Potential Effects of Remdesivir on Tacrolimus Exposure in Transplant Recipients With COVID-19 Infection.

Introduction: Remdesivir has proven to have benefits against COVID-19 infection. However, data supporting drug-drug interactions are insufficient. Clinicians have noticed that calcineurin inhibitor (CNI) levels tend to change after starting remdesivir. This retrospective study aimed to evaluate the effect of remdesivir on CNI levels. Methods: This study included adult solid organ transplant recipients hospitalized for COVID-19 who received remdesivir while on CNI. Patients were excluded if they started on other medications known to interact with CNI. The primary end point was the percentage of change in CNI levels after starting remdesivir. Secondary end points included the time until CNI levels reached a maximum increase in trough levels, the incidence of acute kidney injury (AKI), and the time until CNI levels normalized. Results: Of the 86 patients screened, 61 were included (56 on tacrolimus and 5 on cyclosporine). Most patients received kidney transplants (44.3%), and baseline demographics were similar among the transplanted organs. The median increase in tacrolimus level after starting remdesivir was 84.8%, and only 3 patients had no significant change in CNI levels. The median increase in tacrolimus level was more pronounced in lung and kidney recipients than in heart recipients (96.5% vs. 93.9% vs. 64.6 %, respectively). The median time to maximum increase in tacrolimus trough levels was 3 days, and it took 10 days after the remdesivir course for levels to return to baseline. Conclusion: This retrospective analysis demonstrates that CNI levels were significantly elevated after starting remdesivir. However, future studies are warranted to evaluate this interaction further.

Assessment of Anticoagulant Initiation in Patients With New-Onset Atrial Fibrillation During Emergency Department Visit-Point-by-Point Response.

Patients with atrial fibrillation (AF) have an increased risk of stroke and systemic thromboembolism. Diagnosis of AF is commonly encountered in the emergency department (ED). The purpose of this study was to assess the number of patients with new-onset AF appropriately initiated on oral anticoagulation (AC) during their ED encounter. This retrospective analysis included patients discharged from the ED from July 2016 to July 2021 with a new diagnosis of AF. Patients were excluded if they were on AC before admission. The major endpoint was to identify the percentage of patients discharged from the ED without initiating AC. Minor endpoints included the average CHA2DS2-VASc scores and the reason for not initiating AC. A total of 380 patients were included in the final analysis. Of the 245 patients found to be indicated for AC, only 131 patients (53.5%) were initiated on AC and 114 patients (46.5%) were discharged without initiating AC. Almost half of the patients who presented to the ED with a new diagnosis of AF and indicated for AC were discharged without AC.

Naloxone Versus Methylnaltrexone for Opioid-Induced Constipation in Critically Ill Patients.

BACKGROUND: Opioid-induced constipation (OIC) may occur in up to 81% of critically ill patients and can lead to many complications. Opioid antagonists are a reasonable approach and may be used for managing OIC. OBJECTIVE: The purpose of this study was to assess the efficacy of enteral naloxone (NLX) versus subcutaneous methylnaltrexone (MNTX) for the management of OIC in critically ill patients. METHODS: A retrospective analysis was conducted on adult patients who received NLX or MNTX and a continuous opioid infusion for at least 48 hours. The primary end point was time to resolution of constipation, defined as hours to first bowel movement (BM) after the first dose of an opioid antagonist. Reversal of analgesia was assessed by comparing the total number of morphine milligram equivalents (MME) 24 hours preopioid and postopioid antagonist administration. Univariate and multivariate analyses were conducted to assess treatment response within 48 hours. RESULTS: Baseline characteristics were similar between patients receiving NTX (n = 89) and MNTX (n = 71). However, the time to the first BM with NLX was 18 hours compared with 41 hours with MNTX (P = 0.004). There was no difference in MME requirements 24 hours pre/post NLX or MNTX administration. Naloxone administration was identified as a statistically significant predictor of BM within 48 hours (odds ratio [OR] = 2.68 [1.33-5.38]). CONCLUSION AND RELEVANCE: The time to first BM was shorter with enteral NLX. Both NLX and MNTX appear to be effective for the management of OIC without causing reversal of analgesia. Future controlled, prospective trials comparing these agents are warranted.

Role of environmental toxicants in the development of hypertensive and cardiovascular diseases.

The incidence of hypertension with diabetes mellitus (DM) as a co-morbid condition is on the rise worldwide. In 2000, an estimated 972 million adults had hypertension, which is predicted to grow to 1.56 billion by 2025. Hypertension often leads to diabetes mellitus that strongly puts the patients at an increased risk of cardiovascular, kidney, and/or atherosclerotic diseases. Hypertension has been identified as a major risk factor for the development of diabetes; patients with hypertension are at two-to-three-fold higher risk of developing diabetes than patients with normal blood pressure (BP). Causes for the increase in hypertension and diabetes are not well understood, environmental factors (e.g., exposure to environmental toxicants like heavy metals, organic solvents, pesticides, alcohol, and urban lifestyle) have been postulated as one of the reasons contributing to hypertension and cardiovascular diseases (CVD). The mechanism of action(s) of these toxicants in developing hypertension and CVDs is not well defined. Research studies have linked hypertension with the chronic consumption of alcohol and exposure to metals like lead, mercury, and arsenic have also been linked to hypertension and CVD. Workers chronically exposed to styrene have a higher incidence of CVD. Recent studies have demonstrated that exposure to particulate matter (PM) in diesel exhaust and urban air contributes to increased CVD and mortality. In this review, we have imparted the role of environmental toxicants such as heavy metals, organic pollutants, PM, alcohol, and some drugs in hypertension and CVD along with possible mechanisms and limitations in extrapolating animal data to humans.