Search

Background: The goal was to determine trends in immunosuppression use and its impact on cytomegalovirus (CMV) outcomes over the past 10 years., Methods: This was a single-center longitudinal cohort study of adult kidney recipients transplanted between Jan 2012 and June 2021. Baseline and follow-up data were gathered via chart abstraction and analyzed using univariate and multivariate analyses., Results: Of 2392 kidney transplants conducted, 131 patients did not meet inclusion criteria. The mean age was 52 years, 41% were female, 57% were black, and 19% were CMV high-risk. The use of rabbit anti-thymocyte globulin (RATG) induction (odds ratio [OR] 1.6, 1.3-2.1), tacrolimus (FK) level >8 ng/mL (OR 1.1, 1.09-1.11), CMV D+/R- rates (OR 1.06, 1.02-1.10), white blood cell count <3000 (OR 1.22, 1.18-1.26) and valganciclovir prophylaxis (OR 1.7, 1.6-1.9) have significantly increased over the past 10 years.  Rejection rates (OR 0.86, 0.82-0.91) and BK viremia >2000 (OR 0.91, 0.91-0.98) have decreased. RATG induction (adjusted hazard ratio [aHR] 1.35, 1.2-1.5), FK >8 ng/mL (aHR 3.5, 3.2-3.9), Belatacept conversion (aHR 2.5, 2.1-3.1), and rejection (aHR 1.8, 1.6-2.0) were significant risk factors for developing CMV infection, while mycophenolate mofetil <1500 mg (aHR 0.52, 0.47-0.59), mammalian target of rapamycin inhibitor (mTORi) conversion (0.77, 0.56-0.89), cyclosporine-A conversion (aHR 0.68, 0.56-0.84) were associated with lower risk of CMV infection., Conclusion: Increasing use of potent immunosuppression coupled with higher CMV D+/R- F rates may be driving higher rates of CMV infection. Cyclosporine and mTORi conversion appears to be protective against CMV.  A more individualized immunosuppression regimen based on infection risk merits consideration., (© 2024 Wiley Periodicals LLC.)

Objectives: Peripheral arterial disease (PAD) can reduce wound healing rates by ≤30%. Current literature suggests wound outcomes are improved when management is driven by vascular providers. However, whether this benefit is derived solely from early vascular provider involvement remains unclear., Methods: A retrospective analysis was performed of 80 limbs with chronic wounds and underlying PAD seen at our institution's wound center between July 2022 and July 2023. Arterial disease was defined by the following criteria: (1) prior PAD diagnosis, (2) ankle-brachial-index of <0.9 or toe pressure of <70 mm Hg, or (3) absent peripheral pulses. Patients were divided into early (<6 week) vascular provider exposure (EVE; n = 45) or late/no vascular exposure (LNVE; n = 35). Providers included vascular surgeons and affiliated advanced practitioners. The primary outcome studied was overall time to wound healing. Statistical analysis included χ 2 tests, t test, Pearson correlation, Kaplan-Meier analysis, and Cox regression modeling (variables included in a multivariate model if univariate effect on healing was associated at P < .1)., Results: Baseline demographic profiles were similar between groups with exception of lower baseline albumin (P = .037), more heart failure (P = .013), and more prior peripheral endovascular interventions (P = .013) in the EVE group. Although the initial wound locations and sizes were similar, EVE wounds had significantly higher WIfI wound scores (1.9 ± 0.1 vs 1.6 ± 0.1; P = .039). Although more LNVE patients developed radiographic osteomyelitis (31.8% vs 55.6%; P = .033), fewer underwent operative debridement or amputation (100% vs 63.2%; P = .008). On univariate analysis, healing time tended to be shorter in EVE, but not significantly (P = .089). When controlled for comorbidities, however, healing rates were nearly two-fold higher in EVE (hazard ratio, 2.42; 95% confidence interval, 1.21-4.84). LNVE wounds also took significantly longer to reach checkpoints including time to >75% granulation (P = .05), 15% weekly size decrease (P = .044), and epithelialization (P = .026). LNVE patients required more wound center visits (P = .024) and procedures (P = .005) with a longer time to intervention (P = .041). All EVE patients obtained ankle-brachial indices, with 90.9% of them available at their first wound care visit (P < .001). Although a slightly greater proportion of patients underwent a major amputation in EVE (15.6% vs 11.4%; P = .595), this difference did not attain significance; additionally, 100% of EVE patients had documented discussion of nonsalvageable limbs before amputation., Conclusions: Early exposure to vascular practitioners improves wound healing time, timeliness to intervention, and wound center and hospital resource use in patients with PAD. Further investigation into benefits of vascular involvement within community wound center models could significantly improve awareness and accessibility of arterial wound care in smaller/remote communities., Competing Interests: Disclosures None., (Published by Elsevier Inc.)

Sulfonylureas are associated with hypoglycemia. Whether a racial/ethnic disparity in this safety outcome exists is unknown. We sought to assess the impact of race/ethnicity on severe hypoglycemia associated with sulfonylurea use for type 2 diabetes (T2D). Using Veterans Affairs and Medicare data, Veterans initially receiving metformin monotherapy for T2D between 2004 and 2006 were identified. Sulfonylurea use (either alone or via the addition of a prescription for a sulfonylurea to metformin) was captured and compared to remaining on metformin alone during the follow-up period (2007-2016). Hazard ratios (HR) and 95% confidence intervals (CI) from longitudinal competing risk Cox models were used to measure the association between sulfonylurea use and severe hypoglycemia defined as hospitalization for hypoglycemia. A total of 113,668 Veterans with T2D were included. A higher risk of severe hypoglycemia was associated with the receipt of sulfonylurea prescriptions versus remaining on metformin alone across all groups. The effect was largest among Hispanic Veterans (HR: 7.59, 95%CI:4.32-13.33), followed by Veterans in the other race/ethnicity cohort (HR: 4.57, 95%CI:2.50-8.36) and Non-Hispanic Black Veterans (HR: 3.67, 95%CI:2.78-4.85). The effect was smallest among Non-Hispanic White Veterans (HR: 3.11, 95%CI:2.77-3.48). In conclusion, a higher risk of severe hypoglycemia associated with sulfonylurea prescriptions was observed across all analyses. The relationship was most pronounced for Hispanic Veterans, who had nearly 8 times the risk of severe hypoglycemia with sulfonylureas versus remaining on metformin alone., (© 2023. W. Montague Cobb-NMA Health Institute.)

Medication nonadherence after solid organ transplantation is recognized as an important impediment to long-term graft survival. Yet, assessment of adherence is often not part of routine care. In this Personal Viewpoint, we call for the transplant community to consider implementing a systematic process to screen and assess medication adherence. We believe acceptable tools are available to support integrating adherence assessments into the electronic health record. Creating a standard assessment can be done efficiently and cost-effectively if we come together as a community. More importantly, such monitoring can improve outcomes and strengthen provider-patient relationships. We further discuss the practical challenges and potential rebuttals to our position., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplant-ation., (Copyright © 2024 American Society of Transplantation & American Society of Transplant Surgeons. All rights reserved.)

