Racial and Ethnic Variations in Patients Undergoing Mitral and Tricuspid Valve Surgery.

INTRODUCTION: Prior investigations assessing the impact of race/ethnicity on outcomes after mitral valve (MV) surgery have reported conflicting findings. This analysis aimed to examine the association between race/ethnicity and operative presentation and outcomes of patients undergoing MV and tricuspid valve (TV) surgery. METHODS: We retrospectively analyzed 5984 patients (2730 female, median age 63 y) who underwent MV (n = 4,534, 76%), TV (n = 474, 8%) or both MV and TV (n = 976, 16%) surgery in a statewide collaborative from 2012 to 2021. The influence of race/ethnicity on preoperative characteristics, MV and TV repair rates, and postoperative outcomes was assessed for White (n = 4,244, 71%), Black (n = 1,271, 21%), Hispanic (n = 144, 2%), Asian (n = 171, 3%), and mixed/other race (n = 154, 3%) patients. RESULTS: Black patients, compared to White patients, had higher Society of Thoracic Surgeons predicted risk of morbidity/mortality (24.5% versus 13.1%; P < 0.001) and more comorbid conditions. Compared to White patients, Black and Hispanic patients were less likely to undergo an elective procedure (White 71%, Black 55%, Hispanic 58%; P < 0.001). Degenerative MV disease was more prevalent in White patients (White 62%, Black 41%, Hispanic 43%, Asian 51%, mixed/other 45%; P < 0.05), while rheumatic disease was more prevalent in non-White patients (Asian 28%, Hispanic 26%, mixed/other 25%, Black 17%, White 10%;P < 0.05). After multivariable adjustment, repair rates and adverse postoperative outcomes, including mortality, did not differ by racial/ethnic group. CONCLUSIONS: Patient race/ethnicity is associated with a higher burden of comorbidities at operative presentation and MV disease etiology. Strategies to improve early detection of valvular heart disease and timely referral for surgery may improve outcomes.

Pre-analytical challenges from adsorptive losses associated with thiamine analysis.

Thiamine (vitamin B1) is an essential vitamin serving in its diphosphate form as a cofactor for enzymes in the citric acid cycle and pentose-phosphate pathways. Its concentration reported in the pM and nM range in environmental and clinical analyses prompted our consideration of the components used in pre-analytical processing, including the selection of filters, filter apparatuses, and sample vials. The seemingly innocuous use of glass fiber filters, glass filter flasks, and glass vials, ubiquitous in laboratory analysis of clinical and environmental samples, led to marked thiamine losses. 19.3 nM thiamine was recovered from a 100 nM standard following storage in glass autosampler vials and only 1 nM of thiamine was obtained in the filtrate of a 100 nM thiamine stock passed through a borosilicate glass fiber filter. We further observed a significant shift towards phosphorylated derivatives of thiamine when an equimolar mixture of thiamine, thiamine monophosphate, and thiamine diphosphate was stored in glass (most notably non-silanized glass, where a reduction of 54% of the thiamine peak area was observed) versus polypropylene autosampler vials. The selective losses of thiamine could lead to errors in interpreting the distribution of phosphorylated species in samples. Further, some loss of phosphorylated thiamine derivatives selectively to amber glass vials was observed relative to other glass vials. Our results suggest the use of polymeric filters (including nylon and cellulose acetate) and storage container materials (including polycarbonate and polypropylene) for thiamine handling. Losses to cellulose nitrate and polyethersulfone filters were far less substantial than to glass fiber filters, but were still notable given the low concentrations expected in samples. Thiamine losses were negated when thiamine was stored diluted in trichloroacetic acid or as thiochrome formed in situ, both of which are common practices, but not ubiquitous, in thiamine sample preparation.

Psychometric Modeling to Identify Examinees' Strategy Differences during Testing.

Aptitude test scores are typically interpreted similarly for examinees with the same overall score. However, research has found evidence of examinee differences in strategies, as well as in the continued application of appropriate procedures during testing. Such differences can impact the correlates of test scores, making similar interpretations for equivalent scores questionable. This study presents some item response theory (IRT) models that are relevant to identifying examinee differences in strategies and understanding of test-taking procedures. First, mixture IRT models that identify latent classes of examinees with different patterns of item responses are considered; these models have long been available but unfortunately are not routinely applied. Strategy differences between the classes can then be studied separately by modeling the response patterns with cognitive complexity variables within each class. Secondly, novel psychometric approaches that leverage response time information (in particular, response time residuals) in order to identify both inter and intraindividual variability in response processes are considered. In doing so, a general method for evaluating threats to validity is proposed. The utility of the approach, in terms of providing more interpretable performance estimates and improving the administration of psychological measurement instruments, is then demonstrated with an empirical example.

