One size does not fit all: advanced practice provider considerations for the antimicrobial steward

Advanced practice providers are a diverse and established group of antimicrobial prescribers in both ambulatory and inpatient settings. We outline important considerations for antimicrobial stewardship programs and stewards to consider when engaging this important group of providers

Fish Health Unit Report of Activities Undertaken in 2021

This report summarises the activities undertaken by the Fish Health Unit (FHU) of the Marine Institute (MI) in 2021. The services of the FHU, undertaken on behalf of the State, are largely driven by European legislation on aquatic animal health. New EU Animal Health Law came into force from April 21st 2021. Regulation (EU) 2016/429 lays down the rules for the prevention and control of animal diseases which are transmissible to animal or humans and has replaced the regulatory framework provided by Directive 2006/88/EC. The MI is the Competent Authority (CA) responsible for implementation of aquatic animal health regulation in Ireland

Physical activity, sedentary behaviors and the incidence of type 2 diabetes mellitus: the Multi-Ethnic Study of Atherosclerosis (MESA)

Background: The association between physical activity (PA), sedentary behavior, and incident diabetes has been assessed in whites but is less well investigated in multiethnic populations. Objective: To assess the association between PA, sedentary behavior, and incident diabetes in the Multi-Ethnic Study of Atherosclerosis. Research design and methods Incident diabetes was assessed among adults without prevalent baseline diabetes (2000–2002) at 5 in-person examinations between 2002 and 2012. Baseline PA (moderate, vigorous, and exercise-specific; metabolic equivalents of task-hours/week) and sedentary behaviors (television watching, reading; hours/day) were assessed by questionnaire. HRs were estimated using Cox proportional hazard models. Results: Among 5829 adults (mean age 61.8 years, 54% female, 42% white, 12% Chinese-American, 26% African-American, 21% Hispanic-American), there were 655 incident diabetes cases (median follow-up 11.1 years). After adjustment, diabetes risk was lower in those with brisk or striding compared with none or casual walking pace (HR 0.67; 95% CI 0.54 to 0.84), higher levels of exercise PA (HR for highest vs lowest quartile 0.79; 95% CI 0.63 to 0.98), and any compared with no vigorous PA (HR 0.79; 95% CI 0.66 to 0.95). Race/ethnicity influenced the association of walking pace, exercise PA, and any vigorous PA on diabetes risk, which was only significant among whites. Total leisure sedentary behaviors (HR for highest vs lowest quartile 1.65; 95% CI 1.26 to 2.14) and television watching (HR for highest vs lowest quartile 2.68; 95% CI 1.38 to 5.21) were significantly associated with diabetes risk in multiethnic analyses and were influenced by race/ethnicity. Conclusions: These results confirm the importance of PA and sedentary behavior on diabetes risk in a multiethnic population and demonstrate potential variations across race/ethnic groups

Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, combined with azacitidine in patients with AML

Pevonedistat (TAK-924/MLN4924) is a novel inhibitor of NEDD8-activating enzyme (NAE) with single-agent activity in relapsed/refractory acute myeloid leukemia (AML). We performed a phase 1b study of pevonedistat (PEV) with azacitidine (AZA) based on synergistic activity seen preclinically. Primary objectives included safety and tolerability, and secondary objectives included pharmacokinetics (PK) and disease response. Patients ≥60 years with treatment-naive AML (unfit for standard induction therapy) received PEV 20 or 30 mg/m IV on days 1, 3, and 5 combined with fixed-dose AZA (75 mg/m IV/subcutaneously) on days 1 to 5, 8, and 9, every 28 days. The most common treatment-emergent adverse events were constipation (48%), nausea (42%), fatigue (42%), and anemia (39%). In total, 11 deaths were observed and considered unrelated to study therapy by the investigators. Transient elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were dose limiting. The recommended phase 2 dose (RP2D) of PEV in this combination is 20 mg/m PEV PK was not altered by the addition of AZA. Overall response rate (ORR) based on an intent-to-treat analysis was 50% (20 complete remissions [CRs], 5 complete remission with incomplete peripheral count recovery, 7 partial remissions [PRs]), with an 8.3-month median duration of remission. In patients receiving ≥6 cycles of therapy (n = 23, 44%), ORR was 83%. In patients with TP53 mutations, the composite CR/PR rate was 80% (4/5). Two of these patients stayed on study for >10 cycles. Baseline bone marrow blast percentage or cytogenetic/molecular risk did not influence ORR. This study was registered at www.clinicaltrials.gov as #NCT01814826