Mitral Valve Transcatheter Edge-to-Edge Repair Volumes and Trends.

Background: Despite an association between operator volumes and procedural success, there remains an incomplete understanding of the contemporary utilization and procedural volumes for mitral valve transcatheter edge-to-edge repair (MTEER). We aimed to identify annual operator procedural volumes, temporal trends, and geographic variability for MTEER among Medicare patients in the United States (US). Methods: We queried the National Medicare Provider Utilization and Payment Database for a CPT code (33418) specific for MitraClip device from 2015 through 2019. We analyzed annual operator procedural volumes and incidence and identified longitudinal and geographic trends in MTEER utilization. Results: From 2015 through 2019, a total of 27,034 MTEER procedures were performed among Medicare patients in the US. The nationwide incidence increased from 6.2 per 100,000 patients in 2015 to 23.8 per 100,000 patients in 2019, a 283% increase over the study period (Ptrend < 0.001). The incidence of MTEER by state varied by nearly 900% (range 5.5 to 54.9 per 100,000 person-years). In 2019, the mean annual MTEER operator annual volume was 9.1 MTEER procedures and had grown from 6.2 per year in 2015. Conclusions: In this nationwide study of Medicare beneficiaries in the United States, we identified a significant and sustained increase in the utilization of MTEER devices and operators and growth in annual procedural volumes from 2015 through 2019 with considerable variability in utilization by state. Further studies are needed to understand the clinical impact of variability in utilization and the optimal procedural volumes to ensure high efficacy outcomes and maintain critical access to MTEER therapies.

Cost-Effectiveness of Mitral Valve Repair Versus Replacement for Severe Ischemic Mitral Regurgitation: A Randomized Clinical Trial From the Cardiothoracic Surgical Trials Network

BACKGROUND: The CTSN (Cardiothoracic Surgical Trials Network) recently reported no difference in left ventricular end-systolic volume index or in survival at 2 years between patients with severe ischemic mitral regurgitation (MR) randomized to mitral valve repair or replacement. However, replacement provided more durable correction of MR and fewer cardiovascular readmissions. Yet, costeffectiveness outcomes have not been addressed. METHODS AND RESULTS: We conducted a cost-effectiveness analysis of the surgical treatment of ischemic MR based on the CTSN trial (n=126 for repair; n=125 for replacement). Patient-level data on readmissions, survival, qualityof- life, and US hospital costs were used to estimate costs and quality-adjusted life years per patient over the trial duration and a 10-year time horizon. We performed microsimulation for extrapolation of outcomes beyond the 2 years of trial data. Bootstrap and deterministic sensitivity analyses were done to address parameter uncertainty. In-hospital cost estimates were $78 216 for replacement versus $72 761 for repair (difference: $5455; 95% uncertainty interval [UI]: −7784­21 193) while 2-year costs were $97 427 versus $96 261 (difference: $1166; 95% UI: −16 253­17 172), respectively. Quality-adjusted life years at 2 years were 1.18 for replacement versus 1.23 for repair (difference: −0.05; 95% UI: −0.17 to 0.07). Over 5 and 10 years, the benefits of reduction in cardiovascular readmission rates with replacement increased, and survival minimally improved compared with repair. At 5 years, cumulative costs and quality-adjusted life years showed no difference on average, but by 10 years, there was a small, uncertain benefit for replacement: $118 023 versus $119 837 (difference: −$1814; 95% UI: −27 144 to 22 602) and qualityadjusted life years: 4.06 versus 3.97 (difference: 0.09; 95% UI: −0.87 to 1.08). After 10 years, the incremental cost-effectiveness of replacement continued to improve. CONCLUSIONS: Our cost-effectiveness analysis predicts potential savings in cost and gains in quality-adjusted survival at 10 years when mitral valve replacement is compared with repair for severe ischemic MR. These projected benefits, however, were small and subject to variability. Efforts to further delineate predictors of long-term outcomes in patients with severe ischemic MR are needed to optimize surgical decisions for individual patients, which should yield more cost-effective care. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00807040.

Functional assessment of the acute local and distal transplantation of human neural stem cells after spinal cord injury.

BACKGROUND CONTEXT: Spinal cord injury can lead to severe functional impairments secondary to axonal damage, neuronal loss, and demyelination. The injured spinal cord has limited regrowth of damaged axons. Treatment remains controversial, given inconsistent functional improvement. Previous studies demonstrated functional recovery of rats with spinal cord contusion after transplantation of rat fetal neural stem cells. PURPOSE: We hypothesized that acute transplantation of human fetal neural stem cells (hNSCs) both locally at the injury site as well as distally via intrathecal injection would lead to improved functional recovery compared with controls. STUDY DESIGN/SETTING: Twenty-four adult female Long-Evans hooded rats were randomized into four groups with six animals in each group: two experimental and two control. Functional assessment was measured after injury and then weekly for 6 weeks using the Basso, Beattie, and Bresnahan Locomotor Rating Score. Data were analyzed using two-sample t test and linear mixed-effects model analysis. METHODS: Posterior exposure and laminectomy at T10 level was used. Moderate spinal cord contusion was induced by the Multicenter Animal Spinal Cord Injury Study Impactor with 10-g weight dropped from a height of 25 mm. Experimental subjects received either a subdural injection of hNSCs locally at the injury site or intrathecal injection of hNSCs through a separate distal laminotomy. Controls received control media injection either locally or distally. RESULTS: Statistically significant functional improvement was observed in local or distal hNSCs subjects versus controls (p=.034 and 0.016, respectively). No significant difference was seen between local or distal hNSC subjects (p=.66). CONCLUSIONS: Acute local and distal transplantation of hNSCs into the contused spinal cord led to significant functional recovery in the rat model. No statistical difference was found between the two techniques.

