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OBJECTIVE. The purpose of this article is to assess the effects of a pay-for-performance (PFP) initiative on clinical impact and usage of a radiology peer learning tool. MATERIALS AND METHODS. This retrospective study was performed at a large academic hospital. On May 1, 2017, a peer learning tool was implemented to facilitate radiologist peer feedback including clinical follow-up, positive feedback, and consultation. Subsequently, PFP target numbers for peer learning tool alerts by subspecialty divisions (October 1, 2017) and individual radiologists (October 1, 2018) were set. The primary outcome was report addendum rate (percent of clinical follow-up alerts with addenda), which was a proxy for peer learning tool clinical impact. Secondary outcomes were peer learning tool usage rate (number of peer learning tool alerts per 1000 radiology reports) and proportion of clinical follow-up alerts (percent of clinical follow-ups among all peer learning tool alerts). Outcomes were assessed biweekly using ANOVA and statistical process control analyses. RESULTS. Among 1,265,839 radiology reports from May 1, 2017, to September 29, 2019, a total of 20,902 peer learning tool alerts were generated. The clinical follow-up alert addendum rate was not significantly different between the period before the PFP initiative (9.9%) and the periods including division-wide (8.3%) and individual (7.9%) PFP initiatives (p = .55; ANOVA). Peer learning tool usage increased from 2.2 alerts per 1000 reports before the PFP initiative to 12.6 per 1000 during the division-wide PFP period (5.7-fold increase; 12.6/2.2), to 25.2 in the individual PFP period (11.5-fold increase vs before PFP; twofold increase vs division-wide) (p < .001). The clinical follow-up alert proportion decreased from 37.5% before the PFP initiative, to 34.4% in the division-wide period, to 31.3% in the individual PFP period. CONCLUSION. A PFP initiative improved radiologist engagement in peer learning by marked increase in peer learning tool usage rate without a change in report addendum rate as a proxy for clinical impact.
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Competencia Clínica/estadística & datos numéricos , Grupo Paritario , Radiólogos/educación , Radiología/educación , Reembolso de Incentivo/estadística & datos numéricos , Errores Diagnósticos/prevención & control , Humanos , Radiólogos/economía , Radiología/economía , Derivación y Consulta , Reembolso de Incentivo/economía , Estudios RetrospectivosAsunto(s)
Microcirugia/instrumentación , Técnicas de Sutura/instrumentación , Procedimientos Quirúrgicos Vasculares/instrumentación , Venas/cirugía , Anastomosis Quirúrgica/instrumentación , Anastomosis Quirúrgica/métodos , Diseño de Equipo , Seguridad de Equipos , Humanos , Microcirugia/métodos , Suturas , Procedimientos Quirúrgicos Vasculares/métodosRESUMEN
Aging is characterized by progressive loss of cellular function and integrity. It has been thought to be driven by stochastic molecular damage. However, genetic and environmental maneuvers enhancing mitochondrial function or inhibiting glycolysis extend lifespan and promote healthy aging in many species. In post-fertile Caenorhabditis elegans, a progressive decline in phosphoenolpyruvate carboxykinase with age, and a reciprocal increase in pyruvate kinase shunt energy metabolism from oxidative metabolism to anaerobic glycolysis. This reduces the efficiency and total of energy generation. As a result, energy-dependent physical activity and other cellular functions decrease due to unmatched energy demand and supply. In return, decrease in physical activity accelerates this metabolic shift, forming a vicious cycle. This metabolic event is a determinant of aging, and is retarded by caloric restriction to counteract aging. In this review, we summarize these and other evidence supporting the idea that metabolic reprogramming is a driver of aging. We also suggest strategies to test this hypothesis.
