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1.
Int J Hosp Manag ; 90: 102628, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32834354

RESUMO

Given the emergence of solo dining resulting from the changing family structure and increasingly individualised lifestyle in contemporary Chinese society, this study investigates solo dining in the setting of Chinese restaurants in Macao, including the solo dining motivations, behavioural characteristics, and experiences, taking into considerations the underlying social and cultural factors. Adopting a sequential exploratory mixed-method design, 18 interviews were conducted, followed by a survey with 493 local diners. Findings show that freedom of choice and satisfying hunger are the main motivations for solo dining, and some solo-friendly attributes, food-related attributes, and restaurant characteristics are considered as important elements. Solo dining is perceived positively, partly because its perceptions and experiences are shaped by the diners' socio-cultural backgrounds and unique regional characteristics, in which solo dining is considered relatively common in Macao as opposed to extant literature that has suggested an essentialised assumption about Chinese group-oriented dining preference. Sociocultural insights and managerial implications are provided in catering to the growing solo diner market.

2.
Curr Rheumatol Rep ; 17(3): 15, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25740702

RESUMO

Pulmonary hypertension (PH) is associated with significant morbidity and mortality. While the advent of disease-modifying therapies in the treatment of PH has dramatically increased the life expectancy of these patients, they remain at high risk for perioperative complications. Outcome studies suggest that patients with PH undergoing non-cardiac surgery have higher morbidity and mortality than those without, independent of severity. Despite these risks, more and more of these patients are presenting for non-cardiac surgery. Patients with rheumatologic disorders in particular often have pulmonary arterial hypertension (PAH), a group that is associated with a poorer prognosis. Yet, these patients invariably develop debilitating joint diseases and not uncommonly present for elective surgery. Preoperatively, patients with PH should be appropriately risk stratified based on functional class, etiology, exercise capacity, pulmonary hemodynamics, and the risk of surgery. If the risks and benefits assessment proves favorable, they should undergo optimization prior to surgery, with any chronic therapy continuing without cessation through the perioperative period. A multidisciplinary approach involving all intraoperative physicians is imperative to forming a safe intraoperative plan based on the inherent physiology underlying the patient's disease. Finally, because complications in this patient population often occur postoperatively, patients should be monitored in an appropriate setting with a goal of preventing right ventricular dysfunction. In this review article, we focus on the evaluation, risk stratification, and optimization of patients with PH undergoing non-cardiac surgery.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Hipertensão Pulmonar/fisiopatologia , Assistência Perioperatória/métodos , Humanos , Período Perioperatório
3.
Circulation ; 128(11 Suppl 1): S59-68, 2013 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-24030422

RESUMO

BACKGROUND: Endothelial progenitor cells (EPCs) possess robust therapeutic angiogenic potential, yet may be limited in the capacity to develop into fully mature vasculature. This problem might be exacerbated by the absence of a neovascular foundation, namely pericytes, with simple EPC injection. We hypothesized that coculturing EPCs with smooth muscle cells (SMCs), components of the surrounding vascular wall, in a cell sheet will mimic the native spatial orientation and interaction between EPCs and SMCs to create a supratherapeutic angiogenic construct in a model of ischemic cardiomyopathy. METHODS AND RESULTS: Primary EPCs and SMCs were isolated from Wistar rats. Confluent SMCs topped with confluent EPCs were spontaneously detached from the Upcell dish to create an SMC-EPC bi-level cell sheet. A rodent ischemic cardiomyopathy model was created by ligating the left anterior descending coronary artery. Rats were then immediately divided into 3 groups: cell-sheet transplantation (n=14), cell injection (n=12), and no treatment (n=13). Cocultured EPCs and SMCs stimulated an abundant release of multiple cytokines in vitro. Increased capillary density and improved blood perfusion in the borderzone elucidated the significant in vivo angiogenic potential of this technology. Most interestingly, however, cell fate-tracking experiments demonstrated that the cell-sheet EPCs and SMCs directly migrated into the myocardium and differentiated into elements of newly formed functional vasculature. The robust angiogenic effect of this cell sheet translated to enhanced ventricular function as demonstrated by echocardiography. CONCLUSIONS: Spatially arranged EPC-SMC bi-level cell-sheet technology facilitated the natural interaction between EPCs and SMCs, thereby creating structurally mature, functional microvasculature in a rodent ischemic cardiomyopathy model, leading to improved myocardial function.


