Comparison of Unibody and Non-Unibody Endografts for Abdominal Aortic Aneurysm Repair in Medicare Beneficiaries: The SAFE-AAA Study.

BACKGROUND: Concerns have been raised about the long-term performance of aortic stent grafts for the treatment of abdominal aortic aneurysms, in particular, unibody stent grafts (eg, Endologix AFX AAA stent grafts). Only limited data sets are available to evaluate the long-term risks related to these devices. The SAFE-AAA Study (Comparison of Unibody and Non-Unibody Endografts for Abdominal Aortic Aneurysm Repair in Medicare Beneficiaries Study) was designed with the Food and Drug Administration to provide a longitudinal assessment of the safety of unibody aortic stent grafts among Medicare beneficiaries. METHODS: The SAFE-AAA Study was a prespecified, retrospective cohort study evaluating whether unibody aortic stent grafts are noninferior to non-unibody aortic stent grafts with respect to the composite primary outcome of aortic reintervention, rupture, and mortality. Procedures were evaluated from August 1, 2011, through December 31, 2017. The primary end point was evaluated through December 31, 2019. Inverse probability weighting was used to account for imbalances in observed characteristics. Sensitivity analyses were used to evaluate the effect of unmeasured confounding, including assessment of the falsification end points heart failure, stroke, and pneumonia. A prespecified subgroup included patients treated from February 22, 2016, through December 31, 2017, corresponding to the market release of the most contemporary unibody aortic stent grafts (Endologix AFX2 AAA stent graft). RESULTS: Of 87 163 patients who underwent aortic stent grafting at 2146 US hospitals, 11 903 (13.7%) received a unibody device. The average age of the total cohort was 77.0±6.7 years, 21.1% were female, 93.5% were White, 90.8% had hypertension, and 35.8% used tobacco. The primary end point occurred in 73.4% of unibody device-treated patients versus 65.0% of non-unibody device-treated patients (hazard ratio, 1.19 [95% CI, 1.15-1.22]; noninferior P value of 1.00; median follow-up, 3.4 years). Falsification end points were negligibly different between groups. In the subgroup treated with contemporary unibody aortic stent grafts, the cumulative incidence of the primary end point occurred in 37.5% of unibody device-treated patients and 32.7% of non-unibody device-treated patients (hazard ratio, 1.06 [95% CI, 0.98-1.14]). CONCLUSIONS: In the SAFE-AAA Study, unibody aortic stent grafts failed to meet noninferiority compared with non-unibody aortic stent grafts with respect to aortic reintervention, rupture, and mortality. These data support the urgency of instituting a prospective longitudinal surveillance program for monitoring safety events related to aortic stent grafts.

Disparities in Cardiovascular Mortality Between Black and White Adults in the United States, 1999 to 2019.

BACKGROUND: Black adults experience a disproportionately higher burden of cardiovascular risk factors and disease in comparison with White adults in the United States. Less is known about how sex-based disparities in cardiovascular mortality between these groups have changed on a national scale over the past 20 years, particularly across geographic determinants of health and residential racial segregation. METHODS: We used CDC WONDER (Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research) to identify Black and White adults age ≥25 years in the United States from 1999 to 2019. We calculated annual age-adjusted cardiovascular mortality rates (per 100 000) for Black and White women and men, as well as absolute rate differences and rate ratios to compare the mortality gap between these groups. We also examined patterns by US census region, rural versus urban residence, and degree of neighborhood segregation. RESULTS: From 1999 to 2019, age-adjusted mortality rates declined overall for both Black and White adults. There was a decline in age-adjusted cardiovascular mortality among Black (602.1 to 351.8 per 100 000 population) and White women (447.0 to 267.5), and the absolute rate difference (ARD) between these groups decreased over time (1999: ARD, 155.1 [95% CI, 149.9-160.3]; 2019: ARD, 84.3 [95% CI, 81.2-87.4]). These patterns were similar for Black (824.1 to 526.3 per 100 000) and White men (637.5 to 396.0; 1999: ARD, 186.6 [95% CI, 178.6-194.6]; 2019: ARD, 130.3 [95% CI, 125.6-135.0]). Despite this progress, cardiovascular mortality in 2019 was higher for Black women (rate ratio, 1.32 [95% CI, 1.30-1.33])- especially in the younger (age <65 years) subgroup (rate ratio, 2.28 [95% CI, 2.23-2.32])-as well as for Black men (rate ratio, 1.33 [95% CI, 1.32-1.34]), compared with their respective White counterparts. There was regional variation in cardiovascular mortality patterns, and the Black-White gap differed across rural and urban areas. Cardiovascular mortality rates among Black women and men were consistently higher in communities with high levels of racial segregation compared with those with low to moderate levels. CONCLUSIONS: During the past 2 decades, age-adjusted cardiovascular mortality declined significantly for Black and White adults in the United States, as did the absolute difference in death rates between these groups. Despite this progress, Black women and men continue to experience higher cardiovascular mortality rates than their White counterparts.

Days at home after transcatheter or surgical aortic valve replacement in high-risk patients.

