Assessment of the prevalence of burnout and well-being in solid organ transplant pharmacists.

BACKGROUND: Solid organ transplant (SOT) pharmacist burnout and well-being has not been described. METHODS: A survey of SOT pharmacists was distributed to transplant pharmacy organization listservs. Burnout was assessed with the full 22 item Maslach Burnout Inventory Human Services Survey for Medical Personnel (MBI-HSS-MP) and well-being was assessed with the Mayo Well-Being Index (WBI). Logistic multivariate regression was constructed to identify risk factors for a composite burnout assessment. RESULTS: In total, 230 responses were included (estimated response rate 36.2%). Survey participants were predominantly Caucasian (80.4%), female (79.1%), married/partnered (67.4%), and were within the first 5 years of practice (32.2%) as clinical pharmacist/specialists (87%). According to the MBI-HSS-MP, 63% met criteria for burnout. Comparing the groups with or without burnout, low quality of life (40.4% vs. 9.5%; P<.001), extreme fatigue (52.1% vs. 19%; P<.001), and likelihood of leaving the job for reasons other than retirement (38.5% vs. 10.7%; P<.001) were more common. The incidence of SOT pharmacists with WBI scores ≥ 5 (decreased well-being) was 26.5%. Among clinical pharmacists, risk factors for burnout included > 10 h per week of clinical duties outside of transplant (OR 2.669, P = .021) and extreme fatigue (OR 3.473, P<.001). CONCLUSIONS: Pharmacist burnout in SOT practice was similar to that reported in various pharmacy specialties (53-61%), which impacts clinical workforce retention and personal well-being.

A multicenter case series documenting Medicare Part D plan denials of immunosuppressant drug coverage for organ transplant recipients.

Medicare Part D plans make coverage decisions according to FDA-labeled indications and off-label uses endorsed by two CMS-recognized compendia. Patients who rely on Medicare Part D for immunosuppressive drug coverage are at risk for denied coverage when these medications are prescribed off-label. The purpose of this multicenter collaboration was to assemble a case series documenting situations where immunosuppressive therapies prescribed for transplant patients were denied by Medicare Part D prescription drug plans. This case series documents 66 instances in 39 patients where immunosuppressive drug claims were denied coverage due to off-label use not endorsed by the compendia. Patients were recipients of lung (n = 28, 72%), heart (n = 7, 18%), or liver (n = 4, 10%) transplants. Denied claims were for mycophenolate mofetil (n = 22, 33%), azathioprine (n = 18, 27%), sirolimus (n = 15, 23%), mycophenolate sodium (n = 5, 8%), everolimus (n = 5, 8%), and belatacept (n = 1, 1%). Most denials were upheld across all the levels of attempted appeal, including those escalated to a Medicare Administrative Law Judge. This case series demonstrates a critical flaw in the construct of the Medicare Prescription Drug Benefit. The currently referenced compendia are not up to date and do not reflect best practices in organ transplantation.

Alternatives to immediate release tacrolimus in solid organ transplant recipients: When the gold standard is in short supply.

Given the current climate of drug shortages in the United States, this review summarizes available comparative literature on the use of alternative immunosuppressive agents in adult solid organ transplant recipients including kidney, pancreas, liver, lung, and heart, when immediate-release tacrolimus (IR-TAC) is not available. Alternative options explored include extended-release tacrolimus (ER-TAC) formulations, cyclosporine, belatacept, mammalian target of rapamycin inhibitors, and novel uses of induction therapy for maintenance immunosuppression. Of available alternatives, only ER-TAC formulations are of non-inferior efficacy compared to IR-TAC when used de novo or after conversion in stable kidney transplant recipients (KTRs). All other alternatives were associated with higher rates of biopsy-proven rejection, but improved tolerance from classic adverse effects of IR-TAC including nephrotoxicity and development of diabetes. While most alternative therapies are approved in KTRs, access via third-party payors is an obstacle in non-KTRs. In the setting of IR-TAC shortage, alternate therapeutic options may be plausible depending on the organ population and individual patient situation to ensure appropriate, effective immunosuppression for each patient.

A systematic review of opioid use and multimodal strategies in solid organ transplant recipients and living donors.

The opioid epidemic has impacted analgesia in the postoperative period for solid organ transplant (SOT) donors and recipients. However, optimal pain management and opioid stewardship strategies have not been identified across this unique population. The purpose of this systematic review was to evaluate the impact of perioperative opioid use and to describe multimodal analgesic strategies to reduce opiate use in SOT recipients and living donors. A systematic review was conducted. Electronic searches were performed in Medline, Embase, Google Scholar, and Web of Science through December 31, 2021. Title and abstracts were screened. Relevant articles underwent full-text review. Literature was separated into effects of opioid exposure on post-transplant outcomes, recipient pain management strategies, and living donor pain management strategies. Search yielded 25,190 records, and 63 were ultimately included. The impact of opioid use on post-transplant outcomes was assessed in 19 publications. The risk of graft loss in pretransplant opioid users was assessed in six reports and was found to be higher in the majority (66%) of publications. Opioid minimization strategies were reported in 20 studies in transplant recipients. Twenty-four studies evaluated pain management strategies in living donors. Both populations used a combination of multimodal strategies to minimize opioid use throughout the hospitalization and on discharge. Opioids are associated with select negative outcomes in post-transplant recipients. To minimize their use while also maintaining appropriate analgesia, multimodal pain regimens should be considered in SOT recipients and donors.