Rationale & Objective: Advanced age is a major risk factor for chronic kidney disease (CKD) development, which has high heterogeneity in disease progression. Acute kidney injury (AKI) hospitalization rates are increasing, especially among older adults. Previous AKI epidemiologic analyses have focused on hospitalized populations, which may bias results toward sicker populations. This study examined the association between AKI and incident kidney failure with replacement therapy (KFRT) while evaluating age as an effect modifier of this relationship., Study Design: Retrospective cohort study., Setting & Participants: 24,133 Veterans at least 65 years old with incident CKD stage 4 from 2011 to 2013., Exposures: AKI, AKI severity, and age., Outcomes: KFRT and death., Analytical Approach: The Fine-Gray competing risk regression was used to model AKI and incident KFRT with death as a competing risk. A Cox regression was used to model AKI severity and death., Results: Despite a nonsignificant age interaction between AKI and KFRT, a clinically relevant combined effect of AKI and age on incident KFRT was observed. Compared with our oldest age group without AKI, those aged 65-74 years with AKI had the highest risk of KFRT (subdistribution HR [sHR], 14.9; 95% CI, 12.7-17.4), whereas those at least 85 years old with AKI had the lowest (sHR, 1.71; 95% CI, 1.22-2.39). Once Veterans underwent KFRT, their risk of death increased by 44%. A 2-fold increased risk of KFRT was observed across all AKI severity stages. However, the risk of death increased with worsening AKI severity., Limitations: Our study lacked generalizability, was restricted to ever use of medications, and used inpatient serum creatinine laboratory results to define AKI and AKI severity., Conclusions: In this national cohort, advanced age was protective against incident KFRT but not death. This is likely explained by the high frequency of deaths observed in this population (51.1%). Nonetheless, AKI and younger age are substantial risk factors for incident KFRT.

BACKGROUND LCPT (Envarsus XR®) is a common once-daily, extended-release oral tacrolimus formulation used in kidney transplantation. However, there are minimal evidence-based recommendations regarding optimal dosing and treatment in the de novo and conversion settings. MATERIAL AND METHODS Using Delphi methodology, 12 kidney transplantation experts with LCPT experience reviewed available data to determine potential consensus topics. Key statements regarding LCPT use were generated and disseminated to the panel in an online Delphi survey. Statements were either accepted, revised, or rejected based on the level of consensus, perceived strength of evidence, and alignment with clinical practice. Consensus was defined a priori as ≥75% agreement. RESULTS Twenty-three statements were generated: 14 focused on de novo LCPT use and 9 on general administration or LCPT conversion use. After 2 rounds, consensus was achieved for 11/14 of the former and 7/9 of the latter statements. In a de novo setting, LCPT was recognized as a first-line option based on its safety and efficacy compared to immediate-release tacrolimus. In particular, African Americans and rapid metabolizer populations were identified as preferred for first-line LCPT therapy. In a conversion setting, full consensus was achieved for converting to LCPT to address neurological adverse effects related to immediate-release tacrolimus and for the time required (approximately 7 days) for steady-state LCPT trough levels to be reached. CONCLUSIONS When randomized clinical trials do not replicate current utilization patterns, the Delphi process can successfully generate consensus statements by expert clinicians to inform clinical decision-making for the use of LCPT in kidney transplant recipients.

Introduction: Fragmentation of health care across systems can contribute to mistakes in prescribing and filling medications among patients treated for myocardial infarction (MI). We sought to compare omissions, duplications, and delays in outpatient medications used for secondary prevention among veterans treated for MI at Veterans Affairs (VA) versus non-VA hospitals., Methods: We utilized national VA and Centers for Medicare and Medicaid Services data (2012-2018) to identify veterans 65 years or older hospitalized for MI and measured the use of outpatient medications for secondary prevention in the 30 days after MI among those treated at VA versus non-VA hospitals., Results: A total of 118,456 veterans experiencing MI were included; of which 102,209 were hospitalized at non-VA hospitals. An omission in any medication class occurred more frequently among veterans treated at non-VA versus VA hospitals (82.8% vs 67.8%, P < 0.001). In multivariable modeling, the odds of omissions in any medication class were higher among those treated at non-VA versus VA hospitals (odds ratio: 3.04; 95% CI: 2.88-3.20). Duplications occurred more frequently in veterans treated at non-VA versus VA hospitals: 1.9% versus 1.6% had 1 or more for non-VA versus VA hospitals ( P < 0.001). Veterans treated at non-VA hospitals were more likely to have delays of 3 days or more in prescription fills after hospital discharge (88.4% vs 70.6% across all classes, P < 0.001)., Conclusions: Omissions, duplications, and delays in outpatient prescribing of secondary prevention medications were more common among 118,456 veterans treated at non-VA versus VA hospitals for MI. Interventions aimed at improving care transitions and optimizing medication use among veterans treated at non-VA hospitals should be implemented., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

As healthcare continues its transition toward value-based care, it is increasingly important for transplant pharmacists to demonstrate their impact on patient care, health-related outcomes, and healthcare costs. Evidence-based quality and performance metrics are recognized as crucial tools for measuring the value of service. Yet, there is a lack of well-developed and agreed-upon specific metrics for many clinical pharmacy specialties, including solid organ transplantation. To address this need, a panel of transplant pharmacy specialists conducted a detailed literature review and engaged in several panel discussions to identify quality metrics to be considered for assessing the value of clinical pharmacy services provided to solid organ transplant recipients and living donors. The proposed metrics are based on the Donabedian model and are categorized to coincide with the typical phases of transplant care. The measures focus on key issues that arise in transplant recipients related to medication therapy, including adverse drug events, nonadherence, and clinical outcomes attributable to medication therapy management. This article proposes a comprehensive set of measures, any number of which transplant pharmacists can adopt and measure over time to objectively gauge the value of services they are providing to transplant recipients, the transplant center, and the overall healthcare system., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

An ambulatory medication safety dashboard was developed to identify missing labs, concerning labs, drug interactions, nonadherence, and transitions in care. This system was tested in a 2-year, prospective, cluster-randomized, controlled multicenter study. Pharmacists at 5 intervention sites used the dashboard to address medication safety issues, compared with usual care provided at 5 control sites. A total of 2196 transplant events were included (1300 intervention vs 896 control). During the 2-year study, the intervention arm had a 11.3% (95% confidence interval, 7.1%-15.5%) absolute risk reduction of having ≥1 emergency department (ED) visit (44.2% vs 55.5%, respectively; P < .001, respectively) and a 12.3% (95% confidence interval, 8.2%-16.4%) absolute risk reduction of having ≥1 hospitalization (30.1% vs 42.4%, respectively; P < .001). In those with ≥1 event, the median ED visit rate (2 [interquartile range (IQR) 1, 5] vs 2 [IQR 1, 4]; P = .510) and hospitalization rate (2 [IQR 1, 3] vs 2 [IQR 1, 3]; P = .380) were similar. Treatment effect varied by comorbidity burden, previous ED visits or hospitalizations, and heart or lung recipients. A bioinformatics dashboard-enabled, pharmacist-led intervention reduced the risk of having at least one ED visit or hospitalization, predominantly demonstrated in lower risk patients., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to evaluate opioid use trajectories among a sample of 10,138 Medicaid patients receiving one of six index surgeries: lumbar spine, total knee arthroplasty, cholecystectomy, appendectomy, colon resection, and tonsillectomy., Design: Retrospective cohort., Setting: Administrative claims data., Patients and Participants: Patients, aged 13 years and older, with 15-month continuous Medicaid eligibility surrounding index surgery, were selected from single-state Medicaid medical and pharmacy claims data for surgeries performed between 2014 and 2017., Interventions: None., Main Outcome Measures: Baseline comorbidities and presurgery opioid use were assessed in the 6 months prior to admission, and patients' opioid use was followed for 9 months post-discharge. Generalized linear model with log link and Poisson distribution was used to determine risk of chronic opioid use for all risk factors. Group-based trajectory models identified groups of patients with similar opioid use trajectories over the 15-month study period., Results: More than one in three (37.7 percent) patients were post-surgery chronic opioid users, defined as the dichotomous outcome of filling an opioid prescription 90 or more days after surgery. Key variables associated with chronic post-surgery opioid use include presurgery opioid use, 30-day post-surgery opioid use, and comorbidities. Latent trajectory modeling grouped patients into six distinct opioid use trajectories. Associates of trajectory group membership are reported., Conclusions: Findings support the importance of surgeons setting realistic patient expectations for post-surgical opioid use, as well as the importance of coordination of post-surgical care among patients failing to fully taper off opioids within 1-3 months of surgery.

