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Circadian disruption causes glucose intolerance, cardiac fibrosis, and adipocyte dysfunction in sand rats (Psammomys obesus). Exercise intervention can improve glucose metabolism, insulin sensitivity, adipose tissue function and protect against inflammation. We investigated the influence of exercise on male P. obesus exposed to a short photoperiod (5 h light:19 h dark) and high-energy diet. Exercise reduced glucose intolerance. Exercise reduced cardiac expression of inflammatory marker Ccl2 and Bax:Bcl2 apoptosis ratio. Exercise increased heart:body weight ratio and hypertrophy marker Myh7:Myh6, yet reduced Gata4 expression. No phenotypic changes were observed in perivascular fibrosis and myocyte area. Exercise reduced visceral adipose expression of inflammatory transcription factor Rela, adipogenesis marker Ppard and browning marker Ppargc1a, but visceral adipocyte size was unaffected. Conversely, exercise reduced subcutaneous adipocyte size but did not affect any molecular mediators. Exercise increased ZT7 Bmal1 and Per2 in the suprachiasmatic nucleus and subcutaneous Per2. Our study provides new molecular insights and histological assessments on the effect of exercise on cardiac inflammation, adipose tissue dysfunction and circadian gene expression in P. obesus exposed to short photoperiod and high-energy diet. These findings have implications for the protective benefits of exercise for shift workers in order to reduce the risk of diabetes and cardiovascular disease.
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Tecido Adiposo , Gerbillinae , Intolerância à Glucose , Fotoperíodo , Condicionamento Físico Animal , Animais , Masculino , Intolerância à Glucose/metabolismo , Tecido Adiposo/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Dieta Hiperlipídica/efeitos adversos , Miocárdio/metabolismo , Miocárdio/patologiaRESUMO
Hypervalent iodine catalysis has been widely utilized in olefin functionalization reactions. Intermolecularly, the regioselective addition of two distinct nucleophiles across the olefin is a challenging process in hypervalent iodine catalysis. We introduce here a unique strategy using simple lithium salts for hypervalent iodine catalyst activation. The activated hypervalent iodine catalyst allows the intermolecular coupling of soft nucleophiles such as amides onto electronically activated olefins with high regioselectivity.
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The severe shortage of donor's hearts has increased the mortality of patients on the transplant waiting list. However, donor hearts with valvular dysfunction are rarely used. Utilizing donor hearts with valvular lesions that can be repaired or replaced at the time of transplant will decrease waitlist mortality and offer many patients a second chance in life.
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Transplante de Coração , Doadores de Tecidos , Humanos , Listas de EsperaRESUMO
Surface complexation models (SCM), based mainly on the diffuse double layer (DDL) theory, have been used to predict zeta potential at the crude oil-brine-rock (COBR) interface with limited success. However, DDL is inherently limited in accurately predicting zeta potential by the assumptions that all the brine ions interact with the rock surface at the same plane and by the double layer collapse at higher brine ionic strength (>1M). In this work, a TLM-based SCM captured zeta potential trends at the calcite-brine interface with ionic strength up to 3 M. An extended DDL and TLM-based SCMs were used to predict the electrokinetic properties of a composite carbonate rock showing a different mineralogical composition. The extended TLM-based SCM captured the zeta potential prediction trends and magnitude, highlighting the contribution of the inorganic minerals and organic impurities on the composite carbonate surface. In contrast, the extended DDL-based SCM captured the zeta potential trends but failed to capture the magnitude of the measured zeta potential. Interestingly, the TLM-based SCM predicted a positive SP for the rock-brine interface, which could explain the oil-wet nature of composite carbonate rocks due to electrostatic adsorption of negatively charged carboxylic acids. Conversely, the DDL-based SCM predicted a negative SP, leading to an inaccurate interpretation of the electrokinetic properties at the rock-brine interface. Thus, the use of extended TLM-based SCM was required to accurately predict the zeta potential and account for the adsorption of carboxylic acids on the reservoir composite carbonate surface.
