A qualitative exploration of dentists' opioid prescribing decisions within U.S. veterans affairs facilities.

ABSTRACT: The U.S. Department of Veterans Affairs (VA) is the largest integrated healthcare system in the United States and provides dental care to approximately one-half million veterans annually. In response to the opioid crisis, the VA released several opioid risk mitigation strategies. Although opioid prescribing by VA dentists has decreased on the whole, the implementation experiences at the level of dentists remains unclear. Our objective was to explore the barriers and facilitators that affect opioid decision making for management of acute dental pain among VA dentists. Dentists practicing in the VA facilities with the highest and lowest volume of opioid prescriptions were recruited. Standardized qualitative interviews by telephone followed a semistructured guide designed around the Capability (C), Opportunity (O), Motivation (M), and Behaviour (B) model. Audio recordings were transcribed and independently double-coded using NVivo to identify potential targets for future guideline-based opioid interventions. Of 395 eligible general and specialty dentists, 90 (24.8%) completed an interview representing 33 VA facilities. Opportunities for prescribing opioids included 1) completion of dental procedures associated with acute dental pain, 2) caring for patients who presented with existing dental pain, and 3) responding to patient opioid requests. Capabilities included using resources (eg, electronic medical records), clinical judgement (eg, evaluation of medical history including medication use), communication skills, and ability to screen for opioid misuse. Motivation themes focused on alleviating patients' acute dental pain. Barriers and facilitators of opioid prescribing varied across facilities. The results can offer intervention targets for continued opioid risk mitigation efforts.

Activation of the Amino Acid Response Pathway Blunts the Effects of Cardiac Stress.

BACKGROUND: The amino acid response (AAR) is an evolutionarily conserved protective mechanism activated by amino acid deficiency through a key kinase, general control nonderepressible 2. In addition to mobilizing amino acids, the AAR broadly affects gene and protein expression in a variety of pathways and elicits antifibrotic, autophagic, and anti-inflammatory activities. However, little is known regarding its role in cardiac stress. Our aim was to investigate the effects of halofuginone, a prolyl-tRNA synthetase inhibitor, on the AAR pathway in cardiac fibroblasts, cardiomyocytes, and in mouse models of cardiac stress and failure. METHODS AND RESULTS: Consistent with its ability to inhibit prolyl-tRNA synthetase, halofuginone elicited a general control nonderepressible 2-dependent activation of the AAR pathway in cardiac fibroblasts as evidenced by activation of known AAR target genes, broad regulation of the transcriptome and proteome, and reversal by l-proline supplementation. Halofuginone was examined in 3 mouse models of cardiac stress: angiotensin II/phenylephrine, transverse aortic constriction, and acute ischemia reperfusion injury. It activated the AAR pathway in the heart, improved survival, pulmonary congestion, left ventricle remodeling/fibrosis, and left ventricular function, and rescued ischemic myocardium. In human cardiac fibroblasts, halofuginone profoundly reduced collagen deposition in a general control nonderepressible 2-dependent manner and suppressed the extracellular matrix proteome. In human induced pluripotent stem cell-derived cardiomyocytes, halofuginone blocked gene expression associated with endothelin-1-mediated activation of pathologic hypertrophy and restored autophagy in a general control nonderepressible 2/eIF2α-dependent manner. CONCLUSIONS: Halofuginone activated the AAR pathway in the heart and attenuated the structural and functional effects of cardiac stress.