Objective: This study aims to introduce key concepts and methods that inform the design of studies that seek to quantify the causal effect of social determinants of health (SDOH) on access to and outcomes following organ transplant., Background: The causal pathways between SDOH and transplant outcomes are poorly understood. This is partially due to the unstandardized and incomplete capture of the complex interactions between patients, their neighborhood environments, the tertiary care system, and structural factors that impact access and outcomes. Designing studies to quantify the causal impact of these factors on transplant access and outcomes requires an understanding of the fundamental concepts of causal inference., Methods: We present an overview of fundamental concepts in causal inference, including the potential outcomes framework and direct acyclic graphs. We discuss how to conceptualize SDOH in a causal framework and provide applied examples to illustrate how bias is introduced., Results: There is a need for direct measures of SDOH, increased measurement of latent and mediating variables, and multi-level frameworks for research that examine health inequities across multiple health systems to generalize results. We illustrate that biases can arise due to socioeconomic status, race/ethnicity, and incongruencies in language between the patient and clinician., Conclusions: Progress towards an equitable transplant system requires establishing causal pathways between psychosocial risk factors, access, and outcomes. This is predicated on accurate and precise quantification of social risk, best facilitated by improved organization of health system data and multicenter efforts to collect and learn from it in ways relevant to specialties and service lines., Competing Interests: Disclosure: The authors declare that they have nothing to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The role of the transplant pharmacist is recognized by transplant programs, governmental groups, and professional organizations as an essential part of the transplant multidisciplinary team. This role has evolved drastically over the last decade with the advent of major advances in the science of transplantation and the growth of the field, which necessitate expanded pharmacy services to meet the needs of patients. Data now exist within all realms of the phases of care for a transplant recipient regarding the utility and benefit of a solid organ transplant (SOT) pharmacist. Furthermore, governing bodies now have the opportunity to use Board Certification in Solid Organ Transplant Pharmacotherapy as a mechanism to identify and recognize specialty knowledge and expertise within the field of SOT pharmacotherapy. The purpose of this paper is to provide an overarching review of the current and future state of SOT pharmacy while also identifying major changes to the profession, forthcoming challenges, and expected areas of growth., Competing Interests: Declaration of Competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Lisa Potter reports a relationship with Takeda Pharmaceuticals USA Inc that includes: board membership. Lisa Potter reports a relationship with Veloxis Pharmaceuticals Inc that includes: funding grants and speaking and lecture fees. David Taber reports a relationship with Veloxis Pharmaceuticals Inc that includes: board membership and funding grants. David Taber reports a relationship with Takeda Pharmaceuticals USA Inc that includes: funding grants. David Taber reports a relationship with Merk that includes: funding grants. David Taber reports a relationship with CareDx Inc that includes: funding grants. Rita Alloway reports a relationship with Bristol Myers Squibb Co that includes: funding grants. Rita Alloway reports a relationship with Nobelpharma Co Ltd that includes: funding grants. Rita Alloway reports a relationship with National Institutes of Health that includes: funding grants. Rita Alloway reports a relationship with Veloxis Pharmaceuticals Inc that includes: board membership and speaking and lecture fees. Rita Alloway reports a relationship with Sanofi that includes: speaking and lecture fees. The authors A. B. Lichvar, M. M. Chandran, B. R. Crowther, C. T. Doligalski, and A. J. C. Martinez of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. The following authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. L. M. M. Potter reported serving as an advisory board member for Takeda in Dec 2021. E. A. Cohen reported serving for the speaker bureau of Veloxis that ended in Dec 2021 and receiving an investigator-initiated research grant from Veloxis Pharmaceuticals. D. J. Taber reported serving as a board member of the Veloxis grant and advisory board, Takeda grant, Merck grant, and CareDx grant. R. R. Alloway reported BMS, Nobelpharma, Thinker NEXT grant, Veloxis advisory board, Veloxis, and Sanofi speaker bureau., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aims: To assess if switching to or adding sulfonylureas increases major adverse cardiovascular events (MACE) or severe hypoglycemia versus remaining on metformin alone., Materials and Methods: This was a retrospective, longitudinal cohort utilizing United States Veterans Health Administration and Medicare data. Veterans with type 2 diabetes on metformin monotherapy between 2004 and 2006 were identified. Follow-up occurred through 2016. Those treated with either metformin plus a second-generation sulfonylurea (N = 45,305) or converted from metformin to a second-generation sulfonylurea (N = 2813) were compared to those receiving metformin monotherapy (N = 65,550). Hazard ratios (HR) and 95%CI from longitudinal competing risk Cox models were used to measure the association between sulfonylureas and outcomes., Results: Switching to or adding a sulfonylurea to metformin was associated with 3 times the risk of severe hypoglycemia versus metformin monotherapy (HR:3.44, 95% CI: 3.06,3.85 and HR: 3.08, 95% CI: 2.77,3.42, respectively). Switching to or adding a sulfonylurea to metformin was associated with a 7-19% higher risk of MACE versus metformin monotherapy (HR: 1.07, 95% CI: 1.00,1.14 and HR: 1.19, 95% CI: 1.13,1.25, respectively)., Conclusions: Switching to and adding second-generation sulfonylureas was associated an increase in severe hypoglycemia and MACE versus remaining on metformin alone. In an era where guidelines recommend diabetes therapies based on compelling indications, safety outcomes should be a key consideration when selecting therapy., Competing Interests: Declaration of Competing Interest D Taber has received grants from Merck, Veloxis, CareDx and is on an advisory board for Veloxis and Eurofins. None of these relationships are relevant to this manuscript. This work represents the views of the authors and not those of the Medical University of South Carolina (MUSC) or Veteran Health Administration (VHA)., (Published by Elsevier Ltd.)

Background: Transitions of care (ToC) aim to provide continuity while preventing loss of information that may result in poor outcomes such as hospital readmission. Readmissions not only burden patients, they also increase costs. Given the high prevalence of coronary artery diseases (CAD) in the United States (US), patients with CAD often make up a significant portion of hospital readmissions. Objective: To conduct a systematic review evaluating the impact of pharmacist-driven ToC interventions on post-hospital outcomes for patients with CAD. Methods: MEDLINE, Scopus, and CINAHL were searched from database inception through 03/2020 using key words for CAD and pharmacists. Studies were included if they: (1) identified adults with CAD at US hospitals, (2) evaluated pharmacist-driven ToC interventions, and (3) assessed post-discharge outcomes. Outcomes were summarized qualitatively. Results: Of the 1612 citations identified, 11 met criteria for inclusion. Pharmacist-driven ToC interventions were multifaceted and frequently included medication reconciliation, medication counseling, post-discharge follow-up and initiatives to improve medication adherence. Hospital readmission and emergency room visits were numerically lower among patients receiving vs not receiving pharmacist-driven interventions, with statistically significant differences observed in 1 study. Secondary prevention measures and adherence tended to be more favorable in the pharmacist-driven intervention groups. Conclusion: Eleven studies of multifaceted, ToC interventions led by pharmacists were identified. Readmissions were numerically lower and secondary prevention measures and adherence were more favorable among patients receiving pharmacist-driven interventions. However, sufficiently powered studies are still required to confirm these benefits.