PSMA-targeted dendrimer as an efficient anticancer drug delivery vehicle for prostate cancer.

Prostate cancer (PCa) is the second leading cause of cancer-related deaths among men in the United States. Although early-stage treatments exhibit promising 5-year survival rates, the treatment options for advanced stage disease are constrained, with short survival benefits due to the challenges associated with effective and selective drug delivery to PCa cells. Even though targeting Prostate Specific Membrane Antigen (PSMA) has been extensively explored and is clinically employed for imaging and radio-ligand therapy, the clinical success of PSMA-based approaches for targeted delivery of chemotherapies remains elusive. In this study, we combine a generation 4 hydroxy polyamidoamine dendrimer (PD) with irreversible PSMA ligand (CTT1298) to develop a PSMA-targeted nanoplatform (PD-CTT1298) for selective intracellular delivery of potent chemotherapeutics to PCa. PD-CTT1298-Cy5 exhibits a PSMA IC50 in the nanomolar range and demonstrates selective uptake in PSMA (+) PCa cells via PSMA mediated internalization. When systemically administered in a prostate tumor xenograft mouse model, PD-CTT1298-Cy5 selectively targets PSMA (+) tumors with significantly less accumulation in PSMA (-) tumors or upon blocking of the PSMA receptors. Moreover, the dendrimer clears rapidly from the off-target organs limiting systemic side-effects. Further, the conjugation of an anti-cancer agent, cabozantinib to the PSMA-targeted dendrimer translates to a significantly enhanced anti-proliferative activity in vitro compared to the free drug. These findings highlight the potential of PD-CTT1298 nanoplatform as a versatile approach for selective delivery of high payloads of potent chemotherapeutics to PCa, where dose related systemic side-effects are a major concern.

A PSMA-targeted doxorubicin small-molecule drug conjugate.

We developed a model small-molecule drug conjugate (SMDC) that employed doxorubicin as a representative chemotherapeutic targeted to the cell membrane biomarker PSMA (prostate-specific membrane antigen) expressed on prostate cancer cells. The strategy capitalized on the clatherin-mediated internalization of PSMA to facilitate the selective uptake and release of doxorubicin in the target cells. The SMDC was prepared and assessed for binding kinetics, plasma stability, cell toxicity, and specificity towards PSMA expressing prostate cancer cell lines. We observed high affinity of the SMDC for PSMA (IC50 5 nM) with irreversible binding, as well as specific effectiveness against PSMA(+) cells. These findings validated the strategy for a small molecule-based approach in targeted cancer therapy.

PSMA-targeted SMART molecules outfitted with SN38.

Herein, we report the modular synthesis and evaluation of a prostate-specific membrane antigen (PSMA) targeted small molecule drug conjugate (SMDC) carrying the chemotherapeutic agent, SN38. Due to the fluorogenic properties of SN38, payload release kinetics from the platform was observed in buffers representing the pH conditions of systemic circulation and cellular internalization. It was found that this platform is stable with minimal payload release at physiological pH with most rapid payload release observed at pH values representing the endosome complex. We confirmed selective payload release and chemotherapeutic efficacy for PSMA(+) prostate cancer cells over PSMA(-) cells. These results demonstrate that chemotherapeutic agents with limited solubility can be conjugated to a water-soluble targeting and linker platform without attenuating efficacy.

Trends in the Use of Recombinant Activated Factor VII and Prothrombin Complex Concentrate in Heart Transplant Patients in Virginia.