Assuntos
Endotélio Vascular/fisiologia , Isquemia Miocárdica/patologia , Miócitos de Músculo Liso/fisiologia , Neovascularização Patológica/patologia , Células-Tronco/fisiologia , Animais , Técnicas de Cocultura , Endotélio Vascular/patologia , Feminino , Humanos , Masculino , Ratos , Ratos Wistar , Células-Tronco/patologia , Fatores de Tempo
4.
Circulation ; 128(11 Suppl 1): S79-86, 2013 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-24030424

RESUMO

BACKGROUND: Exogenously delivered chemokines have enabled neovasculogenic myocardial repair in models of ischemic cardiomyopathy; however, these molecules have short half-lives in vivo. In this study, we hypothesized that the sustained delivery of a synthetic analog of stromal cell-derived factor 1-α (engineered stromal cell-derived factor analog [ESA]) induces continuous homing of endothelial progenitor cells and improves left ventricular function in a rat model of myocardial infarction. METHODS AND RESULTS: Our previously designed ESA peptide was synthesized by the addition of a fluorophore tag for tracking. Hyaluronic acid was chemically modified with hydroxyethyl methacrylate to form hydrolytically degradable hydrogels through free-radical-initiated crosslinking. ESA was encapsulated in hyaluronic acid hydrogels during gel formation, and then ESA release, along with gel degradation, was monitored for more than 4 weeks in vitro. Chemotactic properties of the eluted ESA were assessed at multiple time points using rat endothelial progenitor cells in a transwell migration assay. Finally, adult male Wistar rats (n=33) underwent permanent ligation of the left anterior descending (LAD) coronary artery, and 100 µL of saline, hydrogel alone, or hydrogel+25 µg ESA was injected into the borderzone. ESA fluorescence was monitored in animals for more than 4 weeks, after which vasculogenic, geometric, and functional parameters were assessed to determine the therapeutic benefit of each treatment group. ESA release was sustained for 4 weeks in vitro, remained active, and enhanced endothelial progenitor cell chemotaxis. In addition, ESA was detected in the rat heart >3 weeks when delivered within the hydrogels and significantly improved vascularity, ventricular geometry, ejection fraction, cardiac output, and contractility compared with controls. CONCLUSIONS: We have developed a hydrogel delivery system that sustains the release of a bioactive endothelial progenitor cell chemokine during a 4-week period that preserves ventricular function in a rat model of myocardial infarction.


Assuntos
Quimiocina CXCL12/fisiologia , Células Endoteliais/efeitos dos fármacos , Hidrogéis , Infarto do Miocárdio/tratamento farmacológico , Células-Tronco/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos , Animais , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Quimiocina CXCL12/administração & dosagem , Preparações de Ação Retardada , Células Endoteliais/metabolismo , Células Endoteliais/fisiologia , Injeções , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Ratos , Ratos Wistar , Células-Tronco/metabolismo , Células-Tronco/fisiologia , Função Ventricular Esquerda/fisiologia
6.
Circulation ; 124(11 Suppl): S18-26, 2011 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-21911811

RESUMO

BACKGROUND: Experimentally, exogenous administration of recombinant stromal cell-derived factor-1α (SDF) enhances neovasculogenesis and cardiac function after myocardial infarction. Smaller analogs of SDF may provide translational advantages including enhanced stability and function, ease of synthesis, lower cost, and potential modulated delivery via engineered biomaterials. In this study, computational protein design was used to create a more efficient evolution of the native SDF protein. METHODS AND RESULTS: Protein structure modeling was used to engineer an SDF polypeptide analog (engineered SDF analog [ESA]) that splices the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a diproline segment designed to limit the conformational flexibility of the peptide backbone and retain the relative orientation of these segments observed in the native structure of SDF. Endothelial progenitor cells (EPCs) in ESA gradient, assayed by Boyden chamber, showed significantly increased migration compared with both SDF and control gradients. EPC receptor activation was evaluated by quantification of phosphorylated AKT, and cells treated with ESA yielded significantly greater phosphorylated AKT levels than SDF and control cells. Angiogenic growth factor assays revealed a distinct increase in angiopoietin-1 expression in the ESA- and SDF-treated hearts. In addition, CD-1 mice (n=30) underwent ligation of the left anterior descending coronary artery and peri-infarct intramyocardial injection of ESA, SDF-1α, or saline. At 2 weeks, echocardiography demonstrated a significant gain in ejection fraction, cardiac output, stroke volume, and fractional area change in mice treated with ESA compared with controls. CONCLUSIONS: Compared with native SDF, a novel engineered SDF polypeptide analog (ESA) more efficiently induces EPC migration and improves post-myocardial infarction cardiac function and thus offers a more clinically translatable neovasculogenic therapy.