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Envejecimiento/metabolismo , Metabolismo Energético/fisiología , Envejecimiento/fisiología , Animales , HumanosRESUMEN
Aging involves progressive loss of cellular function and integrity, presumably caused by accumulated stochastic damage to cells. Alterations in energy metabolism contribute to aging, but how energy metabolism changes with age, how these changes affect aging, and whether they can be modified to modulate aging remain unclear. In locomotory muscle of post-fertile Caenorhabditis elegans, we identified a progressive decrease in cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C), a longevity-associated metabolic enzyme, and a reciprocal increase in glycolytic pyruvate kinase (PK) that were necessary and sufficient to limit lifespan. Decline in PEPCK-C with age also led to loss of cellular function and integrity including muscle activity, and cellular senescence. Genetic and pharmacologic interventions of PEPCK-C, muscle activity, and AMPK signaling demonstrate that declines in PEPCK-C and muscle function with age interacted to limit reproductive life and lifespan via disrupted energy homeostasis. Quantifications of metabolic flux show that reciprocal changes in PEPCK-C and PK with age shunted energy metabolism toward glycolysis, reducing mitochondrial bioenergetics. Last, calorie restriction countered changes in PEPCK-C and PK with age to elicit anti-aging effects via TOR inhibition. Thus, a programmed metabolic event involving PEPCK-C and PK is a determinant of aging that can be modified to modulate aging.
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Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Regulación del Desarrollo de la Expresión Génica , Glucólisis , Dinámicas Mitocondriales , Fosfoenolpiruvato Carboxiquinasa (ATP)/metabolismo , Piruvato Quinasa/metabolismo , Envejecimiento , Animales , Animales Modificados Genéticamente , Caenorhabditis elegans/genética , Caenorhabditis elegans/crecimiento & desarrollo , Caenorhabditis elegans/ultraestructura , Proteínas de Caenorhabditis elegans/antagonistas & inhibidores , Proteínas de Caenorhabditis elegans/genética , Restricción Calórica , Citosol/enzimología , Citosol/metabolismo , Citosol/ultraestructura , Metabolismo Energético , Mutación , Fosfoenolpiruvato Carboxiquinasa (ATP)/antagonistas & inhibidores , Fosfoenolpiruvato Carboxiquinasa (ATP)/genética , Piruvato Quinasa/antagonistas & inhibidores , Piruvato Quinasa/genética , Interferencia de ARN , Análisis de SupervivenciaRESUMEN
The National Institutes of Health Undiagnosed Diseases Program evaluates patients for whom no diagnosis has been discovered despite a comprehensive diagnostic workup. Failure to diagnose a condition may arise from the mutation of genes previously unassociated with disease. However, we hypothesized that this could also co-occur with multiple genetic disorders. Demonstrating a complex syndrome caused by multiple disorders, we report two siblings manifesting both similar and disparate signs and symptoms. They shared a history of episodes of hypoglycemia and lactic acidosis, but had differing exam findings and developmental courses. Clinical acumen and exome sequencing combined with biochemical and functional studies identified three genetic conditions. One sibling had Smith-Magenis Syndrome and a nonsense mutation in the RAI1 gene. The second sibling had a de novo mutation in GRIN2B, which resulted in markedly reduced glutamate potency of the encoded receptor. Both siblings had a protein-destabilizing homozygous mutation in PCK1, which encodes the cytosolic isoform of phosphoenolpyruvate carboxykinase (PEPCK-C). In summary, we present the first clinically-characterized mutation of PCK1 and demonstrate that complex medical disorders can represent the co-occurrence of multiple diseases.
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Péptidos y Proteínas de Señalización Intracelular/genética , Fosfoenolpiruvato Carboxiquinasa (ATP)/deficiencia , Fosfoenolpiruvato Carboxiquinasa (GTP)/genética , Receptores de N-Metil-D-Aspartato/genética , Síndrome de Smith-Magenis/diagnóstico , Factores de Transcripción/genética , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Preescolar , Análisis Mutacional de ADN , Femenino , Estudios de Asociación Genética , Células HEK293 , Humanos , Datos de Secuencia Molecular , Mutación Missense , Polimorfismo de Nucleótido Simple , Síndrome de Smith-Magenis/genética , TransactivadoresRESUMEN
Extraordinary geogenic concentrations of cadmium (Cd) have been reported for some Jamaican soils. However, the bioavailability of the metal in these soils remains unknown. Here, the bioavailability of Cd in selected Jamaican soils was investigated through the determination of total and sequentially extractable concentrations in paired soil-plant (yam; Dioscorea sp.) samples (n = 24), using neutron activation analysis and atomic absorption spectroscopy as primary analytical techniques. Our results indicate that total soil Cd varied widely (2.2-148.7 mg kg(-1)), and on average, total extractable Cd accounted for ~55 % of the total soil Cd. The exchangeable and oxidizable species averaged 1.5 and 6.4 % of the total Cd, respectively, and, based on Spearman analysis, are the best predictors of yam Cd. There is also good evidence to suggest that variation in the bioavailability of the metal is in part controlled by the geochemical characteristics of the soils analyzed and is best explained by pH, cation exchange capacity (CEC) and organic matter content (% LOI).