OBJECTIVES: To explore trends in intraoperative procoagulant factor concentrate use in patients undergoing heart transplantation (HTx) in Virginia. Secondarily, to evaluate their association with postoperative thrombosis. DESIGN: Patients who underwent HTx were identified using a statewide database. Trends in off-label recombinant activated factor VII (rFVIIa) use and on-label and off-label prothrombin complex concentrate (PCC) use were tested using the Mantel-Haenszel test. Multivariate logistic regression was used to test for an association between procoagulant factor concentrate administration and thrombosis. SETTING: Virginia hospitals performing HTx. PARTICIPANTS: Adults undergoing HTx between 2012 and 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 899 patients who required HTx, 100 (11.1%) received off-label rFVIIa, 69 (7.7%) received on-label PCC, and 80 (8.9%) received off-label PCC. There was a downward trend in the use of rFVIIa over the 10-year period (p = 0.04). There was no trend in on-label PCC use (p = 0.12); however, there was an increase in off-label PCC use (p < 0.001). Patients who received rFVIIa were transfused more and had longer cardiopulmonary bypass time (p < 0.001). Receipt of rFVIIa was associated with increased thrombotic risk (odds ratio [OR] 1.92; 95% CI 1.12-3.29; p = 0.02), whereas on-label and off-label PCC use had no association with thrombosis (OR 0.98, 95% CI 0.49-1.96, p = 0.96 for on-label use; and OR 0.61, 95% CI 0.29-1.30, p = 0.20 for off-label use). CONCLUSIONS: Use of rFVIIa in HTx decreased over the past decade, whereas off-label PCC use increased. Receipt of rFVIIa was associated with thrombosis; however, patients who received rFVIIa were more severely ill, and risk adjustment may have been incomplete.

Structural, Biochemical, and Computational Characterization of Sulfamides as Bimetallic Peptidase Inhibitors.

The sulfonamide function is used extensively as a general building block in various inhibitory scaffolds and, more specifically, as a zinc-binding group (ZBG) of metalloenzyme inhibitors. Here, we provide biochemical, structural, and computational characterization of a metallopeptidase in complex with inhibitors, where the mono- and bisubstituted sulfamide functions are designed to directly engage zinc ions of a bimetallic enzyme site. Structural data showed that while monosubstituted sulfamides coordinate active-site zinc ions via the free negatively charged amino group in a canonical manner, their bisubstituted counterparts adopt an atypical binding pattern divergent from expected positioning of corresponding tetrahedral reaction intermediates. Accompanying quantum mechanics calculations revealed that electroneutrality of the sulfamide function is a major factor contributing to the markedly lower potency of bisubstituted compounds by considerably lowering their interaction energy with the enzyme. Overall, while bisubstituted uncharged sulfamide functions can bolster favorable pharmacological properties of a given inhibitor, their use as ZBGs in metalloenzyme inhibitors might be less advantageous due to their suboptimal metal-ligand properties.

Statewide data on surgical ablation for atrial fibrillation: The data provide a path forward.

OBJECTIVE: Atrial fibrillation (AF), if left untreated, is associated with increased intermediate and long-term morbidity/mortality. Surgical treatment for AF is lacking standardization in patient selection and lesion set, despite clear support from multi-society guidelines. The aim of this study was to analyze a statewide cardiac surgery registry to establish whether or not there is an association between center volume and type of index procedure with performance of surgical ablation (SA) for AF, the lesion set chosen, and ablation technology used. METHODS: Adult, first-time, nonemergency patients with preoperative AF between 2014 and 2022 excluding standalone SA procedures from a statewide registry of Society of Thoracic Surgeons data were included (N = 4320). AF treatment variability by hospital volume (ordered from smallest to largest) and surgery type were examined with χ2 analyses. Hospital-level Spearman correlations compared hospital volume with proportion of AF patients treated with SA. RESULTS: Overall, 37% of patients with AF were ablated at the time of surgery (63% of mitral procedures, 26% of non-mitrals) and 15% had left atrial appendage management only. There was a significant temporal trend of increasing performance of SA for AF over time (Cochran-Armitage = 27.8; P < .001). Hospital cardiac surgery volume did not correlate with the proportion of AF patients treated with SA (rs = 0.19; P = .603) with a rate of SA below the state average for academic centers. Of cases with SA (n = 1582), only 43% had a biatrial lesion set. Procedures that involved mitral surgery were more likely to include a biatrial lesion set (χ2 = 392.3; P < .001) for both paroxysmal and persistent AF. Similarly, ablation technology use was variable by type of concomitant operation (χ2 = 219.0; P < .001) such that radiofrequency energy was more likely to be used in non-mitral procedures. CONCLUSIONS: These results indicate an increase in adoption of SA for AF over time. No association between greater hospital volume or academic status and performance of SA for AF was established. Similar to national data, the type of index procedure remains the most consistent factor in the decision to perform SA with a disconnect between AF pathophysiology and decision making on the type of SA performed. This analysis demonstrates a gap between evidence-based guidelines and real-world practice, highlighting an opportunity to confer the benefits of concomitant SA to more patients.

