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1.
Circ Cardiovasc Qual Outcomes ; : e010874, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39364590

RESUMEN

BACKGROUND: Cardiac rehabilitation (CR) improves outcomes following percutaneous coronary intervention (PCI) but remains underutilized. A liaison-mediated referral (LMR), where a health care professional explains CR's benefits, addresses barriers to participation, and places a referral before discharge, may promote CR use. Our objective was to assess the impact of an LMR on CR participation after PCI. METHODS: This was a retrospective study of patients who underwent PCI across 48 hospitals in Michigan between January 2021 and April 2022 and referred to CR before discharge. Clinical registry data were linked to administrative claims to identify the primary outcome, CR participation, defined as ≥1 CR session within 90 days of discharge. Bayesian hierarchical logistic regression was used to compare CR participation between patients with and without an LMR. For the secondary outcome, frailty proportional hazard modeling compared days elapsed between discharge and first CR session between liaison cohorts. RESULTS: Among 9023 patients referred to CR after PCI, 4323 (47.9%) underwent an LMR (mean age, 69.3 [SD=11] years; 68.3% male) and 3390 (36.7%) attended ≥1 CR session within 90 days of discharge. The LMR cohort had a higher unadjusted CR participation rate (43.1% [95% CI, 41.5%-44.6%] versus 32.4% [95% CI, 31.1%-33.8%]; P<0.001), a higher adjusted odds ratio of attending ≥1 CR session (adjusted odds ratio, 1.21; 95% credible interval, 1.07-1.38), and a shorter delay in attending the first CR session compared with the non-LMR cohort (28 [interquartile range, 19-42] versus 33 [interquartile range, 21-47] days; P<0.001). CONCLUSIONS: An LMR was associated with higher odds of CR participation and may mitigate delays in CR enrollment. This referral strategy may improve CR participation and patient outcomes after PCI.

2.
Epigenetics ; 19(1): 2408843, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39360678

RESUMEN

Cytomegalovirus (CMV) infection and reactivation in solid organ transplant (SOT) recipients increases the risk of viremia, graft failure and death. Clinical studies of CMV serostatus indicate that donor positive recipient negative (D+/R-) patients have greater viremia risk than D-/R-. The majority of patients are R+ having intermediate serologic risk. To characterize the long-term impact of CMV infection and assess viremia risk, we sought to measure the effects of CMV on the recipient immune epigenome. Specifically, we profiled DNA methylation in 156 individuals before lung or kidney transplant. We found that the methylome of CMV positive SOT recipients is hyper-methylated at loci associated with neural development and Polycomb group (PcG) protein binding, and hypo-methylated at regions critical for the maturation of lymphocytes. In addition, we developed a machine learning-based model to predict the recipient CMV serostatus after correcting for cell type composition and ancestry. This CMV episcore measured at baseline in R+ individual stratifies viremia risk accurately in the lung transplant cohort, and along with serostatus the CMV episcore could be a potential biomarker for identifying R+ patients at high viremia risk.


Asunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , Metilación de ADN , Epigénesis Genética , Trasplante de Pulmón , Viremia , Humanos , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/sangre , Trasplante de Pulmón/efectos adversos , Masculino , Femenino , Citomegalovirus/genética , Persona de Mediana Edad , Adulto , Receptores de Trasplantes
3.
JTCVS Open ; 20: 101-111, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39296458

RESUMEN

Objective: Cardiac surgeons experience unpredictable overnight operative responsibilities, with variable rest before same-day, first-start scheduled cases. This study evaluated the frequency and associated impact of a surgeon's overnight operative workload on the outcomes of their same-day, first-start operations. Methods: A statewide cardiac surgery quality database was queried for adult cardiac surgical operations between July 1, 2011, and March 1, 2021. Nonemergency, first-start, Society of Thoracic Surgeons predicted risk of mortality operations were stratified by whether or not the surgeon performed an overnight operation that ended after midnight. A generalized mixed effect model was used to evaluate the effect of overnight operations on a Society of Thoracic Surgeons composite outcome (5 major morbidities or operative mortality) of the first-start operation. Results: Of all first-start operations, 0.4% (239/56,272) had a preceding operation ending after midnight. The Society of Thoracic Surgeons predicted risk of morbidity and mortality was similar for first-start operations whether preceded by an overnight operation or not (overnight operation: 11.3%; no overnight operation: 11.7%, P = .42). Unadjusted rates of the primary outcome were not significantly different after an overnight operation (overnight operation: 13.4%; no overnight operation: 12.3%, P = .59). After adjustment, overnight operations did not significantly impact the risk of major morbidity or mortality for first-start operations (adjusted odds ratio, 1.1, P = .70). Conclusions: First-start cardiac operations performed after an overnight operation represent a small subset of all first-start Society of Thoracic Surgeons predicted risk operations. Overnight operations do not significantly influence the risk of major morbidity or mortality of first-start operations, which suggests that surgeons exercise proper judgment in determining appropriate workloads.

