Electronic health record-enabled routine assessment of medication adherence after solid organ transplantation: the time is now.

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.

Benefits of early vascular provider involvement in wound care center management of patients with underlying arterial disease.

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 χ2 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.

Evolving trends in immunosuppression use and cytomegalovirus infection risk over the past decade in kidney transplantation.

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.

Acute Kidney Injury and Subsequent Kidney Failure With Replacement Therapy Incidence in Older Adults With Advanced CKD: A Cohort Study of US Veterans.

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.

Older adults are at risk of acute kidney injury (AKI) and subsequent nonrecovery from AKI, resulting in long-term dialysis. Hospitalized patients have often been used in the past to study AKI. This could lead to biased conclusions when inferring from sicker populations. That is why we created a national cohort of 24,133 Veterans at least 65 years old with incident chronic kidney disease (CKD) stage 4 to examine the relationship between AKI and age and subsequent kidney failure with replacement therapy (KFRT). The data have showed that AKI and younger age are substantial risk factors for incident KFRT. As for older age, it appears to be protective against KFRT but not death. This is likely explained by the high frequency of deaths observed in our cohort.

Use of LCP-Tacrolimus (LCPT) in Kidney Transplantation: A Delphi Consensus Survey of Expert Clinicians.

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.

Surgical prescription opioid trajectories among state Medicaid enrollees.

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.

Defining the Need for Causal Inference to Understand the Impact of Social Determinants of Health: A Primer on Behalf of the Consortium for the Holistic Assessment of Risk in Transplantation (CHART).

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.