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BACKGROUND: Immune checkpoint inhibitors are associated with unique autoimmune side effects that differ from traditional cytotoxic chemotherapy. Pharmacists may play an important role in providing key supportive care measures necessary to aid patients and oncologists through immune-related adverse events (irAEs). This study aims to evaluate the impact of a pharmacist-managed irAE protocol in an oncology clinic. METHODS: This study is a retrospective chart review of the implementation of a pilot irAE pharmacy protocol. Patients treated with an immune checkpoint inhibitor and subsequently identified to have dermatologic, gastrointestinal, hepatic, or thyroid toxicities and managed under the pilot irAE pharmacy protocol from 1 October 2018 to 28 February 2019 were enrolled. Study endpoints included number of pharmacist interventions and physician satisfaction. Additional endpoints included pharmacotherapy initiated, dose adjustments, and patient follow-ups. RESULTS: From 1 October 2018, to 28 February 2019, 17 patients were referred and approved by their primary oncologists for pharmacy management under the pilot irAE protocol. During the pilot period, pharmacists initiated 21 new medications for the treatment of irAEs, including thyroid hormone replacement in 7 patients (41%) and oral corticosteroids in 6 patients (35%) with a total of 28 dose adjustments. In addition, the pilot protocol included an assessment of physician satisfaction, which showed a reduced number of physician hours per month managing irAEs, increased physician confidence in irAE management, and a desire for continued pharmacist-management of irAEs. CONCLUSIONS: Oncology pharmacists had an impact on management of toxicities in our oncology clinic as indicated by the pharmacist interventions and physician satisfaction.
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Inibidores de Checkpoint Imunológico/efeitos adversos , Conduta do Tratamento Medicamentoso , Farmacêuticos , Corticosteroides/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Feminino , Terapia de Reposição Hormonal , Humanos , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/uso terapêutico , Relações Interprofissionais , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Serviço de Farmácia Hospitalar , Médicos , Projetos Piloto , Estudos Retrospectivos , Hormônios Tireóideos/administração & dosagem , Hormônios Tireóideos/uso terapêuticoRESUMO
The surgical treatment of pulmonary hypertension (PH), with or without pulmonary artery aneurysm, has evolved during the last 40 years from heart-lung transplants to bilateral lung transplants as the treatment of choice for PH patients with preserved right and left ventricular function and without complex cardiac abnomalies.
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Aneurisma , Hipertensão Pulmonar , Transplante de Pulmão , Aneurisma/complicações , Aneurisma/diagnóstico por imagem , Aneurisma/cirurgia , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/cirurgia , Pulmão , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgiaRESUMO
As the incidence of ischemia-reperfusion (I-R) injury has substantially increased, there is a pressing need to develop effective strategies to treat this global health issue. I-R injury can affect all organs and is associated with high morbidity and mortality rates. Pathological settings such as myocardial infarction, stroke, hemorrhagic shock, and solid organ transplant are particularly prone to cause I-R injury. Ischemia (hypoxia) and/or reperfusion (reoxygenation) induces various forms of cellular and structural damage. A major cause of damage is local inflammatory responses, which may spread to produce more advanced systemic inflammation. Management of I-R injury relies primarily on supportive measures, as specific treatment strategies are lacking. Extracellular vesicles (EVs) are cell-secreted nano-scale structures containing various biomolecules involved in cell communication and multiple physiological processes. EVs derived from certain cell types have been shown to exhibit anti-inflammatory, antioxidant, and angiogenic properties. This review provides an overview of EV-based therapeutics for I-R injury in kidneys, liver, heart, lungs, and brain. Additionally, the mechanisms by which EVs protect against I-R injury are discussed. Promising preclinical findings highlight the potential clinical use of EVs for I-R injury.