PSMA-targeted small-molecule drug-conjugates with valine-citrulline and phosphoramidate cleavable linkers.

In this study, we present a modular synthesis and evaluation of two prostate-specific membrane antigen (PSMA) targeted small molecule drug conjugates (SMDCs) incorporating the potent chemotherapeutic agent monomethyl auristatin E (MMAE). These SMDCs are distinguished by their cleavable linker modules: one utilizing the widely known valine-citrulline linker, susceptible to cleavage by cathepsin B, and the other featuring a novel acid-labile phosphoramidate-based (PhosAm) linker. Both SMDCs maintained nanomolar affinity to PSMA. Furthermore, we confirmed the selective release of the payload and observed chemotherapeutic efficacy specifically within PSMA-positive prostate cancer cells, while maintaining cell viability in PSMA-negative cells. These findings not only validate the efficacy of our approach but also highlight the potential of the innovative pH-responsive PhosAm linker. This study contributes significantly to the field and also paves the way for future advancements in targeted cancer therapy.

Phase transitions of ionic fluids in nanoporous electrodes.

In this work, we utilise grand canonical Metropolis Monte Carlo simulations, to establish pore-induced freezing of restricted primitive model fluids. A planar pore model is utilised, with walls that are initially neutral, and either non-conducting or perfectly conducting. The phase of the confined electrolyte (solid/fluid) displays an oscillatory dependence on surface separation, in narrow pores. Conditions are chosen so that the bulk is composed of a stable fluid electrolyte. The tendency for the electrolyte to freeze in narrow pores is somewhat stronger in systems with non-conducting walls. We also demonstrate that an applied potential will, above a threshold value, melt a frozen electrolyte. In these cases, the capacitance, as measured by the average surface charge density divided by the applied potential, will be almost vanishing if the applied potential is below this threshold value. We do not see any evidence for a "superionic fluid", which has been hypothesised to generate a strong capacitance in narrow pores, due to an efficient screening of like-charge repulsions by image charges.

Unexpected impact of preoperative anemia in low-risk isolated coronary artery bypass grafting or single-valve surgical patients: Do not overlook these patients in anemia management!

OBJECTIVE: Preoperative anemia is prevalent in cardiac surgery and independently associated with increased risk for short-term and long-term mortality. The purpose of this study was to examine the effect of preoperative hematocrit (Hct) on outcomes in cardiac surgical patients and whether the effect is comparable across levels of Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM). METHODS: The study consisted of adult, isolated coronary artery bypass grafting (CABG) or single-valve surgical patients in a statewide registry from 2011 to 2022 (N = 29,828). Regressions were used to assess effect of preoperative Hct on STS-defined major morbidity/mortality including the interaction of Hct and STS PROM as continuous variables. RESULTS: Median age was 66 years (58-73 years), STS PROM was 1.02% (0.58%-1.99%), and preoperative Hct was 39.5% (35.8%-42.8%). The sample consisted of 78% isolated CABG (n = 23,261), 10% isolated mitral valve repair/replacement (n = 3119), 12% isolated aortic valve replacement (n = 3448), and 29% were female (n = 8646). Multivariable analyses found that greater Hct was associated with reduced risk of STS-defined morbidity/mortality (odds ratio, 0.96; P < .001). These effects for Hct persisted even after adjustment for intraoperative blood transfusion. The interaction of Hct and STS PROM was significant for morbidity/mortality (odds ratio, 1.01; P < .001). There was a stronger association between Hct levels and morbidity/mortality risk in the patients with the lowest STS risk compared with patients with the greatest STS risk. CONCLUSIONS: Patients with lower risk had a greater association between preoperative Hct and major morbidity and mortality compared with patients with greater risk. Preoperative anemia management is essential across all risk groups for improved outcomes.

Adsorptive-Photocatalytic Performance for Antibiotic and Personal Care Product Using Cu0.5Mn0.5Fe2O4.