4.
RSC Adv ; 14(40): 29658-29664, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39297046

RESUMEN

In this work the bacteria S. aureus and fungi C. albicans were allowed to interact with quartz-based biosensor devices under different flow rates, with and without an anti-fouling coating. These experiments were conducted in order to determine if the level of fouling observed was affected by the flow rate. The biosensor used was an ultra-high frequency acoustic wave device (EMPAS) for investigation of device surface initial interaction of S. aureus or C. albicans under flow of PBS buffer at flow rates between 50 and 200 µL min-1. Surface-bound microbes were also visualized by fluorescence microscopy following these experiments. S. aureus bacteria was able to foul the bare quartz sensors at each flow rate tested, with the greatest degree of fouling observed at a flow rate of 100 µL min-1. C. albicans showed far less fouling of bare devices with the maximum fouling observed at a flow rate of 75 µL min-1. Antifouling MEG-OH coated sensors showed greatly reduced fouling for S. aureus, with between a 90 and 99% reduction in observed frequency change depending on the flow rate used, and between 22 and 90% for C. albicans. Fluorescence images of the microbes following the experiments correlated well with the frequency data, showing a marked decrease in the amount of bacteria seen on MEG-OH-coated surfaces compared to controls.

5.
Sensors (Basel) ; 24(17)2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39275399

RESUMEN

Oxytetracycline (OTC) is a widely employed antibiotic in veterinary treatment and in the prevention of infections, potentially leaving residues in animal-derived food products, such as milk, that are consumed by humans. Given the detrimental effects of prolonged human exposure to antibiotics, it has become imperative to develop precise and sensitive methods for monitoring the presence of OTC in food. Herein, we describe the development and results of a preliminary label-free electrochemical aptasensor with antifouling properties designed to detect OTC in milk samples. The sensor was realized by modifying a gold screen-printed electrode with α-lipoic acid-NHS and an amine-terminated aptamer. Different electrochemical techniques were used to study the steps of the fabrication process and to quantify OTC in the presence of the Fe(CN)64-/Fe(CN)63- redox couple The detectable range of concentrations satisfy the maximum residue limits set by the European Union, with an limit of detection (LOD) of 14 ng/mL in phosphate buffer (BP) and 10 ng/mL in the milk matrix, and a dynamic range of up to 500 ng/mL This study is a steppingstone towards the implementation of a sensitive monitoring method for OTC in dairy products.


Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Técnicas Electroquímicas , Leche , Oxitetraciclina , Oxitetraciclina/análisis , Oxitetraciclina/química , Técnicas Electroquímicas/métodos , Técnicas Biosensibles/métodos , Leche/química , Aptámeros de Nucleótidos/química , Animales , Límite de Detección , Oro/química , Electrodos , Antibacterianos/análisis , Antibacterianos/química , Humanos
6.
Artículo en Inglés | MEDLINE | ID: mdl-39236288

RESUMEN

Nicotine exposure in the context of smoking or vaping worsens airway function. Although commonly thought to exert effects through the peripheral nervous system, we previously showed airway smooth muscle (ASM) expresses nicotinic acetylcholine receptors (nAChRs), particularly alpha7 subtype (α7nAChR) with functional effects on contractility and metabolism. However, the mechanisms of nAChR regulation and downstream effects in ASM are not fully understood. Using human ASM cells from non-asthmatics vs. mild-moderate asthmatics, we tested the hypothesis that nAChR-specific ER chaperones RIC-3 and TMEM35 promote cell surface localization of α7nAChR with downstream influence on its functionality: effects exacerbated by inflammation. We found that mild-moderate asthma and exposure to pro-inflammatory cytokines relevant to asthma promote chaperone and α7nAChR expression in ASM. Downstream, ER stress was linked to nicotine/α7nAChR signaling, where RIC-3 and TMEM35 regulate nicotine-induced ER stress, Ca2+ regulation and ASM cell proliferation. Overall, our data highlights the importance α7nAChR chaperones in mediating and modulating nicotine effects in ASM towards airway contractility and remodeling.