Implications for body weight extremes in solid organ transplantation.

The pharmacokinetic profiles of medications are altered in overweight and underweight patients, but few studies have described these differences in patients with body mass index extremes. As solid organ transplant programs expand their candidate selection criteria to accommodate a growing population of patients with weight extremes, it has become imperative to understand and evaluate the impact weight extremes have on the pharmacokinetics of life-sustaining immunosuppression in this population. This review will describe pharmacokinetic and dosing considerations for weight extremes in solid organ transplant recipients, including changes following bariatric surgeries, non-pharmacologic and pharmacologic management strategies for weight loss and gain, and potential drug-drug interactions with popular weight management products.

The Clinical Conundrum of Cannabis: Current Practices and Recommendations for Transplant Clinicians: An Opinion of the Immunology/Transplantation PRN of the American College of Clinical Pharmacy.

Cannabis, or marijuana, comprises many compounds with varying effects. It has become a treatment option for chronic diseases and debilitating symptoms, and evidence suggests that it has immunomodulatory and antiinflammatory properties. Transplant centers are more frequently facing issues about cannabis, as indications and legalization expand. As of February 2020, 33 states and the District of Columbia have legalized medical cannabis, and 14 have legalized recreational cannabis. Moreover, 8 states have passed legislation prohibiting the denial of transplant listing solely based on cannabis use. Studies demonstrate the potential for significant pharmacokinetic and pharmacodynamic interactions between cannabis and immunosuppression. Additionally, safety concerns include increased risk of myocardial infarction, ischemic stroke, tachyarrhythmias, malignancy, neurocognitive deficits, psychosis, other neuropsychiatric disorders, cannabis use disorder, respiratory symptoms, and infection. A recent retrospective database study found a negative association between documented cannabis use disorder and graft survival, but little additional evidence exists evaluating this relationship. In the absence of robust clinical data, transplant centers need a clear, reasoned, and systematic approach to cannabis. The results of our national survey, unfortunately, found little consensus among institutions. As both recreational and medicinal cannabis become more ubiquitous nationwide, transplant centers will need to develop comprehensive policies to address its use.

The Rochester Relapse Risk Scale: Developing a Standardized Approach to Predicting Substance Relapse in Liver Transplant Candidates.

OBJECTIVES: Substance abuse is a risk factor for nonadherence and graft failure after orthotopic liver transplant. This study aimed to evaluate the ability of an internally developed tool, the Rochester Relapse Risk Scale, to predict substance relapse in liver transplant candidates. MATERIALS AND METHODS: This single-center, retrospective, observational study included adult patients evaluated for orthotopic liver transplant using the Rochester Relapse Risk Scale. Primary outcome was rate of substance relapse, as measured by the risk scale, which stratified patients into relapse risk levels based on the number of factors present. RESULTS: In total, 303 patients (71.6% men, 90.4% White, median age of 55 years [interquartile range, 49-60 y]) were included. Median follow-up time was 212 days (interquartile range, 73-661 d). Seventy-four patients (24.4%) relapsed at 127 days (interquartile range, 55-461 d) after evaluation, with 60.8% who relapsed within 6 months. Relapse rates correlated with assigned risk level, with 8.3% relapsing at low, 19.0% at low-moderate, 25.3% at moderate, 33.8% at moderate-high, and 40.0% at high risk. High-risk cohorts had significantly shorter median time to relapse versus low-risk cohorts (104 vs 154 days; P = .001). CONCLUSIONS: Assignment of relapse risk level according to the Rochester Relapse Risk Scale aligned with rates of relapse. Additional studies are needed to refine the tool, assess inter-rater reliability, and confirm findings in prospective, multicenter studies.

Letermovir for the management of cytomegalovirus infection.

INTRODUCTION: Cytomegalovirus (CMV) is a major cause of morbidity and mortality in immunocompromised patients. Available antivirals are fraught with adverse effects and risk for the development of CMV resistance. Letermovir is a novel antiviral in the late stages of drug development for the treatment and prevention of CMV. Areas covered: A MEDLINE search of the MeSH terms 'letermovir,' 'cytomegalovirus,' 'hematopoietic stem cell transplant,' and 'solid organ transplant,' was last conducted on 15 August 2016. Articles were selected on the basis of their contribution to current knowledge about letermovir. Expert opinion: Letermovir's mechanism of action, pharmacokinetic and pharmacodynamic profile, and favorable efficacy and safety make it an attractive option for both the prevention and treatment of CMV in immunocompromised patients. The lack of cross-resistance with other antivirals and the absence of myelosuppression are two prominent characteristics of letermovir that could support broad use of this product following FDA-approval. One major limitation is its lack of activity against other herpesviruses, which are commonly seen in immunocompromised hosts. We believe that with additional clinical efficacy data, this medication could emerge as a primary option for the prevention and treatment of CMV in the immunocompromised patient population.