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Triacylglycerols are quantitatively the most important storage form of energy for eukaryotic cells. Acyl CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) catalyzes the terminal and only committed step in triacylglycerol synthesis, by using diacylglycerol and fatty acyl CoA as substrates. DGAT plays a fundamental role in the metabolism of cellular diacylglycerol and is important in higher eukaryotes for physiologic processes involving triacylglycerol metabolism such as intestinal fat absorption, lipoprotein assembly, adipose tissue formation, and lactation. DGAT is an integral membrane protein that has never been purified to homogeneity, nor has its gene been cloned. We identified an expressed sequence tag clone that shared regions of similarity with acyl CoA:cholesterol acyltransferase, an enzyme that also uses fatty acyl CoA as a substrate. Expression of a mouse cDNA for this expressed sequence tag in insect cells resulted in high levels of DGAT activity in cell membranes. No other acyltransferase activity was detected when a variety of substrates, including cholesterol, were used as acyl acceptors. The gene was expressed in all tissues examined: during differentiation of NIH 3T3-L1 cells into adipocytes, its expression increased markedly in parallel with increases in DGAT activity. The identification of this cDNA encoding a DGAT will greatly facilitate studies of cellular glycerolipid metabolism and its regulation

Abstract Objective Patients with sickle cell disease (SCD) face inconsistent effective analgesic management, leading to high inpatient healthcare utilization and significant financial burden for healthcare institutions. Current evidence does not provide guidance for inpatient management of acute pain in adults with sickle cell disease. We conducted a retrospective analysis of a longitudinal cohort quality improvement project to characterize the role of individualized care plans on improving patient care and reducing financial burden in high healthcare-utilizing patients with SCD-related pain. Methods Individualized care plans were developed for patients with hospital admissions resulting from pain associated with sickle cell disease. A 2-year prospective longitudinal cohort quality improvement project was performed and retrospectively analyzed. Primary outcome measure was duration of hospitalization. Secondary outcome measures included: pain intensity; 7, 30, and 90-day readmission rates; cost per day; total admissions; total cost per year; analgesic regimen at index admission; and discharge disposition. Results Duration of hospitalization, the primary outcome, significantly decreased by 1.23 days with no worsening of pain intensity scores. Seven-day readmission decreased by 34%. Use of intravenous hydromorphone significantly decreased by 25%. The potential cost saving was $1,398,827 as a result of this quality initiative. Conclusions Implementation of individualized care plans reduced both admission rate and financial burden of high utilizing patients. Importantly, pain outcomes were not diminished. Results suggest that individualized care plans are a promising strategy for managing acute pain crisis in adult sickle cell patients from both care-focused and utilization outcomes.

Abstract Introduction Pain associated with sickle cell disease (SCD) causes severe complications and frequent presentation to the emergency department (ED). Patients with SCD frequently report inadequate pain treatment in the ED, resulting in hospital admission. A retrospective analysis was conducted to assess a quality improvement project to standardize ED care for patients presenting with pain associated with SCD. Methods A 3-year prospective quality improvement initiative was performed. Our multidisciplinary team of providers implemented an ED order set in 2019 to improve care and provide adequate analgesia management. Our primary outcome was the overall hospital admission rate for patients after the intervention. Secondary outcome measures included ED disposition, rate of return to the ED within 72 hours, ED pain scores at admission and discharge, ED treatment time, in-patient length of stay, non-opioid medication use, and opioid medication use. Results There was an overall 67% reduction in the hospital admission rate after implementation of the order set (P = 0.005) and a significant decrease in the percentage admission rate month over month (P = 0.047). Time to the first non-opioid analgesic decreased by 71 minutes (P > 0.001), and there was no change in time to the first opioid medication. The rate of return to the ED within 72 hours remained unchanged (7.0% vs 7.1%) (P = 0.93), and the ED elopement rate remained unchanged (1.3% vs 1.85%) (P = 0.93). After the implementation, there were significant increases in the prescribing of orally administered acetaminophen (7%), celecoxib (1.2%), and tizanidine (12.5%) and intravenous ketamine (30.5%) and ketorolac (27%). ED pain scores at discharge were unchanged for both hospital-admitted (7.12 vs 7.08) (P = 0.93) and non-admitted (5.51 vs 6.11) (P = 0.27) patients. The resulting potential cost reduction was determined to be $193,440 during the 12-month observation period, with the mean cost per visit decreasing by $792. Conclusions Use of a standardized and multimodal ED order set reduced hospital admission rates and the timeliness of analgesia without negatively impacting patients’ pain.