Assuntos
Proteínas Angiogênicas/química , Proteínas Angiogênicas/farmacologia , Quimiocina CXCL12/química , Quimiocina CXCL12/farmacologia , Biologia Computacional/métodos , Neovascularização Fisiológica/efeitos dos fármacos , Engenharia de Proteínas/métodos , Proteínas Angiogênicas/uso terapêutico , Animais , Débito Cardíaco/efeitos dos fármacos , Débito Cardíaco/fisiologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Células Cultivadas , Quimiocina CXCL12/uso terapêutico , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiologia , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos , Modelos Animais , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/prevenção & controle , Neovascularização Fisiológica/fisiologia , Ratos , Ratos Wistar , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Volume Sistólico/efeitos dos fármacos , Volume Sistólico/fisiologia
7.
Trauma Case Rep ; 41: 100680, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35958272

RESUMO

In patients with acute rib fractures, regional anesthesia has the potential to reduce suffering, decrease opiate use, lower rates of in-hospital delirium, and improve pulmonary function. While many regional anesthesia techniques are complex and time consuming, two single injection nerve blocks, the serratus anterior plane block and erector spinae plane block, are particularly fast, safe, and simple methods to anesthetize the chest wall. Herein we describe two cases in which the serratus anterior plane block and erector spinae plane block were each used with great success in achieving improved pain control in trauma patients with multiple rib fractures. We believe that any provider who routinely cares for patients with rib fractures (emergency physicians and trauma surgeons alike) can and should learn to use these straightforward nerve blocks.

8.
HSS J ; 18(3): 344-350, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35846258

RESUMO

Background: With an aging population, orthopedics has become one of the largest and fastest growing surgical fields. However, data on the use of critical care services (CCS) in patients undergoing orthopedic procedures remain sparse. Purpose: We sought to elucidate the prevalence and characteristics of patients requiring CCS and intermediate levels of care after orthopedic surgeries at a high-volume orthopedic medical center. Methods: We retrospectively reviewed inpatient electronic medical record data (2016-2020) at a high-volume orthopedic hospital. Patients who required CCS and intermediate levels of care, including step-down unit (SDU) and telemetry services, were identified. We described characteristics related to patients, procedures, and outcomes, including type of advanced services required and surgery type. Results: Of the 50,387 patients who underwent orthopedic inpatient surgery, 1.6% required CCS and 21.6% were admitted to an SDU. Additionally, 482 (1.0%) patients required postoperative mechanical ventilation and 3602 (7.1%) patients required continuous positive airway pressure therapy. Spine surgery patients were the most likely to require any form of advanced care (45.7%). Conclusions: This retrospective review found that approximately one-fourth of orthopedic surgery patients were admitted to units that provided critical and intermediate levels of care. These results may prove useful to hospitals in estimating needs and allocating resources for advanced and critical care services after orthopedic surgery.

9.
J Clin Invest ; 118(10): 3503-12, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18769631

RESUMO

Emerging metabolomic tools have created the opportunity to establish metabolic signatures of myocardial injury. We applied a mass spectrometry-based metabolite profiling platform to 36 patients undergoing alcohol septal ablation treatment for hypertrophic obstructive cardiomyopathy, a human model of planned myocardial infarction (PMI). Serial blood samples were obtained before and at various intervals after PMI, with patients undergoing elective diagnostic coronary angiography and patients with spontaneous myocardial infarction (SMI) serving as negative and positive controls, respectively. We identified changes in circulating levels of metabolites participating in pyrimidine metabolism, the tricarboxylic acid cycle and its upstream contributors, and the pentose phosphate pathway. Alterations in levels of multiple metabolites were detected as early as 10 minutes after PMI in an initial derivation group and were validated in a second, independent group of PMI patients. A PMI-derived metabolic signature consisting of aconitic acid, hypoxanthine, trimethylamine N-oxide, and threonine differentiated patients with SMI from those undergoing diagnostic coronary angiography with high accuracy, and coronary sinus sampling distinguished cardiac-derived from peripheral metabolic changes. Our results identify a role for metabolic profiling in the early detection of myocardial injury and suggest that similar approaches may be used for detection or prediction of other disease states.