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Injúria Renal Aguda , Vesículas Extracelulares , Células-Tronco Mesenquimais , Traumatismo por Reperfusão , Humanos , RimRESUMO
Extracellular vesicles secreted from adipose-derived mesenchymal stem cells (ADSCs) have therapeutic effects in inflammatory diseases. However, production of extracellular vesicles (EVs) from ADSCs is costly, inefficient, and time consuming. The anti-inflammatory properties of adipose tissue-derived EVs and other biogenic nanoparticles have not been explored. In this study, biogenic nanoparticles are obtained directly from lipoaspirate, an easily accessible and abundant source of biological material. Compared to ADSC-EVs, lipoaspirate nanoparticles (Lipo-NPs) take less time to process (hours compared to months) and cost less to produce (clinical-grade cell culture facilities are not required). The physicochemical characteristics and anti-inflammatory properties of Lipo-NPs are evaluated and compared to those of patient-matched ADSC-EVs. Moreover, guanabenz loading in Lipo-NPs is evaluated for enhanced anti-inflammatory effects. Apolipoprotein E and glycerolipids are enriched in Lipo-NPs compared to ADSC-EVs. Additionally, the uptake of Lipo-NPs in hepatocytes and macrophages is higher. Lipo-NPs and ADSC-EVs have comparable protective and anti-inflammatory effects. Specifically, Lipo-NPs reduce toll-like receptor 4-induced secretion of inflammatory cytokines in macrophages. Guanabenz-loaded Lipo-NPs further suppress inflammatory pathways, suggesting that this combination therapy can have promising applications for inflammatory diseases.
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Tecido Adiposo , Vesículas Extracelulares , Inflamação , Nanopartículas , Tecido Adiposo/química , Anti-Inflamatórios/economia , Anti-Inflamatórios/uso terapêutico , Humanos , Inflamação/terapia , Células-Tronco Mesenquimais/metabolismoRESUMO
BACKGROUND: Cardiac myxomas are common and account for 50% of primary intracardiac tumors. Atypical locations of cardiac myxoma increase the risk of intraoperative iatrogenic injuries. Herein, we report a case of using three-dimensional printing (3D) to facilitate the removal of an atypical cardiac myxoma in a 63-year-old woman. METHODS AND RESULTS: Mass in the high posterior atrial septum was confirmed through imaging. Due to the potential involvement of the mass to surrounding vital structures, 3D printing of the cardiac mass was performed. The tumor was completely resected via median sternotomy and the resulting defect was repaired with the bovine pericardium. The patient had an uncomplicated postoperative course except for the development of sick sinus syndrome. One-year follow-up showed no tumor recurrent. CONCLUSION: 3D printing technology in patients with atypical cardiac tumors enhances our understanding of the extent of the tumor invasion and facilitates planning the operation to avoid intraoperative complications.
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Procedimentos Cirúrgicos Cardíacos/métodos , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/cirurgia , Doença Iatrogênica/prevenção & controle , Complicações Intraoperatórias/prevenção & controle , Modelos Anatômicos , Mixoma/diagnóstico por imagem , Mixoma/cirurgia , Impressão Tridimensional , Animais , Bioprótese , Bovinos , Feminino , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/patologia , Átrios do Coração/cirurgia , Neoplasias Cardíacas/patologia , Septos Cardíacos/diagnóstico por imagem , Septos Cardíacos/cirurgia , Humanos , Pessoa de Meia-Idade , Mixoma/patologia , Invasividade Neoplásica , Pericárdio/transplante , Esternotomia/métodos , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Ventricular assist devices driveline infections are common, recalcitrant, and carry high morbidity and mortality. Herein, we reported a patient with driveline infection that was successfully treated with a combination of systemic antibiotics, surgical debridement, and instillation of absorbable antibiotic beads to the wound bed. METHODS AND RESULTS: A 39-year-old man with nonischemic cardiomyopathy underwent insertion of a continuous flow left ventricular assist device. Four years postoperatively, the patient presented with clinical, laboratory, and radiologic signs of driveline tract infection. He underwent extensive surgical debridement, installation of absorbable antibiotic beads that consisted of calcium sulfate, vancomycin, and tobramycin, into the wound bed, and systemic antibiotics. The patient was free of infection 9 month postoperatively. CONCLUSION: Absorbable calcium sulfate antibiotic beads may serve as a beneficial adjunct to surgical debridement and systemic antibiotics for the treatment of ventricular assist device driveline infection, and merit further investigation.
