Economic implications of an evidence-based sepsis protocol: can we improve outcomes and lower costs?

OBJECTIVE: To determine the financial impact of a sepsis protocol designed for use in the emergency department. DESIGN: Retrospective analysis of a before-after study testing the implications of sepsis protocol. SETTING: Academic, tertiary care hospital in the United States. PATIENTS: Persons with septic shock presenting to the emergency department. INTERVENTIONS: A multifaceted protocol developed from recent scientific literature on sepsis and the Surviving Sepsis Campaign. The protocol emphasized identification of septic patients, aggressive fluid resuscitation, timely antibiotic administration, and appropriateness of antibiotics, along with other adjunctive, supportive measures in sepsis care. MEASUREMENTS AND MAIN RESULTS: We compared patients treated before the protocol with those cared for after the protocol was implemented. Overall hospital costs represented the primary end point, whereas hospital length of stay served as a secondary end point. All hospital costs were calculated based on charges after conversion to costs based on department-specific cost-to-charge ratios. We also attempted to measure the independent impact of the protocol on costs through linear regression. We conducted a sensitivity analysis assessing these end points in the subgroup of subjects who survived their hospitalization. The total cohort included 120 subjects (evenly divided into the before and after cohorts) with a mean age of 64.7 +/- 18.2 yrs and median Acute Physiology and Chronic Health Evaluation II score of 22.5 +/- 8.3. There were more survivors following the protocol's adoption (70.0% vs. 51.7%, p = .040). Median total costs were significantly lower with use of the protocol ($16,103 vs. $21,985, p = .008). The length of stay was also on average 5 days less among the postintervention population (p = .023). A Cox proportional hazard model indicated that the protocol was independently associated with less per-patient cost. Restricting the analysis to only survivors did not appreciably change our observations. CONCLUSIONS: Use of a sepsis protocol can result not only in improved mortality but also in substantial savings for institutions and third party payers. Broader implementation of sepsis treatment protocols represents a potential means for enhancing resource use while containing costs.     

Ultrastructural localization of human platelet thrombospondin, fibrinogen, fibronectin, and von Willebrand factor in frozen thin section

We have investigated the localization of thrombospondin (TSP), fibrinogen, fibronectin, and von Willebrand factor in human platelets by transmission electron microscopy of antibody-stained ultrathin frozen sections. In negatively stained thin sections, alpha granules were identified on the basis of their smooth, roughly spherical shape, size, single limiting electron-lucent 100 A membrane, and frequent presence of electron-dense nucleoid. In contrast, mitochondria exhibited characteristic double membranes and cristae. Sections were separately stained with affinity-purified polyclonal antibodies to these proteins as well as with three monoclonal anti-TSP antibodies. Antibody specificity was documented in radioimmunoassays, by immunofluorescent cross-blocking, and by staining of bands of appropriate mobility in Western blots of whole platelets. Bound antibody was visualized using a 5-nm colloidal gold-avidin conjugate. In resting cells, staining of virtually all alpha granules was observed for all four proteins. In contrast, consistent staining was absent from other organelles, including plasma membranes, mitochondria, and vacuolar structures that may represent the open canalicular system.     

Fibronectin binding to thrombin-stimulated platelets: evidence for fibrin(ogen) independent and dependent pathways

Plasma fibronectin binds in a specific and saturable manner to thrombin- stimulated platelets. gamma-Thrombin stimulated 80% as much fibronectin binding to platelets as alpha-thrombin with conversion of less than or equal to 1% of platelet fibrinogen to fibrin. Afibrinogenemic and normal platelets bound similar quantities of fibronectin in the presence of calcium or magnesium-ethylene glycol tetra-acetic acid (EGTA). These observations indicate that fibronectin can interact with platelets without involvement of fibrin or fibrinogen. Nevertheless, two different effects of fibrin(ogen) on fibronectin binding were observed. First, exogenous fibrinogen inhibited fibronectin binding to thrombin-stimulated platelets. This inhibition was unidirectional, as fibronectin did not inhibit fibrinogen binding to ADP or thrombin- stimulated cells. Second, formaldehyde-fixed cells with surface- associated fibrin bound significant quantities of fibronectin. This interaction required calcium and did not occur on fixed cells with or without surface-bound fibrinogen. A portion of the ligand bound to fixed cells with surface-associated fibrin was modified to form a derivative with a molecular weight identical to that of the fibronectin subunit cross-linked to the alpha-chain of fibrin. This high mol wt derivative was also observed to a variable extent with living cells in the presence of magnesium or calcium but not in the presence of magnesium-EGTA. Thus, fibronectin binds to platelets by at least two mechanisms: (1) a fibrin(ogen)-independent pathway that requires divalent ions and is inhibited by exogenous fibrinogen; and (2) a fibrin-dependent pathway with an absolute calcium requirement. With nonaggregated, thrombin-stimulated platelets, the former pathway appears to predominate.     

