients: A national survey of institutional practices

The safety and efficacy of direct‐acting oral anticoagulants (DOACs) and reversal strategies are not well established in the solid organ transplant population. This was a survey of pharmacists to assess DOAC and urgent reversal practices among adult transplant programs in the United States. A 27‐question survey was distributed to members of transplant pharmacy organization listservs between 5/28/19 and 6/30/19. A total of 115 responses were received from kidney (43.5%), heart (20.0%), lung (18.3%), liver (13.9%), and pancreas (4.4%) transplant programs. DOAC use prior to transplant was mostly prohibited in thoracic programs (77.3%) but more permissive in kidney transplant programs (64.0%). If permitted, apixaban (57.8%) was most preferred. At transplant surgery, reversal of DOAC was performed “as needed” (20.9%) or was not routine (18.3%). DOAC use post‐transplant was more permissive (94.3%). A majority of responders follow FDA recommended dosing in the setting of drug‐drug interactions (51.1%). Major factors influencing DOAC prescribing decisions included renal function, drug‐drug interactions, and insurance. High clinical practice variability exists regarding DOAC utilization and urgent reversal strategies in pre‐, peri‐, and post‐transplant stages. While more research is needed to refine the clinical landscape, many institutions are using DOAC therapy under the perception that they pose a similar risk of bleeding compared to a non‐transplant population.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155952/1/ctr13853_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155952/2/ctr13853.pd

Observations from a systematic review of pharmacist- led research in solid organ transplantation: An opinion paper of the American College of Clinical Pharmacy Immunology/Transplantation Practice and Research Network

IntroductionThe contributions of transplant pharmacists to clinical and translational research in the United States are ill- defined and have not been systematically reviewed.ObjectivesThe American College of Clinical Pharmacy Immunology/Transplantation Practice and Research Network conducted a systematic review of available pharmacist- led research publications involving solid organ transplantation with the intent to quantify and describe pharmacist- led research endeavors and their changes over time.MethodsAn electronic search of Scopus was conducted to identify publications in the field of solid organ transplantation by pharmacist authors between January 1, 1975 and May 25, 2017. Articles were excluded if they were written in non- English languages or originated from non- US countries. Review articles, case reports, surveys, basic science research, pre- clinical studies, and non- transplant research were further excluded. Studies were categorized as one of four phases on the clinical and translational research spectrum, adapted from the Harvard Clinical and Translational Science Center description of a T1 to T4 classification system.ResultsA total of 10- 354 publications were identified by the systematic search with 547 full- text English- language publications included in the analysis. Pharmacists served as the first author in 87% of the articles and as the senior author in 67% of the articles. A total of 71% of the articles included more than one pharmacist author. Transplant pharmacists published more studies that employed a retrospective or observational study design (55% and 78%, respectively). A total of 37% of studies were funded. On the spectrum of clinical and translation research, pharmacists were most involved in T3 (translation to practice) research (72%), followed by T2 (translation to patients) research (23%).ConclusionsTransplant pharmacists are increasingly represented in the US literature and frequently published across domains. Further demonstrating the relevance of pharmacist- delivered interventions and outcomes is a critical area of practice focus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163590/2/jac51294.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163590/1/jac51294_am.pd

Use of direct‐acting oral anticoagulants in solid organ transplantation: A systematic review

The use of direct‐acting oral anticoagulants (DOACs) has increased secondary to the mounting evidence for comparable efficacy and potentially superior safety to vitamin K antagonists (VKAs) in the general population. However, insufficient data regarding DOAC use in solid organ transplant (SOT) recipients and numerous pharmacokinetic and pharmacodynamic considerations limit their use in this highly selected patient population. A systematic review of recent clinical evidence on the safety and efficacy of DOACs compared to VKAs in SOT recipients was conducted. Additional considerations including transplant‐specific strategies for DOAC reversal and common pharmacokinetic/pharmacodynamic concerns were also reviewed. Although current evidence is limited to single‐center retrospective analyses, DOACs, especially apixaban, appear to be a safe and effective alternative to VKAs for SOT recipients with stable graft function and without drug‐drug interactions. Reliable data on DOAC reversal at the time of transplant surgery are lacking, and clinicians should consider idarucizumab, andexanet alfa, and other non‐specific reversal agents on an individual patient basis. There is no evidence supporting deviations from the Food and Drug Administration labeling recommendations for DOAC dosing in the setting of drug‐drug interactions, obesity, and renal function, especially in patients on hemodialysis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/166378/1/phar2485_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/166378/2/phar2485.pd

Time within therapeutic range: A comparison of three tacrolimus formulations in renal transplant recipients

Background: Currently there are three available formulations of tacrolimus in the United States; these include immediate-release capsules (TAC-IR), extended-release capsules (TAC-XL),and extended-release tablets (TAC-XR). Previous studies have demonstrated non-inferiority between the three formulations in terms of efficacy. The purpose of this study was to compare three formulations of tacrolimus (TAC) and assess differences in time within the therapeutic range (TTR) and variability in levels. Results: Renal transplant recipients from January 2013 to October 2017 were retrospectively identified for analysis. Deviation from standard TAC protocol or formulation changes excluded patients. The primary outcome compared percent TTR (TTR %) among 3 TAC formulations over the first 90 days post-transplant. TTR was calculated using the Rosendaal method. Secondary outcomes included differences in TAC levels, TAC dose, eGFR, rejection, patient and graft survival between the TAC formulations. TAC-XR demonstrated a significantly higher TTR % compared to TAC-IR and TAC-XL (62.8% vs. 53.3% vs. 60.9%, p = 0.048). In post-hoc analysis, TAC-XR had a higher TTR % compared to TAC-IR (p = 0.065), which approached statistical significance. Average TAC levels, weight-normalized TAC doses, median dose-normalized TAC levels, rejection rates, eGFR, and graft or patient survival were similar among groups. Conclusion: In the early transplant period, TTR was significantly different among the groups. TAC-XR demonstrated numerically superior time within the therapeutic range. Patient-specific factors such as race, obesity, genetic polymorphisms may impact this variability and clinical outcomes. Further analysis is necessary to understand the effect of each patient-specific factor on TAC exposure