Introduction: Medication errors, adverse events, and nonadherence in organ transplant recipients are common and can lead to suboptimal outcomes. A medication safety dashboard was developed to identify issues in medication therapy., Research Questions: Can a multicenter bioinformatics dashboard accurately identify clinically relevant medication safety issues in US military Veteran transplant recipients?, Design: The dashboard was tested through a 24-month, prospective, cluster-randomized controlled multicenter study. Pharmacists used the dashboard to identify and address potential medication safety issues, which was compared with usual care., Results: Across the 10 sites (5 control sites and 5 intervention sites), 2012 patients were enrolled (1197 intervention vs 831 control). The mean age was 65 (10) years, 95% male, and 27% Black. The dashboard produced 18 132 alerts at a rate of 0.61(0.32) alerts per patient-month, ranging from 0.44 to 0.72 across the 5 intervention sites. Lab-based issues were most common (83.4%), followed by nonadherence (9.4%) and transitions in care (6.4%); 56% of alerts were addressed, taking an average of 43 (29) days. Common responses to alerts included those already resolved by another provider (N = 4431, 44%), the alert not clinically relevant (N = 3131, 31%), scheduling of follow-up labs (N = 591, 6%), and providing medication reconciliation/education (N = 99, 1%). Inaccurate flags significantly decreased over the study by a mean of -0.6% per month (95% CI -0.1 to -1.0; P  = .0265), starting at 13.4% and ending at 2.6%., Conclusion: This multicenter cluster-randomized controlled trial demonstrated that a medication safety dashboard was feasibly deployable across the VA healthcare system, creating valid alerts.

Background: The influence of converting to once daily, extended-release LCP-Tacrolimus (Tac) for those with high tacrolimus variability in kidney transplant recipients (KTRs) is not well-studied., Methods: Single-center, retrospective cohort study of adult KTRs converted from Tac immediate release to LCP-Tac 1-2 years post-transplant. Primary measures were Tac variability, using the coefficient of variation (CV) and time in therapeutic range (TTR), as well as clinical outcomes (rejection, infections, graft loss, death)., Results: A total of 193 KTRs included with a follow-up of 3.2 ± .7 years and 1.3 ± .3 years since LCP-Tac conversion. Mean age was 52 ± 13 years; 70% were African American, 39% were female, 16% living donor and 12% donor after cardiac death (DCD). In the overall cohort, tac CV was 29.5% before conversion, which increased to 33.4% after LCP-Tac (p = .008). In those with Tac CV >30% (n = 86), conversion to LCP-Tac reduced variability (40.6% vs. 35.5%; p = .019) and for those with Tac CV >30% and nonadherence or med errors (n = 16), LCP-Tac conversion substantially reduced Tac CV (43.4% vs. 29.9%; p = .026). TTR significantly improved for those with Tac CV >30% with (52.4% vs. 82.8%; p = .027) or without nonadherence or med errors (64.8% vs. 73.2%; p = .005). CMV, BK, and overall infections were significantly higher prior to LCP-Tac conversion. In the overall cohort, 3% had rejection before conversion and 2% after (p = NS). At end of follow-up, graft and patient survival were 94% and 96%, respectively., Conclusions: In those with high Tac CV, conversion to LCP-Tac is associated with a significant reduction in variability and improvement in TTR, particularly in those with nonadherence or medication errors., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: African Americans (AAs) have reduced access to kidney transplant (KTX). Our center undertook a multilevel quality improvement endeavor to address KTX access barriers, focused on vulnerable populations. This program included dialysis center patient/staff education, embedding telehealth services across South Carolina, partnering with community providers to facilitate testing/procedures, and increased use of high-risk donors., Study Design: This was a time series analysis from 2017 to 2021 using autoregression to assess trends in equitable access to KTX for AAs. Equity was measured using a modified version of the Kidney Transplant Equity Index (KTEI), defined as the proportion of AAs in South Carolina with end-stage kidney disease (ESKD) vs the proportion of AAs initiating evaluation, completing evaluation, waitlisting, and undergoing KTX. A KTEI of 1.00 is considered complete equity; a KTEI of <1.00 is indicative of disparity., Results: From January 2017 to September 2021, 11,487 ESKD patients (64.7% AA) were referred, 6,748 initiated an evaluation (62.8% AA), 4,109 completed evaluation (59.7% AA), 2,762 were waitlisted (60.0% AA), and 1,229 underwent KTX (55.3% AA). The KTEI for KTX demonstrated significant improvements in equity. The KTEI for initiated evaluations was 0.89 in 2017, improving to 1.00 in 2021 (p = 0.0045). Completed evaluation KTEI improved from 0.85 to 0.95 (p = 0.0230), while waitlist addition KTEI improved from 0.83 to 0.96 (p = 0.0072). The KTEI for KTX also improved from 0.76 to 0.91, which did not reach statistical significance (p = 0.0657)., Conclusions: A multilevel intervention focused on improving access to vulnerable populations was significantly associated with reduced disparities for AAs., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: LCP tac has a recommended starting dose of 0.14 mg/kg/day in kidney transplant. The goal of this study was to assess the influence of CYP3A5 on perioperative LCP tac dosing and monitoring., Methods: This was a prospective observational cohort study of adult kidney recipients receiving de-novo LCP tac. CYP3A5 genotype was measured and 90-day pharmacokinetic and clinical were assessed. Patients were classified as CYP3A5 expressors (*1 homozygous or heterozygous) or nonexpressors (LOF *3/*6/*7 allele)., Results: In this study, 120 were screened, 90 were contacted and 52 provided consent; 50 had genotype results, and 22 patients expressed CYP3A5*1. African Americans (AA) comprised 37.5% of nonexpressors versus 81.8% of expressors (P = 0.001). Initial LCP tac dose was similar between CYP3A5 groups (0.145 vs. 0.137 mg/kg/day; P = 0.161), whereas steady state dose was higher in expressors (0.150 vs. 0.117 mg/kg/day; P = 0.026). CYP3A5*1 expressors had significantly more tac trough concentrations of less than 6 ng/ml and significantly fewer tac trough concentrations of more than 14 ng/ml. Providers were significantly more likely to under-adjust LCP tac by 10 and 20% in CYP3A5 expressors versus nonexpressors (P < 0.03). In sequential modeling, CYP3A5 genotype status explained the LCP tac dosing requirements significantly more than AA race., Conclusion: CYP3A5*1 expressors require higher doses of LCP tac to achieve therapeutic concentrations and are at higher risk of subtherapeutic trough concentrations, persisting for 30-day posttransplant. LCP tac dose changes in CYP3A5 expressors are more likely to be under-adjusted by providers., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