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Antibacterianos/administração & dosagem , Cardiomiopatias/terapia , Quimioterapia Adjuvante/métodos , Coração Auxiliar/efeitos adversos , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/etiologia , Adulto , Sulfato de Cálcio/administração & dosagem , Cefadroxila/administração & dosagem , Cefazolina/administração & dosagem , Desbridamento , Formas de Dosagem , Quimioterapia Combinada , Humanos , Masculino , Infecções Relacionadas à Prótese/microbiologia , Staphylococcus aureus , Tobramicina/administração & dosagem , Resultado do Tratamento , Vancomicina/administração & dosagemRESUMO
Patients undergoing heart-kidney transplants who have primary graft dysfunction (PGD) of the heart are at risk of losing both organs, which may cause reluctance on the part of the transplant team to proceed with transplanting the kidney while the transplanted heart is being supported by mechanical device. We describe a case series in which 2 patients received kidney transplants while on veno-arterial ECMO support for PGD after heart transplant. Both patients are alive more than 1 year following transplant, with good cardiac and renal function and no signs of cardiac rejection. Kidney transplant surgery is safe for patients on veno-arterial ECMO support for cardiac PGD. It allows the heart recipient to receive a kidney from the same donor with both immunologic and survival advantages.
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Oxigenação por Membrana Extracorpórea , Transplante de Coração/métodos , Transplante de Rim/métodos , Disfunção Primária do Enxerto/terapia , Aloenxertos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The COVID-19 pandemic has forced governments to create and quickly implement new policies and programs to both mitigate the health effects of the virus and support the income of individuals. Many are wondering whether these income support programs are there to stay or if the current crisis marks a turning point in the debate about the adequate level of intervention by the State. This article tries to establish if public opinion about this issue is affected by current circumstances. Survey data was collected in Quebec at the height of the pandemic. It shows that, compared to earlier surveys, Quebecers are much more tolerant of the level of general taxation that applies to them. It also shows that opinions about the level of taxation are not influenced by having individually benefited from an income support program such as the Canada Emergency Response Benefit. This new openness to possibly higher taxes in the future does not seem to depend on exposure to the current crop of emergency support programs. Other surveys will be required to assess whether these changes are permanent or if they will recede after the crisis is over.
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Most clinically approved drugs (primarily small molecules or antibodies) are rapidly cleared from circulation and distribute throughout the body. As a consequence, only a small portion of the dose accumulates at the target site, leading to low efficacy and adverse side effects. Therefore, new delivery strategies are necessary to increase organ and tissue-specific delivery of therapeutic agents. Nanoparticles provide a promising approach for prolonging the circulation time and improving the biodistribution of drugs. However, nanoparticles display several limitations, such as clearance by the immune systems and impaired diffusion in the tissue microenvironment. To overcome common nanoparticle limitations various functionalization and targeting strategies have been proposed. This review will discuss synthetic nanoparticle and extracellular vesicle delivery strategies that exploit organ-specific features to enhance drug accumulation at the target site.
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Portadores de Fármacos/química , Vesículas Extracelulares/metabolismo , Nanopartículas/química , Animais , Portadores de Fármacos/síntese química , Humanos , Especificidade de ÓrgãosRESUMO
PURPOSE OF REVIEW: This review examines both trimodality therapy (TMT) in the definitive management of bladder cancer as well as the use of adjuvant radiotherapy for bladder cancer with a specific focus on publications from the last 2 years. RECENT FINDINGS: TMT is an effective management strategy for muscle invasive bladder cancer with outcomes similar to radical cystectomy. Effectiveness of this strategy exists in variant histologies and can be personalized with use of biomarkers. There is a role for adjuvant radiotherapy in locally advanced bladder cancer, especially in the age of improved imaging and modern radiotherapy techniques. SUMMARY: This review should provide the reader data necessary to support use of TMT and adjuvant radiation therapy in their clinic.
