Testing a Cloud-Based Model for Active Surveillance of Medical Devices with Analyses of Coronary Stent Safety Using the Data Extraction and Longitudinal Trend Analysis (DELTA) System.

Objective: To demonstrate the use of the Data Extraction and Longitudinal Trend Analysis (DELTA) system in the National Evaluation System for health Technology's (NEST) medical device surveillance cloud environment by analyzing coronary stent safety using real world clinical data and comparing results to clinical trial findings. Design and Setting: Electronic health record (EHR) data from two health systems, the Social Security Death Master File, and device databases were ingested into the NEST cloud, and safety analyses of two stents were performed using DELTA. Participants and Interventions: This is an observational study of patients receiving zotarolimus drug-eluting coronary stents (ZES) or everolimus eluting coronary stents (EES) between July 1, 2015 and December 31, 2017. Results: After exclusions, 3334 patients receiving EES and 1002 receiving ZES were available for study. Analysis using inverse probability weighting showed no significant difference in one-year mortality or major adverse cardiac events (MACE) for EES compared to ZES [Mortality Odds Ratio 0.94 (95% CI 0.81-1.175); p = 0.780] [MACE Odds Ratio 1.04 (95% CI 0.92-1.16; p = 0.551]). Analysis using propensity matching showed no significant difference in EES one-year mortality (547 of 992 alive and available after censoring) compared to ZES (546 of 992) [Log-Rank statistic 0.3348 (p = 0.563)]. Conclusion: Automated cloud-based medical device safety surveillance using EHR data is feasible and was efficiently performed using DELTA. No statistically significant differences in 1-year safety outcomes between ZES and EES were identified using two statistical approaches, consistent with randomized trial findings.

Evaluation of intervertebral body implant performance using active surveillance of electronic health records.

Objectives: To assess the feasibility of using electronic health record (EHR) derived clinical data within an active surveillance setting to evaluate the safety of a novel intervertebral body implant (IVBI) stabilization device. Design: Retrospective, longitudinal observational cohort study comparing clinical outcomes for patients seen through 1 year following spinal fusion surgery. Setting: Lahey Health network, which includes academic tertiary hospitals, outpatient clinics, and independent provider offices in the New England region of the USA. Participants: All spine surgery patients aged 18 or older who underwent thoracic or lumbar spinal arthrodesis surgeries were included. Main outcome measures: The clinical outcomes of patients treated with the CONCORDE Bullet (CB) interbody spine system (DePuy) between April 2015 and December 2018 were compared with those patients receiving alternative spine stabilization interbody device implants. The primary endpoint was reoperation rate at 1 year, with secondary endpoints including the requirement for blood transfusion during index hospitalization, 1 year rate of any cause hospitalization, 1 year rate of surgical site infection, and mortality at 1 year. Results: Among the 606 patients undergoing thoracic or lumbar spinal fusion surgery during the study period, 136 received only the CB. In comparison with patients who did not receive the CB, no significant differences were found in the rate of reoperation at 1 year or the rates of secondary safety outcomes. Conclusions: Data derived from the EHR can be successfully leveraged to assess the safety of IVBI devices, in this case demonstrating no significant differences in the rates of risk-adjusted safety endpoints between patients undergoing spinal surgery with the CB as compared with alternative spinal implants.

Preoperative MRI PI-RADS scores are associated with prostate cancer upstaging on surgical pathology.

INTRODUCTION: Prostate Imaging Reporting and Data System (PI-RADS) scores can help identify clinically significant prostate cancer and improve patient selection for prostate biopsies. However, the role of PI-RADS scores in patients already diagnosed with prostate cancer remains unclear. The purpose of this study was to evaluate the association of PI-RADS scores with prostate cancer upstaging. Upstaging on final pathology harbors a higher risk for biochemical recurrence with important implications for additional treatments, morbidity, and mortality. METHODS: All patients from a single high-volume institution who underwent a prostate multiparametric magnetic resonance imaging and radical prostatectomy between 2016 and 2020 were included in this retrospective analysis. Univariable and multivariable analyses were conducted to investigate potential associations with upstaging events, defined by pT3, pT4, or N1 on final pathology. A logistic regression model was constructed for the prediction of upstaging events based on PI-RADS score, prostate-specific antigen density (PSA-D), and biopsy Gleason grade groups. We built receiver operative characteristic (ROC) curves to measure the area under the curve of different predictive models. RESULTS: Two hundred and ninety-four patients were included in the final analysis. Upstaging events occurred in 137 (46.5%) of patients. On univariable analysis, patients who were upstaged on final pathology had significantly higher PI-RADS scores (odds ratio [OR] 2.34 95% confidence interval [CI] 1.64-3.40, p < 0.001) but similar PSA-D (OR 2.70 95% 0.94-8.43, p = 0.188) compared with patients who remained pT1 or pT2 on final pathology. On multivariable analysis, PI-RADS remained independently significantly associated with upstaging, suggesting it is an independent risk predictor for upstaging. Lymph node metastasis only occurred in patients with PI-RADS 4 or 5 lesions (n = 15). Our model using PSA-D, biopsy Gleason grade, and PI-RADS had a predictive AUC of 0.69 for upstaging events, an improvement from 0.59 using biopsy Gleason grade alone. CONCLUSION: PI-RADS scores are independent predictors for upstaging events and may play an important role in forecasting biochemical recurrence and lymph node metastasis. Modern nomograms should be updated to include PI-RADS to predict lymph node metastases and the likelihood of biochemical recurrence more accurately.

OrbId: Origin-based identification of microRNA targets.

MicroRNAs coordinate networks of mRNAs, but predicting specific sites of interactions is complicated by the very few bases of complementarity needed for regulation. Although efforts to characterize the specific requirements for microRNA (miR) regulation have made some advances, no general model of target recognition has been widely accepted. In this work, we describe an entirely novel approach to miR target identification. The genomic events responsible for the creation of individual miR loci have now been described with many miRs now known to have been initially formed from transposable element (TE) sequences. In light of this, we propose that limiting miR target searches to transcripts containing a miR's progenitor TE can facilitate accurate target identification. In this report we outline the methodology behind OrbId (Origin-based identification of microRNA targets). In stark contrast to the principal miR target algorithms (which rely heavily on target site conservation across species and are therefore most effective at predicting targets for older miRs), we find OrbId is particularly efficacious at predicting the mRNA targets of miRs formed more recently in evolutionary time. After defining the TE origins of > 200 human miRs, OrbId successfully generated likely target sets for 191 predominately primate-specific human miR loci. While only a handful of the loci examined were well enough conserved to have been previously evaluated by existing algorithms, we find ~80% of the targets for the oldest miR (miR-28) in our analysis contained within the principal Diana and TargetScan prediction sets. More importantly, four of the 15 OrbId miR-28 putative targets have been previously verified experimentally. In light of OrbId proving best-suited for predicting targets for more recently formed miRs, we suggest OrbId makes a logical complement to existing, conservation based, miR target algorithms.