This viewpoint aims to "set the stage" and provide the rationale for the proposed development of a large-scale, comprehensive survey assessing transplant patients' perceived unmet immunosuppressive therapy needs. Research in organ transplantation has historically focused on reducing the incidence and impact of rejection on allograft survival and minimizing or eliminating the need for chronic immunosuppressive therapies. There has been less emphasis and investment in therapies to improve patient-reported outcomes including health-related quality of life and side-effects. Patient-focused drug development (PFDD) is a new and important emphasis of the Food and Drug Administration (FDA) that provides a guiding philosophy for incorporating the patient experience into drug development and evaluation. The American Society of Transplantation (AST) Board of Directors commissioned this working group to prepare for the conduct of a comprehensive patient survey assessing unmet immunosuppressive therapy needs. This paper aims to describe the basis for why it is important to conduct this survey and briefly outline the plan for broad stakeholder engagement to ensure the information gained is diverse, inclusive, and relevant for advancing PFDD in organ transplant recipients., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Study Design: Retrospective administrative database review., Objective: Analyze patterns of opioid use in patients undergoing lumbar surgery and determine associated risk factors in a Medicaid population., Summary of Background Data: Opioid use in patients undergoing surgery for degenerative lumbar spine conditions is prevalent and impacts outcomes. There is limited information defining the scope of this problem in Medicaid patients., Materials and Methods: Longitudinal cohort study of adult South Carolina (SC) Medicaid patients undergoing lumbar surgery from 2014 to 2017. All patients had continuous SC Medicaid coverage for 15 consecutive months, including six months before and nine months following surgery. The primary outcome was a longitudinal assessment of postoperative opioid use to determine trajectories and group-based membership using latent modeling. Univariate and multivariable modeling was conducted to assess risk factors for group-based trajectory modeling and chronic opioid use (COU)., Results: A total of 1455 surgeries met inclusion criteria. Group-based trajectory model demonstrated patients fit into five groups; very low use (23.4%), rapid wean following surgery (18.8%), increasing use following surgery (12.9%), slow wean following surgery (12.6%) and sustained high use (32.2%). Variables predicting membership in high opioid use included preoperative opioid use, younger age, longer length of stay, concomitant medications, and readmissions. More than three quarter of patients were deemed COUs (76.4%). On bivariate analysis, patients with degenerative disk disease were more likely to be COUs (24.8% vs. 18.6%; P =0.0168), more likely to take opioids before surgery (88.5% vs. 61.9%; P <0.001) and received higher amounts of opioids during the 30 days following surgery (mean morphine milligram equivalents 59.6 vs. 25.1; P <0.001)., Conclusions: Most SC Medicaid patients undergoing lumbar elective lumbar spine surgery were using opioids preoperatively and continued long-term use postoperatively at a higher rate than previously reported databases. Preoperative and perioperative intake, degenerative disk disease, multiple prescribers, depression, and concomitant medications were significant risk factors., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The past 5 years have witnessed a concerted national effort to assuage the rising tide of the opioid misuse in our country. Surgical procedures often serve as the initial exposure of children to opioids, however the trajectory of use following these exposures remains unclear. We hypothesized that opioid exposure following appendectomy would increase the risk of persistent opioid use among publicly insured children., Study Design: A retrospective longitudinal cohort study was conducted on South Carolina Medicaid enrollees who underwent appendectomy between January 2014 and December 2017 using administrative claims data. The primary outcome was chronic opioid use. Generalized linear models and finite mixture models were employed in analysis., Results: 1789 Medicaid pediatric patients underwent appendectomy and met inclusion criteria. The mean age was 11.1 years and 40.6% were female. Most patients (94.6%) did not receive opioids prior to surgery. Opioid prescribing ≥90 days after surgery (chronic opioid use) occurred in 127 (7.1%) patients, of which 102 (80.3%) had no opioid use in the preexposure period. Risk factors for chronic opioid use included non-naïve opioid status, re-hospitalization more than 30 days following surgery, multiple opioid prescribers, age, and multiple antidepressants/antipsychotic prescriptions. Group-based trajectory analysis demonstrated four distinct post-surgical opioid use patterns: no opioid use (91.3%), later use (6.7%), slow wean (1.9%), and higher use throughout (0.4%)., Conclusion: Opioid exposure after appendectomy may serve as a priming event for persistent opioid use in some children. Eighty percent of children who developed post-surgical persistent opioid use had not received opioids in the 90 days leading up to surgery. Several mutable and immutable factors were identified to target future efforts toward opioid minimization in this at-risk patient population., Level of Evidence: III., (Copyright © 2022. Published by Elsevier Inc.)

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.

Background: Commercial insurance data show that chronic opioid use in opioid-naive patients occurs in 1.5% to 8% of patients undergoing surgical procedures, but little is known about patients with Medicaid., Methods: Opioid prescription data and medical coding data from 4,788 Medicaid patients who underwent cholecystectomy were analyzed to determine opioid use patterns., Results: A total of 54.4% of patients received opioids prior to surgery, and 38.8% continued to fill opioid prescriptions chronically; 27.1% of opioid-naive patients continued to get opioids chronically. Patients who received ≥ 50 MME/d had nearly 8 times the odds of chronic opioid use. Each additional opioid prescription filled within 30 days was associated with increased odds of chronic use (odds ratio: 1.71)., Conclusion: Opioid prescriptions are common prior to cholecystectomy in Medicaid patients, and 38.8% of patients continue to receive opioid prescriptions well after surgical recovery. Even 27.1% of opioid-naive patients continued to receive opioid prescriptions chronically.

Background: Past research has shown that women eligible for statin therapy are less likely than their male counterparts to receive any statin therapy or be prescribed a statin at the guideline-recommended intensity. We compared statin treatment in men and women veterans from a national cohort of older veterans with type 2 diabetes., Methods: The Veterans Health Administration Corporate Data Warehouse and Centers for Medicare and Medicaid Services data were used to create a unique dataset and perform a longitudinal study of veterans with type 2 diabetes from 2007 to 2016. Mixed-effects logistic regression was used to model the association between the primary exposure (sex) and statin use., Results: The study included 714,212 veterans with diabetes, including 9,608 women, with an overall mean age of 75.9 years. In the unadjusted model for any statin use, women veterans had a 14% significantly lower odds of having any statin use compared with men. After adjusting for all covariates, including markers of Veterans Administration care use (service-connected disability rating, Veterans Administration use, and primary care visits) that serve as proxies for access and mental health comorbidities (depression and psychiatric disorder), this disparity narrowed from 14% to 3% and was no longer statistically significant. In the model for high-intensity statin therapy (high-intensity vs. low or none), women were 10% less likely than men to use high-intensity statins in the base model that included only time and sex. After adjusting for all measured covariates, the direction of the association changed and women had 16% higher odds of high-intensity statin use compared with men (odds ratio, 1.16; 95% confidence interval, 1.03-1.31)., Conclusions: Consistent with prior research, in the unadjusted analysis a significant sex disparity was observed in statin use, with lower rates observed in women. For the outcome of any statin use, after adjustment for covariates that included variables that are proxies for access as well as psychiatric and depression comorbidities, this disparity lost statistical significance and narrowed. In the high-intensity statin versus low or none model, the direction of the association changed after controlling for measured covariates and women had a 16% higher odds of high-intensity statin use compared with men. This study highlights a persistent health disparity in lipid-lowering therapy for women veterans. Additional research is needed to further elucidate the reasons for and develop interventions to mitigate this persistent sex disparity in cholesterol management for veterans with diabetes., (Published by Elsevier Inc.)