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Neoplasias da Bexiga Urinária/terapia , Terapia Combinada , Cistectomia , Humanos , Imunoterapia , Invasividade Neoplásica , Tratamentos com Preservação do Órgão , Radioterapia Adjuvante , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
BACKGROUND: Craniospinal irradiation (CSI) is an important part of curative radiation therapy (RT) for many types of pediatric brain or solid tumors. After conventional CSI, long term survivors may experience sequelae due to unintended dose to normal tissue. Volumetric modulated arc therapy (VMAT) CSI reduces off-target doses at the cost of greater complexity and error risk, and we describe our initial experience in a group of pediatric patients with solid tumors presenting with disseminated or recurrent disease. PROCEDURE: Pediatric patients with brain tumors were identified at Children's Hospital Los Angeles from 2013 to 2015. Clinical characteristics, acute toxicity, and radiotherapy data were abstracted from their medical records. We identified 19 patients who received VMAT CSI. Quality assurance was performed with a cylindrical detector array and ion chamber measurements at the arc junctions. RESULTS: Patients had medulloblastoma or supratentorial primitive neuro-ectodermal tumor (n = 14, 11 high risk), germ cell tumors (two), relapsed neuroblastoma (two), and atypical teratoid/rhabdoid tumor (one). The most common acute toxicity was hematologic, including leukopenia (11% grade [Gr] 2, 26% Gr 3, and 63% Gr 4), anemia (89% Gr 2), and thrombocytopenia (16% Gr 1-2, 26% Gr 3, and 37% Gr 4). Despite leukopenia, we encountered only two Gr 3 infections (urinary tract and lung). The majority required blood products (89% red blood cells and 68% platelets). Weight loss was also common (47% Gr 1 and 26% Gr 2). CONCLUSIONS: VMAT CSI, along with chemotherapy and anesthesia, is feasible with supportive care. Daily image-guided RT improves accuracy and reduces the risk of spinal cord overdose without increasing treatment time. Further research is needed to determine whether reducing doses to organs, such as thyroid, heart, or hippocampus, offsets the risk of increased volume of low-dose irradiation.
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Neoplasias Encefálicas/radioterapia , Radiação Cranioespinal/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Órgãos em Risco/efeitos da radiação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos RetrospectivosRESUMO
Histological transformation (HT) of follicular lymphoma (FL) to an aggressive lymphoma after chemotherapy remains a key issue. The incidence of HT after radioimmunotherapy (RIT) is unknown. This single institution study analysed the risk of HT in FL after treatment with yttrium-90 ibritumomab tiuxetan in 115 consecutive patients treated during 1987-2012. RIT was administered for progressive FL in 111 (97%) patients and as first-line therapy in the remaining 4. 28% (n = 32) had HT, occurring at a median of 60 months from diagnosis and 20 months after RIT. 48% (12/25) of patients who received fludarabine developed HT. The estimated 10-year risk of HT in the fludarabine and non-fludarabine groups was 67% and 26% respectively (P = 0·015). Only prior fludarabine was significantly associated with predicting the risk of HT after RIT. 8% (9/115) of patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia (tMDS/AML) at a median of 41·4 months (range, 5-89). The estimated 10-year risk of tMDS/AML in non-fludarabine treated patients (n = 90) versus fludarabine treated (n = 25) was 13% and 29%, respectively. The estimated overall risk of FL undergoing HT at 10 years without fludarabine exposure appears similar to patients reported in the literature that have not received RIT. Patients with prior purine-analogue therapy are at significantly higher risk of HT.
