Deliriogenic Medication Prescribing and Delirium in Hospitalized, Non-Critically Ill Older People.

Objective Describe the incidence of delirium and associated outcomes among hospitalized, non-critically ill older people. Design Single-center, retrospective chart review. Setting A 217-bed academic teaching hospital in Cambridge, Massachusetts affiliated with Harvard Medical School. Patients People 65 years of age or older, admitted to a general medicine unit between January 1 and August 31, 2021, who were prescribed one or more deliriogenic medications prior to or during admission. Interventions Patient electronic medical records were reviewed for deliriogenic medications prescribed and administered during admission and associated clinical outcomes. Results The percentage of patients who developed delirium was 13% overall. The most implicated deliriogenic medications were benzodiazepines, antipsychotics, and histamine-2 receptor antagonists (H2RAs). Seventy-three percent of deliriogenic home medications were continued upon admission. Subgroup analyses of those with delirium had a mean length-of-stay of 20 days compared with 6 days in those who did not develop delirium. Those with delirium tended to have more deliriogenic medications used during admission. Conclusion This review describes the incidence of delirium for non-critically ill older people who were prescribed at least one deliriogenic medication. Of all the deliriogenic agents reviewed, moderate quality clinical evidence supports the association between use and development of delirium except for H2RAs, which have low-quality evidence. Pharmacist-driven efforts to deprescribe deliriogenic medications in at-risk patient populations may be better focused on agents with higher-quality evidence.

Outcomes of hepatitis C virus nucleic acid testing positive donors in aviremic recipients with delayed direct-acting antiviral initiation.

The use of allografts from hepatitis C virus (HCV) Nucleic Acid Testing (NAT)+ donors into HCV NAT- recipients has been reported to be efficacious in a handful of studies. However, these studies have not reflected real-world practice where the initiation of direct-acting antivirals (DAA) is dependent on insurance coverage. A single-center, retrospective chart review of HCV NAT- recipients who underwent solid organ transplantation (SOT) from a HCV NAT+ donor between April 1, 2019 and May 27, 2020 was conducted. Sixty-one HCV NAT- patients underwent SOT with a HCV NAT+ organ, with 59 transplant recipients included for evaluation: 22 kidney (KT), 18 liver (LiT), 10 heart (HT), nine lung (LuT). HCV transmission occurred in 100% of recipients. Average time to DAA initiation was POD 46.3 ± 25 days. SVR12 was achieved in 98% (56/57; two patients ineligible for analysis). Treatment failure occurred in one LuT on glecaprevir/pibrentasvir with P32del and Q80K mutations. No patients developed fibrosing cholestatic hepatitis. Two patients died, secondary to anastomotic complication (LuT) and pulmonary embolism (HT). Clinically significant rejection was diagnosed and treated in two HT (one patient with ACR2 and one with ACR2/pAMR2) and one LiT (RAI 5/9). Six patients (10.2%) had documented adverse effects attributed to DAA therapy, primarily gastrointestinal.

The Role of mTOR Inhibitors in the Management of Viral Infections: A Review of Current Literature.

Viruses are the leading cause of infections after solid organ transplant. The antiviral properties of mammalian target of rapamycin inhibitors (mTORis) have been ascribed to a variety of mechanisms and historical data have supported their use over other immunosuppressants for a myriad of viruses. Herein, we summarize the most current data to highlight the role of mTORis in the management of viral infections after solid organ transplant. The mTORis play a clear role in the management of cytomegalovirus, and have data supporting their potential use for BK virus and human herpesvirus 8-related Kaposi sarcoma. No data definitively supports mTORis for use in Epstein-Barr virus-mediated posttransplant lymphoproliferative disorder or hepatitis C virus viral replication. Although theoretically an advantageous therapy for hepatitis C virus-related liver allograft fibrosis and human immunodeficiency virus, mTORi use specifically for these indications is less attractive with modern treatments currently available. Data surrounding mTORi efficacy in preventing rejection, and their toxicity profile must be balanced with their potential antiviral effects in combination with patient-specific factors.

Daptomycin use in pediatric patients.

PURPOSE: Currently available evidence on the use of daptomycin in pediatric patients is reviewed and evaluated. SUMMARY: Although guidelines on the treatment of methicillin-resistant Staphylococcus aureus infections recommend daptomycin for use in pediatric patients, that recommendation is primarily based on expert opinion. A literature search for articles on pediatric daptomycin use identified three pharmacokinetic studies, three case reports, and one retrospective review. The limited body of published evidence indicates that pediatric patients may require higher daptomycin doses than adult patients in order to attain therapeutic serum concentrations. Pharmacokinetic studies in pediatric patients demonstrated faster daptomycin clearance (CL) and a decreased area under the concentration-time curve (AUC) relative to values reported in adults. Daptomycin appears to have a shorter half-life in patients 2-6 years of age relative to those 12-17 years of age. A retrospective review of 16 cases in which pediatric patients were treated with daptomycin for invasive gram-positive infections indicated positive outcomes after the addition of daptomycin to standard therapy. Overall, daptomycin appears to be well tolerated in pediatric patients. CONCLUSION: Due to the limited nature of the available literature, use of daptomycin in pediatric patients should be limited to situations in which other options are not viable due to toxicity, local susceptibility patterns, or likely treatment failure. As a result of faster drug CL and lower AUC values, higher doses may be necessary in pediatric patients to achieve serum concentrations similar to those seen with adult dosing.