Background: Surgical quality improvement initiatives may impact sociodemographic groups differentially. The objective of this analysis was to assess the trajectory of surgical morbidity by race and age over time within a Regional Collaborative Quality Initiative., Study Design: Adults undergoing eligible general surgery procedures in South Carolina Surgical Quality Collaborative hospitals were analyzed for the presence of at least 1 of 22 morbidities between August 2015 and February 2020. Surgery-level multivariable logistic regression assessed the racial differences in morbidity over time, stratified by age group (18 to 64 years, 65 years and older), and adjusting for potential patient- and surgical-level confounders., Results: A total of 30,761 general surgery cases were analyzed, of which 28.4% were performed in Black patients. Mean morbidity rates were higher for Black patients than non-Black patients (8.5% vs 6.0%, p < 0.0001). After controlling for race and other confounders, a significant decrease in monthly mean morbidity through time was observed in each age group (odds ratio [95% CI]: age 18 to 64 years, 0.986 [0.981 to 0.990]; age 65 years and older, 0.991 [0.986 to 0.995]). Comparing morbidity rates from the first 4 months of the collaborative to the last 4 months reveals older Black patients had an absolute decrease in morbidity of 6.2% compared with 3.6% for older non-Black patients. Younger Black patients had an absolute decrease in morbidity of 4.7% compared with a 3.0% decrease for younger non-Black patients., Conclusions: Black patients had higher morbidity rates than non-Black patients even when controlling for confounders. The reasons for these disparities are not apparent. Morbidity improved over time in all patients with older Black patients seeing a larger absolute decrease in morbidity., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Racial disparities following pancreas transplantation (PTX) are poorly defined., Methods: This was a large-scale, single-center, longitudinal cohort study including adult PTX recipients. Patients were grouped by race to allow for comparisons., Results: 287 PTX recipients were included; 125 (43.5%) were African American (AA). At baseline, AAs had a significantly higher proportion of T2DM (19.4% vs. 5.7%, p = 0.001), were younger, and more likely to be female. AAs experienced significantly higher rates of pancreatic leaks and post-operative bleeding. PTX rejection was comparable, however, kidney rejection tended to be higher among AA SPKs. Long-term mean HgbA1C levels were significantly higher among AAs (6.9% vs. 6.3%, p = 0.039). Patient and graft survival was comparable between groups, but early patient survival tended to be lower in AAs., Conclusions: This study demonstrated significant perioperative health disparities among AA PTX recipients, including poorer glycemic control and more early deaths, despite similar long-term patient and graft survival., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The new kidney allocation changes with elimination of donor service areas (DSAs) and Organ Procurement and Transplantation Network regions were initiated to improve equity in organ allocation. The aim of this evaluation was to determine the operational, financial, and recipient-related effect of the new allocation system on a large rural transplantation program., Study Design: A retrospective, cross-sectional analysis of organ offers, allograft outcomes, and attributed costs in a comparative time cohort, before (December 16, 2020 to March 14, 2021) and after (March 15, 2021 to June 13, 2021) the allocation change was performed. Outcomes were limited to adult, solitary, deceased donor kidney transplantations., Results: We received 198,881 organ offers from 3,886 organ donors at our transplantation center from December 16, 2020 to June 31, 2021: 87,643 (1,792 organ donors) before the change and 111,238 (2094 organ donors) after the change, for a difference of +23,595 more offers (+302 organ donors). This resulted in 6.5 more organs transplanted vs a predicted loss of 4.9 per month. Local organ offers dropped from 70% to 23%. There was a statistically significantly increase in donor terminal serum creatinine (1.2 ± 0.86 mg/dL vs 2.2 ± 2.3 mg/dL, p < 0.001), kidney donor profile index (KDPI) (39 ± 20 vs 48 ± 22, p = 0.017), cold ischemia time (16 ± 7 hours vs 21 ± 6 hours, p < 0.001), and delayed graft function rates (23% vs 40%, p = 0.020)., Conclusion: The new kidney allocation policy has led to an increase in KDPI of donors with longer cold ischemia time, leading to higher delayed graft function rates. This has resulted in increasing logistical and financial burdens on the system. Implementing large-scale changes in allocation based predominantly on predictive modeling needs to be intensely reassessed during a longer follow up., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The optimal treatment for end-stage kidney disease is renal transplant. However, only 1 in 5 (21.5%) patients nationwide receiving dialysis are on a transplant waitlist. Factors associated with patients not initiating a transplant evaluation are complex and include patient specific factors such as transplant knowledge and self-efficacy. Research Question: Can a dialysis center-based educational video intervention increase dialysis patients' transplant knowledge, self-efficacy, and transplant evaluations initiated? Design: Dialysis patients who had not yet completed a transplant evaluation were provided a transplant educational video while receiving hemodialysis. Patients' transplant knowledge, self-efficacy to initiate an evaluation, and dialysis center rates of transplant referral and evaluation were assessed before and after this intervention. Results: Of 340 patients approached at 14 centers, 252 (74%) completed the intervention. The intervention increased transplant knowledge (Likert scale 1 to 5: 2.53 [0.10] vs 4.62 [0.05], P  < .001) and transplant self-efficacy (2.55 [0.10] to 4.33 [0.07], P  < .001. The incidence rate per 100 patient years of transplant evaluations increased 85% (IRR 1.85 [95% CI: 1.02, 3.35], P  = .0422) following the intervention. The incidence rates of referrals also increased 56% (IRR 1.56 [95% CI: 1.03, 2.37], P  = .0352), while there was a nonsignificant 47% increase in incidence rates of waitlist entries (IRR 1.47 [95% CI: 0.45, 4.74], P  = .5210). Conclusion: This dialysis center-based video intervention provides promising preliminary evidence to conduct a large-scale randomized controlled trial to test its effectiveness in increasing self-efficacy of dialysis patients to initiate a transplant evaluation.

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., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Veterans suffer disproportionate health impacts from the opioid epidemic, including overdose, suicide, and death. Prediction models based on electronic medical record data can be powerful tools for identifying patients at greatest risk of such outcomes. The Veterans Health Administration implemented the Stratification Tool for Opioid Risk Mitigation (STORM) in 2018. In this study we propose changes to the original STORM model and propose alternative models that improve risk prediction performance. The best of these proposed models uses a multivariate generalized linear mixed modeling (mGLMM) approach to produce separate predictions for overdose and suicide-related events (SRE) rather than a single prediction for combined outcomes. Further improvements include incorporation of additional data sources and new predictor variables in a longitudinal setting. Compared to a modified version of the STORM model with the same outcome, predictor and interaction terms, our proposed model has a significantly better prediction performance in terms of AUC (84% vs. 77%) and sensitivity (71% vs. 66%). The mGLMM performed particularly well in identifying patients at risk for SREs, where 72% of actual events were accurately predicted among patients with the 100,000 highest risk scores compared with 49.7% for the modified STORM model. The mGLMM's strong performance in identifying true cases (sensitivity) among this highest risk group was the most important improvement given the model's primary purpose for accurately identifying patients at most risk for adverse outcomes such that they are prioritized to receive risk mitigation interventions. Some predictors in the proposed model have markedly different associations with overdose and suicide risks, which will allow clinicians to better target interventions to the most relevant risks., Supplementary Information: The online version contains supplementary material available at 10.1007/s10742-021-00263-7., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2021.)

Background: The aim was to evaluate the effects of music on patients' anxiety and satisfaction after undergoing dialysis access procedures under moderate sedation., Methods: Patients (n = 30) undergoing moderate sedation for dialysis access procedures were evaluated at a single institution. Each patient filled out a survey preoperatively and postoperatively using the short form State-Trait Anxiety Inventory (STAI-6). Patient-selected music was provided by using a MP3 player with noise canceling headphones., Results: Postoperatively, 77% of patients perceived music intervention as very or extremely helpful in decreasing anxiety during the procedure. Further, 93% of patients were somewhat or very satisfied with their procedure. The average pain rating was 3.1 on a scale of 0-10, in which 70% of patients had no to mild pain and 30% of patients rated moderate to severe pain. In comparison to prior procedures without music, 63% of patients rated better experience with the music intervention, 37% rated a similar experience, and 3.7% rated having a worse experience. Approximately, 93% of patients were willing to repeat procedure with music and would recommend it to other patients. Preoperative anxiety average score was 35.6 ± 13 and was reduced postoperatively to 28.9 ± 12.9 ( P = .006). Preoperatively, 23% of patients rated high anxiety and postoperatively only 6.7% of patients rated high anxiety ( P = .016)., Conclusion: Music is an easy, feasible, inexpensive intervention that may reduce patients' anxiety and improve satisfaction during moderate sedation procedures and in the postoperative period.