7.
Am J Physiol Lung Cell Mol Physiol ; 327(4): L547-L556, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39189800

RESUMEN

Bronchial airways and lung parenchyma undergo both static and dynamic stretch in response to normal breathing as well as in the context of insults such as mechanical ventilation (MV) or in diseases such as asthma and chronic obstructive pulmonary disease (COPD) which lead to airway remodeling involving increased extracellular matrix (ECM) production. Here, the role of fibroblasts is critical, but the relationship between stretch- and fibroblast-induced ECM remodeling under these conditions is not well-explored. Piezo (PZ) channels play a role in mechanotransduction in many cell and organ systems, but their role in mechanical stretch-induced airway remodeling is not known. To explore this, we exposed human lung fibroblasts to 10% static stretch on a background of 5% oscillations for 48 h, with no static stretch considered controls. Collagen I, fibronectin, alpha-smooth muscle actin (α-SMA), and Piezo 1 (PZ1) expression was determined in the presence or absence of Yoda1 (PZ1 agonist) or GsMTx4 (PZ1 inhibitor). Collagen I, fibronectin, and α-SMA expression was increased by stretch and Yoda1, whereas pretreatment with GsMTx4 or knockdown of PZ1 by siRNA blunted this effect. Acute stretch in the presence and absence of Yoda1 demonstrated activation of the ERK pathway but not Smad. Measurement of [Ca2+]i responses to histamine showed significantly greater responses following stretch, effects that were blunted by knockdown of PZ1. Our findings identify an essential role for PZ1 in mechanical stretch-induced production of ECM mediated by ERK phosphorylation and Ca2+ influx in lung fibroblasts. Targeting PZ channels in fibroblasts may constitute a novel approach to ameliorate airway remodeling by decreasing ECM deposition.NEW & NOTEWORTHY The lung is an inherently mechanosensitive organ that can respond to mechanical forces in adaptive or maladaptive ways, including via remodeling resulting in increased fibrosis. We explored the mechanisms that link mechanical forces to remodeling using human lung fibroblasts. We found that mechanosensitive Piezo channels increase with stretch and mediate extracellular matrix formation and the fibroblast-to-myofibroblast transition that occurs with stretch. Our data highlight the importance of Piezo channels in lung mechanotransduction toward remodeling.


Asunto(s)
Fibroblastos , Canales Iónicos , Pulmón , Mecanotransducción Celular , Humanos , Pulmón/metabolismo , Pulmón/citología , Fibroblastos/metabolismo , Canales Iónicos/metabolismo , Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Remodelación de las Vías Aéreas (Respiratorias) , Actinas/metabolismo , Células Cultivadas , Estrés Mecánico , Colágeno Tipo I/metabolismo , Colágeno Tipo I/genética , Calcio/metabolismo , Venenos de Araña , Péptidos y Proteínas de Señalización Intercelular
8.
Ann Am Thorac Soc ; 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39137381