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Cadmio/análisis , Monitoreo del Ambiente , Contaminantes del Suelo/análisis , Suelo/química , JamaicaRESUMEN
Hyaluronan, a macromolecular glycosaminoglycan, is normally synthesized by hyaluronan synthases at the plasma membrane using cytosolic UDP-GlcUA and UDP-GlcNAc substrates and extruding the elongating chain into the extracellular space. The cellular metabolism (synthesis and catabolism) of hyaluronan is dynamic. UDP-GlcNAc is also the substrate for O-GlcNAc transferase, which is central to the control of many cytosolic pathways. This Perspective outlines recent data for regulation of hyaluronan synthesis and catabolism that support a model that hyaluronan metabolism can be a rheostat for controlling an acceptable normal range of cytosolic UDP-GlcNAc concentrations in order to maintain normal cell functions.
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Fenómenos Fisiológicos Celulares/fisiología , Citosol/metabolismo , Ácido Hialurónico/biosíntesis , Ácido Hialurónico/metabolismo , Modelos Biológicos , Uridina Difosfato N-Acetilglucosamina/metabolismo , Animales , Endosomas/metabolismo , Glucuronosiltransferasa/metabolismo , Humanos , Hialuronano SintasasRESUMEN
OBJECTIVE: We have previously reported inpatient imaging utilization trends at our institution from fiscal year (FY) 1984 through FY 2002. In this study, we assessed the trends in imaging utilization for inpatients from FY 2003 through FY 2012. MATERIALS AND METHODS: In this institutional review board-approved retrospective study performed at a 793-bed tertiary care academic institution, we reviewed imaging utilization in adult inpatients from October 1, 2002, through September 30, 2012 (FY 2003 through FY 2012), and recorded the gross number of imaging studies coded by modality (conventional [radiography and fluoroscopy], ultrasound, nuclear medicine, CT, and MRI) and associated relative value units (RVUs). We used linear regression to assess trends in number of imaging studies and RVUs per case-mix-adjusted admission (CMAA). RESULTS: The total number of imaging studies, as well as the number of CT, nuclear medicine, and conventional studies adjusted for case mix, decreased (p=0.02, p=0.0006, p=0.0008, and p=0.001, respectively); CT per CMAA increased until FY 2009 and then decreased through FY 2012. Utilization of ultrasound and MRI did not change significantly (p=0.15 and p=0.22, respectively). Unadjusted global RVUs increased until FY 2009 and then showed a slight decrease through FY 2012 (p=0.04), whereas RVUs per CMAA did not change significantly (p=0.18). CONCLUSION: After decades of continued rise, imaging utilization for inpatients significantly decreased by most measures between FY 2009 and FY 2012. Future studies to evaluate the contribution of various factors to this decline, including efforts to reduce inappropriate use of imaging and concerns about potential harms of radiation exposure, may be helpful in optimizing imaging utilization and resource planning.
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Diagnóstico por Imagen/estadística & datos numéricos , Diagnóstico por Imagen/tendencias , Hospitalización/estadística & datos numéricos , Hospitalización/tendencias , Pautas de la Práctica en Medicina/estadística & datos numéricos , Pautas de la Práctica en Medicina/tendencias , Revisión de Utilización de Recursos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Boston/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
CREB-binding protein (CBP)/p300 interacting transactivator with glutamic acid (Glu) and aspartic acid (Asp)-tail 2 (Cited2) was recently shown to be essential for gluconeogenesis in the adult mouse. The metabolic function of Cited2 in mouse embryonic stem cells (mESCs) remains elusive. In the current study, the metabolism of glucose was investigated in mESCs, which contained a deletion in the gene for Cited2 (Cited2(Δ/-)). Compared with its parental wild type counterpart, Cited2(Δ/-) ESCs have enhanced glycolysis, alternations in mitochondria morphology, reduced glucose oxidation, and decreased ATP content. Cited2 is recruited to the hexokinase 1 (HK1) gene promoter to regulate transcription of HK1, which coordinates glucose metabolism in wild type ESCs. Reduced glucose oxidation and enhanced glycolytic activity in Cited2(Δ/-) ESCs correlates with defective differentiation during hypoxia, which is reflected in an increased expression of pluripotency marker (Oct4) and epiblast marker (Fgf5) and decreased expression of lineage specification markers (T, Gata-6, and Cdx2). Knockdown of hypoxia inducible factor-1α in Cited2(Δ/-) ESCs re-initiates the expression of differentiation markers T and Gata-6. Taken together, a deletion of Cited2 in mESCs results in abnormal mitochondrial morphology and impaired glucose metabolism, which correlates with a defective cell fate decision.