The relative efficacy of bridging with low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) in left ventricular assist device (LVAD) patients has not been established. We performed a retrospective, longitudinal cohort study to evaluate safety and efficacy of bridging strategies including all adult LVAD patients implanted at the Medical University of South Carolina from August 2014 to July 2017. In addition to LMWH and UFH exposure, we recorded any time period a patient did not receive a bridging agent for a subtherapeutic international normalized ratio (INR) value as a control group; these events were defined as nonbridging (NB) events. Multivariable Cox regression survival models were utilized for analysis. There were 563 episodes evaluated in 50 patients. Compared with NB events, UFH (adjusted hazard ratio [aHR], 3.75; 95% CI, 1.45-9.73; p = 0.007) and LMWH (aHR, 2.25; 95% CI, 1.03-4.94; p = 0.043) were both associated with an increased risk of bleeding. Compared with NB events, LMWH was not associated with a decreased risk of clotting events (aHR, 1.56; 95% CI, 0.28-8.73; p = 0.616). In the 381 NB events, a nonsignificant signal was noted toward increased risk of thrombotic events in those with an INR ≤ 1.5 (aHR, 2.99; 95% CI, 0.57-15.8; p = 0.2). Among all 563 episodes, those with a baseline INR ≥ 2.0 demonstrated an increased risk of bleeding events (aHR, 2.35; 95% CI, 1.18-5.69; p = 0.016). Our data suggest that the efficacy of LMWH bridging in LVAD patients warrants further investigation., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

Background and Objectives: Subclinical acute rejection is associated with poor outcomes in kidney transplant recipients. As an alternative to surveillance biopsies, noninvasive screening has been established with a blood gene expression profile. Donor-derived cellfree DNA (cfDNA) has been used to detect rejection in patients with allograft dysfunction but not tested extensively in stable patients. We hypothesized that we could complement noninvasive diagnostic performance for subclinical rejection by combining a donor-derived cfDNA and a gene expression profile assay., Design, Setting, Participants, & Measurements: We performed a post hoc analysis of simultaneous blood gene expression profile and donor-derived cfDNA assays in 428 samples paired with surveillance biopsies from 208 subjects enrolled in an observational clinical trial (Clinical Trials in Organ Transplantation-08). Assay results were analyzed as binary variables, and then, their continuous scores were combined using logistic regression. The performance of each assay alone and in combination was compared., Results: For diagnosing subclinical rejection, the gene expression profile demonstrated a negative predictive value of 82%, a positive predictive value of 47%, a balanced accuracy of 64%, and an area under the receiver operating curve of 0.75. The donor-derived cfDNA assay showed similar negative predictive value (84%), positive predictive value (56%), balanced accuracy (68%), and area under the receiver operating curve (0.72). When both assays were negative, negative predictive value increased to 88%. When both assays were positive, positive predictive value increased to 81%. Combining assays using multivariable logistic regression, area under the receiver operating curve was 0.81, significantly higher than the gene expression profile ( P <0.001) or donor-derived cfDNA alone ( P =0.006). Notably, when cases were separated on the basis of rejection type, the gene expression profile was significantly better at detecting cellular rejection (area under the receiver operating curve, 0.80 versus 0.62; P =0.001), whereas the donor-derived cfDNA was significantly better at detecting antibody-mediated rejection (area under the receiver operating curve, 0.84 versus 0.71; P =0.003)., Conclusions: A combination of blood-based biomarkers can improve detection and provide less invasive monitoring for subclinical rejection. In this study, the gene expression profile detected more cellular rejection, whereas donor-derived cfDNA detected more antibody-mediated rejection., (Copyright © 2021 by the American Society of Nephrology.)

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., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

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., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: The Organ Procurement and Transplantation Network (OPTN) approved changes to the US kidney allocation system in 2019. The potential effects of this policy change using transplant rates normalized to end-stage kidney disease (ESKD) incidence have not been investigated., Objective: To estimate how the OPTN kidney allocation policy will affect areas of the US currently demonstrating low rates of kidney transplant, when accounting for the regional burden of ESKD., Design, Setting, and Participants: This cross-sectional population-based economic evaluation analyzed access of patients with ESKD to kidney transplant in the US. Participants included patients with incident ESKD, those on the kidney transplant wait list, and those who received a kidney transplant. Data were collected from January 1 to December 31, 2017, and were analyzed in 2019., Main Outcomes and Measures: The probability of a patient with ESKD being placed on the transplant wait list or receiving a deceased donor kidney transplant. States and donor service areas (DSAs) were compared for gains and losses in rates of transplanted kidneys under the new allocation system. Transplant rates were normalized for ESKD burden., Results: A total of 122 659 patients had incident ESKD in the US in 2017 (58.2% men; mean [SD] age, 62.8 [15.1] years). The probability of a patient with ESKD receiving a deceased donor kidney transplant varied 3-fold across the US (from 6.36% in West Virginia to 18.68% in the District of Columbia). Modeling of the OPTN demonstrates that DSAs from New York (124%), Georgia (65%), and Illinois (56%) are estimated to experience the largest increases in deceased donor kidney allocation. Other than Georgia, these states have kidney transplant rates per incident ESKD cases above the mean (of 50 states plus the District of Columbia, New York is 16th and Illinois is 24th). In contrast, DSAs from Nevada (-74%), Ohio (-67%), and North Carolina (-61%)-each of which has a transplant rate per incident ESKD cases significantly below the mean-are estimated to experience the largest decreases in deceased donor allocation (of 50 states plus the District of Columbia, North Carolina is 34th, Ohio is 38th, and Nevada is 47th)., Conclusions and Relevance: The new OPTN-approved kidney allocation policy may result in worsening geographic disparities in access to transplants when measured against the burden of ESKD within a particular region of the US.