BACKGROUND: Days at home (DAH) quantifies time spent at home after a medical event but has not been fully evaluated for TAVR. We sought to compare 1- and 5-year DAH (DAH365, DAH1825) among high-risk patients participating in a randomized trial of transcatheter aortic valve replacement (TAVR) with a self-expanding bioprosthesis versus surgical aortic valve replacement (SAVR). METHODS: We linked data from the U.S. CoreValve High Risk Trial to Medicare Fee-for-Service claims in 456 patients with 450 (234 TAVR/216 SAVR) and 427 (222 TAVR/205 SAVR) analyzed at 1 and 5 years. DAH was calculated as the number of days alive and spent outside of a hospital, skilled nursing facility, rehabilitation, long-term acute care hospital, emergency department, or observation stay. RESULTS: Mean DAH365 was higher in patients who underwent TAVR compared with SAVR (295.1 ± 106.9 vs 267.8 ± 122.3, difference in days 27.2 [95% CI 6.0, 48.5], P = .01). Compared with SAVR, TAVR patients had a shorter index length of stay (LOS) (7.4 ± 4.5 vs 12.5 ± 9.0, difference in days -5.1 [-6.5, -3.8], P < .001). The largest contributions to decreased DAH365 were mortality days and total facility days after discharge from the index hospitalization (mortality days-TAVR: 34.7 ± 93.1 vs SAVR: 48.0 ± 108.8, difference in days -13.3 [95% CI -32.1, 5.5], P = .17; total facility days-TAVR: 27.9 ± 47.4 vs SAVR: 36.7 ± 48.9, difference in days -8.8 [95% CI -17.8, 0.1], P = .05). Mean DAH1825 was numerically but not statistically significantly higher in TAVR (TAVR: 1154.2 ± 659.0 vs SAVR: 1067.6 ± 697.3, difference in days 86.6 [95% CI -42.3, 215.6], P = .19). Landmark analysis showed no difference in DAH from years 1 to 5 (TAVR: 1040.4 ± 477.5 vs SAVR: 1022.9 ± 489.3, P = .74). CONCLUSIONS: In the U.S. CoreValve High Risk Trial linked to Medicare, high-risk patients undergoing TAVR spend an average of 27 additional DAH compared with SAVR in the first year after the procedure due to a shorter index LOS and the additive effect of fewer but nonsignificantly different mortality and total facility days after discharge from the index hospitalization compared with SAVR. After the first year, both groups spend a similar number of DAH. These results describe the postprocedural course of high-risk patients from a patient-centered perspective, which may guide expectations regarding longitudinal health care needs and inform shared decision-making.

Longitudinal outcomes following peripheral vascular intervention among older persons living with HIV.

BACKGROUND: Persons living with human immunodeficiency virus (HIV, PLWH) have an increased risk of peripheral artery disease (PAD) in comparison to the general population. However, a gap remains in understanding optimal management for this condition. This study assesses longitudinal outcomes associated with peripheral endovascular intervention (PVI) for PAD among PLWH. METHODS: All Medicare fee-for-service patients undergoing femoropopliteal artery PVI between April 1, 2015 and December 31, 2018 were identified and stratified by HIV serostatus. The primary outcome was major adverse limb events (MALE), defined as major amputation or arterial embolism/thrombosis following an index procedure. The subdistribution hazard was used to evaluate the association between HIV serostatus and MALE, accounting for the competing risk of death. Results were adjusted for sociodemographics and major comorbidities. RESULTS: Of 168,553 patients who underwent PVI, 357 (0.21%) were PLWH. The average age was 77.0 ± 7.6 years; 80.3% had hypertension, 70.3% had hyperlipidemia, and 24.6% had tobacco use disorder. Compared to those without HIV, PLWH were younger and had a higher burden of cardiovascular risk factors. MALE were substantially more frequent among PLWH, with a cumulative incidence of 24.6%, compared to 14.5% among those without HIV. The adjusted subdistribution hazard ratio was 1.26 (95% CI 1.00-1.58, p = 0.05). The use of guideline-directed statin therapy was low in both groups in the 90 days following revascularization (57.9% in PLWH vs 58.1% in those without HIV, p = 0.95). CONCLUSION: Among US Medicare beneficiaries, PLWH had poorer long-term outcomes following PVI. Greater attention to the management of symptomatic PAD is warranted for the HIV population, particularly following revascularization.

Comparative performance of distinct frailty measures among patients undergoing percutaneous left atrial appendage closure.

AIMS: Frailty is associated with increased morbidity and mortality in patients undergoing left atrial appendage closure (LAAC). This study aimed to compare the performance of two claims-based frailty measures in predicting adverse outcomes following LAAC. METHODS: We identified patients 66 years and older who underwent LAAC between October 1, 2016, and December 31, 2019, in Medicare fee-for-service claims. Frailty was assessed using the previously validated Hospital Frailty Risk Score (HFRS) and Kim Claims-based Frailty Index (CFI). Patients were identified as frail based on HFRS ≥5 and CFI ≥0.25. RESULTS: Of the 21,787 patients who underwent LAAC, frailty was identified in 45.6% by HFRS and 15.4% by CFI. There was modest agreement between the two frailty measures (kappa 0.25, Pearson's correlation 0.62). After adjusting for age, sex, and comorbidities, frailty was associated with higher risk of 30-day mortality, 1-year mortality, 30-day readmission, long hospital stay, and reduced days at home (p < .01 for all) regardless of the frailty measure used. The addition of frailty to standard comorbidities significantly improved model performance to predict 1-year mortality, long hospital stay, and reduced days at home (Delong p-value < .001). CONCLUSION: Despite significant variation in frailty detection and modest agreement between the two frailty measures, frailty status remained highly predictive of mortality, readmissions, long hospital stay, and reduced days at home among patients undergoing LAAC. Measuring frailty in clinical practice, regardless of the method used, may provide prognostic information useful for patients being considered for LAAC, and may inform shared decision-making in this population.

