Temporal Changes in Mortality After Transcatheter and Surgical Aortic Valve Replacement: Retrospective Analysis of US Medicare Patients (2012–2019)

BACKGROUND: The treatment of aortic stenosis is evolving rapidly. Pace of change in the care of patients undergoing transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) differs. We sought to determine differences in temporal changes in 30‐day mortality, 30‐day readmission, and length of stay after TAVR and SAVR. METHODS AND RESULTS: We conducted a retrospective cohort study of patients treated in the United States between 2012 and 2019 using data from the Medicare Data Set Analytic File 100% Fee for Service database. We included consecutive patients enrolled in Medicare Parts A and B and aged ≥65 years who had SAVR or transfemoral TAVR. We defined 3 study cohorts, including all SAVR, isolated SAVR (without concomitant procedures), and elective isolated SAVR and TAVR. The primary end point was 30‐day mortality; secondary end points were 30‐day readmission and length of stay. Statistical models controlled for patient demographics, frailty measured by the Hospital Frailty Risk Score, and comorbidities measured by the Elixhauser Comorbidity Index (ECI). Cox proportional hazard models were developed with TAVR versus SAVR as the main covariates with a 2‐way interaction term with index year. We repeated these analyses restricted to full aortic valve replacement hospitals offering both SAVR and TAVR. The main study cohort included 245 269 patients with SAVR and 188 580 patients with TAVR, with mean±SD ages 74.3±6.0 years and 80.7±6.9 years, respectively, and 36.5% and 46.2% female patients, respectively. Patients with TAVR had higher ECI scores (6.4±3.6 versus 4.4±3) and were more frail (55.4% versus 33.5%). Total aortic valve replacement volumes increased 61% during the 7‐year span; TAVR volumes surpassed SAVR in 2017. The magnitude of mortality benefit associated with TAVR increased until 2016 in the main cohort (2012: hazard ratio [HR], 0.76 [95% CI, 0.67–0.86]; 2016: HR, 0.39 [95% CI, 0.36–0.43]); although TAVR continued to have lower mortality rates from 2017 to 2019, the magnitude of benefit over SAVR was attenuated. A similar pattern was seen with readmission, with a lower risk of readmission from 2012 to 2016 for patients with TAVR (2012: HR, 0.68 [95% CI, 0.63–0.73]; 2016: HR, 0.43 [95% CI, 0.41–0.45]) followed by a lesser difference from 2017 to 2019. Year over year, TAVR was associated with increasingly shorter lengths of stay compared with SAVR (2012: HR, 1.91 [95% CI, 1.84–1.98]; 2019: HR, 5.34 [95% CI, 5.22–5.45]). These results were consistent in full aortic valve replacement hospitals. CONCLUSIONS: The rate of improvement in TAVR outpaced SAVR until 2016, with the recent presence of U‐shaped phenomena suggesting a narrowing gap between outcomes. Future longitudinal research is needed to determine the long‐term implications of lowering risk profiles across treatment options to guide case selection and clinical care

Temperature Affects the Tripartite Interactions between Bacteriophage WO, Wolbachia, and Cytoplasmic Incompatibility

Wolbachia infections are a model for understanding intracellular, bacterial symbioses. While the symbiosis is often studied from a binary perspective of host and bacteria, it is increasingly apparent that additional trophic levels can influence the symbiosis. For example, Wolbachia in arthropods harbor a widespread temperate bacteriophage, termed WO, that forms virions and rampantly transfers between coinfections. Here we test the hypothesis that temperatures at the extreme edges of an insect's habitable range alter bacteriophage WO inducibility and in turn, Wolbachia densities and the penetrance of cytoplasmic incompatibility. We report four key findings using the model wasp, Nasonia vitripennis: First, both cold treatment at 18 C and heat treatment at 30 C reduce Wolbachia densities by as much as 74% relative to wasps reared at 25 C. Second, in all cases where Wolbachia densities decline due to temperature changes, phage WO densities increase and inversely associate with Wolbachia densities. Heat has a marked effect on phage WO, yielding phage densities that are 552% higher than the room temperature control. Third, there is a significant affect of insect family on phage WO and endoysmbiont densities. Fourth, at extreme temperatures, there was a temperature-mediated adjustment to the density threshold at which Wolbachia cause complete cytoplasmic incompatibility. Taken together, these results demonstrate that temperature simultaneously affects phage WO densities, endosymbiont densities, and the penetrance of cytoplasmic incompatibility. While temperature shock enhances bacteriophage inducibility and the ensuing bacterial mortality in a wide range of medically and industrially-important bacteria, this is the first investigation of the associations in an obligate intracellular bacteria. Implications to a SOS global sensing feedback mechanism in Wolbachia are discussed

