Multiple abnormal peripheral blood gene expression assay results are correlated with subsequent graft loss after kidney transplantation.

BACKGROUND: The aim of this study was to correlate peripheral blood gene expression profile (GEP) results during the first post-transplant year with outcomes after kidney transplantation. METHODS: We conducted a prospective, multicenter observational study of obtaining peripheral blood at five timepoints during the first post-transplant year to perform a GEP assay. The cohort was stratified based on the pattern of the peripheral blood GEP results: Tx-all GEP results normal, 1 Not-TX had one GEP result abnormal and >1 Not-TX two or more abnormal GEP results. We correlated the GEP results with outcomes after transplantation. RESULTS: We enrolled 240 kidney transplant recipients. The cohort was stratified into the three groups: TX n = 117 (47%), 1 Not-TX n = 59 (25%) and >1 Not-TX n = 64 (27%). Compared to the TX group, the >1 Not-TX group had lower eGFR (p < .001) and more chronic changes on 1-year surveillance biopsy (p = .007). Death censored graft survival showed inferior graft survival in the >1 Not-TX group (p < .001) but not in the 1 Not-TX group. All graft losses in the >1 Not-TX group occurred after 1-year post-transplant. CONCLUSIONS: We conclude that a pattern of persistently Not-TX GEP assay correlates with inferior graft survival.

Clinical Utility of the OmniGraf Biomarker Panel in the Care of Kidney Transplant Recipients (CLARITY): Protocol for a Prospective, Multisite Observational Study.

BACKGROUND: Death with a functioning allograft has become the leading category of graft loss in kidney transplant recipients at all time points. Previous analyses have demonstrated that causes of death in kidney transplant recipients are predominated by comorbidities strongly associated with immunosuppressant medications. Adverse drug events (ADEs) have been strongly associated with nonadherence, health care utilization, and graft loss; clinicians face a difficult decision on whether making immunosuppressant adjustments in the face of ADEs will improve symptomology or simply increase the risk of acute rejection. Clinicians also face a treatment quandary in 50% of kidney transplant recipients with stage 3 or worse chronic kidney disease at 1 year post transplantation, as progressive decline in renal function has been strongly associated with inferior allograft survival. OBJECTIVE: The primary objective of the CLinical Utility of the omnigrAf biomarkeR Panel In The Care of kidneY Transplant Recipients (CLARITY) trial is to evaluate change in renal function over time in kidney transplant recipients who are undergoing OmniGraf monitoring in conjunction with monitoring of their medication-related symptom burden (MRSB). A secondary objective of this study is to identify the impact of OmniGraf use in conjunction with patient-reported MRSB as part of clinical care on patients' self-efficacy and quality of life. METHODS: CLARITY is a 3-year prospective, multisite, observational study of 2000 participants with a matched control, measuring the impact of real-time patients' MRSB and the OmniGraf biomarker panel on change in renal function over time. Secondary outcome measures include the Patient-Reported Outcomes Measurement Information System (PROMIS) Self-Efficacy for Managing Chronic Conditions-Managing Medications and Treatment-Short Form 4a; the PROMIS-29 Profile (version 2.1); the PROMIS Depression Scale, hospitalizations-subcategorized for hospitalizations owing to infections; treated rejections, MRSB, and proportion of participants with overall graft survival at year 3 post transplantation; graft loss or death during the 3-year study follow-up period; and change in provider satisfaction. RESULTS: The primary outcome measure of the study will be a comparison of the slope change in estimated glomerular filtration rate from baseline to the end of follow-up between study participants and a matched control group. Secondary outcome measures include changes over time in PROMIS Self-Efficacy for Managing Chronic Conditions-Managing Medications and Treatment-Short Form 4a, the PROMIS-29 Profile (version 2.1), and PROMIS Depression Scale in the study group, as well as a comparison of hospitalizations and causes, rejections, and graft and patient survival compared between participants and a matched cohort. The anticipated first enrollment in the study is October 2022 with data analysis and publication expected in October 2027. CONCLUSIONS: Through this report, we describe the study design, methods, and outcome measures that will be utilized in the ongoing CLARITY trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT05482100; https://clinicaltrials.gov/ct2/show/NCT05482100. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/41020.