RESUMEN

RATIONALE: Pulmonary rehabilitation (PR) is a clinically and cost-effective outpatient treatment for COPD that remains highly underutilized. Existing analyses of PR utilization patterns have been largely focused on patient characteristics, however hospital level analysis is lacking, and is needed to inform interventions aimed at improving utilization after COPD hospitalization. OBJECTIVE: To evaluate PR utilization across hospitals after COPD hospitalization in the state of Michigan, with the goal of characterizing hospital level variation and identifying the characteristics of high-performing hospitals. METHODS: This is a retrospective study of patients with a COPD hospitalization between 1/1/18 and 12/31/21 using claims data from the Michigan Value Collaborative (MVC) and hospital data from the American Hospital Association annual survey. Our primary outcome was initiation of PR within 30 days of discharge. Chi-square tests and ANOVA were used to test for differences in patient and hospital covariates. Multilevel logistic regression was used to analyze associations between patient covariates and the primary outcome, and to characterize hospital level variation. RESULTS: A total of 36,389 patients and 99 hospitals were included in the analysis. The majority of patients were older than 65 years of age, female, White, and Medicare fee-for-service insured. The rate of PR initiation within 30 days after hospitalization was 0.8%. Adjusted rates of PR initiation by hospital ranged from 0.4-2.0%. Compared to the set reference groups, being female, in the 5th Distressed Community Index quintile, and being older than 85 years of age independently decreased the odds of initiating PR. Some variation in initiation rate was attributed to the hospital level (7% ICC 0.07, 95% CI 0.03-0.15). The median odds ratio was 1.6 for PR initiation by hospital. CONCLUSIONS: Rates of PR initiation after COPD hospitalization are universally low across all hospitals, though there is some variation. Interventions targeted at patients alone are not sufficient to improve utilization. Hospital-based strategies to improve PR utilization after discharge, adapted from those being successfully used with cardiac rehabilitation, should be further explored.

9.
J Am Med Dir Assoc ; 25(10): 105203, 2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39142638

RESUMEN

OBJECTIVES: This study examines the perspectives of key stakeholders in home health toward Medicare's Home Health Value Based Purchasing (HHVBP) program, piloted among home health agencies (HHAs) in 9 states from 2016 to 2021, and based on initial performance, was expanded to the remaining 41 (nonpilot) states in January 2023. DESIGN: We conducted semistructured interviews wherein we inquired participants' views toward and experiences with HHVBP. We used convenience and purposive sampling to obtain diversity in HHA size, geography, and quality. SETTING AND PARTICIPANTS: We conducted interviews from July 2022 to May 2023 with HHA leaders, staff, and clinicians, advocacy and trade organization leaders, and policy experts from pilot and nonpilot states. METHODS: We used thematic analysis to develop a codebook that included framework-derived, a priori, and inductive codes. We identified key themes and subthemes accordingly. RESULTS: Forty-seven stakeholders representing 25 unique organizations participated: 22 (47%) from pilot states and 25 (53%) from nonpilot states; of these, 24 (51%) were HHA leaders, 13 (28%) were organizational leaders, and 10 (21%) were clinicians; 26 (55%) were centered in the Northeast, 9 (19%) in the West, 7 (15%) had a national presence, and 5 (11%) were centered across the South. Four key themes emerged. There were (1) wide variations in awareness, understanding, and attitudes toward HHVBP regardless of pilot status or stakeholder type; (2) concerns about aspects of HHVBP, including consequences for HHAs and patients; (3) a range of strategies used by HHAs to address HHVBP; (4) other concurrent issues that HHAs were navigating alongside HHVBP. CONCLUSIONS AND IMPLICATIONS: Despite HHVBP's national implementation, awareness of and attitudes toward HHVBP varied across stakeholders from pilot and nonpilot states, as did efforts to address it. Although some viewed the policy favorably, others were concerned it could negatively impact HHAs and patients. Understanding the experiences of stakeholders is vital for illuminating the intended and unintended consequences of HHVBP policy.