Multipersona Hypovisors: Securing Mobile Devices through High-Performance Light-Weight Subsystem Isolation

Funded by Naval Postgraduate SchoolWe propose and detail a system called multipersona Hypovisors for providing light-weight isolation for enhancing security on Multipersona mobile devices, particularly with respect to the current memory constraints of these devices. Multipersona Hypovisors leverage Linux kernel cGroups and namespaces to establish independent process container, al-lowing isolation of the Multipersona process tree from other simultaneous instances of Multipersona and the hypovisor which is an underlying Angstrom-based embedded Linux distributions designed to add additional security to the system. The system incorporates a wide range of data integrity tools in the embedded hypovisor, and an SE Linux-enabled kernel for mandatory access control and integrity tools for transparent auditing of running Multipersona instances. A prototype is presented which uses integrity tools external to the Multipersona container to audit it for malicious activity, and also has the ability to support a multipersona environment with multiple encrypted personas existing individually or simultaneously on the device. Two versions are demonstrated, one which allows cold-swapping of personas for high-assurance scenarios and also one that supports hot-swapping. Analysis shows that the hypovisor has a 40-50 MB impact on the overall memory footprint for the system.Naval Postgraduate School under contract N00244-11-P-2026L-3 Communications National Security Solutions CenterN00244-11-P-202

Limited Access to Aortic Valve Procedures in Socioeconomically Disadvantaged Areas

Background To explore how differences in local socioeconomic deprivation impact access to aortic valve procedures and the treatment of aortic valve disease, in comparison to other open and minimally invasive surgical procedures. Methods and Results Procedure volume data were obtained from the Healthcare Cost and Utilization Project from 18 states from 2016 to 2019 and merged with area deprivation index data, an index of zip code‐level socioeconomic distress. We estimate the relationship between local deprivation ranking and differences in volumes of aortic valve replacement, which include transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR), versus coronary artery bypass graft surgery and laparoscopic colectomy (LC). All regressions control for state and year fixed effects and an array of zip code‐level characteristics. TAVR procedures have increased over time across all zip codes. The rate of increase is negatively correlated with deprivation ranking, regardless of the higher share of hospitalizations per population in high deprivation areas. Distributional analysis further supports these findings, showing that lower area deprivation index areas account for a disproportionately large share of SAVR, TAVR, and LC procedures in our sample relative to their share of all hospitalizations in our sample. By comparison, the cumulative distribution of coronary artery bypass graft procedures was nearly identical to that of total hospitalizations, suggesting that this procedure is equitably distributed. Regressions show high area deprivation index areas have lower prevalence of SAVR (β=−15.1%, [95% CI, −26.8 to −3.5]), TAVR (β=−9.1%, [95% CI, −18.0 to −0.2]), and LC (β=−19.9%, [95% CI, −35.4 to −4.4]), with no statistical difference in the prevalence of coronary artery bypass graft (β=−2.5%, [95% CI, −12.7 to 7.6]), a widespread and commonly performed procedure. In the population aged ≥80 years, results show high area deprivation index areas have a lower prevalence of TAVR (β=−11.9%, [95% CI, −18.7 to −5.2]) but not SAVR (β=−0.8%, [95% CI, 8.1 to 6.3]), LC (β=−3.5%, [95% CI, −13.4 to −6.4]), or coronary artery bypass graft (β=5.2%, [95% CI, −1.1 to 1.1]). Conclusions People living in high deprivation areas have less access to life‐saving technologies, such as SAVR, and even moreso to device‐intensive minimally invasive procedures such as TAVR and LC