Parkinson's disease patients with freezing of gait have more severe voice impairment than non-freezers during "ON state".

BACKGROUND: Speech disorders and freezing of gait (FOG) in Parkinson's disease (PD) may have some common pathological mechanisms. The purpose of this study was to compare the acoustic parameters of PD patients with dopamine-responsive FOG (PD-FOG) and without FOG (PD-nFOG) during "ON state" and explore the ability of "ON state" voice features in distinguishing PD-FOG from PD-nFOG. METHODS: A total of 120 subjects, including 40 PD patients with dopamine-responsive FOG, 40 PD-nFOG, and 40 healthy controls (HCs) were recruited. All subjects underwent neuropsychological tests. Speech samples were recorded through the sustained vowel pronunciation tasks during the "ON state" and then analyzed by the Praat software. A set of 27 voice features was extracted from each sample for comparison. Support vector machine (SVM) was used to build mathematical models to classify PD-FOG and PD-nFOG. RESULTS: Compared with PD-nFOG, the jitter, the standard deviation of fundamental frequency (F0SD), the standard deviation of pulse period (pulse period SD) and the noise-homophonic-ratio (NHR) were increased, and the maximum phonation time (MPT) was decreased in PD-FOG. The above voice features were correlated with the freezing of gait questionnaire (FOGQ). The average accuracy, specificity, and sensitivity of SVM models based on 27 voice features for classifying PD-FOG and PD-nFOG were 73.57%, 75.71%, and 71.43%, respectively. CONCLUSIONS: PD-FOG have more severe voice impairment than PD-nFOG during "ON state".

Medicare's Value-Based Purchasing And 30-Day Mortality At Hospitals Caring For High Proportions Of Black Adults.

The care of Black adults is highly concentrated at a limited set of US hospitals that often have limited resources. In 2011, the Medicare Hospital Value-Based Purchasing (VBP) Program began financially penalizing or rewarding hospitals based on thirty-day mortality rates for target conditions (myocardial infarction, heart failure, and pneumonia). Because the VBP Program has disproportionately penalized resource-constrained hospitals caring for high proportions of Black adults since its implementation in 2011, clinicians, health system leaders, and policy makers have worried that the program may unintentionally be widening racial disparities in health outcomes. Using Medicare claims for beneficiaries ages sixty-five and older who were hospitalized for three target conditions at 2,908 US hospitals participating in the VBP Program, we found that thirty-day mortality rates were consistently higher for two of three conditions at hospitals with high proportions of Black adults compared with other hospitals. There was no evidence of a differential change in thirty-day mortality among all Medicare beneficiaries with targeted conditions at high-proportion Black hospitals versus other hospitals seven years after the implementation of the VBP Program. However, gaps in mortality between these sites did widen in the subgroup of Black adults with pneumonia. These findings highlight that important concerns remain about the regressive nature and equity implications of national pay-for-performance programs.

Community Socioeconomic Status, Acute Cardiovascular Hospitalizations, and Mortality in Medicare, 2003 to 2019.

BACKGROUND: Socioeconomically disadvantaged communities in the United States disproportionately experience poor cardiovascular outcomes. Little is known about how hospitalizations and mortality for acute cardiovascular conditions have changed among Medicare beneficiaries in socioeconomically disadvantaged and nondisadvantaged communities over the past 2 decades. METHODS: Medicare files were linked with the Centers for Disease Control and Prevention's social vulnerability index to examine age-sex standardized hospitalizations for myocardial infarction, heart failure, ischemic stroke, and pulmonary embolism among Medicare fee-for-service beneficiaries ≥65 years of age residing in socioeconomically disadvantaged communities (highest social vulnerability index quintile nationally) and nondisadvantaged communities (all other quintiles) from 2003 to 2019, as well as risk-adjusted 30-day mortality among hospitalized beneficiaries. RESULTS: A total of 10 942 483 Medicare beneficiaries ≥65 years of age were hospitalized for myocardial infarction, heart failure, stroke, or pulmonary embolism (mean age, 79.2 [SD, 8.7] years; 53.9% female). Although age-sex standardized myocardial infarction hospitalizations declined in socioeconomically disadvantaged (990-650 per 100 000) and nondisadvantaged communities (950-570 per 100 000) from 2003 to 2019, the gap in hospitalizations between these groups significantly widened (adjusted odds ratio 2003, 1.03 [95% CI, 1.02-1.04]; adjusted odds ratio 2019, 1.14 [95% CI, 1.13-1.16]). There was a similar decline in hospitalizations for heart failure in socioeconomically disadvantaged (2063-1559 per 100 000) and nondisadvantaged communities (1767-1385 per 100 000), as well as for ischemic stroke, but the relative gap did not change for both conditions. In contrast, pulmonary embolism hospitalizations increased in both disadvantaged (146-184 per 100 000) and nondisadvantaged communities (153-184 per 100 000). By 2019, risk-adjusted 30-day mortality was similar between hospitalized beneficiaries from socioeconomically disadvantaged and nondisadvantaged communities for myocardial infarction, heart failure, and ischemic stroke but was higher for pulmonary embolism (odds ratio, 1.10 [95% CI, 1.01-1.20]). CONCLUSIONS: Over the past 2 decades, hospitalizations for most acute cardiovascular conditions decreased in both socioeconomically disadvantaged and nondisadvantaged communities, although significant disparities remain, while 30-day mortality is now similar across most conditions.