11.
J Patient Cent Res Rev ; 11(2): 81-87, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39044850

RESUMEN

Purpose: The impact of central nervous system (CNS) prophylaxis in diffuse large B-cell lymphoma (DLBCL) is contentious. The CNS International Prognostic Index (IPI) calculator offers prognostic guidance in identifying those patients who may be at highest risk of disease progression or relapse to the CNS. However, it is unclear whether this tool has guided clinician decision-making in a real-world setting. Studies have suggested that CNS prophylaxis may not offer clinically significant benefit in terms of preventing CNS disease progression. Given this, we investigated the utilization of CNS prophylaxis within our own population and documentation of the CNS-IPI score. Methods: We retrospectively evaluated patients with newly diagnosed DLBCL between January 1, 2014, and December 31, 2017. Patients were assessed for receipt of CNS prophylaxis in the form of intrathecal (IT) chemotherapy and/or high-dose intravenous (IV) methotrexate. CNS-IPI scores were calculated for all patients who received CNS prophylaxis or those who experienced CNS disease. Long-term outcomes at five years from diagnosis included CNS progression/relapse and survival. Results: Of 234 patients who met criteria, 20 (8.6%) received either IV methotrexate or IT chemotherapy; most received IT methotrexate. No patients in the IT prophylaxis group developed CNS disease, while two of eight IV methotrexate patients experienced CNS disease involvement. The incidence of CNS progression was 3.7% in the no prophylaxis group and 10% in those who received prophylaxis. Conclusions: This study revealed low utilization of CNS prophylaxis and CNS-IPI documentation in a community hospital system. Given large differences between groups, claims of CNS prophylaxis efficacy are unable to be made. CNS relapse rates were consistent with existing literature and promote continued evaluation of the utility of current CNS prophylaxis approaches in DLBCL. New unambiguously effective therapeutic approaches are needed and may encourage a higher rate of standardized use.

13.
Am J Med ; 137(10): 974-982.e1, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38866304

RESUMEN

BACKGROUND: Prior nonmelanoma skin cancer (NMSC), a biomarker of cumulative lifetime sun exposure, is associated with reduced fracture risk later in life. The mechanism is unknown. METHODS: Prospective cohort analysis of 1099 community-dwelling adults aged 50-80 years with baseline and 10-year follow-up assessments. Histopathologically-confirmed NMSC diagnosis was established by linkage with the Tasmanian Cancer Registry. Bone mineral density (BMD) and vertebral deformity were quantified by DXA, 25-hydroxyvitamin D (25(OH)D) by radioimmunoassay, bone microarchitecture by high-resolution peripheral quantitative CT, melanin density by spectrophotometry, and skin photosensitivity and clinical fracture by questionnaire. 25(OH)D <50 nmol/L was considered deficient. RESULTS: Participants with an NMSC reported prior to baseline were less likely to sustain an incident vertebral deformity over 10 years (RR = 0.74, P = .036). There were similar reductions for other fracture types but these did not reach significance. Prior NMSC was associated with baseline (RR = 1.23, P = .005) and 10-year longitudinal (RR = 5.9, P = .014) vitamin D sufficiency and greater total body BMD (ß = 0.021g/cm2, P = .034), but not falls risk or muscle strength. The relationship between prior NMSC and bone microarchitecture was age-dependent (pinteraction < 0.05). In the oldest age tertile, prior NMSC was associated with greater volumetric BMD (ß = 57.8-62.6, P = .002-0.01) and less porosity (ß = -4.6 to -5.2, P = .002-0.009) at cortical, compact cortical and outer transitional zones. CONCLUSIONS: Prior NMSC was associated with fewer incident fractures in community-dwelling older adults. This protective association is most likely mediated by modifiable fracture risk factors associated with an outdoor lifestyle, including 25(OH)D, BMD, and bone microarchitecture.


Asunto(s)
Densidad Ósea , Neoplasias Cutáneas , Deficiencia de Vitamina D , Vitamina D , Humanos , Anciano , Masculino , Femenino , Neoplasias Cutáneas/epidemiología , Persona de Mediana Edad , Anciano de 80 o más Años , Estudios Prospectivos , Vitamina D/sangre , Vitamina D/análogos & derivados , Deficiencia de Vitamina D/complicaciones , Fracturas Óseas/epidemiología , Fracturas Óseas/etiología , Tasmania/epidemiología
14.
Biosensors (Basel) ; 14(6)2024 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-38920591

RESUMEN

The overall 5-year survival rate of ovarian cancer (OC) is generally low as the disease is often diagnosed at an advanced stage of progression. To save lives, OC must be identified in its early stages when treatment is most effective. Early-stage OC causes the upregulation of lysophosphatidic acid (LPA), making the molecule a promising biomarker for early-stage detection. An LPA assay can additionally stage the disease since LPA levels increase with OC progression. This work presents two methods that demonstrate the prospective application for detecting LPA: the electromagnetic piezoelectric acoustic sensor (EMPAS) and a chemiluminescence-based iron oxide nanoparticle (IONP) approach. Both methods incorporate the protein complex gelsolin-actin, which enables testing for detection of the biomarker as the binding of LPA to the complex results in the separation of gelsolin from actin. The EMPAS was characterized with contact angle goniometry and atomic force microscopy, while gelsolin-actin-functionalized IONPs were characterized with transmission electron microscopy and Fourier transform infrared spectroscopy. In addition to characterization, LPA detection was demonstrated as a proof-of-concept in Milli-Q water, buffer, or human serum, highlighting various LPA assays that can be developed for the early-stage detection of OC.