Assuntos
Biomarcadores/sangue , Traumatismos Cardíacos/sangue , Traumatismos Cardíacos/diagnóstico , Infarto do Miocárdio/sangue , Infarto do Miocárdio/metabolismo , Idoso , Animais , Células Cultivadas , Seio Coronário/metabolismo , Feminino , Traumatismos Cardíacos/metabolismo , Humanos , Isótopos , Cinética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Miócitos Cardíacos/metabolismo , Ratos , Padrões de Referência , Reprodutibilidade dos Testes , Fatores de Tempo
10.
ACS Chem Neurosci ; 12(20): 3898-3914, 2021 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-34607428

RESUMO

Propofol, one of the most commonly used intravenous general anesthetics, modulates neuronal function by interacting with ion channels. The mechanisms that link propofol binding to the modulation of distinct ion channel states, however, are not understood. To tackle this problem, we investigated the prokaryotic ancestors of eukaryotic voltage-gated Na+ channels (Navs) using unbiased photoaffinity labeling (PAL) with a diazirine derivative of propofol (AziPm), electrophysiological methods, and mutagenesis. AziPm inhibits Nav function in a manner that is indistinguishable from that of the parent compound by promoting activation-coupled inactivation. In several replicates (8/9) involving NaChBac and NavMs, we found adducts at residues located at the C-terminal end of the S4 voltage sensor, the S4-S5 linker, and the N-terminal end of the S5 segment. However, the non-inactivating mutant NaChBac-T220A yielded adducts that were different from those found in the wild-type counterpart, which suggested state-dependent changes at the binding site. Then, using molecular dynamics simulations to further elucidate the structural basis of Nav modulation by propofol, we show that the S4 voltage sensors and the S4-S5 linkers shape two distinct propofol binding sites in a conformation-dependent manner. Supporting the PAL and MD simulation results, we also found that Ala mutations of a subset of adducted residues have distinct effects on gating modulation of NaChBac and NavMs by propofol. The results of this study provide direct insights into the structural basis of the mechanism through which propofol binding promotes activation-coupled inactivation to inhibit Nav channel function.


Assuntos
Anestésicos Gerais , Propofol , Canais de Sódio Disparados por Voltagem , Sítios de Ligação , Canais Iônicos , Propofol/farmacologia , Canais de Sódio Disparados por Voltagem/metabolismo
11.
J Med Econ ; 12(2): 124-35, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19566483

RESUMO

OBJECTIVE: Compare treatment persistence, healthcare utilisation and costs for patients treated with escitalopram versus other SSRI/SNRIs in a real-world setting. METHODS: Patients with a diagnosis for major depressive disorder (MDD) and at least one prescription for an SSRI or SNRI were identified from the Ingenix Impact Database (2002-2005). The baseline and study observation periods were defined as the 6 months before and after the index date (first date for an SSRI /SNRI pharmacy claim). Comparisons were made between patients initiated on escitalopram versus other SSRI/SNRIs using descriptive statistics and multivariate regressions. RESULTS: Escitalopram patients (n=10,465) had better treatment persistence compared to patients initiated on other SSRI/SNRIs (n=28,310): the hazard ratio of all discontinuation was 0.96 (95% confidence interval [CI]=0.94-0.99) for the escitalopram therapy (p=0.003), and the hazard ratio of switching to another second-generation antidepressant was 0.91 (95% CI=0.87-0.94) for the escitalopram therapy (p<0.001). Escitalopram patients also had fewer inpatient service and emergency room visits. Adjusted average total all-cause healthcare costs and inpatient services costs were $839 and $405 lower in the escitalopram group (both p<0.05). CONCLUSIONS: Escitalopram may be associated with lower healthcare utilisation and costs among adult MDD patients compared to other SSRI/SNRIs.


Assuntos
Citalopram/economia , Transtorno Depressivo Maior/tratamento farmacológico , Custos de Cuidados de Saúde , Serviços de Saúde/estatística & dados numéricos , Adesão à Medicação , Inibidores Seletivos de Recaptação de Serotonina/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Citalopram/uso terapêutico , Custos e Análise de Custo , Bases de Dados como Assunto , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Adulto Jovem
12.
Reg Anesth Pain Med ; 44(9): 854-859, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31300592