Synergistic and antibiofilm activity of DNase I and glucose oxidase loaded chitosan nanoparticles against dual-species biofilms of Listeria monocytogenes and Salmonella.

Salmonella and Listeria monocytogenes are two of the most common foodborne pathogens in the food industry. They form dual-species biofilms, which have a higher sensitivity to antimicrobial treatment and a greater microbial adhesion. In this experiment, we loaded DNase I and glucose oxidase (GOX) on chitosan nanoparticles (CSNPs) to explore their inhibitory effects on and disruption of dual-species biofilms of Salmonella enterica and L. monocytogenes. Transmission electron microscopy (TEM) showed that CSNP-DNase-GOX and CSNPs were spherical in shape. CSNP-DNase-GOX was shifted and altered compared to the infrared peaks of CSNPs. CSNPs loaded with DNase I and GOX showed an increase in the particle size and an alteration in the polydispersity index (PDI) and the zeta potential. Compared to free DNase I or GOX, DNase I and GOX loaded on CSNPs had higher stability at different temperatures. CSNP-DNase-GOX was more effective in inhibiting dual-species biofilms than CSNP-GOX. Scanning electron microscopy (SEM) and fluorescence microscopy were used to observe the structure of the biofilm, which further illustrated that CSNP-DNase-GOX disrupted the dual-species biofilms of S. enterica and L. monocytogenes.

Progression of Frailty and Cardiovascular Outcomes Among Medicare Beneficiaries.

Background: Frailty is associated with adverse cardiovascular outcomes independent of age and comorbidities, yet the independent influence of frailty progression remains uncertain. Methods: Medicare Fee-for-service beneficiaries ≥ 65 years at cohort inception with continuous enrollment from 2003-2015 were included. Frailty trajectory was measured by annualized change in a validated claims-based frailty index (CFI) over a 5-year period. Linear mixed effects models, adjusting for baseline frailty, were used to estimate CFI change over a 5-year period. Survival analysis was used to evaluate associations of frailty progression and future health outcomes (major adverse cardiovascular and cerebrovascular events [MACCE], all-cause death, heart failure, myocardial infarction, ischemic stroke, and days alive at home [DAH] within the following calendar year). Results: 26.4 million unique beneficiaries were included (mean age 75.4 ± 7.0 years, 57% female, 13% non-White). In total, 20% had frailty progression, 66% had no change in frailty, and 14% frailty regression over median follow-up of 2.4 years. Compared to those without a change in CFI, when adjusting for baseline frailty, those with frailty progression had significantly greater risk of incident MACCE (hazard ratio [HR] 2.30, 95% confidence interval [CI] 2.30-2.31), all-cause mortality (HR 1.59, 95% CI 1.58-1.59), acute myocardial infarction (HR 1.78, 95% CI 1.77-1.79), heart failure (HR 2.78, 95% CI 2.77-2.79), and stroke (HR 1.78, 95% CI 1.77-1.79). There was also a graded increase in risk of each outcome with more rapid progression and significantly fewer DAH with the most rapid vs. the slowest progression group (270.4 ± 112.3 vs. 308.6 ± 93.0 days, rate ratio 0.88, 95% CI 0.87-0.88, p < 0.001). Conclusions: In this large, nationwide sample of Medicare beneficiaries, frailty progression, independent of baseline frailty, was associated with fewer DAH and a graded risk of MACCE, all-cause mortality, myocardial infarction, heart failure, and stroke compared to those without progression.

Astilbin inhibited neutrophil extracellular traps in gouty arthritis through suppression of purinergic P2Y6 receptor.