Asunto(s)
Biomarcadores de Tumor , Lisofosfolípidos , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/diagnóstico , Técnicas Biosensibles , Gelsolina , Actinas , Detección Precoz del Cáncer
15.
Elife ; 122024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38884443

RESUMEN

Chitin is an abundant biopolymer and pathogen-associated molecular pattern that stimulates a host innate immune response. Mammals express chitin-binding and chitin-degrading proteins to remove chitin from the body. One of these proteins, Acidic Mammalian Chitinase (AMCase), is an enzyme known for its ability to function under acidic conditions in the stomach but is also active in tissues with more neutral pHs, such as the lung. Here, we used a combination of biochemical, structural, and computational modeling approaches to examine how the mouse homolog (mAMCase) can act in both acidic and neutral environments. We measured kinetic properties of mAMCase activity across a broad pH range, quantifying its unusual dual activity optima at pH 2 and 7. We also solved high-resolution crystal structures of mAMCase in complex with oligomeric GlcNAcn, the building block of chitin, where we identified extensive conformational ligand heterogeneity. Leveraging these data, we conducted molecular dynamics simulations that suggest how a key catalytic residue could be protonated via distinct mechanisms in each of the two environmental pH ranges. These results integrate structural, biochemical, and computational approaches to deliver a more complete understanding of the catalytic mechanism governing mAMCase activity at different pH. Engineering proteins with tunable pH optima may provide new opportunities to develop improved enzyme variants, including AMCase, for therapeutic purposes in chitin degradation.


Asunto(s)
Quitina , Quitinasas , Simulación de Dinámica Molecular , Quitinasas/metabolismo , Quitinasas/química , Animales , Concentración de Iones de Hidrógeno , Ratones , Quitina/metabolismo , Quitina/química , Conformación Proteica , Cristalografía por Rayos X , Unión Proteica , Ligandos , Cinética , Acetilglucosamina/metabolismo , Acetilglucosamina/química , Modelos Moleculares
16.
Sci Rep ; 14(1): 13630, 2024 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-38871777

RESUMEN

This cross-sectional study investigated differences in the plasma metabolome in two groups of adults that were of similar age but varied markedly in body composition and dietary and physical activity patterns. Study participants included 52 adults in the lifestyle group (LIFE) (28 males, 24 females) and 52 in the control group (CON) (27 males, 25 females). The results using an extensive untargeted ultra high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) metabolomics analysis with 10,535 metabolite peaks identified 486 important metabolites (variable influence on projections scores of VIP ≥ 1) and 16 significantly enriched metabolic pathways that differentiated LIFE and CON groups. A novel metabolite signature of positive lifestyle habits emerged from this analysis highlighted by lower plasma levels of numerous bile acids, an amino acid profile characterized by higher histidine and lower glutamic acid, glutamine, ß-alanine, phenylalanine, tyrosine, and proline, an elevated vitamin D status, higher levels of beneficial fatty acids and gut microbiome catabolism metabolites from plant substrates, and reduced levels of N-glycan degradation metabolites and environmental contaminants. This study established that the plasma metabolome is strongly associated with body composition and lifestyle habits. The robust lifestyle metabolite signature identified in this study is consistent with an improved life expectancy and a reduced risk for chronic disease.