The amount of antibiotics and personal care products entering local sewage systems and ultimately natural waters is increasing and raising concerns about long-term human health effects. We developed an adsorptive photocatalyst, Cu0.5Mn0.5Fe2O4 nanoparticles, utilizing co-precipitation and calcination with melamine, and quantified its efficacy in removing paraben and oxytetracycline (OTC). During melamine calcination, Cu0.5Mn0.5Fe2O4 recrystallized, improving material crystallinity and purity for the adsorptive-photocatalytic reaction. Kinetic experiments showed that all four parabens and OTC were removed within 120 and 45 min. We found that contaminant adsorption and reaction with active radicals occurred almost simultaneously with the photocatalyst. OTC adsorption could be adequately described by the Brouers-Sotolongo kinetic and Freundlich isotherm models. OTC photocatalytic degradation started with a series of reactions at different carbon locations (i.e., decarboxamidation, deamination, dehydroxylation, demethylation, and tautomerization). Further toxicity testing showed that Zea mays L. and Vigna radiata L. shoot indexes were less affected by treated water than root indexes. The Zea mays L. endodermis thickness and area decreased considerably after exposure to the 25% (v/v)-treated water. Overall, Cu0.5Mn0.5Fe2O4 nanoparticles exhibit a remarkable adsorptive-photocatalytic performance for the degradation of tested antibiotics and personal care products.

Enhanced degradation of herbicides in groundwater using sulfur-containing reductants and spinel zinc ferrite activated persulfate.

A challenge to successfully implementing an injection-based remedial treatment in aquifers is to ensure that the oxidative reaction is efficient and lasts long enough to contact the contaminated plume. Our objective was to determine the efficacy of zinc ferrite nanocomposites (ZnFe2O4) and sulfur-containing reductants (SCR) (i.e., dithionite; DTN and bisulfite; BS) to co-activate persulfate (S2O82-; PS) and treat herbicide-contaminated water. We also evaluated the ecotoxicity of the treated water. While both SCRs delivered excellent PS activation in a 1:0.4 ratio (PS:SCR), the reaction was relatively short-lived. By including ZnFe2O4 in the PS/BS or PS/DTN activations, herbicide degradation rates dramatically increased by factors of 2.5 to 11.3. This was due to the SO4- and OH reactive radical species that formed. Radical scavenging experiments and ZnFe2O4 XPS spectra results revealed that SO4- was the dominant reactive species that originated from S(IV)/PS activation in solution and from the Fe(II)/PS activation that occurred on the ZnFe2O4 surface. Based on liquid chromatography mass spectrometry (LC-MS), atrazine and alachlor degradation pathways are proposed that involve both dehydration and hydroxylation. In 1-D column experiments, five different treatment scenarios were run using 14C-labeled and unlabeled atrazine, and 3H2O to quantify changes in breakthrough curves. Our results confirmed that ZnFe2O4 successfully prolonged the PS oxidative treatment despite the SCR being completely dissociated. Toxicity testing showed treated 14C-atrazine was more biodegradable than the parent compound in soil microcosms. Post-treatment water (25 %, v/v) also had less impact on both Zea Mays L. and Vigna radiata L. seedling growth, but more impact on root anatomies, while ≤4 % of the treated water started to exert cytotoxicity (<80 % viability) on ELT3 cell lines. Overall, the findings confirm that ZnFe2O4/SCR/PS reaction is efficient and relatively longer lasting in treating herbicide-contaminated groundwater.

Dietary factors potentially impacting thiaminase I-mediated thiamine deficiency.

Fish population declines from thiamine (vitamin B1) deficiency have been widespread in ecologically and economically valuable organisms, ranging from the Great Lakes to the Baltic Sea and, most recently, the California coast. Thiamine deficiencies in predatory fishes are often attributed to a diet of prey fishes with high levels of thiamine-degrading (e.g., thiaminase) enzymes, such as alewives, rainbow smelt, and anchovies. Since their discovery, thiaminase I enzymes have been recognized for breaking down thiamine into its pyrimidine and thiazole moieties using various nucleophilic co-substrates to afford cleavage, but these studies have not thoroughly considered other factors that could modify enzyme activity. We found the thiaminase I enzyme from Clostridium botulinum efficiently degrades thiamine in the presence of pyridoxine (vitamin B6) as a co-substrate but has relatively limited activity in the presence of nicotinic acid (vitamin B3). Using fluorescence measurements, thiamine degradation in an over-the-counter complete multivitamin formulation was inhibited, and a B-complex formulation required co-substrate supplementation for maximal thiamine depletion. These studies prompted the evaluation of specific constituents contributing to thiaminase I inhibition by both chromatography and fluorescence assays: Cu2+ potently and irreversibly inhibited thiamine degradation; ascorbic acid was a strong but reversible inhibitor; Fe2+, Mn2+ and Fe3+ modulated thiamine degradation to a lesser degree. The enhancement by pyridoxine and inhibition by Cu2+ extended to thiaminase-mediated degradation from Burkholderia thailandensis, Paenibacillus thiaminolyticus, and Paenibacillus apiarius in tryptic soy broth supernatants. These co-substrate limitations and the common presence of inhibitory dietary factors complement recent studies reporting that the intended function of thiaminase enzymes is to recycle thiamine breakdown products for thiamine synthesis, not thiamine degradation.

