Analytical Validation of Esopredict, an Epigenetic Prognostic Assay for Patients with Barrett's Esophagus.

EsopredictTM is a prognostic assay that risk-stratifies Barrett's esophagus patients to predict future progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). Established based on foundational studies at Johns Hopkins University, a risk algorithm was developed and clinically validated in two independent studies (n = 320). EsopredictTM is currently offered as a clinical test under the Clinical Laboratory Improvement Amendments (CLIA) guidelines. Here we present the analytical validation by repeated testing of FFPE tissues (n = 26 patients), cell lines, and contrived DNA controls to determine assay performance regarding analytical sensitivity (as defined by the limit of detection (LOD)), analytical specificity (as defined by the limit of blank (LOB)), accuracy as determined from the average positive and negative agreement, repeatability, and reproducibility. The LOD for the assay at 1.5% DNA methylation was significantly higher than the LOB, as determined by an unmethylated DNA control (0% methylated DNA). Inter- and intra-assay average positive agreement (APA) were 88% and 94%, respectively, while average negative agreement (ANA) values were 90% and 94%, respectively. Average inter- and intra-assay precision were <9% and <5% coefficient of variation (CV), respectively. These results confirm that EsopredictTM is a highly reproducible, sensitive, and specific risk categorization assay for the prediction of progression to HGD or EAC within 5 years.

The utility of a genetic progression risk test for Barrett esophagus.

This study sought to characterize the utility of a gene methylation-based biomarker test that has been validated to predict progression towards esophageal adenocarcinoma. Barrett esophagus (BE) is a precursor condition for esophageal adenocarcinoma (EAC) with somewhat variable approaches among gastroenterologists toward managing neoplastic progression risk. Capsulomics has developed a validated multigene DNA methylation-based biomarker assay performed on BE biopsies designed to address this variability by classifying BE patients into progression risk groups. In the current study, a survey was administered to practicing gastroenterologists in order to assess the potential impact of this assay on clinical practice. In this context, 89% (95% Cl: 85.4-92.6%) of surveyed physicians felt strongly that the multigene Barrett Esophagus test helped resolve uncertainties and optimize care of patients with BE by impacting their decisions on surveillance intervals and use of active treatments, such as ablation. The assay significantly impacted surveillance intervals for both high-risk (22.0 no assay vs 12.3 months with assay; P = 1.7E-8) and low-risk (7.9 no assay vs 11.4 months with assay, P = 8.8E-4) stratified case results. Finally, the assay also significantly impacted decisions to pursue active ablation treatments in both high-risk (5% recommending ablation without assay vs 42% with assay; P = 3.7E-11) and low-risk (42% recommending ablation without assay vs 29% with assay; P = .049) stratified case results. Results demonstrated a strong effect of the assay on clinical decision making, even in conjunction with established clinical guidelines.

Assessment of Ergonomic Strain and Positioning During Bronchoscopic Procedures: A Feasibility Study.

BACKGROUND: Poor ergonomics place health care workers at risk for work-related overuse injuries. Repetitive and prolonged hand maneuvers, such as those performed during endoscopic procedures, may lead to musculoskeletal complaints and work-related injuries. However, the prevalence of health care-related work injuries among physicians is thought to be underreported and there is a paucity of literature investigating the impact of ergonomic strain on bronchoscopy. We designed a feasibility study to explore the differences in ergonomic strain and muscle activity of bronchoscopists. MATERIALS AND METHODS: A prospective study of bronchoscopic procedures was performed in a simulated environment. Preselected target areas were identified and airway sampling was performed with real-time ergonomic assessment utilizing electromyogram (EMG), grip strength, and musculoskeletal use and motion analysis. RESULTS: Procedural data was obtained for all procedures (78 bronchoscopies by 13 subjects) for both ergonomic and EMG scores. Experienced bronchoscopists demonstrated less EMG burden (P=0.007) and improved ergonomic positioning (P=0.007) during bronchoscopy when compared with less experienced bronchoscopists. Procedures performed with rotational-head bronchoscopes trended toward improved ergonomics (P=0.15) and lower EMG scores (P=0.88). A significant improvement in ergonomic scores was seen with the rotational-head bronchoscope when targeting the left upper lobe (P=0.036). CONCLUSION: Poor ergonomic positioning and excessive muscle strain appear present within bronchoscopy procedures but may be improved in those with more bronchoscopy experience. Technological advances in bronchoscope design may also have the potential to improve procedural ergonomics. Additional prospective studies are warranted to define the long-term impact on bronchoscopic ergonomics.

Impact of Video Game Cross-Training on Learning Bronchoscopy. A Pilot Randomized Controlled Trial.

Background: Video game playing requires many of the same skill sets as medical procedures such as bronchoscopy. These include visual-spatial awareness, rapid decision making, and psychomotor skills. The role of video game cross-training on learning bronchoscopy is unknown. Objective: We studied the association of baseline video gaming experience with, and the impact of short-term video game playing on, visual-spatial awareness and acquisition of basic bronchoscopic skills among medical trainees. Methods: Bronchoscopy-naive medical trainees underwent formal didactic and hands-on instruction on basic bronchoscopy, along with a baseline assessment measuring bronchoscopic and visual-spatial skills. Half of the subjects were subsequently randomized to playing a videogame (Rocket League) for 8 weeks. All participants returned at 4 weeks for a refresher course and at 8 weeks for a final assessment. Results: Thirty subjects completed the study, 16 of them in the intervention arm who all met the minimum video game playing time requirement. At baseline, video game players had significantly lower airway collision rates (6.82 collisions/min vs. 11.64 collisions/min; P = 0.02) and higher scores on the Purdue Visual Spatial Test: Visualization of Rotations test (27.5 vs. 23.54; P = 0.04). At completion, the intervention group had no significant differences in airway collisions, bronchoscopy time, or Bronchoscopy Skills and Tasks Assessment Tool scores. There was moderate correlation between airway collision rate and mean Purdue Visual Spatial Test: Visualization of Rotations score (Spearman's rho, -0.59; P < 0.001). Conclusion: At baseline, learners with former video game-playing experience have higher visual-spatial awareness and fewer airway collisions. The impact of video game playing as an aid to simulation-based bronchoscopic education is uncertain.