Background: Prescription opioid rates have been found to vary on a county and state level. We aim to find if significant hospital-level and regional-level variation in opioid prescription rates exists in a pediatric orthopedic setting. Methods: We conducted a retrospective cohort study of children ages 10-18 who sustained an ACL injury between 2012-2016, from 39 hospitals throughout the United States, found through the Pediatric Health Information System. Patients were divided into four regions according to the regional census of hospital admission, and demographics were recorded. Primary outcomes were hospital-level variation in opioid prescription rates using a mixed effects linear regression model to compare mean differences in average opioid prescription rate. Results: 11,452 pediatric patients were analyzed for regional-level variation in opioid prescription rates. Of those patients 7,879 were analyzed for hospital-level variation in opioid prescription rates based on if the hospital of incidence had a sample size of at least 250 patients over the five-year span (16 of the 43 hospitals fit this criteria). The most common demographics were patients ages 16-18 (n=5,613; 49.01%), white (n=6,588; 57.53%), and male (n=5,905; 51.56%). The 11,452 patients were divided into four regions: (1) Northeast (n=2,409; 21.04%), (2) Midwest (n=2,499; 21.82%), (3) South (n=3,869; 33.78%), and (4) West (n=2,675; 23.36%). After adjustment, significant variation in opioid prescription rates was found to exist at both a hospital-level using a random intercept and random slope model (-2LL=17882.381, p<.05) and at a regional-level by comparing mean differences in average opioid prescription rate (p<.05). Conclusions: Significant variation of opioid prescription rates exists at both a hospital-level and a regional-level over the last five years in a pediatric orthopedic setting. The findings of this study build off previous findings from the Centers for Disease Control, which found significant variation existed in opioid prescription rates on a state-wide level. Given the recent guidelines proposed by the CDC to control and limit prescription opioids (as of March 2016), future studies finding the impact of the guidelines on variation of prescription rates in a pediatric orthopedic setting could be beneficial. [Table: see text][Figure: see text]

While genome sequencing has expanded our knowledge of symbiosis, role assignment within multi-species microbiomes remains challenging due to genomic redundancy and the uncertainties of in vivo impacts. We address such questions, here, for a specialized nitrogen (N) recycling microbiome of turtle ants, describing a new genus and species of gut symbiont—Ischyrobacter davidsoniae (Betaproteobacteria: Burkholderiales: Alcaligenaceae)—and its in vivo physiological context. A re-analysis of amplicon sequencing data, with precisely assigned Ischyrobacter reads, revealed a seemingly ubiquitous distribution across the turtle ant genus Cephalotes, suggesting ≥50 million years since domestication. Through new genome sequencing, we also show that divergent I. davidsoniae lineages are conserved in their uricolytic and urea-generating capacities. With phylogenetically refined definitions of Ischyrobacter and separately domesticated Burkholderiales symbionts, our FISH microscopy revealed a distinct niche for I. davidsoniae, with dense populations at the anterior ileum. Being positioned at the site of host N-waste delivery, in vivo metatranscriptomics and metabolomics further implicate I. davidsoniae within a symbiont-autonomous N-recycling pathway. While encoding much of this pathway, I. davidsoniae expressed only a subset of the requisite steps in mature adult workers, including the penultimate step deriving urea from allantoate. The remaining steps were expressed by other specialized gut symbionts. Collectively, this assemblage converts inosine, made from midgut symbionts, into urea and ammonia in the hindgut. With urea supporting host amino acid budgets and cuticle synthesis, and with the ancient nature of other active N-recyclers discovered here, I. davidsoniae emerges as a central player in a conserved and impactful, multipartite symbiosis.