Association of Radial Artery Access with Reduced Incidence of Acute Kidney Injury.

Objectives: To determine if radial artery (RA) access compared with femoral artery (FA) access for percutaneous coronary intervention (PCI) is associated with a lower incidence of acute kidney injury (AKI). Background: AKI results in substantial morbidity and cost following PCI. Prior studies comparing the occurrence of AKI associated with radial artery (RA) versus femoral artery (FA) access have mixed results. Methods: Using a large state-wide database, 14,077 patients (8,539 with RA and 5,538 patents with FA access) were retrospectively compared to assess the occurrence of AKI following PCI. To reduce selection bias and balance clinical data across the two groups, a novel machine learning method called a Generalized Boosted Model was conducted on the arterial access site generating a weighted propensity score for each variable. A logistic regression analysis was then performed on the occurrence of AKI following PCI using the weighted propensity scores from the Generalized Boosted Model. Results: As shown in other studies, multiple variables were associated with an increase in AKI after PCI. Only RA access (OR 0.82; 95% CI 0.74-0.91) and male gender (OR 0.80; 95% CI 0.72-0.89) were associated with a lower occurrence of AKI. Based on the calculated Mehran scores, patients were stratified into groups with an increasing risk of AKI. RA access was consistently found to have a lower risk of AKI compared with FA access across these groups of increasing risk. Conclusions: Compared with FA access, RA access is associated with an 18% lower rate of AKI following PCI. This effect was observed among different levels of risk for developing AKI. Although developed from a retrospective analysis, this study supports the use of RA access when technically possible in a diverse group of patients.

Multiple Arterial Graft Use in Coronary Artery Bypass Surgery: Surgeon Perspective vs Practice.

BACKGROUND: Despite supportive evidence and guidelines, the use of multiple arterial grafts (MAGs) in coronary artery bypass grafting remains low. We sought to determine surgeon perception of personal MAG use and compare this with actual MAG use. METHODS: We conducted a statewide surgeon survey of MAG use, presence of a hospital MAG protocol, and barriers for MAG use, with a response rate of 78% (n = 25). Surgeon survey responses were compared with actual Society of Thoracic Surgeons patient data from January 1, 2017, to December 31, 2020 using χ2 or Fisher's exact tests. RESULTS: Of 5299 patients who had first-time, nonemergent, isolated coronary artery bypass grafting (≥2 grafts) by responding surgeons, 16% received MAG (n = 825). MAG use in patients whose surgeons self-designated as "routine" MAG users was 21% vs 7% for "nonroutine" users. Surgeons with a hospital protocol for MAG use utilized MAG more often (18% vs 14%, P = .001). Surgeons who were unconvinced by the data on the benefits of MAGs used MAGs in 11% vs 22% in surgeons who were convinced. MAG use increased over time, particularly from before to after the survey (13.1% vs 30.5%, P < .001). CONCLUSIONS: Although MAG use increased over time, barriers to routine use remain. In surgeons who reported routine use, only 21% of their patients received MAGs. Hospital protocols, education, and increased awareness may reduce barriers to use and encourage evidence-based clinical practice.

Do Tobacco Companies Have an Incentive to Promote "Harm Reduction" Products?: The Role of Competition.

