Recent Publications by CFE Educators

Deciphering the genetic basis of prostate-specific antigen (PSA) levels may improve their utility for prostate cancer (PCa) screening. Using genome-wide association study (GWAS) summary statistics from 95,768 PCa-free men, we conducted a transcriptome-wide association study (TWAS) to examine impacts of genetically predicted gene expression on PSA. Analyses identified 41 statistically significant (p  0.05/12,192 = 4.10 × 10) associations in whole blood and 39 statistically significant (p  0.05/13,844 = 3.61 × 10) associations in prostate tissue, with 18 genes associated in both tissues. Cross-tissue analyses identified 155 statistically significantly (p  0.05/22,249 = 2.25 × 10) genes. Out of 173 unique PSA-associated genes across analyses, we replicated 151 (87.3%) in a TWAS of 209,318 PCa-free individuals from the Million Veteran Program. Based on conditional analyses, we found 20 genes (11 single tissue, nine cross-tissue) that were associated with PSA levels in the discovery TWAS that were not attributable to a lead variant from a GWAS. Ten of these 20 genes replicated, and two of the replicated genes had colocalization probability of >0.5: CCNA2 and HIST1H2BN. Six of the 20 identified genes are not known to impact PCa risk. Fine-mapping based on whole blood and prostate tissue revealed five protein-coding genes with evidence of causal relationships with PSA levels. Of these five genes, four exhibited evidence of colocalization and one was conditionally independent of previous GWAS findings. These results yield hypotheses that should be further explored to improve understanding of genetic factors underlying PSA levels.

Immunotherapy has revolutionised the treatment of advanced hepatocellular carcinoma (HCC). In addition, several phase III trials of immunotherapy in combination with surgical or locoregional therapies for early-to intermediate-stage HCC have recently reported positive results, and other phase III trials in the same patient population are currently in progress. As the application of immunotherapy is shifting to include patients with earlier stages of HCC, one looming question now emerges: What is the role of immunotherapy in the pre-liver transplant population? Liver transplantation is a potentially curative therapy for HCC and confers the additional advantage of restoring a normal, healthy liver. In pre-transplant patients, immunotherapy may improve downstaging success and tumour control at the cost of some immunologic risks. These include immune-related toxicities, which are particularly relevant in a uniquely vulnerable population with chronic liver disease, and the possibility of acute rejection after transplantation. Ultimately, the goal of immunotherapy in this population will be to effectively expand access to liver transplantation while preserving pre- and post-transplant outcomes. In this review, we discuss the mechanisms supporting combination immunotherapy, summarise key recent clinical data from major immunotherapy trials, and explore how immunotherapy can be applied in the neoadjuvant setting prior to liver transplantation in selected high-risk patients.

INTRODUCTION

Medication errors during hospital discharge can lead to adverse outcomes, medication-related readmissions, and increased health care costs. Pharmacist-led medication reconciliation at discharge is a potential solution to mitigate poor outcomes and optimize medication safety.

OBJECTIVES

This study aimed to quantify medication errors identified at discharge and characterize the severity of patient harm prevented following pharmacist-led discharge medication reconciliation. Cost avoidance analysis was conducted to determine its associated financial impact.

METHODS

Patients discharged from an adult internal medicine service during October 2022, were included in this one-month pilot prospective quality improvement study. Number of errors at discharge were documented, categorized by type, and adjudicated for severity of potential harm. Error severity was classified based on a modified National Coordinating Council for Medication Error Reporting and Prevention Medication Error Index. Cost avoidance was calculated based on whether each error would have resulted in additional medical encounters and length of stay.

RESULTS

Thirty-one patients were included in the analysis. Forty errors were identified by pharmacist-led medication reconciliation at discharge, with a mean of 1.3±1.9 errors per patient and 68% of patients having at least one error. The most common errors were duplication of therapy (25%) and medication access barriers at discharge (25%). The severity of errors included low (22.5%), serious (75%), and life-threatening harm (2.5%). Thirty-five percent of errors could have led to emergency visits or hospital readmissions. The estimated total cost for errors was $25,600. Pharmacist labor cost for reconciliation was $816. Cost avoidance was $24,784 from the 14 errors at discharge that could have resulted in additional emergency or inpatient visits.

CONCLUSION

Pharmacist-led medication reconciliation at discharge may prevent harm from reaching patients, decrease cost from unnecessary health encounters, and stop the error from continuing across transitions of care.

OBJECTIVE

To assess the impact of bimekizumab on physical functioning, sleep, work productivity and overall health-related quality of life (HRQoL) in patients with non-radiographic (nr-) and radiographic (r-) axial spondyloarthritis (axSpA) in the phase 3 studies BE MOBILE 1 and 2.

METHODS

Patients were randomised to subcutaneous bimekizumab 160 mg or placebo every 4 weeks; from Week 16, all patients received bimekizumab 160 mg every 4 weeks. We report the following outcomes to Week 52: Bath Ankylosing Spondylitis Functional Index (BASFI), Medical Outcomes Study Sleep Scale Revised (MOS-Sleep-R) Index II, Work Productivity and Activity Impairment: axSpA (WPAI:axSpA), Short Form-36 Physical and Mental Component Summary (SF-36 PCS/MCS) and Ankylosing Spondylitis Quality of Life (ASQoL).

RESULTS

At Week 16, bimekizumab-randomised patients demonstrated significantly greater improvement from baseline versus placebo in BASFI, SF-36 PCS and ASQoL (p0.001), and numerically greater improvements in MOS-Sleep-R Index II and WPAI:axSpA scores. Higher proportions of bimekizumab-randomised versus placebo-randomised patients at Week 16 achieved increasingly stringent thresholds for improvements in BASFI (0 to ≤4), and thresholds for meaningful improvements in SF-36 PCS (≥5-point increase from baseline) and ASQoL (≥4-point decrease from baseline). Responses were sustained or further improved to Week 52, where 60%-70% of bimekizumab-treated patients achieved BASFI ≤4 and meaningful improvements in SF-36 PCS and ASQoL, regardless of whether originally randomised to bimekizumab or placebo.

CONCLUSION

Bimekizumab treatment led to early improvements in physical function, sleep, work productivity and overall HRQoL at Week 16 in patients across the full axSpA disease spectrum. Improvements were sustained to Week 52.

TRIAL REGISTRATION NUMBERS

NCT03928704; NCT03928743.