Does body mass index affect outcomes for aortic valve replacement surgery for aortic stenosis?

BACKGROUND: Obesity is a worldwide healthcare concern, and its association with several chronic diseases is well documented. However, the effect obesity may have on the acute care delivery is not well understood, and in cardiac surgery, reports are conflicting. The purpose of this study is to evaluate the effect of obesity in an isolated aortic valve replacement population. The hypothesis is that increasing body mass index (BMI) will portend worse long-term outcomes and greater short-term resource utilization secondary to perioperative complications but will not affect perioperative mortality. METHODS: Data were collected on 1,066 patients undergoing isolated AVR between January 2000 and December 2010. All definitions follow The Society of Thoracic Surgeons guidelines. Body mass indexes were calculated and used both as a continuous independent variable and to categorize patients into three BMI groups. Long-term mortality follow-up was by Social Security Death Index search. Standard bivariate and multivariate comparisons were performed with hierarchical models used for odds ratios. RESULTS: When controlling for standard covariates that negatively impact outcome (sex, age, renal failure needing dialysis, diabetes mellitus, and current smoker), BMI was not predictive for either operative mortality or a composite morbidity-mortality outcome. When divided into three equal-sized groups, there was again no statistical difference among groups for mortality or for the composite variable. Separate analyses for females and males yielded the same lack of correlation. Long-term follow-up out to 12 years shows that the low BMI group has statistically worse survival than the moderate or high BMI groups. CONCLUSIONS: Increasing BMI has no independent association with worsened outcomes in the short or long term, and overweight patients have a survival benefit after surgery. Patients who are at the lower end of the BMI scale, however, are at increased risk for poor long-term survival.

Cost of Gram-negative resistance.

OBJECTIVE: It is unclear that infections with Gram-negative rods resistant to at least one major class of antibiotics (rGNR) have a greater effect on patient morbidity than infections caused by sensitive strains (sGNR). We wished to test the hypothesis that rGNR infections are associated with higher resource utilization. DESIGN: Retrospective observational cohort study of prospectively collected data. SETTING: University hospital surgical intensive care unit and ward. PATIENTS: Surgical patients with at least one GNR infection. MEASUREMENTS: We compared admissions treated for rGNR infection with those with sGNR infections. Primary outcomes were total hospital costs and hospital length of stay. Other outcomes included antibiotic treatment cost, in-hospital death, and intensive care unit length of stay. After univariate analysis comparing outcomes after rGNR infection with those after sGNR infection, multivariate linear regression models for hospital cost and length of stay were created to account for potential confounders. MAIN RESULTS: Cost data were available for 604 surgical admissions treated for at least one GNR infection (Centers for Disease Control and Prevention criteria), 137 (23%) of which were rGNR infections. Admissions with rGNR infections were associated with a higher severity of illness at the time of infection (Acute Physiology and Chronic Health Evaluation II score, 17.6 +/- 0.6 vs. 13.9 +/- 0.3), had higher median hospital costs ($80,500 vs. $29,604, p < .0001) and median antibiotic costs ($2,607 vs. $758, p < .0001), and had longer median hospital length of stay (29 vs. 13 days, p < .0001) and median intensive care unit length of stay (13 days vs. 1 day, p < .0001). Infection with rGNR within the first 7 days of admission was independently predictive of increased hospital cost (incremental increase in median hospital cost estimated at $11,075; 95% confidence interval, $3,282-$20,099). CONCLUSIONS: Early infection with rGNR is associated with a high economic burden, which is in part related to increased antibiotic utilization compared with infection with sensitive organisms. Efforts to control overuse of antibiotics should be pursued.

The FEMA GRAS assessment of cinnamyl derivatives used as flavor ingredients.

This publication is the seventh in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. Elements that are fundamental to the safety evaluation of flavor ingredients include exposure, structural analogy, metabolism, pharmacokinetics and toxicology. Flavor ingredients are evaluated individually and in the context of the available scientific information on the group of structurally related substances. Scientific data relevant to the safety evaluation of the use of cinnamyl derivatives as flavoring ingredients is evaluated.

The safety assessment of fragrance materials.

Safety evaluation of the large number of diverse chemicals used as fragrance ingredients follows a systematic prioritization of data generation and analysis, consideration of exposure and critical analysis of the quality of the available information. In prior publications the research priorities used by the Research Institute for Fragrance Materials (RIFM), and the methods of exposure estimation used by industry have been summarized. This paper provides details of the approach used by the RIFM Expert Panel (REXPAN), to examine the dermal effects, systemic toxicity and environmental consequences of the use of and exposure to fragrance materials, which allow a reliable determination of safe use under intended conditions. The key to the usefulness of this analysis is the grouping of more than 2600 discrete ingredients into classes, based on chemical structures. Research sponsored by RIFM, data supplied by member companies, and relevant published reports from many sources are all considered during hazard characterization. A discussion is provided of REXPAN's decision tree approach to assessing the dermal, systemic and environmental endpoints and the types and quality of data included. This overall process results in well-documented conclusions which are provided to the International Fragrance Association (IFRA) as the basis for consideration of a new or existing Fragrance Material Standard and to industry for appropriate product risk management actions.