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BACKGROUND: Sepsis is common and expensive, and evidence suggests that sepsis order sets may help to improve care. Very incomplete evidence exists regarding the effects of sepsis order sets on the value of care produced by hospitals or the societal costs of sepsis care. RESEARCH QUESTION: In patients hospitalized for sepsis, is the receipt a of a sepsis order set vs no order set associated with improved value of care, defined as decreased hospital mortality, decreased hospital direct variable costs, and decreased societal spending on hospitalizations? STUDY DESIGN AND METHODS: This retrospective cohort study included patients discharged with sepsis International Classification of Diseases, Tenth Revision, codes over 2 years from a large integrated delivery system. Using a propensity score, sepsis order set users were matched to nonusers to study the association between sepsis order set use and the value of care from the hospital and societal perspective. The association between order set receipt and hospital mortality, direct variable cost, and hospital revenue also were examined in a priori defined subgroups of sepsis severity and hospital mortality. RESULTS: The study included 97,249 patients, with 52,793 patients (54%) receiving the sepsis order set. The propensity score match analysis included 55,542 patients, with 27,771 patients in each group. Recipients of the sepsis order set showed a 3.3% lower hospital mortality rate and a $1,487 lower median direct variable total cost (P < .01 for both). Median payer-neutral reimbursement (PNR), a proxy for hospital revenue and thus societal costs, was $465 lower for sepsis order set users (P < .01). Receipt of the sepsis order set was associated with a $1,022 increase in contribution margin, the difference between direct variable costs and PNR per patient. INTERPRETATION: Receipt of the sepsis order set was associated with improved value of care, from both a hospital and societal perspective.
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BACKGROUND: Coronary artery disease (CAD) outcomes consistently improve when they are routinely measured and provided back to physicians and hospitals. However, few centers around the world systematically track outcomes, and no global standards exist. Furthermore, patient-centered outcomes and longitudinal outcomes are under-represented in current assessments. METHODS AND RESULTS: The nonprofit International Consortium for Health Outcomes Measurement (ICHOM) convened an international Working Group to define a consensus standard set of outcome measures and risk factors for tracking, comparing, and improving the outcomes of CAD care. Members were drawn from 4 continents and 6 countries. Using a modified Delphi method, the ICHOM Working Group defined who should be tracked, what should be measured, and when such measurements should be performed. The ICHOM CAD consensus measures were designed to be relevant for all patients diagnosed with CAD, including those with acute myocardial infarction, angina, and asymptomatic CAD. Thirteen specific outcomes were chosen, including acute complications occurring within 30 days of acute myocardial infarction, coronary artery bypass grafting surgery, or percutaneous coronary intervention; and longitudinal outcomes for up to 5 years for patient-reported health status (Seattle Angina Questionnaire [SAQ-7], elements of Rose Dyspnea Score, and Patient Health Questionnaire [PHQ-2]), cardiovascular hospital admissions, cardiovascular procedures, renal failure, and mortality. Baseline demographic, cardiovascular disease, and comorbidity information is included to improve the interpretability of comparisons. CONCLUSIONS: ICHOM recommends that this set of outcomes and other patient information be measured for all patients with CAD.
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Consenso , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/terapia , Hospitalización/estadística & datos numéricos , Encuestas y Cuestionarios/normas , Anciano , Causas de Muerte , Puente de Arteria Coronaria/métodos , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/fisiopatología , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/métodos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Regulatory pathways for protein glycosylation are poorly understood, but expression of branchpoint enzymes is critical. A key branchpoint enzyme is the T-synthase, which directs synthesis of the common core 1 O-glycan structure (T-antigen), the precursor structure for most mucin-type O-glycans in a wide variety of glycoproteins. Formation of active T-synthase, which resides in the Golgi apparatus, requires a unique molecular chaperone, Cosmc, encoded on Xq24. Cosmc is the only molecular chaperone known to be lost through somatic acquired mutations in cells. We show that Cosmc is an endoplasmic reticulum (ER)-localized adenosine triphosphate binding chaperone that binds directly to human T-synthase. Cosmc prevents the aggregation and ubiquitin-mediated degradation of the T-synthase. These results demonstrate that Cosmc is a molecular chaperone in the ER required for this branchpoint glycosyltransferase function and show that expression of the disease-related Tn antigen can result from deregulation or loss of Cosmc function.
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Retículo Endoplásmico/metabolismo , Chaperonas Moleculares/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Células CHO , Línea Celular Tumoral , Secuencia Conservada , Cricetinae , Cricetulus , Disulfuros/metabolismo , Retículo Endoplásmico/efectos de los fármacos , Retículo Endoplásmico/enzimología , Chaperón BiP del Retículo Endoplásmico , Glicosilación/efectos de los fármacos , Aparato de Golgi/efectos de los fármacos , Aparato de Golgi/enzimología , Proteínas de Choque Térmico/metabolismo , Humanos , Membranas Intracelulares/efectos de los fármacos , Membranas Intracelulares/enzimología , Leupeptinas/farmacología , Proteínas Mutantes/metabolismo , Especificidad de Órganos/efectos de los fármacos , Inhibidores de Proteasoma , Señales de Clasificación de Proteína , Transporte de Proteínas/efectos de los fármacos , Solubilidad/efectos de los fármacos , Transferasas/aislamiento & purificación , Transferasas/metabolismo , Ubiquitinación/efectos de los fármacos , Vertebrados/metabolismoRESUMEN
Cellular turnover is associated with exposure of surface phosphatidylserine (PS) in apoptotic cells, leading to their phagocytic recognition and removal. But recent studies indicate that surface PS exposure is not always associated with apoptosis. Here we show that several members of the human galectin family of glycan binding proteins (galectins-1, -2, and -4) induce PS exposure in a carbohydrate-dependent fashion in activated, but not resting, human neutrophils and in several leukocyte cell lines. PS exposure is not associated with apoptosis in activated neutrophils. The exposure of PS in cell lines treated with these galectins is sustained and does not affect cell viability. Unexpectedly, these galectins bind well to activated T lymphocytes, but do not induce either PS exposure or apoptosis, indicating that galectin's effects are cell specific. These results suggest novel immunoregulatory contribution of galectins in regulating leukocyte turnover independently of apoptosis.