Risk factors and trajectories of opioid use following total knee replacement.

BACKGROUND: Opioids are commonly used to manage orthopedic pain in those undergoing total knee arthroplasty (TKA). There are limited studies assessing patterns of perioperative opioid use and risk factors for chronic use in patients undergoing TKA. METHODS: This is a retrospective longitudinal cohort study of Medicaid enrollees undergoing TKA between 2014 and 2017 using de-identified medical and pharmacy claims. The primary outcome was chronic opioid use (opioid prescription filled 90-270 days following TKA). Trajectory group membership was determined by identifying distinct groups of patients with similar patterns of daily morphine milligram equivalent (MME) values during the postsurgery follow-up period. RESULTS: In total, 1666 TKA surgeries performed in 1507 patients were included; 69% of patients were classified as chronic opioid users. Multivariable analyses identified prior opioid use, high opioid doses during the month after TKA, concomitant mood therapies and benzodiazepines, and comorbid conditions as important risk factors. Group-based trajectory analysis identified five distinct post-TKA surgery opioid use phenotypes with several key characteristics predicting group membership. CONCLUSIONS: This large-scale analysis demonstrated that chronic opioid use was common after TKA surgery and established several important risk factors for chronic use following TKA. Novel analysis revealed five distinct opioid use trajectories and identified key characteristics to help guide clinicians when determining perioperative opioid use. Results demonstrate that interventional studies attempting to reduce opioids after TKA are needed if reductions in long-term use are to be realized in this high-risk patient population.

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

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

The impact of race on metabolic, graft, and patient outcomes after pancreas transplantation.

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.

Safety and Efficacy of Perioperative Sublingual Tacrolimus in Pancreas Transplant Compared With Oral Tacrolimus.

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.

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

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

A comprehensive review of the impact of tacrolimus intrapatient variability on clinical outcomes in kidney transplantation.

Tacrolimus (Tac) is widely used to prevent rejection and graft loss in solid organ transplantation. A limiting characteristic of Tac is the high intra and interpatient variability associated with its use. Routine therapeutic drug monitoring (TDM) is necessary to facilitate Tac management and to avoid undesirable clinical outcomes. However, whole blood trough concentrations commonly utilized in TDM are not strong predictors of the detrimental clinical outcomes of interest. Recently, researchers have focused on Tac intrapatient variability (Tac IPV) as a novel marker to better assess patient risk. Higher Tac IPV has been associated with a number of mechanisms leading to shortened graft survival. Medication nonadherence (MNA) is considered to be the primary determinant of high Tac IPV and perhaps the most modifiable risk factor. An understanding of the methodology behind Tac IPV is imperative to its recognition as an important prognostic measure and integration into clinical practice. Therapeutic interventions targeting MNA and reducing Tac IPV are crucial to improving long-term graft survival.