BACKGROUND: Gouty arthritis (GA), a common inflammatory condition triggered by monosodium urate crystal accumulation, often necessitates safer treatment alternatives due to the limitations of current therapies. Astilbin, a flavonoid from Smilax glabra Roxb, has demonstrated potential in traditional Chinese medicine for its anti-inflammatory properties. However, the anti-GA effect and its underlying mechanism have not been fully elucidated. PURPOSE: This study aimed to investigate the therapeutic potential of astilbin in GA, focusing on its effects on neutrophil extracellular traps (NETs), as well as the potential molecular target of GA both in vitro and in vivo. STUDY DESIGN: Firstly, astilbin inhibited the citrullinated histone H3 (Cit h3) protein levels and reduced the NETs formation in neutrophils stimulated by monosodium urate (MSU). Secondly, we wondered the effect of astilbin on migration of neutrophils and dimethyl-sulfoxide (DMSO)-differentiated HL-60 (dHL-60) cells under the stimulation of MSU. Then, the effect of astilbin on suppressing NETs through purinergic P2Y6 receptor (P2Y6R) and Interlukin-8 (IL-8)/ CXC chemokine receptor 2 (CXCR2) pathway was investigated. Also, the relationship between P2Y6R and IL-8/CXCR2 was explored in dHL-60 cells under stimulation of MSU. Finally, we testified the effect of astilbin on reducing NETs in GA through suppressing P2Y6R and then down-regulating IL-8/CXCR2 pathway. METHODS: MSU was used to induce NETs in neutrophils and dHL-60 cells. Real-time formation of NETs and migration of neutrophils were monitored by cell living imaging with or without MSU. Then, the effect of astilbin on NETs formation, P2Y6R and IL-8/CXCR2 pathway were detected by immunofluorescence (IF) and western blotting. P2Y6R knockdown dHL-60 cells were established by small interfering RNA to investigate the association between P2Y6R and IL-8/CXCR2 pathway. Also, plasmid of P2Y6R was used to overexpress P2Y6R in dHL-60 cells, which was employed to explore the role of P2Y6R in astilbin inhibiting NETs. Within the conditions of knockdown and overexpression of P2Y6R, migration and NETs formation were assessed by transmigration assay and IF staining, respectively. In vivo, MSU-induced GA mice model was established to assess the effect of astilbin on inflammation by haematoxylin-eosin and ELISA. Additionally, the effects of astilbin on neutrophils infiltration, NETs, P2Y6R and IL-8/CXCR2 pathway were analyzed by IF, ELISA, immunohistochemistry (IHC) and western blotting. RESULTS: Under MSU stimulation, astilbin significantly suppressed the level of Cit h3 and NETs formation including the fluorescent expressions of Cit h3, neutrophils elastase, myeloperoxidase, and intra/extracellular DNA. Also, results showed that MSU caused NETs release in neutrophils as well as a trend towards recruitment of dHL-60 cells to MSU. Astilbin could markedly decrease expressions of P2Y6R and IL-8/CXCR2 pathway which were upregulated by MSU. By silencing P2Y6R, the expression of IL-8/CXCR2 pathway and migration of dHL-60 cells were inhibited, leading to the suppression of NETs. These findings indicated the upstream role of P2Y6R in the IL-8/CXCR2 pathway. Moreover, overexpression of P2Y6R was evidently inhibited by astilbin, causing a downregulation in IL-8/CXCR2 pathway, migration of dHL-60 cells and NETs formation. These results emphasized that astilbin inhibited the IL-8/CXCR2 pathway primarily through P2Y6R. In vivo, astilbin administration led to marked reductions in ankle swelling, inflammatory infiltration as well as neutrophils infiltration. Expressions of P2Y6R and IL-8/CXCR2 pathway were evidently decreased by astilbin and P2Y6R inhibitor MRS2578 either alone or in combination. Also, astilbin and MRS2578 showed notable effect on reducing MSU-induced NETs formation and IL-8/CXCR2 pathway whether used alone or in combination, parallelly demonstrating that astilbin decreased NETs formation mainly through P2Y6R. CONCLUSION: This study revealed that astilbin suppressed NETs formation via downregulating P2Y6R and subsequently the IL-8/CXCR2 pathway, which evidently mitigated GA induced by MSU. It also highlighted the potential of astilbin as a promising natural therapeutic for GA.

Outcomes of Atrial Fibrillation Ablation Among Older Adults in the United States: A Nationwide Study.

BACKGROUND: Pulmonary vein isolation (PVI) is increasingly recommended as first-line therapy for atrial fibrillation. Recent data suggest growing PVI volumes but rising complication rates, although comprehensive real-world outcomes including both inpatient and outpatient encounters remain unclear. OBJECTIVES: The purpose of this study was to evaluate patient characteristics, population rates, and 30-day outcomes of PVI in a nationwide sample of U.S. adults aged >65 years. METHODS: First-time PVIs were identified among U.S. Medicare fee-for-service beneficiaries using Current Procedural Terminology procedural codes. Comorbidities were ascertained using International Classification of Diseases-10th Revision diagnosis codes associated with each procedural claim. Outcomes included periprocedural complications, all-cause hospitalizations, and mortality at 30 days. RESULTS: From January 2017 through December 2021, a total of 227,133 patients underwent PVI (mean age 72.5 years, 42% women, 92.7% White) with an increasing comorbidity burden over time. PVI volume increased from 83.8 (2017) to 111.6 per 100,000 patient-years (2021), which was driven by outpatient procedures (87.8% of all PVIs). Concurrently, there was a significant decrease in complication rates (3.9% in 2017 vs 3.1% in 2021; P < 0.001) and hospitalizations (8.8% vs 7.0%; P < 0.001), with no significant change in mortality (0.4%; P = 0.08). The most common periprocedural complications were bleeding (1.8%), pericardial effusion (1.4%), and vascular access damage (0.8%). CONCLUSIONS: The use of PVI has steadily increased among older patients in contemporary U.S. clinical practice; yet, cumulative complication and hospitalization rates at 30 days have decreased over time, with stably low rates of short-term mortality despite rising comorbidity burden among treated patients. These data may reassure patients and providers on the safety of PVI as an increasingly common first-line procedure for atrial fibrillation.