Review and Evaluation of mHealth Apps in Solid Organ Transplantation: Past, Present, and Future.

With the rapid and widespread expansion of smartphone availability and usage, mobile health (mHealth) has become a viable multipurpose treatment medium for the US healthcare system. Methods: The purpose of this review is to identify posttransplant mHealth applications that support patient self-management or a patient-provider relationship and aim to improve clinical outcomes. The interventions were then analyzed and evaluated to identify current gaps and future needs of mHealth apps in solid organ transplantation. Results: The authors found a nearly universal dichotomy between perceived utility and sustained use, with most studies demonstrating significant attrition during the course of the intervention. In addition, interoperability continues to be a challenge. Conclusions: The authors present potential methods for mitigating the identified barriers and gaps in mHealth apps for solid organ transplant recipients.

A Critical Analysis of the Specific Pharmacist Interventions and Risk Assessments During the 12-Month TRANSAFE Rx Randomized Controlled Trial.

BACKGROUND: Medication safety issues have detrimental implications on long-term outcomes in the high-risk kidney transplant (KTX) population. Medication errors, adverse drug events, and medication nonadherence are important and modifiable mechanisms of graft loss. OBJECTIVE: To describe the frequency and types of interventions made during a pharmacist-led, mobile health-based intervention in KTX recipients and the impact on patient risk levels. METHODS: This was a secondary analysis of data collected during a 12-month, parallel-arm, 1:1 randomized clinical controlled trial including 136 KTX recipients. Participants were randomized to receive either usual care or supplemental, pharmacist-driven medication therapy monitoring and management using a smartphone-enabled app integrated with telemonitoring of blood pressure and glucose (when applicable) and risk-based televisits. The primary outcome was pharmacist intervention type. Secondary outcomes included frequency of interventions and changes in risk levels. RESULTS: A total of 68 patients were randomized to the intervention and included in this analysis. The mean age at baseline was 50.2 years; 51.5% of participants were male, and 58.8% were black. Primary pharmacist intervention types were medication reconciliation and patient education, followed by medication changes. Medication reconciliation remained high throughout the study period, whereas education and medication changes trended downward. From baseline to month 12, we observed an approximately 15% decrease in high-risk patients and a corresponding 15% increase in medium- or low-risk patients. CONCLUSION AND RELEVANCE: A pharmacist-led mHealth intervention may enhance opportunities for pharmacological and nonpharmacological interventions and mitigate risk levels in KTX recipients.

Significant hospitalization cost savings to the payer with a pharmacist-led mobile health intervention to improve medication safety in kidney transplant recipients.

This was an economic analysis of a 12-month, parallel arm, randomized controlled trial in adult kidney recipients 6 to 36 months posttransplant (NCT03247322). All participants received usual posttransplant care, while the intervention arm received supplemental clinical pharmacist-led medication therapy monitoring and management, via a smartphone-enabled mHealth app, integrated with risk-based televisits. Hospitalization charges were captured from the study institution accounts payable and non-study institution hospitalization charges were estimated using multiple imputation. Multivariable modeling was used to assess the impact of the intervention on charges. The intervention significantly reduced rates of hospitalization (1.08 per patient-year in the control arm vs 0.65 per patient-year in the intervention arm, p = .007). The control arm had estimated hospitalization costs of $870,468 vs $390,489 in the intervention arm. Modeling demonstrated a 49% lower hospitalization charge risk in the intervention arm (RR 0.51, 95% CI 0.28-0.91; p = .022). From a payer or societal perspective, the net estimated cost savings, after accounting for intervention delivery costs, was $368,839, with a return on investment (ROI) of $4.30 for every $1 spent. These results demonstrate that a mHealth-enabled, pharmacist-led intervention significantly reduced hospitalization costs for payers over a 12-month period and has a positive ROI.

Impact of Anesthesiologist Experience on Early Outcomes in Adult Orthotopic Liver Transplantation.