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Células Madre Embrionarias/metabolismo , Glucólisis/fisiología , Mitocondrias/metabolismo , Proteínas Represoras/metabolismo , Transactivadores/metabolismo , Transcripción Genética/fisiología , Adenosina Trifosfato/biosíntesis , Adenosina Trifosfato/genética , Animales , Antígenos de Diferenciación/genética , Antígenos de Diferenciación/metabolismo , Hipoxia de la Célula/fisiología , Células Madre Embrionarias/citología , Glucosa/genética , Glucosa/metabolismo , Hexoquinasa/biosíntesis , Hexoquinasa/genética , Ratones , Ratones Noqueados , Mitocondrias/genética , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Oxidación-Reducción , Proteínas Represoras/genética , Transactivadores/genéticaRESUMEN
The promyelocytic leukemia protein is a well known tumor suppressor, but its role in metabolism is largely unknown. Mice with a deletion in the gene for PML (KO mice) exhibit altered gene expression in liver, adipose tissue, and skeletal muscle, an accelerated rate of fatty acid metabolism, abnormal glucose metabolism, constitutive AMP-activating kinase (AMPK) activation, and insulin resistance in skeletal muscle. Last, an increased rate of energy expenditure protects PML KO mice from the effects of obesity induced by a Western diet. Collectively, our study uncovers a previously unappreciated role of PML in the regulation of metabolism and energy balance in mice.
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Metabolismo Energético/genética , Proteínas Nucleares/genética , Obesidad/genética , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Adipoquinas/genética , Tejido Adiposo/metabolismo , Animales , Western Blotting , Temperatura Corporal/genética , Antígenos CD36/genética , Dieta/efectos adversos , Ácidos Grasos/metabolismo , Expresión Génica , Transportador de Glucosa de Tipo 4/genética , Hígado/metabolismo , Ratones , Ratones de la Cepa 129 , Ratones Noqueados , Músculo Esquelético/metabolismo , Proteínas Nucleares/deficiencia , Obesidad/etiología , Obesidad/metabolismo , Oxidación-Reducción , Proteína de la Leucemia Promielocítica , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Transcripción/deficiencia , Proteínas Supresoras de Tumor/deficienciaRESUMEN
The biogeochemical fate of organic matter (OM) entering soils is an important issue that must be examined to better understand its roles in nitrogen cycling and as a natural modulator of soil-atmospheric carbon fluxes. Despite these critical roles, there are uncertainties in estimating the contribution of this feedback mechanism due in part to a lack of molecular-level information regarding the origin and labile and refractory inventories of OM in soils. In this study, we used a multi-analytical approach to determine molecular-level information for the occurrence and stabilization of OM in a bird guano concretion of the Late Miocene or Pliocene age in Jamaica. We determined the specific organic structures persisting in the concretion and the possible contribution of fossil organic matter to the OM pool in modern environments. Our results indicate that aliphatic species, presumably of a highly polymethylenic nature [(CH2)n], may significantly contribute to the stable soil-C pool. Although not as significant, proteins and carbohydrates were also enriched in the sample, further suggesting that fossil organic matter may contribute to carbon and nitrogen pools in present day soil organic matter.