Out-of-Pocket Drug Costs for Medicare Beneficiaries With Cardiovascular Risk Factors Under the Inflation Reduction Act.

BACKGROUND: High out-of-pocket prescription drug costs contribute to financial toxicity, medication nonadherence, and adverse cardiovascular (CV) outcomes. Policymakers recently passed the Inflation Reduction Act, which will cap Medicare out-of-pocket drug costs at $2,000/year and expand full low-income subsidies (LIS). It is unclear how these provisions will affect Medicare beneficiaries with CV risk factors and/or conditions. OBJECTIVES: The authors sought to characterize the population of Medicare beneficiaries with CV risk factors/conditions experiencing out-of-pocket prescription drug costs >$2,000/year and estimate their potential savings under the Inflation Reduction Act's spending cap; identify sociodemographic characteristics associated with out-of-pocket costs >$2,000/year; and characterize beneficiaries newly eligible for LIS under the Inflation Reduction Act. METHODS: This was a cross-sectional study of Medicare beneficiaries aged ≥65 years with ≥1 CV risk factor/condition from 2016 to 2019. RESULTS: An annual estimated 34,056,335 ± 855,653 Medicare beneficiaries (mean ± SE) had ≥1 CV risk factor/condition, of whom 1,020,484 ± 77,055 experienced out-of-pocket drug costs >$2,000/year. The likelihood of experiencing out-of-pocket drug costs >$2,000/year was lower among adults ≥75 years vs 65 to 74 years (adjusted OR: 0.67; 95% CI: 0.49-0.93) and for low-income vs higher-income adults. Among beneficiaries currently spending >$2,000/year, estimated median out-of-pocket drug savings would be $855/year and total annual savings $1,723,031,307 ± $91,150,609 under the Inflation Reduction Act. An estimated 1,289,861 beneficiaries would also become newly eligible for LIS. CONCLUSIONS: More than 1 million older adults with CV risk factors and/or conditions spend >$2,000/year out-of-pocket on prescription drugs and will likely benefit from the Inflation Reduction Act's cap, with estimated total out-of-pocket savings of $1.7 billion/year, while another 1.3 million will also become newly eligible for LIS.

Days at Home After Transcatheter Versus Surgical Aortic Valve Replacement in Low-Risk Patients.

BACKGROUND: Days at home (DAH) represents an important patient-oriented outcome that quantifies time spent at home after a medical event; however, this outcome has not been fully evaluated for low-surgical-risk patients undergoing transcatheter aortic valve replacement (TAVR). We sought to compare 1- and 2-year DAH (DAH365 and DAH730) among low-risk patients participating in a randomized trial of TAVR with a self-expanding bioprosthesis versus surgical aortic valve replacement (SAVR). METHODS: Using Medicare-linked data from the Evolut Low Risk trial, we identified 619 patients: 606 (322 TAVR/284 SAVR) and 593 (312 TAVR/281 SAVR) were analyzed at 1 and 2 years, respectively. DAH was calculated as days alive and spent outside a hospital, inpatient rehabilitation, skilled nursing facility, long-term acute care hospital, emergency department, or observation stay. Mean DAH was compared using the t test. RESULTS: The mean (SD) age and female sex were 74.7 (5.1) and 74.3 (4.9) years and 34.6% (115/332) and 30.3% (87/287) in TAVR and SAVR, respectively. Postprocedural discharge to rehabilitation occurred in ≤3.0% (≤10/332) in TAVR and 4.5% (13/287) in SAVR. The mean DAH365 was comparable in TAVR versus SAVR (352.2±45.4 versus 347.8±39.0; difference in days, 4.5 [95% CI, 2.3-11.2]; P=0.20). DAH730 was also comparable in TAVR versus SAVR (701.6±106.0 versus 699.6±94.5; difference in days, 2.0 [-14.1 to 18.2]; P=0.81). Secondary outcomes DAH30 and DAH90 were higher in TAVR (DAH30, 26.0±3.6 versus 20.7±6.4; difference in days, 5.3 [4.5-6.2]; P<0.001; DAH90, 85.1±8.3 versus 78.7±13.6; difference in days, 6.4 [4.6-8.2]; P<0.001). CONCLUSIONS: In the Evolut Low Risk trial linked to Medicare, low-risk patients undergoing TAVR spend a similar number of days at home at 1 and 2 years compared with SAVR. Days spent at home at 30 and 90 days were higher in TAVR. In contrast to higher-risk patients studied in prior work, there is no clear advantage of TAVR versus SAVR for DAH in the first 2 years after AVR in low-surgical-risk patients.

pH-Activated Scallop-Type Nanoenzymes for Oxidative Stress Amplification and Photothermal Enhancement of Antibacterial and Antibiofilm Effect.