Background: High tacrolimus intrapatient variability (tac IPV) is associated with poor outcomes in kidney transplantation, including rejection, donor-specific antibodies, and graft loss. A common cause of high tac IPV is related to patient nonadherence, but this is yet to be conclusively demonstrated., Methods: This was a longitudinal cohort study comprising adult kidney recipients, who received transplants between 2015 and 2017, with follow-ups through February 2020. The goal of this study was to identify the most common etiologies of tac levels outside the typical range, which lead to high tac IPV, and assess the etiology-specific associations between high tac IPV and graft outcomes. Multivariate Cox regression was used to assess time-to-event analyses., Results: In total, 537 adult kidney recipients were included; 145 (27%) were identified as having a high tac IPV (>40%) 3-102 months post-transplant. Common etiologies of tac levels significantly outside the standard goal range (6-12 ng/mL) leading to high tac IPV included patient nonadherence (20%), infections (19%), tac-related toxicities (17%), and undocumented issues (27%). In multivariable Cox modeling, those with high tac IPV because of nonadherence had a 3.5 times higher risk of late acute rejection (P = 0.019) and 2.2 times higher risk of late graft loss (P = 0.044). No other etiologies in the typical tac level range were significantly associated with either acute rejection or graft loss., Conclusions: Although high tac IPV has many causes, only high tac IPV caused by nonadherence is consistently associated with poor allograft outcomes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Early posttransplant, the administration of oral or enteral medications in pancreas transplant is challenging because of the management of postoperative ileus and gastroparesis. The use of sublingual tacrolimus may offer a promising alternative. The objective of this study was to compare the pharmacokinetics and perioperative outcomes between oral and sublingual tacrolimus in pancreas transplant., Materials and Methods: This was a single-center, retrospective study of pancreas transplants between January 1, 2011, and July 1, 2018. We transitioned our tacrolimus protocol from oral to sublingual dosing in pancreas transplant patients beginning January 1, 2017., Results: This analysis included 54 pancreas transplant recipients, with 17 patients on sublingual tacrolimus matched to 37 patients on oral tacrolimus. Within the sublingual group, it took a mean of 3.2 days to achieve a therapeutic tacrolimus trough level (≥8 ng/mL) compared with a mean of 3.8 days in the oral group (P = .175). There was no difference in the incidence of hyperkalemia and supratherapeutic tacrolimus levels between groups. The conversion factor from sublingual to oral in this patient population was 0.67, which was different than what has been reported in other populations. Clinical outcomes were similar between groups., Conclusions: Sublingual tacrolimus use in pancreas transplant patients appears to be a safe and effective strategy to avoid oral or intravenous therapy in the perioperative period and may reduce the time to achieve therapeutic levels.

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., (Published by Elsevier Inc.)

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., (Copyright © 2021 by the American Society of Nephrology.)

Background: Surgical quality improvement efforts are challenging due to the multidisciplinary nature of care, difficulties obtaining reliable data, and variability in quality metrics. The objective of this analysis was to assess whether participation in a regional collaborative quality initiative was associated with decreased in-hospital surgical complication in South Carolina., Study Design: In-hospital surgical complication rates were determined using a statewide all-payer claims data set. Retrospective, univariate, and longitudinal multivariable analyses were performed and adjustments were made to account for aggregated hospital-level patient characteristics., Results: The analysis included 275,387 general surgery cases performed in South Carolina hospitals between January 2016 and December 2018. Eight hospitals involved in the South Carolina Surgical Quality Collaborative (SCSQC) performed 56,179 cases and 51 non-SCSQC hospitals performed 219,208 cases. Univariate analysis revealed SCSQC hospitals performed operations in older patients (p < 0.0001) and patients with higher mean Charlson Comorbidity Index scores (p < 0.0001). SCSQC hospitals had higher mean in-hospital surgical complication rates at the surgery level compared with non-SCSQC hospitals (8.3% vs 7.0%; p < 0.0001). However, in multivariable analyses, the rate ratio for in-hospital surgical complication in SCSQC hospitals was 0.994 (95% CI, 0.989 to 0.998; p = 0.008) per month compared with non-SCSQC hospitals. This suggests a 21.6% (95% CI, 7.2% to 39.6%) proportional decrease in the rate of in-hospital surgical complication during 3 years associated with participation in the regional collaborative quality initiative., Conclusions: Structured collaboration between facilities, reliable data abstraction support, timely data review, and active member participation resulted in outcomes improvements for participating hospitals compared with hospitals that did not participate in a regional collaborative quality initiative., (Published by Elsevier Inc.)

Objectives: Tonsillectomy (with or without adenoidectomy) is a common pediatric surgical procedure requiring post-operative analgesia. Because of the respiratory depression effects of opioids, clinicians strive to limit the use of these drugs for analgesia post-tonsillectomy. The objective of this study was to identify demographic and medication use patterns predictive of persistent opioid dispensing (as a proxy for opioid use) to pediatric patients post-tonsillectomy., Patients and Methods: Retrospective cohort of South Carolina (USA) Medicaid-insured children and adolescents 0-18 years old without malignancy who had tonsillectomy in 2014-2017. We evaluated opioid dispensing pre-surgery and in the 30 days exposure period after hospital discharge. The main outcome, persistent opioid dispensing, was defined as any subject dispensed ≥1 opioid prescription 90-270 days after discharge. Group-based trajectory analyses described post-procedure opioid dispensing trajectories., Results: There were 11,578 subjects representing 12,063 tonsillectomy procedures. Few (3.5%) procedures were followed by persistent opioid dispensing. Any opioid dispensing during the exposure period was associated with an increased odds of persistent opioid dispensing status during the follow up period (OR 1.51 for 1-6 days of exposure and OR 1.65 for 7-30 days of opioid exposure), as was pre-procedure opioid dispensing, having >1 tonsillectomy procedure, and having complex chronic medical conditions. Group-based trajectory analyses identified 4 distinct patterns of post-discharge opioid dispensing., Conclusions: Any opioid dispensing during the 30 days after tonsillectomy increased the odds of persistent opioid dispensing by > 50%. Multivariable and group-based trajectory analyses identified patient and procedure variables that correlate with persistent opioid dispensing, primarily driven by groups receiving pre-tonsillectomy opioids and a second group who experienced multiple episodes of tonsillectomy., (Copyright © 2021. Published by Elsevier B.V.)

Background: Maintaining access to kidney transplantation during a pandemic is a challenge, particularly for centers that serve a large rural and minority patient population with an additional burden of travel. The aim of this article was to describe our experience with the rollout and use of a virtual pretransplantation evaluation platform to facilitate ongoing transplant waitlisting during the early peak of the COVID-19 pandemic., Study Design: This is a retrospective analysis of the process improvement project implemented to continue the evaluation of potential kidney transplantation candidates and ensure waitlist placement during the COVID-19 pandemic. Operational metrics include transplantation volume per month, referral volume per month, pretransplantation patients halted before completing an evaluation per month, evaluations completed per month, and patients waitlisted per month., Results: Between April and September 2020, a total of 1,258 patients completed an evaluation. Two hundred and forty-seven patients were halted during this time period before completing a full evaluation. One hundred and fifty-two patients were presented at selection and 113 were placed on the waitlist. In addition, the number of patients in the active referral phase was able to be reduced by 46%. More evaluations were completed within the virtual platform (n = 930 vs n = 880), yielding similar additions to the waitlist in 2020 (n = 282) vs 2019 (n = 308) despite the COVID-19 pandemic., Conclusions: The virtual platform allowed continued maintenance of a large kidney transplantation program despite the inability to have in-person visits. The value of this platform will likely transform our approach to the pretransplantation process and provides an additional valuable method to improve patient equity and access to transplantation., (Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

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., (© 2020 Pharmacotherapy Publications, Inc.)

Immunosuppression regimens used in solid organ transplant have evolved significantly over the past 70 years in the United States. Early immunosuppression and targets for allograft success were measured by incidence and severity of allograft rejection and 1-year patient survival. The limited number of agents, infancy of human leukocyte antigen (HLA) matching techniques and lack of understanding of immunoreactivity limited the early development of effective regimens. The 1980s and 1990s saw incredible advancements in these areas, with acute rejection rates halving in a short span of time. However, the constant struggle to achieve the optimal balance between under- and overimmunosuppression is weaved throughout the history of transplant immunosuppression. The aim of this paper is to discuss the different eras of immunosuppression and highlight the important milestones that were achieved while also discussing this in the context of rational agent selection and regimen design. This discussion sets the stage for how we can achieve optimal long-term outcomes during the next era of immunosuppression, which will move from universal protocols to patient-specific optimization., (© 2020 Pharmacotherapy Publications, Inc.)