BACKGROUND: Liver transplantation is a complex surgical procedure. The experience of the anesthesiologist, and its potential relationship to patient morbidity and mortality, is yet to be determined. We sought to explore this possible association using our institutional training patterns as the subject of study. METHODS: This is a single center retrospective analysis investigating the association of an anesthesiologist's experience with liver transplantation and its potential effect on early patient outcomes in adult liver transplant recipients from January 2010 to September 2016. Training of team members consisted of a 6-month period of clinical shadowing with a senior anesthesiologist and co-staffing 8 liver transplant procedures before solo staffing a liver transplant. Specifically, patient outcomes for the first 5 transplants after this training were investigated. RESULTS: The only independent risk factor for early death or early graft loss was the amount of packed red blood cells administered during transplantation. With respect to secondary outcomes, the amount of packed red blood cells and hospitalization at the time of transplant were associated with the number of days on a ventilator, length of intensive care unit stay, and overall hospital length of stay. CONCLUSIONS: The results of this study conclude that the training model currently in place for our new team members has no negative impact on patient outcomes after liver transplantation.

Pharmacist-Led Mobile Health Intervention and Transplant Medication Safety: A Randomized Controlled Clinical Trial.

BACKGROUND AND OBJECTIVES: Medication safety events are predominant contributors to suboptimal graft outcomes in kidney transplant recipients. The goal of this study was to examine the efficacy of improving medication safety through a pharmacist-led, mobile health-based intervention. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a 12-month, single-center, prospective, parallel, two-arm, single-blind, randomized controlled trial. Adult kidney recipients 6-36 months post-transplant were eligible. Participants randomized to intervention received supplemental clinical pharmacist-led medication therapy monitoring and management via a mobile health-based application, integrated with risk-guided televisits and home-based BP and glucose monitoring. The application provided an accurate medication regimen, timely reminders, and side effect surveys. Both the control and intervention arms received usual care, including serial laboratory monitoring and regular clinic visits. The coprimary outcomes were to assess the incidence and severity of medication errors and adverse events. RESULTS: In total, 136 kidney transplant recipients were included, 68 in each arm. The mean age was 51 years, 57% were male, and 64% were Black individuals. Participants receiving the intervention experienced a significant reduction in medication errors (61% reduction in the risk rate; incident risk ratio, 0.39; 95% confidence interval, 0.28 to 0.55; P<0.001) and a significantly lower incidence risk of Grade 3 or higher adverse events (incident risk ratio, 0.55, 95% confidence interval, 0.30 to 0.99; P=0.05). For the secondary outcome of hospitalizations, the intervention arm demonstrated significantly lower rates of hospitalizations (incident risk ratio, 0.46; 95% confidence interval, 0.27 to 0.77; P=0.005). CONCLUSIONS: We demonstrated a significant reduction in medication errors, adverse events, and hospitalizations using a pharmacist-led, mobile health-based intervention.

Impact of a pharmacist-led, mHealth-based intervention on tacrolimus trough variability in kidney transplant recipients: A report from the TRANSAFE Rx randomized controlled trial.

PURPOSE: Nonadherence is a leading cause of death-censored allograft loss in kidney transplant recipients. Strong associations have tied tacrolimus intrapatient variability (IPV) to degree of nonadherence and high tacrolimus IPV to clinical endpoints such as rejection and allograft loss. Nonadherence is a dynamic, complex problem best targeted by multidimensional interventions, including mobile health (mHealth) technologies. METHODS: This was a secondary planned analysis of a 12-month, parallel, 2-arm, semiblind, 1:1 randomized controlled trial involving 136 adult kidney transplant recipients. The primary aims of the TRANSAFE Rx study were to assess the efficacy of a pharmacist-led, mHealth-based intervention in improving medication safety and health outcomes for kidney transplant recipients as compared to usual care. RESULTS: Patients were randomized equally to 68 patients per arm. The intervention arm demonstrated a statistically significant decrease in tacrolimus IPV over time as compared to the control arm (P = 0.0133). When analyzing a clinical goal of tacrolimus IPV of less than 30%, the 2 groups were comparable at baseline (P = 0.765), but significantly more patients in the intervention group met this criterion at month 12 (P = 0.033). In multivariable modeling, variables that independently impacted tacrolimus IPV included time, treatment effect, age, and warm ischemic time. CONCLUSION: This secondary planned analysis of an mHealth-based, pharmacist-led intervention demonstrated an association between the active intervention in the trial and improved tacrolimus IPV. Further prospective studies are required to confirm the mutability of tacrolimus IPV and impact of reducing tacrolimus IPV on long-term clinical outcomes.