Introduction: Variation in opioid exposure has been documented in many pediatric fields; however, little is currently known about the extent of these findings during the perioperative period. The purpose of this study was to examine perioperative opioid exposure on a national level among patients undergoing anterior cruciate ligament (ACL) reconstruction using an administrative database. Our aims were to assess the impact of hospitals and a variety of demographic factors on (1) the likelihood of perioperative opioid exposure and (2) the variability in relative opioid exposure. Methods: The Pediatric Health Information Systems Database (PHIS) was used to identify pediatric patients (≤ 18 years old) across 52 hospitals undergoing ACL reconstruction between January 2008 and December 2017. Administered opioids in morphine milligram equivalents were discretized into quintiles to represent relative opioid exposure (ROE). A hurdle generalized additive model was estimated to identify demographic factors predictive of (1) the receipt of any opioid medication and (2) the ROE among those receiving opioids. Results: Of the 19,821 patients meeting study inclusion criteria, 17,350 (88%) were administered opioid medications perioperatively. There was no temporal trend in perioperative opioid utilization or ROE over the study period. Patients in an inpatient (OR = 0.260 [0.221, 0.305]) or observation unit (OR = 0.349 [0.305, 0.401]) context were less likely to be administered opioids. Female patients (OR = 0.896 [0.813, 0.987]) were less likely to be administered opioids, while patients on commercial insurance had a higher ROE (OR = 1.09 [1.023, 1.161]). Patient age and hospital-level time trends predicted opioid administration and exposure (max p < 0.001). Discussion: Gender, age, surgical setting, hospital type, and insurance status, in part, predicted perioperative opioid exposure among pediatric patients undergoing ACL reconstruction surgery. Exposure has not declined in recent years and varies significantly between hospitals. Although this study primarily served to document demographic variability in perioperative opioid exposure in pediatric patients undergoing ACL reconstruction, the understanding of variability in perioperative opioid utilization and exposure rate could stand to be further explored.

Mycobacteriophage Superphikiman is a cluster J bacteriophage which was isolated from soil collected in Philadelphia, PA. Superphikiman has a 109,799-bp genome with 239 predicted genes, including 2 tRNA genes.

Background: Pediatric patients sustaining anterior cruciate ligament (ACL) or related injuries are at high risk for opioid exposure in the acute, perioperative and postoperative phases of injury. Early and repeated exposure to these medications may increase the risk of future misuse. While variation in opioid prescribing practices has been documented in the outpatient setting and other realms of pediatric care, perioperative opioid exposure in this procedural cohort has not been previously examined on a national level. Purpose: To assess for demographic, temporal, regional, and hospital-level variability in perioperative opioid exposure in pediatric ACL patients. Methods: The Pediatric Health Information Systems Database (PHIS) was used to identify pediatric patients (≤18 years old) undergoing surgical treatment for ACL injury between January 2008 and December 2017. Perioperative opioids were converted to a morphine equivalent dose (MED) and summed for each patient. A hierarchical bayesian regression was performed to identify demographic factors that predicted opioid exposure while adjusting for the effect of hospital. Results: The study cohort included 23,071 patients across 52 hospitals. We report model estimates in Table 1 and mean MME by hospital in Figure 1. Compared to older adolescents (15-18yo), younger adolescents (11-14yo; b=-0.13 95% Credible Interval[-0.19, -0.07]) and children <10yo (b=-1.62 [-1.72, -1.52]) received less MED. Patients located in an observation unit (b=-1.15 [-1.25, -1.06]) or an inpatient unit (b=-1.31;[-1.42, -1.20]) received less MED than patients in an ambulatory surgical setting. Patients with commercial insurance also were dispensed more MED compared to those with other payers (b=0.10 [0.04, 0.16]). Female patients received less opioids than male patients (b=-0.08 [-0.13, -0.02]). Of the hospital random effects, the 95% credible intervals of 24 (46%) intercepts and 21 (40%) slopes did not include zero. Conclusions: This administrative database study identified hospital and patient-level characteristics predictive of perioperative narcotic exposure among pediatric ACL patients. Those who were older, in an ambulatory surgery setting, or had commercial insurance received more opioids. Cumulative perioperative opioid exposure has not declined on a national level in recent years and significant variability in opioid exposure exists between hospitals. Future work should seek to identify and utilize opioid-minimizing practices that appear present in some clinical settings. [Table: see text][Figure: see text]