Asunto(s)
Estilo de Vida Saludable , Metaboloma , Metabolómica , Humanos , Masculino , Femenino , Metabolómica/métodos , Persona de Mediana Edad , Adulto , Estudios Transversales , Composición Corporal , Cromatografía Líquida de Alta Presión , Ácidos y Sales Biliares/metabolismo , Ácidos y Sales Biliares/sangre , Ejercicio Físico/fisiología , Estilo de Vida
17.
Am J Manag Care ; 30(6): 276-284, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38912953

RESUMEN

OBJECTIVES: To understand hospitals' approaches to spending reduction in commercial episode-based payment programs and inform incentive design. STUDY DESIGN: Qualitative arm of an explanatory sequential mixed-methods study involving semistructured interviews with hospital leaders participating in a statewide quality improvement collaborative with novel episode-based incentive payments introduced by the state's largest commercial payer. METHODS: We recruited 21 leaders from 8 purposively selected, diverse hospitals with both high and low performance. Video teleconference-based interviews followed a standardized protocol and addressed 4 domains: choice of clinical condition for evaluation, strategies for episode spending reduction, best practices for success in earning incentives, and barriers to achievement. Rapid qualitative analysis with purposeful data reduction was employed to generate a matrix of key themes within the study domains. RESULTS: Strategies were similar between high- and low-performing hospitals. When selecting conditions, some hospitals focused on areas of underperformance, aiming for improvement opportunities, whereas others chose conditions already achieving highest efficiency. Many tried to synergize with other ongoing improvement initiatives and clinical areas with established leaders and champions. Key strategies included data-driven improvement, care standardization, and protocol dissemination. Best practices for success included readmission prevention and postacute care spending containment. CONCLUSIONS: The findings highlighted hospitals' most common strategies and approaches, providing several insights into optimal design of commercial episode-based incentives: They must be lucrative enough to earn attention or consistent with larger federal programs; hospitals need opportunities to succeed through both improved performance and sustained excellence; and programs may incur malalignment between hospitals and credentialed physicians.


Asunto(s)
Reembolso de Incentivo , Humanos , Economía Hospitalaria , Mejoramiento de la Calidad , Investigación Cualitativa , Estados Unidos , Entrevistas como Asunto , Episodio de Atención
18.
Artículo en Inglés | MEDLINE | ID: mdl-38692480

RESUMEN

OBJECTIVE: Women are less likely to receive guideline-recommended cardiovascular care, but evaluation of sex-based disparities in cardiac surgical procedures is limited. Receipt of concomitant atrial fibrillation (AF) procedures during nonmitral cardiac surgery was compared by sex for patients with preoperative AF. METHODS: Patients with preoperative AF undergoing coronary artery bypass grafting and/or aortic valve replacement at any of the 33 hospitals in Michigan from 2014 to 2022 were included. Patients with prior cardiac surgery, transcatheter AF procedure, or emergency/salvage status were excluded. Hierarchical logistic regression identified predictors of concomitant AF procedures, account for hospital and surgeon as random effects. RESULTS: Of 5460 patients with preoperative AF undergoing nonmitral cardiac surgery, 24% (n = 1291) were women with a mean age of 71 years. Women were more likely to have paroxysmal (vs persistent) AF than men (80% vs 72%; P < .001) and had a higher mean predicted risk of mortality (5% vs 3%; P < .001). The unadjusted rate of concomitant AF procedure was 59% for women and 67% for men (P < .001). After risk adjustment, women had 26% lower adjusted odds of concomitant AF procedure than men (adjusted odds ratio, 0.74; 95% CI, 0.64-0.86; P < .001). Female sex was the risk factor associated with the lowest odds of concomitant AF procedure. CONCLUSIONS: Women are less likely to receive guideline recommended concomitant AF procedure during nonmitral surgery. Identification of barriers to concomitant AF procedure in women may improve treatment of AF.