The impact of pretransplant opioid exposure on healthcare utilization and costs in kidney transplant.

STUDY OBJECTIVE: Opioid use has been associated with significant morbidity and mortality in the United States. Studies within kidney transplantation have also shown increased risk of mortality, graft loss, and complications in kidney transplant recipients who use opioids prior to transplant. The objective of this analysis was to identify if recent pretransplant opioid exposure would be an effective risk-stratifier for patients at risk for readmissions and readmission costs. Further, the objective was to see if a brief assessment of recent opioid use could predict chronic opioid use post-transplant." PATIENTS AND DESIGN: This study was a single-center, retrospective cohort analysis of adult renal transplant recipients between January 2010 and December 2016 assessing the impact of pretransplant opioid use on posttransplant readmissions at 1 year postsurgery, as well as it's ability to identify patients at risk of chronic opioid use post-transplant. Opioid use was identified using medication reconciliation or a national prescription database, and readmissions and normalized costs for hospitalizations were identified via the Vizient clinical database. MAIN RESULTS: Pretransplant opioid exposure occurred in 271 (24%) of 1129 patients transplanted during the study time period. There were no differences in index hospitalization length of stay or cost; however, patients with opioid exposure were significantly more likely to have been admitted within 1-year postsurgery (51 vs. 43%, p = 0.023), had more readmissions per patient (0.93 vs. 0.72, p = 0.010), and had higher normalized readmissions costs ($12,556 vs. $8344, p = 0.009). Patients with opioid exposure were also more likely to be admitted for readmissions, had more admissions per patient, and had higher readmission costs at 30 and 90 days postsurgery. There were no differences in preventability of readmissions between cohorts or in general causes of readmissions. A multivariable logistic regression demonstrated that being opioid experienced and having a history of diabetes mellitus were independently associated with readmissions at 1 year postsurgery. In addition, having opioid exposure at the time of transplant, a history of diabetes mellitus, and younger age were independently associated with chronic opioid use after transplant. CONCLUSION: This study demonstrated that recent exposure to opioids prior to kidney transplant was significantly and independently associated with increased readmissions and readmission costs at multiple timepoints up to 1 year posttransplant as well as chronic opioid use after transplant.It also demonstrated that a brief assessment of recent opioid use may be able to identify patients at risk for chronic opioid use. Because opioid use is associated with multiple diseases, it is important to continue to study the association of opioid use, and the potential for disease-modifying interactions, with various clinical outcomes.

Impact of a multidisciplinary multimodal opioid minimization initiative in kidney transplant recipients.

Opioid use after kidney transplant has been shown to be a risk factor for chronic opioid use, which leads to an increased risk of mortality. The purpose of this study was to evaluate the early impact of a multimodal pain regimen and education quality improvement program on opioid use after kidney transplant 2 months after implementation. This was a retrospective, single-center analysis of post-operative opioid use, comparing the average daily Morphine milligram equivalents (MME) of the patients who received education on opioids and a multimodal pain regimen (preoperative TAP/QL block, scheduled APAP and gabapentin) compared to a historical control group. Despite having no differences in pre-transplant opioid exposure, daily and overall inpatient opioid utilization was significantly reduced in the multimodal pain protocol cohort (38.6 vs 8.0 MME/day; P < .001); 5% of patients in the multimodal pain protocol cohort were discharged with an opioid prescription, compared to 96% of controls (P < .001). Our early results demonstrate that a multimodal pain protocol can effectively and dramatically reduce short-term opioid utilization in kidney transplant recipients.

Preliminary assessment of safety and adherence to a once-daily immunosuppression regimen in kidney transplantation: Results of a randomized controlled pilot study.

Medication non-adherence is common after transplant and a major contributor to graft loss. The objective of this pilot study was to obtain preliminary safety and adherence data of a complete once-daily immunosuppression regimen of Extended-release-tacrolimus (LCP-tac), everolimus, and prednisone vs LCP-tac, mycophenolate Twice daily (BID), and prednisone through a randomized controlled pilot study of 40 patients (20 in each arm). At 3 ± 2 months post-transplant, patients were randomized to receive LCP-tac and everolimus once daily or LCP-tac and mycophenolate BID (control arm) for 6 months; 80 met eligibility, and 40 were randomized. Mean age was 51 ± 14 years, 33% were female, 45% African American, and 55% had a Calculated panel reactive antibody (cPRA) >20%. Both regimens were well-tolerated, and medication side effect burden tended to be less severe in the intervention group. Self-reported high medication adherence decreased in the control arm from baseline to 6 months (80%-59%), while remaining the same in the intervention arm throughout the study (45%-47%). For safety assessment, there was no rejection, graft loss, or death in either arm. These results provide preliminary evidence of the safety of a novel once-daily immunosuppression regimen. The impact of this once-daily regimen on medication adherence requires a larger long-term study.

