Nicole A. Pilch

Improved Patient Safety and Outcomes With a Comprehensive Interdisciplinary Improvement Initiative in Kidney Transplant Recipients

Although kidney transplant recipients at the authors’ institution had a short length of stay (LOS), delayed discharges and early readmissions were common; medication use and safety were at the core of these issues. A multidisciplinary quality improvement initiative was developed that targeted eliminating these issues. The team developed key initiatives including improved medication reconciliation, development of a diabetes management service, and improved discharge medication dispensing, delivery, education, and scrutiny. Follow-up analysis demonstrated reduced medication discrepancies by >2 per patient and obtaining 100% adherence with reconciliation. Pharmacists reviewed discharge medications, reaching 100% by study end, leading to a 40% reduction in medication safety issues. LOS remained short, and delayed discharges were reduced by 14%; 7-day readmission rates decreased by 50%. Acute rejection and infection rates also significantly decreased. In conclusion, a multidisciplinary quality improvement initiative can improve medication safety in kidney transplant patients, which can lead to improved clinical outcomes.

Improving Transplant Patient Safety Through Pharmacist Discharge Medication Reconciliation

Greater than 50% of medication errors are estimated to occur during transitions of care, and solid‐organ transplant recipients are at an increased risk for errors due to significant changes in their medication regimen following transplantation. This prospective, observational study with a historical control group was conducted to evaluate the discharge process for transplant recipients and determine if transplant pharmacist involvement would improve safety. During the prospective period, a total of 191 errors were made on discharge medication reconciliations (n = 64, mean rate 3.0 per patient); however, pharmacists prevented 119 of these errors (1.9 errors per patient). In the retrospective period, none of the 430 errors identified were prevented at the time of discharge (n = 128, p < 0.0001). The 72 errors not prevented at the time of discharge in the prospective cohort were identified by the pharmacist at the patients first clinic visit (1.1 errors per patient). In the historical cohort, all 430 errors made at discharge persisted until at least the time of the first clinic visit (3.4 errors per patient, p < 0.0001). This study demonstrates that transplant recipients are at a high risk for medication errors and that transplant pharmacist involvement leads to improved safety through the significant reduction of medication errors.

Prospective randomized controlled trial of rabbit antithymocyte globulin compared with IL-2 receptor antagonist induction therapy in kidney transplantation.

Objective:The aim of this study was to determine the safety and efficacy of induction with rabbit antithymocyte globulin (RATG) compared with interleukin-2 receptor antagonists in a racially diverse kidney transplant patient population under modern immunosuppression. Background:The optimal induction therapy in patients at risk for rejection, particularly black recipients, in the modern era of immunosuppression with flow cytometry-based cross-matching is unclear. Methods:This was a prospective, risk-stratified, randomized, single-center, open-label study of 200 consecutively enrolled patients in a large academic teaching center. Patients were randomized to receive either daclizumab or basiliximab versus RATG for induction in combination with tacrolimus, mycophenolate mofetil, and corticosteroids. Patients were stratified between groups to ensure equal numbers of black, retransplants, high panel reactive antibodies (PRAs) (>20%), and prolonged cold ischemic times (>24 hours) in each group. Primary outcome measure is treatment efficacy defined as the incidence of biopsy-proven acute rejection and estimated creatinine clearance. Patients were followed up for 12 months. Renal transplant recipients were included if they were adult (≥18 years old) and received an allograft from a deceased, living unrelated, or nonhuman leukocyte antigen identical living-related donor. Results:A total of 200 patients (n = 98 in the interleukin-2 receptor antagonists, and n = 102 in the RATG) were enrolled from February 2009 through July 2011. One-year acute rejection rates were low and similar between groups (10% in the interleukin-2 receptor antagonist group vs 6% in the RATG group; P = 0.30). Creatinine clearance was also similar between groups (interleukin-2 receptor antagonist group 56 ± 20 mL/min per 1.73 m2 vs RATG group 55 ± 22 mL/min per 1.73 m2; P = 0.73). Subanalysis of recipient race revealed that in blacks only RATG was protective against 6- and 12-month acute rejection, without an increased risk of infection. Induction did not affect rejection rates according to recipient calculated PRAs; however, RATG was associated with an increased risk of BK virus in low-PRA patients. Conclusions and Relevance:RATG induction provides improved protection against early acute rejection in black renal transplant recipients, whereas sensitized patients do not seem to demonstrate a similar benefit from this therapy. This study is registered at Clinicaltrials.gov (NCT00859131).

Leflunomide efficacy and pharmacodynamics for the treatment of BK viral infection.

BACKGROUND AND OBJECTIVES BK virus is an infection in kidney transplantation patients jeopardizing graft survival. Unfortunately, there is no consensus on treatment of BK viremia and nephropathy. Leflunomide has been studied for the treatment of BK viremia and nephropathy, but there are limited data on the utility of leflunomide therapeutic drug monitoring. This study aimed to determine if a pharmacodynamic relationship exists between BK viral load reduction and leflunomide metabolite, A77 1726, serum concentrations. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study was a retrospective, single-center, longitudinal analysis of patients identified with BK viremia with or without nephropathy. Patients were grouped according to whether they received leflunomide. All BK viral PCR and A77 1726 concentrations were analyzed to determine pharmacodynamics, and were correlated with clinical outcomes. RESULTS Of 76 patients identified, 52 received leflunomide therapy and 24 did not. Patients who received leflunomide were further analyzed according to A77 1726 concentrations and BK clearance; there was no difference in BK clearance. There was a lack of correlation between A77 1726 concentrations and log change in BK viral PCR concentration. Multivariate analysis demonstrated that mycophenolate mofetil discontinuation, BK viremia without nephropathy, and mean BK viral load were significantly associated with BK viral clearance; leflunomide use lacked this association. CONCLUSIONS Pharmacodynamic analysis revealed no association between A77 1726 concentrations and BK viral PCR reductions. Multivariate analysis demonstrated that leflunomide therapy was not associated with BK viral clearance. Randomized studies are needed to determine the utility of leflunomide for BK viremia and nephropathy.