19.
Am J Physiol Lung Cell Mol Physiol ; 327(2): L150-L159, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38771147

RESUMEN

Alteration in the normal mechanical forces of breathing can contribute to changes in contractility and remodeling characteristic of airway diseases, but the mechanisms that mediate these effects in airway cells are still under investigation. Airway smooth muscle (ASM) cells contribute to both contractility and extracellular matrix (ECM) remodeling. In this study, we explored ASM mechanisms activated by mechanical stretch, focusing on mechanosensitive piezo channels and the key Ca2+ regulatory protein stromal interaction molecule 1 (STIM1). Expression of Ca2+ regulatory proteins, including STIM1, Orai1, and caveolin-1, mechanosensitive ion channels Piezo-1 and Piezo-2, and NLRP3 inflammasomes were upregulated by 10% static stretch superimposed on 5% cyclic stretch. These effects were blunted by STIM1 siRNA. Histamine-induced [Ca2+]i responses and inflammasome activation were similarly blunted by STIM1 knockdown. These data show that the effects of mechanical stretch in human ASM cells are mediated through STIM1, which activates multiple pathways, including Piezo channels and the inflammasome, leading to potential downstream changes in contractility and ECM remodeling.NEW & NOTEWORTHY Mechanical forces on the airway can contribute to altered contractility and remodeling in airway diseases, but the mechanisms are not clearly understood. Using human airway smooth muscle cells exposed to cyclic forces with static stretch to mimic breathing and static pressure, we found that the effects of stretch are mediated through STIM1, resulting in the activation of multiple pathways, including Piezo channels and the inflammasome, with potential downstream influences on contractility and remodeling.


Asunto(s)
Miocitos del Músculo Liso , Molécula de Interacción Estromal 1 , Humanos , Molécula de Interacción Estromal 1/metabolismo , Molécula de Interacción Estromal 1/genética , Miocitos del Músculo Liso/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Inflamasomas/metabolismo , Estrés Mecánico , Mecanotransducción Celular , Músculo Liso/metabolismo , Canales Iónicos/metabolismo , Caveolina 1/metabolismo , Caveolina 1/genética , Transducción de Señal , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Calcio/metabolismo , Células Cultivadas , Contracción Muscular/fisiología , Remodelación de las Vías Aéreas (Respiratorias)/fisiología , Proteína ORAI1/metabolismo , Proteína ORAI1/genética
20.
Circ Cardiovasc Qual Outcomes ; 17(7): e010459, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38770653

RESUMEN

BACKGROUND: Home health care (HHC) has been increasingly used to improve care transitions and avoid poor outcomes, but there is limited data on its use and efficacy following coronary artery bypass grafting. The purpose of this study was to describe HHC use and its association with outcomes among Medicare beneficiaries undergoing coronary artery bypass grafting. METHODS: Retrospective analysis of 100% of Medicare fee-for-service files identified 77 331 beneficiaries undergoing coronary artery bypass grafting and discharged to home between July 2016 and December 2018. The primary exposure of HHC use was defined as the presence of paid HHC claims within 30 days of discharge. Hierarchical logistic regression identified predictors of HHC use and the percentage of variation in HHC use attributed to the hospital. Propensity-matched logistic regression compared mortality, readmissions, emergency department visits, and cardiac rehabilitation enrollment at 30 and 90 days after discharge between HHC users and nonusers. RESULTS: A total of 26 751 (34.6%) of beneficiaries used HHC within 30 days of discharge, which was more common among beneficiaries who were older (72.9 versus 72.5 years), male (79.4% versus 77.4%), White (90.2% versus 89.2%), and not Medicare-Medicaid dual eligible (6.7% versus 8.8%). The median hospital-level rate of HHC use was 31.0% (interquartile range, 13.7%-54.5%) and ranged from 0% to 94.2%. Nearly 30% of the interhospital variation in HHC use was attributed to the discharging hospital (intraclass correlation coefficient, 0.296 [95% CI, 0.275-0.318]). Compared with non-HHC users, those using HHC were less likely to have a readmission or emergency department visit, were more likely to enroll in cardiac rehabilitation, and had modestly higher mortality within 30 or 90 days of discharge. CONCLUSIONS: A third of Medicare beneficiaries undergoing coronary artery bypass grafting used HHC within 30 days of discharge, with wide interhospital variation in use and mixed associations with clinical outcomes and health care utilization.


Asunto(s)
Puente de Arteria Coronaria , Servicios de Atención de Salud a Domicilio , Medicare , Readmisión del Paciente , Humanos , Puente de Arteria Coronaria/mortalidad , Puente de Arteria Coronaria/efectos adversos , Estados Unidos , Masculino , Femenino , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Factores de Tiempo , Anciano de 80 o más Años , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/terapia , Factores de Riesgo , Alta del Paciente , Beneficios del Seguro , Rehabilitación Cardiaca , Planes de Aranceles por Servicios , Bases de Datos Factuales , Servicio de Urgencia en Hospital
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