The effect of targeted insurer-mandated prescription monitoring on opioid prescribing patterns.

OBJECTIVES: The purpose of this study was to determine the impact of a mandate from 2 large insurers in South Carolina for mandatory review of the state's prescription drug monitoring program (PDMP) for controlled substance (CS) prescriptions for more than 5 days' supply on the proportion of opioid prescriptions for less than or equal to 5 days in a statewide adult population. In addition, changes in the mean morphine milligram equivalents (MME) per day for prescriptions for 5 days or less were described to evaluate prescribing changes. DESIGN, SETTING AND PARTICIPANTS: All prescriptions for opioids written for and filled by adults (≥ 18 years of age) and reported to the PDMP from January 1, 2010, to December 31, 2017, were included in an interrupted time series analysis. OUTCOME MEASURES: An interrupted time series analysis was performed to determine if there was a significant change in the proportion of opioid prescriptions for less than or equal to 5 days' supply. RESULTS: Overall opioid prescriptions decreased over the time period by 11.5%, including a decreasing rate of opioid prescriptions for less than or equal to 5 days' supply. There was no statistical difference in the slope between the pre- and postmandate cohorts (P = 0.077, r2 = 0.951). There was not an identified corresponding increase in the MME per day of prescriptions. CONCLUSION: Our analysis found that 2 major insurer mandates that occurred in South Carolina in 2016, which required a review of the state PDMP for CS prescriptions for more than 5 days' supply, did not have a significant impact on the proportion of opioid prescriptions for less than or equal to 5 days' supply in the statewide population. In addition, we did not find any concern that prescribers attempted to circumvent the requirement by inappropriately adjusting dosing instructions.

Dosing Requirements of Extended-Release Tacrolimus (Astagraf XL) in African American Kidney Transplant Recipients Converted from Immediate-Release Tacrolimus (AAAKTRS).

BACKGROUND: The formal recommendation for converting twice-daily tacrolimus immediate release (IR) to once-daily tacrolimus extended release (ER) is a 1:1 dose conversion. However, more recent clinical analysis has shown that this may not be true; some patients may require a higher dose. In addition, de novo dosing tacrolimus ER has revealed that African Americans require approximately 20%-30% higher doses than Caucasians to achieve similar levels. As a result, this study sought to identify the appropriate dose conversion in the African American kidney transplant population, a population at high risk of rejection. METHODS: This was a single-center, prospective, open-label study comparing the difference in dose-normalized trough and total daily dose necessary to reach steady-state therapeutic goal, after conversion from tacrolimus IR to tacrolimus ER, in 25 African American kidney transplant recipients. RESULTS: After conversion to tacrolimus ER, there was a significant decrease in dose-normalized trough (C0) (0.44 versus 0.59, P = 0.03). Statistically significant differences were seen in both total daily and weight-based doses, when reported as actual values (15 versus 10 mg and 0.16 versus 0.11 mg/kg, respectively), as well as when standardized to achieve a target tacrolimus C0 of 8 ng/mL (18.1 versus 13.6 mg and 0.17 versus 0.15 mg/kg, respectively). The median standardized dose conversion required was 1.3 [1.0, 1.4], for the overall population. There were no instances of biopsy-proven acute rejection, allograft loss, or study drug discontinuation. CONCLUSIONS: This single-center, open-label conversion study demonstrated that there was a statistically and clinically significant decrease in dose-normalized trough after conversion from tacrolimus IR to tacrolimus ER in an African American kidney transplant population and that a 1:1 dose conversion is unlikely to meet therapeutic goals.

Using informatics and mobile health to improve medication safety monitoring in kidney transplant recipients.

