Falsely Elevated Tacrolimus (FK506) Trough Levels in a Liver Transplant Recipient.

Antibody-conjugated magnetic immunoassay (ACMIA) for tacrolimus (FK506) may detect falsely elevated tacrolimus trough levels, a commonly underreported event. We report a case of falsely elevated whole-blood tacrolimus levels in a patient post-orthotopic liver transplantation. A 71-year-old male patient underwent liver transplantation in 2012. Post-transplantation, the patient was immediately started on tacrolimus for maintenance immunosuppression. His most recent dose was 0.5 mg four times weekly. During monitoring, trough levels were at 25.9 ng/mL using ACMIA. After this result, a decision was made to hold tacrolimus. After holding tacrolimus for seven days, detected trough levels were still continually greater than 20 ng/mL. Upon suspicion of falsely elevated results, liquid chromatography with mass spectroscopy (LC-MS) was used to check tacrolimus trough levels. Results showed normal trough levels of 7.6 ng/mL. Because of its narrow therapeutic window, tacrolimus levels need to be carefully monitored throughout treatment. When high tacrolimus levels are detected using ACMIA without a correlating clinical scenario, trough levels should be re-confirmed using LC-MS to prevent clinical decisions from being made based on falsely elevated results.

Scoring big: Aligning inpatient clinical pharmacy services through implementation of an electronic scoring system.

PURPOSE: Data are limited on utilizing a comprehensive scoring system in the electronic health record to help prioritize, align, and standardize clinical pharmacy services across multiple hospitals and practice models within a health system. The purpose of this article is to describe the development and implementation of an electronic scoring system to help inpatient pharmacists prioritize patient care activities and standardize clinical services across a diverse health system. SUMMARY: Inpatient pharmacists from all specialty areas across the health system partnered with health information technology pharmacists to develop a scoring system directly integrated into the electronic health record that would help triage patient care, identify opportunities for pharmacist intervention, and prioritize clinical pharmacy services. Individual variables were built based on documented patient parameters such as use of high-risk medications, pharmacy consults, laboratory values, disease states, and patient acuity. Total overall scores were assigned to patients based on the sum of the scores for the individual variables, which update automatically in real time. The total scores were designed to help inpatient pharmacists prioritize patients with higher scores, thus reducing the need for manual chart review to identify high-risk patients. CONCLUSION: An electronic scoring system with a tiered point system developed for inpatient pharmacists creates a method to prioritize and align clinical pharmacy services across a health system with diverse pharmacy practice models.

Implementation of routine Clostridioides difficile infection (CDI) primary prophylaxis in lung transplant recipients.

Lung transplant recipients are at an increased risk for Clostridioides difficile infection (CDI), and those who develop CDI post-transplant can have worsened outcomes including graft failure and death. We sought to describe the efficacy and safety of primary CDI prophylaxis with oral vancomycin among 86 adult lung transplant recipients. Overall, we observed a 9.3% (8/86) incidence of CDI among patients receiving prophylaxis, with the majority of infections occurring a median of 25 days after completion of prophylaxis. Furthermore, we observed a 4.7% incidence of VRE infection/colonization. Opportunities exist to optimize the duration of CDI prophylaxis to balance the benefits and risks in lung transplant recipients.

Developments in pharmacotherapeutic agents for hepatitis B - how close are we to a functional cure?

INTRODUCTION: Hepatitis B virus (HBV) remains a public health concern given its global prevalence and potential complications including hepatocellular carcinoma (HCC). Current therapies, including nucleos(t)ide analogs (NA) and interferons (IFN), are effective in chronic treatment of HBV but rarely provide a functional cure due to inadequate host response and the presence of viral DNA. Therefore, novel therapies that enhance the innate immune response while suppressing DNA transcription may provide definitive treatment of HBV. AREAS COVERED: In this review, the authors provide a brief overview of commonly used agents and their efficacy in treatment of HBV. Newer therapies with direct antiviral agents such as bepirovirsen (antisense oligonucleotide (ASO)) and entry inhibitors such as bulevirtide have shown efficacy in reducing viral load but demonstrate further reductions in conjunction with immune modulators such as therapeutic vaccines. EXPERT OPINION: Combination therapy is far superior to monotherapy alone, necessitating the need for both immunomodulators and direct antiviral agents in chronic treatment of HBV. Therapies that target covalently closed circular (cccDNA) with immunomodulators like therapeutic vaccines have shown promising results and may ultimately achieve functional cure. However, therapies need to be evaluated in the context of the patient, considering both financial and socioeconomic factors.

Hepatitis E Diagnosis and Management After Liver, Kidney, or Heart Transplant: A Single-Center Experience.

BACKGROUND: Transplant-related hepatitis E virus (HEV) infection is a rarely recognized phenomenon with significant clinical importance given its potential to result in chronic hepatitis posttransplant. METHODS: We retrospectively evaluated HEV diagnosis and treatment after liver, kidney, and heart transplant in a single center. We identified patients diagnosed with HEV by serologic testing and evaluated their treatment regimens. RESULTS: Fifteen transplant recipients (12 liver, 2 kidney, and 1 heart) presented with elevated liver enzymes and were positive for HEV IgM antibody. Liver enzymes normalized in 4 patients after being treated with ribavirin. One of the 4 patients had 2 recurrences with positive HEV RNA results following ribavirin treatment but recovered after 12 months of ribavirin therapy. After treatment with reduction in immunosuppression without antiviral treatment, 6 of 8 patients' liver enzymes normalized. One of these patients died of acute pancreatitis 2 months after testing positive for HEV IgM antibody. CONCLUSIONS: The potential for complications related to active HEV infections in transplant recipients necessitates prompt diagnosis and treatment to prevent irreversible damage. Diagnosis with HEV reverse transcriptase-polymerase chain reaction should follow a positive HEV IgM antibody test. This manuscript provides evidence that ribavirin antiviral therapy and reducing immunosuppression are effective treatments for HEV infections in liver, kidney, and heart transplant recipients, which has not been sufficiently investigated in the population of the United States. Larger multicenter studies are needed to confirm the risks and benefits of using ribavirin antiviral therapy as first-line therapy of HEV posttransplant.