INTRODUCTION: Some cigarette companies have started to talk about replacing cigarettes with less harmful alternatives, which might include nicotine vaping products (NVPs), heated tobacco products (HTPs), and oral nicotine delivery products. We consider market competition as a primary driver of whether cigarette companies follow through on their stated intentions. AIMS AND METHODS: We focus on the behavior of cigarette companies in the United States. We compare competition in the pre- and post-2012 time periods, analyze the impact of the growth in NVPs on smoking prevalence and cigarette company profits, and examine the potential future role of competition. RESULTS: Since 2006, consumers have broadened their use of non-combustible nicotine delivery products (NCNDPs) to include, inter alia, NVPs, HTPs, and oral nicotine pouches. U.S. cigarette companies have acquired major stakes in each of these product categories which corresponds to a period of rapidly declining adult smoking prevalence, especially among younger adults (ages 18-24 years). The shifting dynamics of the nicotine product marketplace are also reflected in cigarette company stock prices. While cigarette companies are likely to promote HTPs and nicotine delivery products over NVPs, their incentives will be directly related to competition from independent firms, which in turn will depend on government regulation. CONCLUSIONS: Although cigarette companies will back alternatives to combusted tobacco when threatened by competition, the prospects for their lasting conversion to NCNDPs will depend on the extent of such competition, which will be influenced by government regulation of tobacco products. IMPLICATIONS: Regulations that limit competition from independent firms while also protecting cigarette company profits risk slowing or even reversing recent declines in smoking, especially among youth and young adults. Regulations that reduce the appeal and addictiveness of combusted tobacco products, such as higher cigarette taxes or a reduced nicotine standard, will encourage smokers to quit and/or switch to less harmful non-combusted forms of tobacco. The regulation of non-combustible nicotine delivery products and cigarettes should be proportionate to their relative risks, so that smokers have incentives to switch from combustibles to safer alternatives, and cigarette companies have incentives to promote safer products.

Barriers to atrial fibrillation ablation during mitral valve surgery.

BACKGROUND: Nearly 40% of patients with atrial fibrillation (AF) undergoing mitral valve surgery do not receive concomitant ablation despite societal guidelines. We assessed barriers to implementation of this evidence-based practice through a survey of cardiac surgeons in 2 statewide quality collaboratives. METHODS: Adult cardiac surgeons across 2 statewide collaboratives were surveyed on their knowledge and practice regarding AF ablation. Questions concerning experience, clinical practice, case scenarios, and barriers to implementation were included. RESULTS: Among 66 respondents (66 of 135; 48.9%), the majority reported "very comfortable/frequently use" cryoablation (53 of 66; 80.3%) and radiofrequency (55 of 66; 83.3%). Only 12.1% (8/66) were not aware of the recommendations. Approximately one-half of the respondents reported learning AF ablation in fellowship (50.0%; 33 of 66) or attending courses (47.0%; 31 of 66). Responses to clinical scenarios demonstrated wide variability in practice patterns. One-half of the respondents reported no barriers; others cited increased cross-clamp time, excessive patient risk, and arrhythmia incidence as obstacles. Desired interventions included cardiology/electrophysiology support, protocols, pacemaker rate information, and education in the form of site visits, videos and proctors. CONCLUSIONS: Knowledge of evidence-based recommendations and practice patterns vary widely. These data identify several barriers to implementation of concomitant AF ablation and suggest specific interventions (mentorship/support, protocols, research, and education) to overcome these barriers.

Hospital variability in modifiable factors driving coronary artery bypass charges.

OBJECTIVE: Coronary artery bypass grafting is associated with significant interhospital variability in charges. Drivers of hospital charge variability remain elusive. We identified modifiable factors associated with statewide interhospital variability in hospital charges for coronary artery bypass grafting. METHODS: Charge data were used as a surrogate for cost. Society of Thoracic Surgeons data from Maryland institutions and charge data from the Maryland Health Care Commission were linked to characterize interhospital charge variability for coronary artery bypass grafting. Multivariable linear regression was used to identify perioperative factors independently related to coronary artery bypass grafting charges. Of the factors independently associated with charges, we analyzed which factors varied between hospitals. RESULTS: A total of 10,337 patients underwent isolated coronary artery bypass grafting at 9 Maryland hospitals from 2012 to 2016, of whom 7532 patients were available for analyses. Mean normalized charges for isolated coronary artery bypass grafting varied significantly among hospitals, ranging from $30,000 to $57,000 (P < .001). Longer preoperative length of stay, operating room time, and major postoperative morbidity including stroke, renal failure, prolonged ventilation, reoperation, and deep sternal wound infection were associated with greater hospital charges. Incidence of major postoperative events, except stroke and deep sternal wound infection, was variable between hospitals. In a univariate linear regression model, patient risk profile only accounted for approximately 10% of statistical variance in charges. CONCLUSIONS: There is significant charge variability for coronary artery bypass grafting among hospitals within the same state. By targeting variation in preoperative length of stay, operating room time, postoperative renal failure, prolonged ventilation, and reoperation, cardiac surgery programs can realize cost savings while improving quality of care for this resource-intense patient population.