PURPOSE: The development, testing, and preliminary validation of a technology-enabled, pharmacist-led intervention aimed at improving medication safety and outcomes in kidney transplant recipients are described. SUMMARY: Medication safety issues, encompassing medication errors (MEs), medication nonadherence, and adverse drug events (ADEs), are a predominant cause of poor outcomes after kidney transplantation. However, a limited number of clinical trials assessing the effectiveness of technology in improving medication safety and outcomes in transplant recipients have been conducted. Through an iterative, evidence-based approach, a technology-enabled intervention aimed at improving posttransplant medication safety outcomes was developed, tested, and preliminarily validated. Early acceptability and feasibility results from a prospective, randomized controlled trial assessing the effectiveness of this system are reported here. Of the 120 patients enrolled into the trial at the time of writing, 60 were randomly assigned to receive the intervention. At a mean ± S.D. follow-up of 5.8 ± 4.0 months, there were 2 patient dropouts in the intervention group, resulting in a retention rate of 98%, which was higher than the expected 90% retention rate. CONCLUSION: The development and deployment of a comprehensive medication safety monitoring dashboard for kidney transplant recipients is feasible and acceptable to patients in the current healthcare environment. An ongoing randomized controlled clinical trial is assessing whether such a system reduces MEs and ADRs, leading to improved patient outcomes.

The impact of time-varying clinical surrogates on disparities in African-American kidney transplant recipients - a retrospective longitudinal cohort study.

An improved understanding of the impact of clinical surrogates on disparities in African-American (AA) kidney transplantation (KTX) is needed. We conducted a 10-year retrospective longitudinal cohort study of electronically abstracted clinical data assessing the impact of surrogates on disparities in KTX. Clinical surrogates were assessed by posttransplant year (1, 2, 3 or 4) and defined as acute rejection (Banff ≥1A), mean SBP >140 mmHg, tacrolimus variability (CV) >40%, mean glucose >160 mg/dl and mean hemoglobin <10 g/dl. We utilized landmark methodology to minimize immortal time bias and logistic and survival regression to assess outcomes; 1610 KTX were assessed (54.2% AAs), with 1000, 468, 368 and 303 included in the year 1, 2, 3 and 4 complete case analyses, respectively. AAs had significantly higher odds of developing a clinical surrogate, which increased in posttransplant years three and four [OR year 1 1.99 (1.38-2.88), year 2 1.77 (1.20-2.62), year 3 2.35 (1.49-3.71), year 4 2.85 (1.72-4.70)]. Adjusting for the five clinical surrogates in survival models explained a significant portion of the higher risks of graft loss in AAs in post-transplant years three and four. Results suggest focusing efforts on improving late clinical surrogate management within AAs may help mitigate racial disparities in KTX.

Improving Transplant Medication Safety Through a Pharmacist-Empowered, Patient-Centered, mHealth-Based Intervention: TRANSAFE Rx Study Protocol.

BACKGROUND: Medication errors, adverse drug events, and nonadherence are the predominant causes of graft loss in kidney transplant recipients and lead to increased healthcare utilization. Research has demonstrated that clinical pharmacists have the unique education and training to identify these events early and develop strategies to mitigate or prevent downstream sequelae. In addition, studies utilizing mHealth interventions have demonstrated success in improving the control of chronic conditions that lead to kidney transplant deterioration. OBJECTIVE: The goal of the prospective, randomized TRANSAFE Rx study is to measure the clinical and economic effectiveness of a pharmacist-led, mHealth-based intervention, as compared to usual care, in kidney transplant recipients. METHODS: TRANSAFE Rx is a 12-month, parallel, two-arm, 1:1 randomized controlled clinical trial involving 136 participants (68 in each arm) and measuring the clinical and economic effectiveness of a pharmacist-led intervention which utilizes an innovative mobile health application to improve medication safety and health outcomes, as compared to usual posttransplant care. RESULTS: The primary outcome measure of this study will be the incidence and severity of MEs and ADRs, which will be identified, categorized, and compared between the intervention and control cohorts. The exploratory outcome measures of this study are to compare the incidence and severity of acute rejections, infections, graft function, graft loss, and death between research cohorts and measure the association between medication safety issues and these events. Additional data that will be gathered includes sociodemographics, health literacy, depression, and support. CONCLUSIONS: With this report we describe the study design, methods, and outcome measures that will be utilized in the ongoing TRANSAFE Rx clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03247322: https://clinicaltrials.gov/ct2/show/NCT03247322 (Archived by WebCite at http://www.webcitation.org/6xcSUnuzW).