RESUMO

BACKGROUND: Arthroplasty is one of the most commonly performed procedures in the USA with projections of continuous growth. As this field undergoes continuous changes, the goal of this study was to provide an analysis of patient-related and healthcare system-related trends. This is important as it allows practitioners, administrators and policy makers to allocate needed resources appropriately. METHODS: The study included total knee arthroplasty (TKA) and total hip arthroplasty (THA) procedures from 2006 to 2016. Demographic information, comorbidities and complications were extracted and analyzed from the Premier Healthcare database. RESULTS: The surgical volume increased annually over the observation period by an average of 5.54% for TKA and 7.02% for THA, respectively. The average age of the patient population and the types of anesthesia used remained relatively consistent over time. Comorbidity burden increased, especially for obesity (16.52% in 2006 and 29.77% in 2016 for TKA, 11.15% in 2006 and 20.92% in 2016 for THA), obstructive sleep apnea (OSA) (6.82% in 2006 and 17.03% in 2016 for TKA, 4.69% in 2006 and 12.72% in 2016 for THA) and renal insufficiency (2.81% in 2006 and 7.01% in 2016 for TKA, 2.78% in 2006 and 6.43% in 2016 for THA). Minor trends of increases were also observed in the prevalence of liver disease, depression and hypothyroidism. All postoperative complications were trending lower except for acute renal failure, where an increase was noted (4.39% in 2006 and 8.10% in 2016 for TKA, 4.99% in 2006 and 8.42% in 2016 for THA). DISCUSSION: Significant trends in the care of patients who undergo TKA and THA were identified. Individuals undergoing these procedures presented with a higher prevalence of comorbidities. Despite these trajectories, complications declined over time. These data can be used to inform future research and to allocate resources to address changes in populations cared for and complications encountered.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Humanos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
13.
Emerg Med Clin North Am ; 36(4): 645-663, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30296997

RESUMO

Infective endocarditis (IE) is an uncommon infection of cardiac valves associated with bacteremia. It increasingly affects elderly patients with chronic disease and artificial cardiac devices. The presentation, however, remains subtle and varied, with nonspecific symptoms ranging from those resembling a mild viral infection to septic shock and multiorgan failure. IE carries potential to cause significant morbidity and mortality through its impact on cardiac function and from embolic complications. Blood cultures prior to antibiotics and obtaining prompt echocardiography are key diagnostic steps, followed by proper selection of empiric antibiotics and, in many cases, collaboration with infectious disease, cardiology, and cardiothoracic surgery specialists.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/complicações , Endocardite , Bacteriemia/tratamento farmacológico , Endocardite/tratamento farmacológico , Endocardite/epidemiologia , Endocardite/etiologia , Humanos , Morbidade/tendências , Prognóstico , Estados Unidos/epidemiologia
14.
Methods Enzymol ; 602: 339-368, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29588038

RESUMO

Voltage-gated ion channels (VGICs) of excitable tissues are emerging as targets likely involved in both the therapeutic and toxic effects of inhaled and intravenous general anesthetics. Whereas sevoflurane and propofol inhibit voltage-gated Na+ channels (Navs), sevoflurane potentiates certain voltage-gated K+ channels (Kvs). The combination of these effects would dampen neural excitability and, therefore, might contribute to the clinical endpoints of general anesthesia. As the body of work regarding the interaction of general anesthetics with VGICs continues to grow, a multidisciplinary approach involving functional, biochemical, structural, and computational techniques, many of which are detailed in other chapters, has increasingly become necessary to solve the molecular mechanism of general anesthetic action on VGICs. Here, we focus on electrophysiological and modeling approaches and methodologies to describe how our work has elucidated the biophysical basis of the inhibition Navs by propofol and the potentiation of Kvs by sevoflurane.


Assuntos
Anestésicos Gerais/farmacologia , Eletrofisiologia/métodos , Ativação do Canal Iônico/efeitos dos fármacos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Canais de Sódio Disparados por Voltagem/metabolismo , Animais , Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Simulação por Computador , Eletrodos , Eletrofisiologia/instrumentação , Células HEK293 , Humanos , Ativação do Canal Iônico/fisiologia , Modelos Biológicos , Oócitos , Técnicas de Patch-Clamp/instrumentação , Técnicas de Patch-Clamp/métodos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/agonistas , Propofol/farmacologia , Proteínas Recombinantes/metabolismo , Sevoflurano/farmacologia , Transfecção/instrumentação , Transfecção/métodos , Bloqueadores do Canal de Sódio Disparado por Voltagem/farmacologia , Xenopus laevis
15.
J Gen Physiol ; 150(9): 1299-1316, 2018 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-30018038