Ferric phosphate (FePOs) nanoenzymes can express peroxidase (POD) activity under the dual stimulation of an acidic environment and high H2O2 concentrations. In living organisms, this generates reactive oxygen species (ROS) in sites of lesion infection, and thus FePOs nanoenzymes can act as antimicrobial agents. Here, CeO2 and ZnO2 were immobilized in a scallop-type FePOs nanoenzyme material loaded with a photosensitizer, indocyanine green, to synthesize a multifunctional cascade nanoparticle system (FePOs-CeO2-ZnO2-ICG, FCZI NPs). H2O2 concentrations could be adjusted through the ZnO2 self-activation response to the slightly acidic environment in biofilms, further promoting the release of ROS from the POD-like reaction of FePOs, achieving amplification of oxidative stress, DNA and cell membrane damage, and exploiting the photodynamic/photothermal effects of indocyanine green to enhance the antibiofilm effects. CeO2 can remove redundant ROS by switching from Ce4+ to Ce3+ valence, enhancing its ability to fight chronic inflammation and oxidative stress and thus promoting the regeneration of tissues around infection. By maintaining the redox balance of normal cells, increasing ROS at the infection site, eliminating redundant ROS, and protecting normal tissues from damage, the synthesized system maximizes the elimination of biofilms and treatment at the infection site. Therefore, this work may pave the way for the application of biocompatible nanoenzymes.

White matter hyperintensities burden in the frontal regions is positively correlated to the freezing of gait in Parkinson's disease.

Objective: Previous studies have reported that white matter hyperintensities (WMHs) are associated with freezing of gait (FOG), but it is not clear whether their distribution areas have correlations with FOG in Parkinson's disease (PD) and the potential influencing factors about WMHs. Methods: Two hundred and forty-six patients with PD who underwent brain MRI were included. Participants were divided into PD with FOG (n = 111) and PD without FOG (n = 135) groups. Scheltens score was used to assess the WMHs burden in the areas of deep white matter hyperintensities (DWMHs), periventricular hyperintensities (PVHs), basal ganglia hyperintensities (BGHs), and infratentorial foci of hyperintensities (ITF). Whole brain WMHs volume was evaluated by automatic segmentation. Binary logistic regression was used to evaluate relationships between WMHs and FOG. The common cerebrovascular risk factors that may affect WMHs were evaluated by mediation analysis. Results: There were no statistical differences between PD with and without FOG groups in whole brain WMHs volume, total Scheltens score, BGHs, and ITF. Binary logistic regression showed that the total scores of DWMHs (OR = 1.094; 95% CI, 1.001, 1.195; p = 0.047), sum scores of PVHs and DWMHs (OR = 1.080; 95% CI, 1.003, 1.164; p = 0.042), especially the DWMHs in frontal (OR = 1.263; 95% CI, 1.060, 1.505 p = 0.009), and PVHs in frontal caps (OR = 2.699; 95% CI, 1.337, 5.450; p = 0.006) were associated with FOG. Age, hypertension, and serum alkaline phosphatase (ALP) are positively correlated with scores of DWMHs in frontal and PVHs in frontal caps. Conclusion: These results indicate that WMHs distribution areas especially in the frontal of DWMHs and PVHs play a role in PD patients with FOG.

Long term risk of death and readmission after hospital admission with covid-19 among older adults: retrospective cohort study.

OBJECTIVES: To characterize the long term risk of death and hospital readmission after an index admission with covid-19 among Medicare fee-for-service beneficiaries, and to compare these outcomes with historical control patients admitted to hospital with influenza. DESIGN: Retrospective cohort study. SETTING: United States. PARTICIPANTS: 883 394 Medicare fee-for-service beneficiaries age ≥65 years discharged alive after an index hospital admission with covid-19 between 1 March 2020 and 31 August 2022, compared with 56 409 historical controls discharged alive after a hospital admission with influenza between 1 March 2018 and 31 August 2019. Weighting methods were used to account for differences in observed characteristics. MAIN OUTCOME MEASURES: All cause death within 180 days of discharge. Secondary outcomes included first all cause readmission and a composite of death or readmission within 180 days. RESULTS: The covid-19 cohort compared with the influenza cohort was younger (77.9 v 78.9 years, standardized mean difference -0.12) and had a lower proportion of women (51.7% v 57.3%, -0.11). Both groups had a similar proportion of black beneficiaries (10.3% v 8.1%, 0.07) and beneficiaries with dual Medicaid-Medicare eligibility status (20.1% v 19.2%; 0.02). The covid-19 cohort had a lower comorbidity burden, including atrial fibrillation (24.3% v 29.5%, -0.12), heart failure (43.4% v 49.9%, -0.13), and chronic obstructive pulmonary disease (39.2% v 52.9%, -0.27). After weighting, the covid-19 cohort had a higher risk (ie, cumulative incidence) of all cause death at 30 days (10.9% v 3.9%; standardized risk difference 7.0%, 95% confidence interval 6.8% to 7.2%), 90 days (15.5% v 7.1%; 8.4%, 8.2% to 8.7%), and 180 days (19.1% v 10.5%; 8.6%, 8.3% to 8.9%) compared with the influenza cohort. The covid-19 cohort also experienced a higher risk of hospital readmission at 30 days (16.0% v 11.2%; 4.9%, 4.6% to 5.1%) and 90 days (24.1% v 21.3%; 2.8%, 2.5% to 3.2%) but a similar risk at 180 days (30.6% v 30.6%;-0.1%, -0.5% to 0.3%). Over the study period, the 30 day risk of death for patients discharged after a covid-19 admission decreased from 17.9% to 7.2%. CONCLUSIONS: Medicare beneficiaries who were discharged alive after a covid-19 hospital admission had a higher post-discharge risk of death compared with historical influenza controls; this difference, however, was concentrated in the early post-discharge period. The risk of death for patients discharged after a covid-19 related hospital admission substantially declined over the course of the pandemic.