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The Beck Depression Inventory II (BDI-II) has been suspected of overestimating the level of depression in individuals that endure chronic pain. Using a sample (N = 345) of male military veterans with chronic pain enrolled in an outpatient treatment program, a factor analysis on the BDI-II revealed a "Somatic Complaints" factor along with 2 other factors we labeled "Negative Rumination" and "Mood." Standardized scores were provided for each BDI-II factor score, Total score, and Total minus Somatic score. The internal consistency reliabilities (Gilmer-Feldt and alpha coefficients) for all scores were found to be clinically acceptable. Item-Total score correlations found that all of the BDI-II items were good discriminators (r > .30). We conclude that the normative data provided in this study should help control for somatic responding by male chronic pain veterans on the BDI-II. We highly recommend that clinicians and researchers use the norm-referenced method when interpreting BDI-II scores from individuals suffering from chronic pain.
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Dolor Crónico/psicología , Trastorno Depresivo/psicología , Escalas de Valoración Psiquiátrica/normas , Psicometría/métodos , Veteranos/psicología , Adulto , Anciano , Anciano de 80 o más Años , Trastorno Depresivo/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Caloric restriction (CR) markedly extends life span and improves the health of a broad number of species. Energy metabolism fundamentally contributes to the beneficial effects of CR, but the underlying mechanisms that are responsible for this effect remain enigmatic. A multidisciplinary approach that involves quantitative proteomics, immunochemistry, metabolic quantification, and life span analysis was used to determine how CR, which occurs in the Caenorhabditis elegans eat-2 mutants, modifies energy metabolism of the worm, and whether the observed modifications contribute to the CR-mediated physiological responses. A switch to fatty acid metabolism as an energy source and an enhanced rate of energy metabolism by eat-2 mutant nematodes were detected. Life span analyses validated the important role of these previously unknown alterations of energy metabolism in the CR-mediated longevity of nematodes. As observed in mice, the overexpression of the gene for the nematode analog of the cytosolic form of phosphoenolpyruvate carboxykinase caused a marked extension of the life span in C. elegans, presumably by enhancing energy metabolism via an altered rate of cataplerosis of tricarboxylic acid cycle anions. We conclude that an increase, not a decrease in fuel consumption, via an accelerated oxidation of fuels in the TCA cycle is involved in life span regulation; this mechanism may be conserved across phylogeny.
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Caenorhabditis elegans/metabolismo , Restricción Calórica , Ciclo del Ácido Cítrico/fisiología , Longevidad/fisiología , Animales , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Mutación , Oxidación-Reducción , Receptores Nicotínicos/genética , Receptores Nicotínicos/metabolismoRESUMEN
Serine is generally classified as a nutritionally nonessential (dispensable) amino acid, but metabolically, serine is indispensible and plays an essential role in several cellular processes. Serine is the major source of one-carbon units for methylation reactions that occur via the generation of S-adenosylmethionine. The regulation of serine metabolism in mammalian tissues is thus of critical importance for the control of methyl group transfer. In addition to the well known role of d-serine in the brain, l-serine has recently been implicated in breast cancer and other tumors due in part to the genomic copy number gain for 3-phosphoglycerate dehydrogenase, the enzyme that controls the entry of glycolytic intermediates into the pathway of serine synthesis. Here, we review recent information regarding the synthesis of serine and the regulation of its metabolism and discuss the role played by phosphoenolpyruvate carboxykinase in this process.
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Encéfalo/metabolismo , Fosfoenolpiruvato Carboxiquinasa (ATP)/metabolismo , Fosfoenolpiruvato Carboxiquinasa (GTP)/metabolismo , Fosfoglicerato-Deshidrogenasa/metabolismo , S-Adenosilmetionina/metabolismo , Serina/metabolismo , Animales , Humanos , Metilación , Fosfoenolpiruvato Carboxiquinasa (ATP)/genética , Fosfoenolpiruvato Carboxiquinasa (GTP)/genética , Fosfoglicerato-Deshidrogenasa/genética , S-Adenosilmetionina/genética , Serina/genéticaRESUMEN
PURPOSE: The aim of this study was to assess whether an integrated imaging computerized physician order entry (CPOE) system with embedded decision support for imaging can be accepted clinically. METHODS: The study was performed in a health care delivery network with an affiliated academic hospital. After pilot testing and user feedback, a Web-enabled CPOE system with embedded imaging decision support was phased into clinical use between 2000 and 2010 across outpatient, emergency department, and inpatient settings. The primary outcome measure was meaningful use, defined as the proportion of imaging studies performed with orders electronically created (EC) or electronically signed by an authorized provider. The secondary outcome measure was adoption, defined as the proportion of imaging studies that were ordered electronically, irrespective of who entered the order in the CPOE system. Univariate and multivariate regression analyses were performed to estimate trends and the significance of practice settings, examination modality, and body part to outcome measures. Chi-square statistics were used to assess differences across specialties. RESULTS: A total of 4.1 million imaging studies were performed during the study period. From 2000 to 2010, significant increases in meaningful use (for EC studies, from 0.4% to 61.9%; for electronically signed studies, from 0.4% to 92.2%; P < .005) and the adoption of CPOE (from 0.5% to 94.6%, P < .005) were observed. The use of EC studies was greatest in the emergency department and inpatient settings. Meaningful use varied across specialties; surgical subspecialties had the lowest rates of EC studies. CONCLUSIONS: Imaging CPOE with embedded decision support integrated into the IT infrastructure of the health care enterprise and clinicians' workflow can be broadly accepted clinically.