Impact of a pharmacy‐led nursing education on discharge opioid prescribing after kidney transplant

A major contributor to the opioid epidemic is prescribing in the postoperative setting. There remains the need for opioid stewardship both postoperatively and upon discharge in kidney transplant recipients. In October 2017, pharmacist-led education was given to all transplant nursing staff at a single center with the goal of optimizing postoperative pain control through education and empowerment of nurses. Furthermore, the education focus was to advance nursing knowledge, enhance patient assessment, and reform patient education. Clinical pharmacists continued to work with the transplant team to base a patient's discharge analgesia on inpatient analgesia use. This study assessed the impact of the nursing education on discharge analgesic prescribing patterns after kidney transplant admission. Opioid prescribing on transplant discharge was significantly lower after the education (pre 68.3% vs post 11.1%, P <.001). Transplant admission was shortened by 1 day (6 vs 5 days, P =.03). Over time, a significant downtrend in opioid prescribing was observed on discharge from 86.1% in 2015 to 49.6% in 2017 and 8.5% in 2018 (P <.001). If opioid therapy was required on discharge in the posteducation group, tramadol was predominantly prescribed (7/13 opioid prescriptions, 53.9%). Thus, opioid minimization and pain management using nonopioid analgesic prescribing on discharge are feasible in an adult kidney transplant population with proper nursing collaboration and education

A call for transplant stewardship: The need for expanded evidence‐based evaluation of induction and biologic‐based cost‐saving strategies in kidney transplantation and beyond

Rising expenditures threaten healthcare sustainability. While transplant programs are typically considered profitable, transplant medications are expensive and frequently targeted for cost savings. This review aims to summarize available literature supporting cost‐containment strategies used in solid organ transplant. Despite widespread use of these tactics, we found the available evidence to be fairly low quality. Strategies mainly focus on induction, particularly rabbit antithymocyte globulin (rATG), given its significant cost and the lack of consensus surrounding dosing. While there is higher‐quality evidence for high single‐dose rATG, and dose‐rounding protocols to reduce waste are likely low risk, more aggressive strategies, such as dosing rATG by CD3+ target‐attainment or on ideal‐body‐weight, have less robust support and did not always attain similar efficacy outcomes. Extrapolation of induction dosing strategies to rejection treatment is not supported by any currently available literature. Cost‐saving strategies for supportive therapies, such as IVIG and rituximab also have minimal literature support. Deferral of high‐cost agents to the outpatient arena is associated with minimal risk and increases reimbursement, although may increase complexity and cost‐burden for patients and infusion centers. The available evidence highlights the need for evaluation of unique patient‐specific clinical scenarios and optimization of therapies, rather than simple blanket application of cost‐saving initiatives in the transplant population.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/170795/1/ctr14372_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/170795/2/ctr14372.pd

Pain Interference in End Stage Kidney Disease is Associated with Changes in Gut Microbiome Features Before and After Kidney Transplantation.

BACKGROUND: Pain, a common debilitating symptom among kidney transplant recipients (KTRs), is among the most common and undertreated symptoms after kidney transplantation. AIMS: Characterize associations between gut microbiome features and pain interference before and after kidney transplantation. DESIGN: Longitudinal, repeated measures study, collecting fecal specimens and pain interference data pretransplant and 3 months posttransplant. SETTING: Participants were recruited at the kidney transplant clinic at the University of Illinois Hospital &amp; Health Sciences System. PARTICIPANTS/SUBJECTS: 19 living donor kidney transplant recipients. METHODS: We assessed fecal microbial community structure with shotgun metagenomic sequencing; we used pain interference scores derived from the Patient-Reported Outcomes Measurement Information System-57. RESULTS: We measured a reduction in the Shannon diversity index in both groups after transplantation but observed no significant differences between groups at either time point. We did observe significant differences in fecal microbial Bray-Curtis similarity index among those reporting pain interference pre- transplant versus no pain interference at 3-months posttransplant (R&nbsp;=&nbsp;.306, p&nbsp;=&nbsp;.022), and between pain interference groups at posttransplant (R&nbsp;=&nbsp;.249, p&nbsp;=&nbsp;.041). Pairwise models showed significant differences between groups posttransplant in relative abundances of several taxa, including a 5-fold reduction.ßin Akkermansia among those with pain interference and a higher relative abundance of taxa associated with chronic inflammation in those with pain interference posttransplant. Functional gene analysis identified two features that were significantly enriched in those with pain interference, including a peptide transport system gene. CONCLUSIONS: Gut microbiota community structure differs between groups with and without pain interference at 3 months after kidney transplantation. Several taxa involved in intestinal barrier integrity and chronic inflammation were associated with posttransplant pain