Bridging the Chasm between Pregnancy and Health over the Life Course: A National Agenda for Research and Action.

BACKGROUND: Many pregnant people find no bridge to ongoing specialty or primary care after giving birth, even when clinical and social complications of pregnancy signal need. Black, indigenous, and all other women of color are especially harmed by fragmented care and access disparities, coupled with impacts of racism over the life course and in health care. METHODS: We launched the initiative "Bridging the Chasm between Pregnancy and Health across the Life Course" in 2018, bringing together patients, advocates, providers, researchers, policymakers, and systems innovators to create a National Agenda for Research and Action. We held a 2-day conference that blended storytelling, evidence analysis, and consensus building to identify key themes related to gaps in care and root causes of inequities. In 2019, more than 70 stakeholders joined six working groups to reach consensus on strategic priorities based on equity, innovation, effectiveness, and feasibility. FINDINGS: Working groups identified six key strategic areas for bridging the chasm. These include: 1) progress toward eliminating institutional and interpersonal racism and bias as a requirement for accreditation of health care institutions, 2) infrastructure support for community-based organizations, 3) extension of holistic team-based care to the postpartum year and beyond, with integration of doulas and community health workers on the team, 4) extension of Medicaid coverage and new quality and pay-for-performance metrics to link maternity care and primary care, 5) systems to preserve maternal narratives and data across providers, and 6) alignment of research with women's lived experiences. CONCLUSIONS: The resulting agenda presents a path forward to remedy the structural chasms in women's health care, with key roles for advocates, policymakers, researchers, health care leaders, educators, and the media.

Clinical outcomes with unfractionated heparin monitored by anti-factor Xa vs. activated partial Thromboplastin time.

Anti-factor Xa (anti-Xa) monitoring of unfractionated heparin (UFH) is associated with less time to achieve therapeutic anticoagulation compared to the activated partial thromboplastin time (aPTT). However, it is unknown whether clinical outcomes differ between these methods of monitoring. The aim of this research was to compare the rate of venous thrombosis and bleeding events in patients that received UFH monitored by anti-Xa compared to the aPTT. A retrospective review of electronic health records identified adult patients that received UFH given intravenously (IV) for ≥2 days, with either anti-Xa or aPTT monitoring at an academic tertiary care hospital. This was a pre/post study design conducted between January 1 to December 30, 2014 (aPTT), and January 1 to December 30, 2016 (anti-Xa). All UFH adjustments were based on institutional nomograms. The primary outcome was venous thrombosis and the secondary outcome was bleeding, both of which occurred between UFH administration and discharge from the index hospitalization. A total of 2500 patients were in the anti-Xa group and 2847 patients aPTT group. Venous thrombosis occurred in 10.2% vs 10.8% of patients in the anti-Xa and aPTT groups, respectively (P = .49). Bleeding occurred in 33.7% vs 33.6% of patients in the anti-Xa and aPTT groups, respectively (P = .94). Anti-Xa monitoring was not an independent predictor of either outcome in multivariate logistic regression analyses. Our study found no difference in clinical outcomes between anti-Xa and aPTT-based monitoring of UFH IV.

Evaluation of Potential Drug-Drug Interactions in Adults in the Intensive Care Unit: A Systematic Review and Meta-Analysis.

INTRODUCTION: There is an increased risk of potential drug-drug interactions (pDDIs) in critically ill patients based on the number of drugs received. The occurrence of pDDIs and clinical significance is not well described. OBJECTIVE: The aim was to provide insight into important clinical issues and offer guidance on drug-drug interaction (DDI) surveillance through the performance of a systematic review. METHODS: Five targeted objectives were developed, a priori, which guided study selection and data abstraction. Two independent reviewers extracted the definition, frequency, type, and clinical significance of pDDIs. A meta-analysis was performed to evaluate the proportion of patients exposed to a pDDI. Three data sources (PubMed, Embase, and Scopus) were utilized for the search to include studies that evaluated pDDIs in adult critically ill patients. Included studies in the systematic review and meta-analysis were required to be full text. RESULTS: A total of 39 studies met inclusion criteria. Definitions of pDDIs were diverse. Frequency of pDDIs varied by study, but was most commonly between one and five pDDIs per patient. Fifty-eight percent of patients were exposed to at least one pDDI during their intensive care unit admission. Types of pDDIs identified were numerous, with aspirin being the most common drug involved. As expected, not all pDDIs were clinically significant. Clinical significance was determined by varied definitions and sources. CONCLUSIONS: Improving the understanding of clinically significant pDDIs and alerts that clinicians encounter may guide better development of surveillance through clinical decision support and decrease alert fatigue.

Anticoagulation with bivalirudin during deep hypothermic circulatory arrest in a patient with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia is a well-recognized complication of anticoagulation with heparin. We present the case of a patient with recent heparin-induced thrombocytopenia who subsequently needed surgery on an emergency basis for acute type A aortic dissection. This article reports the successful use of bivalirudin, a direct thrombin inhibitor, as an alternative to heparin throughout cardiopulmonary bypass and deep hypothermic circulatory arrest. We contend that bivalirudin is a safe alternative to heparin when performing surgery for aortic dissection and should be considered as an option for use in patients who present with heparin-induced thrombocytopenia.