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Leucemia Mieloide Aguda/etiologia , Linfoma Folicular/terapia , Síndromes Mielodisplásicas/etiologia , Segunda Neoplasia Primária/etiologia , Radioimunoterapia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/etiologia , Radioimunoterapia/métodos , Fatores de Risco , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Vidarabina/efeitos adversos , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico , Adulto Jovem , Radioisótopos de Ítrio/efeitos adversos , Radioisótopos de Ítrio/uso terapêuticoRESUMO
Intraoperative permanent Cesium-131 (Cs-131) brachytherapy can provide a viable alternative to WBRT with excellent response rates and minimal toxicity. This study reports the results of the prospective trial of the impact of intraoperative Cs-131 on neurocognitive function and quality of life (QoL) in patients with resected brain metastases. Between 2010 and 2012, 24 patients with newly diagnosed metastasis to the brain were accrued on a prospective protocol and treated with Cs-131 brachytherapy seeds after surgical resection. Physicians administered the mini-mental status examination (MMSE) and functional assessment of cancer therapy-brain (FACT-Br) questionnaire to all patients before treatment and again every 2 months for the duration of 6 months with additional follow-up again at 12 months. Wilcoxon rank sum test was used to analyze statistically significant changes in MMSE over time and paired t test was used to analyze changes in FACT-BR. There was a statistical improvement in overall FACT-BR score at 4 and 6 months of follow-up when compared to baseline (162 vs. 143, P = 0.004; 164 vs. 143, P = 0.005 respectively) with a non-significant trend toward improvement at 2 and 12 months (154 vs. 143, P = 0.067; 159 vs. 149, P = 0.4). MMSE score was statistically improved at 4 and up to 12 months compared to pre-treatment MMSE (30 vs. 29, P = 0.017; 30 vs. 29, P = 0.001 respectively). Patients with brain metastasis who received intra-operative permanent Cs-131 brachytherapy implants saw an improvement of their neurocognitive status and self-assessment of QoL. In addition to the excellent local control of metastasis, this approach may contribute to the improvements in cognitive function and QOL.
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Braquiterapia , Neoplasias Encefálicas/radioterapia , Radioisótopos de Césio/uso terapêutico , Cognição/fisiologia , Irradiação Craniana , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , Taxa de SobrevidaRESUMO
Subgaleal fluid collection is a rare phenomenon of scalp swelling among young infants and, in many cases, adolescents. As fluid accumulates in the subgaleal space, it presents as a soft, ill-defined, fluctuant, mobile swelling not limited to suture lines. This condition is associated with vacuum-assisted devices and forceps during delivery in infancy. Beyond infancy, this condition can be seen spontaneously or, most commonly, after minor head traumas. Such minor traumas that have been reported in recent years include hair pulling or hair braiding. Early recognition of this condition and its complications is essential for appropriate treatment and management. In this case report, we highlight the importance of subgaleal fluid collection being considered a differential diagnosis of headaches, particularly in children and adolescents who present with excessive hair pulling or hair braiding.
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We report the case of a 64-year-old adult male with a rapidly recurring metastatic lung carcinoma in the right atrium of the heart. Advanced-stage lung carcinomas can metastasize to other organs such as the heart, bones, brain, liver, adrenal glands, and lymphatic system, although actual rates of metastasis to the heart are relatively quite low. This patient was diagnosed with a right atrial mass that was determined through pathology to be a result of an existing non-small cell lung carcinoma. This mass, despite resection, reappeared two weeks later at the same location and with a similar size to the previous metastatic tumor. This case highlights the importance of closely monitoring sites of resected tumors for potential regrowth and complications.
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The implementation of an organisation-wide EMR system in 2019 included single sign-on technology for nurses and midwives. This first-in-Australia study extended the use of this technology to enable nurses and midwives to tap-to-witness for high-risk medications, blood and blood products, and expressed breast milk. A saving of 7 seconds per interaction was observed with nurses and midwives reporting appreciation for ongoing EMR enhancement to reduce EMR-related documentation burden.