Pre‐existing diabetes significantly increases the risk of graft failure and mortality following renal transplantation

The aim of this study was to examine the impact of pre‐existing diabetes mellitus (DM) on acute rejection, graft loss, and mortality following kidney transplant and whether glycemic control or cardiovascular disease (CVD) risk control with medications influenced outcomes. This was a cohort study of 1002 renal transplants conducted between 2000 and 2008. Patients were included if they received a kidney transplant within the allotted time and were at least 18 yr of age. Cox regression was used to assess acute rejection, graft failure, or death controlling for relevant sociodemographic, clinical, and post‐transplant variables. Five‐yr patient survival (83% vs. 93%, p < 0.001) and graft survival (74% vs. 79%, p = 0.005) were significantly lower in patients with pre‐existing DM. Sequential Cox regression models demonstrated that pre‐existing DM was consistently associated with a higher risk of death (HR 2.3–3.0, p < 0.01) and graft failure (HR 1.5–1.8, p < 0.04) in all models except after adjusting for CVD medication use (HR 1.9, p = 0.174 and HR 1.5, p = 0.210, respectively). These data suggest pre‐existing DM is a significant risk factor for graft failure and death following renal transplantation and aggressive CVD risk reduction with medications may be an important strategy to reduce mortality and graft failure.

Critical analysis of valganciclovir dosing and renal function on the development of cytomegalovirus infection in kidney transplantation.

Cytomegalovirus (CMV) infection is one of the most common and important opportunistic infections following kidney transplantation. It causes significant morbidity and mortality. Valganciclovir (VGCV) is the drug of choice for prophylaxis to prevent CMV infection.

Safe use of highly steatotic livers by utilizing a donor/recipient clinical algorithm

The aim of this study was to assess the long‐term safety and clinical outcomes associated with the utilization of highly steatotic donor livers utilizing a specific donor/recipient matching algorithm. This was a prospective, observational, single‐center, 10‐yr follow‐up study. Highly steatotic livers were utilized according to a donor/recipient algorithm that guided the surgeon to use highly steatotic donor organs judiciously in low‐risk recipients. This study initially compared fat assessment based on frozen‐section Ehrlichs hematoxylin and eosin (H&E) to reperfusion biopsy fat assessment and demonstrated that H&E is an insensitive analysis to determine degree of steatosis. Patients were divided into three groups based on donor steatosis (group 1: <30% steatosis, group 2: 30–60% steatosis, group 3: >60% steatosis), and clinical outcomes were assessed. One hundred and sixteen patients were included in the analysis. Patients that received severely steatotic livers (>60% fat) showed increased reperfusion liver injury and delayed return of liver function in the early postoperative period, demonstrated by biochemical markers. However, there were no differences in primary non‐function, postoperative complications, length of stay, and patient and graft survival. Using rigorous donor/recipient matching through a detailed algorithm, these data demonstrate that normal liver allograft outcomes are not superior to those in highly steatotic grafts.

Generic Immunosuppression: Deciphering the Message Our Patients are Receiving:

Background: The introduction of generic immunosuppressants elicited controversy within the transplant community and it is unknown whether patient attitudes mirror the ambiguity of provider perceptions. With the current health care economic crisis, it is necessary to consider generic immunosuppression as an option. A greater understanding of patient perceptions would enhance vital communication between providers and patients to facilitate education and appropriate monitoring. Objective: To evaluate transplant recipients’ perceptions of generic versus brand immunosuppressants based on experience with these agents and the willingness of patients to convert treatment from brand to generic formulations based on socioeconomic variables and baseline demographics. Methods: Key informant interviews were conducted to inform the development of the survey instrument. The survey was distributed to solid organ transplant recipients at a large, academic medical center from October to December 2010. RESULTS: Nine patients participated in key informant interviews. Financial considerations and provider recommendations were the most commonly identified factors to influence perceptions of generic immunosuppressants. A total of 255 patients completed the survey; treatment in 81 (32%) participants had been converted to a generic immunosuppressant. Those currently receiving a generic immunosuppressant expressed higher beliefs of generic and brand equivalency (75% vs 54%, p = 0.006) and an increased willingness to convert treatment to a generic given equivalent cost (51 % vs 32%, p = 0.024). African American participants were found to have a decreased belief of generic and brand equivalency compared to other ethnicities (60% vs 75%, p = 0.013). Participants with an annual income of less than

Nutritional Supplements in Critical Illness

30,000 had higher beliefs of generic and brand equivalency (60% vs 40%, p = 0.0001). Education level and age did not impact beliefs of generic efficacy or willingness to convert therapy. Conclusions: Patient ethnicity, income, and experience with generic immunosuppressants appear to contribute to perceptions of generic immunosuppressants. The prevalence of generic immunosuppressant use supports the importance of communication of this issue between providers and patients.

Clinical outcomes associated with the early postoperative use of heparin in pancreas transplantation.

Poor nutritional intake during critical illness can contribute to increased morbidity and mortality. Although nutrition strategies for critically ill patients attempt to provide essential macronutrients, recent evidence suggests that certain micronutrients and supplements may improve wound healing and decrease infectious and inflammatory complications. This review will focus on mechanism of action, adverse effects and drug interactions reported in the literature, and appropriate dosing and outcomes data for specific nutritional supplements in various critically ill adult populations.