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Centros Médicos Académicos/estadística & datos numéricos , Sistemas de Apoyo a Decisiones Clínicas/estadística & datos numéricos , Diagnóstico por Imagen/estadística & datos numéricos , Hospitales Urbanos/estadística & datos numéricos , Sistemas de Entrada de Órdenes Médicas/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Boston , Integración de SistemasRESUMEN
OBJECTIVE: Variation in emergency department head computed tomography (CT) use in patients with atraumatic headaches between hospitals is being measured nationwide. However, the magnitude of interphysician variation within a hospital is currently unknown. We hypothesized that there was significant variation in the rates of physician head CT use, both overall and for patients diagnosed with atraumatic headaches. METHODS: This cross-sectional study was conducted in the emergency department of a large urban academic hospital, and institutional review board approval was obtained. All emergency department visits from 2009 were analyzed, and the primary outcome measure was whether or not head CT was performed. Logistic regression was used to control for patient, physician, and visit characteristics potentially associated with head CT ordering. The degree of interphysician variability was tested, both before and after controlling for these variables. RESULTS: Of 55,286 emergency department patient encounters, 4919 (8.9%) involved head CT examinations. Unadjusted head CT ordering rates per physician ranged from 4.4% to 16.9% overall and from 15.2% to 61.7% in patients diagnosed with atraumatic headaches, with both rates varying significantly between physicians. Two-fold variation in head CT ordering overall (6.5%-13.5%) and approximately 3-fold variation in head CT ordering for atraumatic headaches (21.2%-60.1%) persisted even after controlling for pertinent variables. CONCLUSION: Emergency physicians vary significantly in their use of head CT both overall and in patients with atraumatic headaches. Further studies are needed to identify strategies to reduce interphysician variation in head CT use.
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Servicios Médicos de Urgencia/estadística & datos numéricos , Cabeza/diagnóstico por imagen , Cefalea/diagnóstico por imagen , Pautas de la Práctica en Medicina/estadística & datos numéricos , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
PURPOSE: To determine the effect of evidence-based clinical decision support (CDS) on the use and yield of computed tomographic (CT) pulmonary angiography for acute pulmonary embolism (PE) in the emergency department (ED). MATERIALS AND METHODS: Institutional review board approval was obtained for this HIPAA-compliant study, which was performed between October 1, 2003, and September 30, 2009, at a 793-bed quaternary care institution with 60,000 annual ED visits. Use (number of examinations per 1000 ED visits) and yield (percentage of examinations positive for acute PE) of CT pulmonary angiography were compared before and after CDS implementation in August 2007. The authors included all adult patients presenting to the ED and developed and validated a natural language processing tool to identify acute PE diagnoses. Linear trend analysis was used to assess for variation in CT pulmonary angiography use. Logistic regression was used to determine variation in yield after controlling for patient demographic and clinical characteristics. RESULTS: Of 338,230 patients presenting to the ED, 6838 (2.0%) underwent CT pulmonary angiography. Quarterly CT pulmonary angiography use increased 82.1% before CDS implementation, from 14.5 to 26.4 examinations per 1000 patients (P<.0001) between October 10, 2003, and July 31, 2007. After CDS implementation, quarterly use decreased 20.1%, from 26.4 to 21.1 examinations per 1000 patients between August 1, 2007, and September 30, 2009 (P=.0379). Overall, 686 (10.0%) of the CT pulmonary angiographic examinations performed during the 6-year period were positive for PE; subsequent to CDS implementation, yield by quarter increased 69.0%, from 5.8% to 9.8% (P=.0323). CONCLUSION: Implementation of evidence-based CDS in the ED was associated with a significant decrease in use, and increase in yield, of CT pulmonary angiography for the evaluation of acute PE.
