Effectiveness of Healthcare Delivery, Quality, and Safety a Patient Education Bundle on Venous Thromboembolism Prophylaxis Administration by Sex.

INTRODUCTION: Venous thromboembolism (VTE) is a frequent cause of preventable harm among hospitalized patients. Many prescribed prophylaxis doses are not administered despite supporting evidence. We previously demonstrated a patient-centered education bundle improved VTE prophylaxis administration broadly; however, patient-specific factors driving nonadministration are unclear. We examine the effects of the education bundle on missed doses of VTE prophylaxis by sex. METHODS: We performed a post-hoc analysis of a nonrandomized controlled trial to evaluate the differences in missed doses by sex. Pre-intervention and intervention periods for patients admitted to 16 surgical and medical floors between 10/2014-03/2015 (pre-intervention) and 04/2015-12/2015 (intervention) were compared. We examined the conditional odds of (1) overall missed doses, (2) missed doses due to patient refusal, and (3) missed doses for other reasons. RESULTS: Overall, 16,865 patients were included (pre-intervention 6853, intervention 10,012), with 2350 male and 2460 female patients (intervention), and 6373 male and 5682 female patients (control). Any missed dose significantly reduced on the intervention floors among male (odds ratio OR 0.55; 95% confidence interval CI, 0.44-0.70, P < 0.001) and female (OR 0.59; 95% CI, 0.47-0.73, P < 0.001) patients. Similar significant reductions ensued for missed doses due to patient refusal (P < 0.001). Overall, there were no sex-specific differences (P-interaction >0.05). CONCLUSIONS: Our intervention increased VTE prophylaxis administration for both female and male patients, driven by decreased patient refusal. Patient education should be applicable to a wide range of patient demographics representative of the target group. To improve future interventions, quality improvement efforts should be evaluated based on patient demographics and drivers of differences in care.

Burn injury influences the T cell homeostasis in a butyrate-acid sphingomyelinase dependent manner.

Following burn injury, a key factor for patients susceptible to opportunistic infections is immune suppression. Butyrate levels are important in maintaining a functional immune system and these levels can be altered after injury. The acid sphingomyelinase (Asm) lipid signaling system has been implicated in a T cell actions with some evidence of being influenced by butyrate. Here, we hypothesized that burn-injury changes in butyrate levels would mediate Asm activity and, consequently, T cell homeostasis. We demonstrate that burn injury temporally decreases butyrate levels. We further determined that T cell Asm activity is increased by butyrate and decreased after burn injury. We additionally observed decreased T cell numbers in Asm-deficient, burn-injured, and microbiota-depleted mice. Finally, we demonstrate that butyrate reduced T cell death in an Asm-dependent manner. These data suggest that restoration of butyrate after burn injury may ameliorate the T cell lost observed in burn-injured patients by Asm regulation.

Fecal Microbiota Transplant Restores Mucosal Integrity in a Murine Model of Burn Injury.

The gut microbiome is a community of commensal organisms that are known to play a role in nutrient production as well as gut homeostasis. The composition of the gut flora can be affected by many factors; however, the impact of burn injury on the microbiome is not fully known. Here, we hypothesized that burn-induced changes to the microbiome would impact overall colon health. After scald-burn injury, cecal samples were analyzed for aerobic and anaerobic colony forming units, bacterial community, and butyrate levels. In addition, colon and total intestinal permeabilities were determined. These parameters were further determined in a germ-reduced murine model. Following both burn injury and germ reduction, we observed decreases in aerobic and anaerobic bacteria, increased colon permeability and no change to small intestinal permeability. After burn injury, we further observed a significant decrease in the butyrate producing bacteria R. Gnavus, C. Eutactus, and Roseburia species as well as decreases in colonic butyrate. Finally, in mice that underwent burn followed by fecal microbiota transplant, bacteria levels and mucosal integrity were restored. Altogether our data demonstrate that burn injury can alter the microbiome leading to decreased butyrate levels and increased colon permeability. Of interest, fecal microbiota transplant treatment was able to ameliorate the burn-induced changes in colon permeability. Thus, fecal transplantation may represent a novel therapy in restoring colon health after burn injury.

The T. brucei TRM5 methyltransferase plays an essential role in mitochondrial protein synthesis and function.

All tRNAs undergo post-transcriptional chemical modifications as part of their natural maturation pathway. Some modifications, especially those in the anticodon loop, play important functions in translational efficiency and fidelity. Among these, 1-methylguanosine, at position 37 (m(1)G37) of the anticodon loop in several tRNAs, is evolutionarily conserved and participates in translational reading frame maintenance. In eukaryotes, the tRNA methyltransferase TRM5 is responsible for m(1)G formation in nucleus-encoded as well as mitochondria-encoded tRNAs, reflecting the universal importance of this modification for protein synthesis. However, it is not clear what role, if any, mitochondrial TRM5 serves in organisms that do not encode tRNAs in their mitochondrial genomes. These organisms may easily satisfy the m(1)G37 requirement through their robust mitochondrial tRNA import mechanisms. We have explored this possibility in the parasitic protist Trypanosoma brucei and show that down-regulation of TRM5 by RNAi leads to the expected disappearance of m(1)G37, but with surprisingly little effect on cytoplasmic translation. On the contrary, lack of TRM5 causes a marked growth phenotype and a significant decrease in mitochondrial functions, including protein synthesis. These results suggest mitochondrial TRM5 may be needed to mature unmethylated tRNAs that reach the mitochondria and that could pose a problem for translational fidelity. This study also reveals an unexpected lack of import specificity between some fully matured and potentially defective tRNA species.