RESUMO

Propofol is widely used in the clinic for the induction and maintenance of general anesthesia. As with most general anesthetics, however, our understanding of its mechanism of action remains incomplete. Local and general anesthetics largely inhibit voltage-gated Na+ channels (Navs) by inducing an apparent stabilization of the inactivated state, associated in some instances with pore block. To determine the biophysical and molecular basis of propofol action in Navs, we investigated NaChBac and NavMs, two prokaryotic Navs with distinct voltage dependencies and gating kinetics, by whole-cell patch clamp electrophysiology in the absence and presence of propofol at clinically relevant concentrations (2-10 µM). In both Navs, propofol induced a hyperpolarizing shift of the pre-pulse inactivation curve without any significant effects on recovery from inactivation at strongly hyperpolarized voltages, demonstrating that propofol does not stabilize the inactivated state. Moreover, there was no evidence of fast or slow pore block by propofol in a non-inactivating NaChBac mutant (T220A). Propofol also induced hyperpolarizing shifts of the conductance-voltage relationships with negligible effects on the time constants of deactivation at hyperpolarized voltages, indicating that propofol does not stabilize the open state. Instead, propofol decreases the time constants of macroscopic activation and inactivation. Adopting a kinetic scheme of Nav gating that assumes preferential closed-state recovery from inactivation, a 1.7-fold acceleration of the rate constant of activation and a 1.4-fold acceleration of the rate constant of inactivation were sufficient to reproduce experimental observations with computer simulations. In addition, molecular dynamics simulations and molecular docking suggest that propofol binding involves interactions with gating machinery in the S4-S5 linker and external pore regions. Our findings show that propofol is primarily a positive gating modulator of prokaryotic Navs, which ultimately inhibits the channels by promoting activation-coupled inactivation.


Assuntos
Proteínas de Bactérias/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Propofol/farmacologia , Canais de Sódio/efeitos dos fármacos , Canais de Sódio Disparados por Voltagem/efeitos dos fármacos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Células HEK293 , Humanos , Cinética , Mutação , Técnicas de Patch-Clamp , Canais de Sódio/genética , Canais de Sódio/metabolismo , Canais de Sódio Disparados por Voltagem/metabolismo
16.
J Altern Complement Med ; 24(5): 505-513, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29420050

RESUMO

PURPOSE: Medical students have higher rates of depression and psychologic distress than the general population, which may negatively impact academic performance and professional conduct. This study assessed whether 10-20 min of daily mindfulness meditation for 30 days, using a mobile phone application, could decrease perceived stress and improve well-being for medical students. METHODS: Eighty-eight medical students were stratified by class year and randomized to either intervention or control groups to use the mobile application Headspace, an audio-guided mindfulness meditation program, for 30 days. All participants completed the Perceived Stress Scale (PSS), Five-Facet Mindfulness Questionnaire (FFMQ), and General Well-Being Schedule (GWBS) at baseline (T1), 30 days (T2), and 60 days (T3). Repeated measures analysis of variance (rANOVA) was conducted for intervention versus control groups across T1, T2, and T3 to examine differences in stress, mindfulness, and well-being. RESULTS: There was a significant interaction between time and treatment group for perceived stress and well-being. Perceived stress significantly decreased for the intervention group from T1 to T3 (F[2,142] = 3.98, p < 0.05). General well-being significantly increased for the intervention group compared to the control group from T1 to T2, and the increase was sustained through T3 (F[2,144] = 3.36, p < 0.05). CONCLUSIONS: These results highlight that a mobile audio-guided mindfulness meditation program is an effective means to decrease perceived stress in medical students, which may have implications on patient care. Integrating mindfulness training into medical school curricula for management of school- and work-related stress may lead to fewer negative physician outcomes (e.g., burnout, anxiety, and depression) and improved physician and patient outcomes. This has implications for a broad group of therapists and healthcare providers, ultimately improving quality of healing and patient care.


Assuntos
Meditação/métodos , Atenção Plena/métodos , Aplicativos Móveis , Estresse Psicológico/terapia , Estudantes de Medicina , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudantes de Medicina/psicologia , Estudantes de Medicina/estatística & dados numéricos , Adulto Jovem
17.
J Am Acad Orthop Surg Glob Res Rev ; 2(10): e058, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30656249

RESUMO

INTRODUCTION: Joint arthroplasty practice is highly dynamic to adapt to economic changes and advances in medicine. This study provides updates of the current perioperative practice on healthcare resource utilization. METHODS: The study included total knee arthroplasty, total hip arthroplasty, and total shoulder arthroplasty within the healthcare cost and utilization project New York State database from 2007 to 2013 (ie, 202,100, 127,872, and 8858 cases, respectively). RESULTS: A higher proportion of sicker patients were prevalent over time. The length of stay decreased continuously. However, total hospital charges increased after adjusting for inflation. The incidence of wound infection and transfusion decreased steadily over time, whereas acute renal failure has been on the rise. There was an increased utilization of echocardiography, while decreased among other resources. DISCUSSION: Total knee arthroplasty, total hip arthroplasty, and total shoulder arthroplasty changed toward sicker patients with shorter length of stay, fewer complications, and less resource utilization. However, overall costs increased over time.