Association of Pretransplantion Opioid Use with Graft Loss or Death in Liver Transplantation Patients with Model of End-Stage Liver Disease Exceptions.

BACKGROUND: Up to 77% of liver transplantation candidates experience pain, and the majority are prescribed opioids. Previous studies have shown increased readmissions and mortality in liver transplant recipients who were prescribed opioids before transplantation. Our aim was to identify specific populations that are at the highest risk for deleterious outcomes with opioid use before transplantation. STUDY DESIGN: This was a single-center retrospective cohort study of adult receiving liver transplants between 2010 and 2016 to assess the impact of pretransplantation opioid use on mortality and graft loss after liver transplantation. RESULTS: A total of 446 liver transplant recipients were included in the study, 148 (33%) of which were identified as pretransplantation opioid users. Opioid use increased significantly during the course of the study. There were no differences in the overall cohort between opioid users and non-opioid users with regard to graft or patient outcomes. However, the influence of opioid use on outcomes varied based on Model for End-Stage Liver Disease (MELD) and functional status. In patients with any MELD exception, opioid use was an independent predictor of time to graft loss or death (adjusted hazard ratio 2.36; 95% CI 1.05 to 5.28; p = 0.037). It also independently predicted time to graft loss or death in patients with low laboratory MELD scores (adjusted hazard ratio 2.38; 95% CI 1.10 to 5.13; p = 0.027). CONCLUSIONS: In our 6-year retrospective cohort, pretransplantation opioid use based on medication reconciliation was independently associated with time to graft loss or mortality in liver transplant recipients with MELD exceptions and laboratory MELD scores ≤15.

Morbid obesity and functional status as predictors of surgical complication after renal transplantation.

BACKGROUND: This study evaluated the impact of body mass index (BMI) and patient functional status on the risk for surgical complications after kidney transplant. METHODS: This retrospective cohort study of adult kidney transplant recipients grouped patients by baseline Karnofsky status (low function ≤ 70%) and further stratified by morbid obesity (BMI ≥ 35 kg/m2) to assess surgical complication risk. RESULTS: 736 patients were included with surgical complications occurring in 25%. Logistic regression analysis with interaction terms demonstrated that morbid obesity and low functional status conditionally impact risk with an OR of 2.8 [95% CI (1.1-7.3)]. Within the functional status cohort, BMI ≥35 kg/m2 was associated with increased risk of surgical complication, superficial wound infection, and DGF. Independent predictors for surgical complications included diabetes and morbid obesity with low functional status. There was no significant difference in graft loss or death across the cohorts. CONCLUSIONS: While neither morbid obesity nor poor functional status alone predicts increased complications, the combined presence is associated with significant increase in risk for surgical complications after renal transplantation.

Liver Transplantation in the Obese Cirrhotic Patient.

Despite the rapidly increasing prevalence of obesity in the transplant population, the optimal management of obese liver transplant candidates remains undefined. Setting strict body mass index cutoffs for transplant candidacy remains controversial, with limited data to guide this practice. Body mass index is an imperfect measure of surgical risk in this population, partly due to volume overload and variable visceral adiposity. Weight loss before transplantation may be beneficial, but it remains important to avoid protein calorie malnutrition and sarcopenia. Intensive lifestyle modifications appear to be successful in achieving weight loss, though the durability of these interventions is not known. Pretransplant and intraoperative bariatric surgeries have been performed, but large randomized controlled trials are lacking. Traditional cardiovascular comorbidities are more prevalent in obese individuals and remain the basis for pretransplant cardiovascular evaluation and risk stratification. The recent US liver transplant experience demonstrates comparable patient and graft survival between obese and nonobese liver transplant recipients, but obesity presents important medical and surgical challenges during and after transplant. Specifically, obesity is associated with an increased incidence of wound infections, wound dehiscence, biliary complications and overall infection, and confers a higher risk of posttransplant obesity and metabolic syndrome-related complications. In this review, we examine current practices in the obese liver transplant population, offer recommendations based on the currently available data, and highlight areas where additional research is needed.