Opioid prescription patterns in a children's hospital from 2012 to 2016.

STUDY OBJECTIVE: Pain management is a widely discussed topic, especially in the setting of the current opioid epidemic. Previous studies have shown that the use of opioids increased in the adult population. We aimed to look at the use of narcotic and non-narcotic pain medications at a large pediatric hospital to discern if patterns of pediatric pain management changed over time. METHODS: 58,402 analgesic prescriptions of patients 0-21 years of age were analyzed from May 2012 to November 2016. A logistic regression model was fitted to examine the association of age, sex, primary diagnosis, and the length of hospital stay with probability of opioid prescription. RESULTS: 36,560 patients aged 0-21 years (mean: 10.5, median: 11.0, and standard deviation (SD): 7.42) received analgesic pain medications. 21,847 (59.8 percent) patients were prescribed more than one analgesic. There was a male predominance in patients <15 years of age; however, in adolescents >16 years, females constituted 57.1 percent of patients. Data also showed a statistically significant reduction of opioid prescriptions from 2012 to 2016 (p < 0.001). Age and length of hospital stay were directly associated with opioid prescription (p < 0.001). CONCLUSION: Data show that there is a decrease in overall opioid prescriptions among pediatric patients, which may be secondary to new Food and Drug Administration regulations and increased awareness of morbidity associated with opioid use. Not surprisingly, increased hospital stay and increase in age lead to more analgesic prescriptions. Further investigation is needed to determine the differences within opioid prescription patterns.

PEGylation of anti-MerTK Antibody Modulates Ocular Biodistribution.

Here, we explore whether PEGylation of antibodies can modulate their biodistribution to the eye, an organ once thought to be immune privileged but has recently been shown to be accessible to IV-administered large molecules, such as antibodies. We chose to PEGylate an anti-MerTK antibody, a target with known potential for ocular toxicity, to minimize biodistribution to retinal pigment epithelial cells (RPEs) in the eye by increasing the hydrodynamic volume of the antibody. We used site-specific conjugation to an engineered cysteine on anti-MerTK antibody to chemically attach 40-kDa branched or linear PEG polymers. Despite reduced binding to MerTK on cells, site-specifically PEGylated anti-MerTK retained similar potency in inhibiting MerTK-mediated macrophage efferocytosis of apoptotic cells. Importantly, we found that PEGylation of anti-MerTK significantly reduced MerTK receptor occupancy in RPE cells in both naïve mice and MC-38 tumor-bearing mice, with the branched PEG exhibiting a greater effect than linear PEG. Furthermore, similar to unconjugated anti-MerTK, PEGylated anti-MerTK antibody triggered type I IFN response and exhibited antitumor effect in syngeneic mouse tumor studies. Our results demonstrate the potential of PEGylation to control ocular biodistribution of antibodies.

Aifm2, a NADH Oxidase, Supports Robust Glycolysis and Is Required for Cold- and Diet-Induced Thermogenesis.

Brown adipose tissue (BAT) is highly metabolically active tissue that dissipates energy via UCP1 as heat, and BAT mass is correlated negatively with obesity. The presence of BAT/BAT-like tissue in humans renders BAT as an attractive target against obesity and insulin resistance. Here, we identify Aifm2, a NADH oxidoreductase domain containing flavoprotein, as a lipid droplet (LD)-associated protein highly enriched in BAT. Aifm2 is induced by cold as well as by diet. Upon cold or ß-adrenergic stimulation, Aifm2 associates with the outer side of the mitochondrial inner membrane. As a unique BAT-specific first mammalian NDE (external NADH dehydrogenase)-like enzyme, Aifm2 oxidizes NADH to maintain high cytosolic NAD levels in supporting robust glycolysis and to transfer electrons to the electron transport chain (ETC) for fueling thermogenesis. Aifm2 in BAT and subcutaneous white adipose tissue (WAT) promotes oxygen consumption, uncoupled respiration, and heat production during cold- and diet-induced thermogenesis. Aifm2, thus, can ameliorate diet-induced obesity and insulin resistance.