Enhancing the Antibiofilm Activity of ß-1,3-Glucanase-Functionalized Nanoparticles Loaded With Amphotericin B Against Candida albicans Biofilm.

Candida biofilm-related infections cause increased morbidity and mortality in patients with a reduced immune response. Traditional antifungal therapies have proven to be insufficient as the biofilm matrix acts as a perfusion barrier. Thus, novel methods are required to improve drug delivery and kill Candida within the biofilm. In this study, chitosan nanoparticles (CSNPs) loaded with Amphotericin B (AMB), which were functionalized with ß-1,3-glucanase (Gls), were fabricated (CSNPs-AMB-Gls), and their antibiofilm activity against Candida albicans biofilm was evaluated in vitro. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were employed to examine biofilm architecture and cell viability. CSNPs-AMB-Gls inhibited planktonic cell growth and biofilm formation effectively and exhibited the highest efficacy on the removal of a mature biofilm than free AMB or CSNPs-AMB. The created nanoparticles (NPs) were found to penetrate the biofilm so as to directly interfere with the cells inside and disassemble the biofilm matrix. CSNPs-AMB-Gls could also eradicate biofilms from clinical isolates. These results suggest the potential applicability of CSNPs-AMB-Gls for the treatment of Candida biofilm-related infections.

Race, sex and age disparities in echocardiography among Medicare beneficiaries in an integrated healthcare system.

OBJECTIVE: To identify potential race, sex and age disparities in performance of transthoracic echocardiography (TTE) over several decades. METHODS: TTE reports from five academic and community sites within a single integrated healthcare system were linked to 100% Medicare fee-for-service claims from 1 January 2005 to 31 December 2017. Multivariable Poisson regression was used to estimate adjusted rates of TTE utilisation after the index TTE according to baseline age, sex, race and comorbidities among individuals with ≥2 TTEs. Non-white race was defined as black, Asian, North American Native, Hispanic or other categories using Medicare-assigned race categories. RESULTS: A total of 15 870 individuals (50.1% female, mean 72.2±12.7 years) underwent a total of 63 535 TTEs (range 2-55/person) over a median (IQR) follow-up time of 4.9 (2.4-8.5) years. After the index TTE, the median TTE use was 0.72 TTEs/person/year (IQR 0.43-1.33; range 0.12-26.76). TTE use was lower in older individuals (relative risk (RR) for 10-year increase in age, 0.91, 95% CI 0.89 to 0.92, p<0.001), women (RR 0.97, 95% CI 0.95 to 0.99, p<0.001) and non-white individuals (RR 0.95, 95% CI 0.93 to 0.97, p<0.001). Black women in particular had the lowest relative use of TTE (RR 0.92, 95% CI 0.88 to 0.95, p<0.001). The only clinical conditions associated with increased TTE use after multivariable adjustment were heart failure (RR 1.04, 95% CI 1.00 to 1.08, p=0.04) and chronic obstructive pulmonary disease (RR 1.05, 95% CI 1.00 to 1.10, p=0.04). CONCLUSIONS: Among Medicare beneficiaries with multiple TTEs in a single large healthcare system, the median TTE use after the index TTE was 0.72 TTEs/person/year, although this varied widely. Adjusted for comorbidities, female sex, non-white race and advancing age were associated with decreased TTE utilisation.

Increasing risk of mortality across the spectrum of aortic stenosis is independent of comorbidity & treatment: An international, parallel cohort study of 248,464 patients.

BACKGROUND: While large scientific and medical evidence has demonstrated the increased risk of death and cardiovascular mortality in patients with severe AS, the independent contribution of moderate AS to an increased risk of death remains uncertain. METHODS AND FINDINGS: We conducted a multicenter study including a cohort of 30,865 US patients and another cohort of 217,599 Australian patients with equivalent echocardiographic and aortic valve profiling over the same period (2003-2017). During a median 5.2 years (US) and 4.4 years (Australian) follow-up, the risk of death (hazard ratio) of patients with moderate AS as compared to those without AS was 1.66 (95%CI 1.52-1.80) and 1.37 (95%CI 1.34-1.41) in the US and Australian cohorts, even after adjusting this analysis for age and sex. This increased risk of death and cardiovascular mortality (odds ratio) in patients with moderate AS was consistent also across subgroups of left ventricular ejection fraction (LVEF) (subgroups of LVEF < 40%, 40-49%, 50-59%, and ≥ 60%: OR of moderate AS for CV mortality 2.0 [95%CI 1.4-2.7], 1.7 [95%CI 1.2-2.4], 1.5 [95%CI 1.1-1.9], and 1.4 [95%CI 1.2-1.6], respectively). CONCLUSIONS: The findings of this study suggest that patients with moderate AS have a potential increased risk of death and cardiovascular mortality, regardless of age, sex, and LVEF. Hence, these data suggest the need to develop specific strategies to detect and treat individuals with moderate AS.