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Angiografía/estadística & datos numéricos , Sistemas de Apoyo a Decisiones Clínicas/estadística & datos numéricos , Servicios Médicos de Urgencia/estadística & datos numéricos , Embolia Pulmonar/diagnóstico por imagen , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Femenino , Humanos , Masculino , Massachusetts/epidemiología , Persona de Mediana Edad , Prevalencia , Reproducibilidad de los Resultados , Medición de Riesgo , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
Overexpression of the Ski oncogene induces oncogenic transformation of chicken embryo fibroblasts (CEFs). However, unlike most other oncogene-transformed cells, Ski-transformed CEFs (Ski-CEFs) do not display the classical Warburg effect. On the contrary, Ski transformation reduced lactate production and glucose utilization in CEFs. Compared with CEFs, Ski-CEFs exhibited enhanced TCA cycle activity, fatty acid catabolism through ß-oxidation, glutamate oxidation, oxygen consumption, as well as increased numbers and mass of mitochondria. Interestingly, expression of PPARγ, a key transcription factor that regulates adipogenesis and lipid metabolism, was dramatically elevated at both the mRNA and protein levels in Ski-CEFs. Accordingly, PPARγ target genes that are involved in lipid uptake, transport, and oxidation were also markedly up-regulated by Ski. Knocking down PPARγ in Ski-CEFs by RNA interference reversed the elevated expression of these PPARγ target genes, as well as the shift to oxidative metabolism and the increased mitochondrial biogenesis. Moreover, we found that Ski co-immunoprecipitates with PPARγ and co-activates PPARγ-driven transcription.
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Pollos/metabolismo , Glucólisis/fisiología , PPAR gamma/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Adipogénesis/fisiología , Animales , Embrión de Pollo , Pollos/genética , Técnicas de Silenciamiento del Gen , Metabolismo de los Lípidos/fisiología , Mitocondrias/genética , Mitocondrias/metabolismo , Oxidación-Reducción , Consumo de Oxígeno/fisiología , PPAR gamma/genética , Proteínas Proto-Oncogénicas/genética , Transcripción Genética/fisiologíaRESUMEN
BACKGROUND: To assess patterns of use of abdominal imaging in the emergency department (ED) from 1990 to 2009. METHODS: We retrospectively reviewed data on adult ED patients treated between 1990 and 2009 at our university-affiliated quaternary care institution. Examinations were coded by abdominal imaging modality: x-ray, sonography, CT, or MRI. Proportional costs for each imaging modality were evaluated using relative value units (RVUs). Chi-square tests were used to assess for significant trends. RESULTS: The intensity of abdominal imaging per 1,000 ED visits increased 19.3% from 1990-2009 (p = 0.0050). The number of abdominal CT scans per 1,000 ED visits increased 17.5-fold (p < 0.0001). Similarly, the number of abdominal MRIs per 1,000 ED visits increased from 0 to 1.0 (p < 0.0001), and the number of abdominal sonographs per 1,000 ED visits increased 51.6% (p = 0.0198). However, the number of x-ray examinations per 1,000 ED visits decreased 81.6% (p < 0.0001). Abdominal imaging RVUs per 1,000 ED visits increased 2.7-fold (p < 0.0001), due primarily to CT imaging, which accounted for 14% of RVUs in 1990 and 76% of RVUs in 2009. CONCLUSIONS: The intensity of abdominal imaging examinations per 1,000 ED visits and the number of abdominal imaging RVUs increased significantly over a 20-year period. CT replaced x-ray as the most common abdominal imaging modality for evaluation of ED patients. In light of these increasing costs as well as the increased radiation exposure of CT, clinical decision rules and computerized decision support may be needed to ensure appropriate utilization of abdominal CT in the ED.