18.
J Gen Physiol ; 150(9): 1317-1331, 2018 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-30018039

RESUMO

Voltage-gated sodium (NaV) channels are important targets of general anesthetics, including the intravenous anesthetic propofol. Electrophysiology studies on the prokaryotic NaV channel NaChBac have demonstrated that propofol promotes channel activation and accelerates activation-coupled inactivation, but the molecular mechanisms of these effects are unclear. Here, guided by computational docking and molecular dynamics simulations, we predict several propofol-binding sites in NaChBac. We then strategically place small fluorinated probes at these putative binding sites and experimentally quantify the interaction strengths with a fluorinated propofol analogue, 4-fluoropropofol. In vitro and in vivo measurements show that 4-fluoropropofol and propofol have similar effects on NaChBac function and nearly identical anesthetizing effects on tadpole mobility. Using quantitative analysis by 19F-NMR saturation transfer difference spectroscopy, we reveal strong intermolecular cross-relaxation rate constants between 4-fluoropropofol and four different regions of NaChBac, including the activation gate and selectivity filter in the pore, the voltage sensing domain, and the S4-S5 linker. Unlike volatile anesthetics, 4-fluoropropofol does not bind to the extracellular interface of the pore domain. Collectively, our results show that propofol inhibits NaChBac at multiple sites, likely with distinct modes of action. This study provides a molecular basis for understanding the net inhibitory action of propofol on NaV channels.


Assuntos
Proteínas de Bactérias/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Propofol/farmacologia , Canais de Sódio/efeitos dos fármacos , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Flúor , Células HEK293 , Humanos , Larva , Espectroscopia de Ressonância Magnética , Técnicas de Patch-Clamp , Canais de Sódio/genética , Canais de Sódio/metabolismo , Xenopus laevis
19.
J Educ Perioper Med ; 20(3): E624, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30510972

RESUMO

BACKGROUND: Point-of-care ultrasonography (PoCUS) provides real-time, dynamic clinical evidence for providers to make potentially lifesaving medical decisions; however, these tools cannot be used effectively without appropriate training. Although there is always the option of traditional didactic methods, there has been a recent trend toward a "reverse classroom" web-based model using online e-learning modules. Our objective was to collect pilot data that would justify a future randomized controlled trial, comparing traditional didactics to an e-learning PoCUS curriculum for lung ultrasonography (LUS) and the focused assessment with sonography in trauma (FAST) exam. METHODS: Anesthesiology interns, residents (CA 1-3), and fellow trainees enrolled in a LUS and FAST exam course and were randomized to receive didactic lectures or e-learning. Trainees completed knowledge pre- and posttests. Surveys were administered to gauge learning satisfaction. All trainees completed a hands-on-training (HOT) workshop. Image acquisition was assessed through practical tests before HOT, immediately after HOT, and 5 months later. RESULTS: Eighteen trainees completed the study. There was no evidence of a difference in change in LUS knowledge test score from baseline to posttest between the e-learning and didactic groups (difference in median percentage point change [95 % CI]: 6.6 [-10.0, 23.2]; P = .411). There was no evidence of a difference in LUS knowledge posttest scores (difference in median percentage points [95% CI]: -0.9 [-4.8, 3.0]; P = .629), FAST knowledge posttest score (0 [incalculable]; P = .999), or post-HOT practical test score (-4.2 [-24.6, 16.3]; P = .672) between groups. There was no evidence of a difference in degree of satisfaction with learning experience between groups (odds ratios [95% CI]: 1.75 [0.31, 9.94]; P = .528). CONCLUSIONS: There was no evidence of a difference between the e-learning and traditional didactic groups in learning or satisfaction outcomes. These results justify establishing an adequately powered, randomized controlled trial assessing the noninferiority of e-learning to traditional didactics for teaching LUS and FAST.

