Impact of a Multidisciplinary Long-Term Opioid Therapy Safety Program at a Military Tertiary Academic Medical Center.

OBJECTIVE: In light of the ongoing opioid crisis, Naval Medical Center Portsmouth (NMCP) created the Long-Term Opioid Therapy Safety (LOTS) program to reduce risks and improve long-term opioid therapy outcomes. Our primary outcome was change in compliance with the recommended safety metrics. DESIGN: This is a retrospective cohort study performed at NMCP, a large military academic medical center providing comprehensive medical care to DoD beneficiaries. The NMCP LOTS program provides both patient and provider narcotic education as well as medical record auditing. The NMCP LOTS program promotes adherence to published CDC, the DVA, and DoD guidelines. METHODS: Anonymized data were compiled each fiscal quarter and were analyzed retrospectively. Adult patients prescribed opioids for at least 90 days without a gap of 30 days between prescriptions were included in this study. The investigators recorded and reported provider compliance with LOTS metrics over the same period. RESULTS: Compliance with the recommended safety metrics improved. We noted a decrease in the number of long-term opioid patients, concurrent benzodiazepine prescriptions, and patients prescribed greater than 90 morphine equivalents per day during the observation period. The number of naloxone prescriptions for LOTS patients also increased, reflecting improved guideline adherence. CONCLUSION: Systematic education and feedback to providers are effective in creating a system and culture of opioid reduction, safe opioid prescribing, and system accountability. This article presents a comprehensive approach to modifying prescribing patterns of long-term opioids in a large healthcare system.

EIF4A3 deficient human iPSCs and mouse models demonstrate neural crest defects that underlie Richieri-Costa-Pereira syndrome.

Biallelic loss-of-function mutations in the RNA-binding protein EIF4A3 cause Richieri-Costa-Pereira syndrome (RCPS), an autosomal recessive condition mainly characterized by craniofacial and limb malformations. However, the pathogenic cellular mechanisms responsible for this syndrome are entirely unknown. Here, we used two complementary approaches, patient-derived induced pluripotent stem cells (iPSCs) and conditional Eif4a3 mouse models, to demonstrate that defective neural crest cell (NCC) development explains RCPS craniofacial abnormalities. RCPS iNCCs have decreased migratory capacity, a distinct phenotype relative to other craniofacial disorders. Eif4a3 haploinsufficient embryos presented altered mandibular process fusion and micrognathia, thus recapitulating the most penetrant phenotypes of the syndrome. These defects were evident in either ubiquitous or NCC-specific Eif4a3 haploinsufficient animals, demonstrating an autonomous requirement of Eif4a3 in NCCs. Notably, RCPS NCC-derived mesenchymal stem-like cells (nMSCs) showed premature bone differentiation, a phenotype paralleled by premature clavicle ossification in Eif4a3 haploinsufficient embryos. Likewise, nMSCs presented compromised in vitro chondrogenesis, and Meckel's cartilage was underdeveloped in vivo. These findings indicate novel and essential requirements of EIF4A3 for NCC migration and osteochondrogenic differentiation during craniofacial development. Altogether, complementary use of iPSCs and mouse models pinpoint unique cellular mechanisms by which EIF4A3 mutation causes RCPS, and provide a paradigm to study craniofacial disorders.

The Use of Magnetic Resonance Cholangiopancreatography (MRCP) in the Setting of Acute Pancreatitis: When is it Most Useful?

CONTEXT: The usefulness of MRCP in the workup of acute pancreatitis has long been debated. METHODS: 2013-2016 chart review data were collected by the authors from adult patients with acute pancreatitis who also had received Magnetic Resonance Cholangiopancreatography (MRCP). Those patients were categorized by diagnosis and according to whether or not the MRCP changed healthcare services. RESULTS: Changes in care were significantly correlated with diagnosis and elevated liver function tests (LFT). The patients who benefitted most from MRCP were those with acute gallstone pancreatitis (r = 0.298, n = 109, p = 0.002) and patients with elevated LFT (r = 0.219, n = 89, p= 0.040). The most common way that MRCP influenced the care of patients with acute gallstone pancreatitis was by allowing providers to forego intraoperative cholangiogram (IOC) when MRCP results were negative (r = 0.335, n = 109, p < 0.001). CONCLUSIONS: The authors conclude that this was not the most cost effective management practice since the cost of intraoperative cholangiogram was about one quarter that of MRCP. Limiting MRCP use in patients with acute gallstone pancreatitis and preferentially using IOC at the time of surgery can likely decrease hospital costs without compromising care.