20.
J Manag Care Pharm ; 13(7): 561-9, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17874862

RESUMO

BACKGROUND: Many therapies exist for treating adult attention-deficit/hyperactivity disorder (ADHD), also referred to as attention-deficit disorder (ADD), but there is no research regarding cost differences associated with initiating alternative ADD/ADHD drug therapies in adults. OBJECTIVE: To compare from the perspective of a large self-insured employer the risk-adjusted direct health care costs associated with 3 alternative drug therapies for ADD in newly treated patients: extended-release methylphenidate (osmotic release oral system-MPH), mixed amphetamine salts extended release (MAS-XR), or atomoxetine. METHODS: We analyzed data from a US claims database of 5 million beneficiaries from 31 large self-insured employers (1999-2004). Analysis was restricted to adults aged 18 to 64 years with at least 1 diagnosis of ADD/ADHD (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 314.0x--attention deficit disorder; 314.00--attention deficit disorder without hyperactivity; or 314.01--attention-deficit disorder with hyperactivity) and at least 1 pharmacy claim for OROS-MPH, MAS-XR, or atomoxetine identified using National Drug Codes. In preliminary analysis, we calculated the duration of index ADHD drug therapy as time from index therapy initiation to a minimum 60-day gap. Because the median duration of index ADHD drug therapy was found to be approximately 90 days, the primary measures were total direct medical plus drug costs and medical-only costs computed over 6 months following therapy initiation. Adults were required to have continuous eligibility 6 months before and 6 months after their latest drug therapy initiation and no ADHD therapy during the previous 6 months. Cost was measured as the payment amount made by the health plan to the provider rather than billed charges, and it excluded patient copayments and deductibles. Medical costs included costs incurred for all-cause inpatient and outpatient/other services. Costs were adjusted for inflation to 2004 U.S. dollars using the consumer price index for medical care. T tests were used for descriptive cost comparisons. Generalized linear models (GLMs) were used to compare costs of adults receiving alternative therapies, adjusting for demographic characteristics, substance abuse, depression, and the Charlson Comorbidity Index. RESULTS: Of the 4,569 patients who received 1 of these 3 drug therapies for ADHD, 31.8% received OROS-MPH for a median duration of 99 days of therapy, 34.0% received MAS-XR for a median 128 days, and 34.2% received atomoxetine for a median 86 days. In the 6-month follow-up period, the mean (standard deviation) total medical and drug costs were $2,008 ($3,231) for OROS-MPH, $2,169 ($4,828) for MAS-XR, and $2,540 ($4,269) for atomoxetine-treated adults. The GLM for patient characteristics suggested that 6-month, risk-adjusted mean medical costs, excluding drug costs, for adults treated with OROS-MPH were $142 less (10.4%, $1,220 vs. $1,362) compared with MAS-XR (P =0.022) and $132 less (9.8%, $1,220 vs. $1,352) compared with atomoxetine (P =0.033); risk-adjusted mean medical costs were not significantly different between MAS-XR and atomoxetine. The GLM comparison of risk-adjusted total direct costs, including drug cost, was on average $156 less (8.0%, $1,782 vs. $1,938) for OROS-MPH compared with MAS-XR (P = 0.017) and $226 less (11.3%, $1,782 vs. $2,008) compared with atomoxetine (P <0.001); the risk-adjusted total direct costs were not significantly different between MAS-XR and atomoxetine. Two high-cost outliers (greater than 99.96th percentile, 1 each for OROS-MPH and atomoxetine) accounted for $47 (30%) of the $156 cost difference between OROS-MPH and MAS-XR and $11 (5%) of the $226 cost difference between OROS-MPH and atomoxetine, and the medical diagnoses for the highest-cost claims for these 2 outlier patients were unrelated to ADHD. CONCLUSIONS: After adjusting for patient characteristics including substance abuse, depression, and the Charlson Comorbidity Index, adults treated with OROS-MPH had, on average, slightly lower medical and total medical and drug costs than those treated with MAS-XR or atomoxetine over the 6-month period after drug therapy initiation. Approximately 30% of the cost difference compared with MAS-XR was attributable to 1 high-cost outlier with medical diagnoses for the highest-cost claim that were unrelated to ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/economia , Custos de Cuidados de Saúde , Inibidores da Captação Adrenérgica/economia , Inibidores da Captação Adrenérgica/uso terapêutico , Adulto , Anfetaminas/economia , Anfetaminas/uso terapêutico , Cloridrato de Atomoxetina , Estimulantes do Sistema Nervoso Central/economia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Custos e Análise de Custo/métodos , Bases de Dados Factuais/estatística & dados numéricos , Preparações de Ação Retardada/economia , Preparações de Ação Retardada/uso terapêutico , Feminino , Humanos , Seguro Saúde/estatística & dados numéricos , Seguro de Serviços Farmacêuticos/economia , Seguro de Serviços Farmacêuticos/estatística & dados numéricos , Masculino , Programas de Assistência Gerenciada/economia , Programas de Assistência Gerenciada/estatística & dados numéricos , Metilfenidato/economia , Metilfenidato/uso terapêutico , Pessoa de Meia-Idade , Análise Multivariada , Propilaminas/economia , Propilaminas/uso terapêutico , Reprodutibilidade dos Testes , Fatores de Tempo
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