Epidemiology and outcomes of ventilator-associated pneumonia in a large US database

OBJECTIVES: To evaluate risk factors for ventilator-associated pneumonia (VAP), as well as its influence on in-hospital mortality, resource utilization, and hospital charges. DESIGN: Retrospective matched cohort study using data from a large US inpatient database. PATIENTS: Patients admitted to an ICU between January 1998 and June 1999 who received mechanical ventilation for > 24 h. MEASUREMENTS: Risk factors for VAP were examined using crude and adjusted odds ratios (AORs). Cases of VAP were matched on duration of mechanical ventilation, severity of illness on admission (predicted mortality), type of admission (medical, surgical, trauma), and age with up to three control subjects. Mortality, resource utilization, and billed hospital charges were then compared between cases and control subjects. RESULTS: Of the 9,080 patients meeting study entry criteria, VAP developed in 842 patients (9.3%). The mean interval between intubation, admission to the ICU, hospital admission, and the identification of VAP was 3.3 days, 4.5 days, and 5.4 days, respectively. Identified independent risk factors for the development of VAP were male gender, trauma admission, and intermediate deciles of underlying illness severity (on admission) [AOR, 1.58, 1.75, and 1.47 to 1.70, respectively]. Patients with VAP were matched with 2,243 control subjects without VAP. Hospital mortality did not differ significantly between cases and matched control subjects (30.5% vs 30.4%, p = 0.713). Nevertheless, patients with VAP had a significantly longer duration of mechanical ventilation (14.3 +/- 15.5 days vs 4.7 +/- 7.0 days, p < 0.001), ICU stay (11.7 +/- 11.0 days vs 5.6 +/- 6.1 days, p < 0.001), and hospital stay (25.5 +/- 22.8 days vs 14.0 +/- 14.6 days, p < 0.001). Development of VAP was also associated with an increase of > $40,000 USD in mean hospital charges per patient ($104,983 USD +/- $91,080 USD vs $63,689 USD+/- $75,030 USD, p < 0.001). CONCLUSIONS: This retrospective matched cohort study, the largest of its kind, demonstrates that VAP is a common nosocomial infection that is associated with poor clinical and economic outcomes. While strategies to prevent the occurrence of VAP may not reduce mortality, they may yield other important benefits to patients, their families, and hospital systems.     

O等位基因引起ABO基因型与表现型定型差异

保证输血时血清学方面的安全,首要的是对受血者与献血者ABO血型定型,血清学检查通常分两个步骤.正定型通常使用鼠源单克隆抗体检测红细胞表面是否存在A或B抗原.互补的实验即反定型,利用当红细胞上缺乏A或B抗原时,人群可天然产生相对应的抗体的原理,检测血清中是否存在抗-A或者抗-B抗体.确定了受血者红细胞表面的ABO抗原以及血浆中的抗体,便能确定血型,为其提供相合的血液.     

Fluid balance and cardiac function in septic shock as predictors of hospital mortality

Introduction

Septic shock is a major cause of morbidity and mortality throughout the world. Unfortunately, the optimal fluid management of septic shock is unknown and currently is empirical.

Methods

A retrospective analysis was performed at Barnes-Jewish Hospital (St. Louis, Missouri). Consecutive patients (n = 325) hospitalized with septic shock who had echocardiographic examinations performed within 24 hours of shock onset were enrolled.

Results

A total of 163 (50.2%) patients with septic shock died during hospitalization. Non-survivors had a significantly larger positive net fluid balance within the 24 hour window of septic shock onset (median (IQR): 4,374 ml (1,637 ml, 7,260 ml) vs. 2,959 ml (1,639.5 ml, 4,769.5 ml), P = 0.004). The greatest quartile of positive net fluid balance at 24 hours and eight days post-shock onset respectively were found to predict hospital mortality, and the greatest quartile of positive net fluid balance at eight days post-shock onset was an independent predictor of hospital mortality (adjusted odds ratio (AOR), 1.66; 95% CI, 1.39 to 1.98; P = 0.004). Survivors were significantly more likely to have mild left ventricular dysfunction as evaluated by bedside echocardiography and non-survivors had slightly elevated left ventricular ejection fraction, which was also found to be an independent predictor of outcome.

Conclusions

Our data confirms the importance of fluid balance and cardiac function as outcome predictors in patients with septic shock. A clinical trial to determine the optimal administration of intravenous fluids to patients with septic shock is needed.     

Diamond-Blackfan syndrome: evidence against cell-mediated erythropoietic suppression

The profound anemia of Diamond-Blackfan syndrome (DBS) is due to marrow red cell failure, but the pathogenesis is not understood. Studies by others indicated cell-mediated erythropoietic suppression in this condition. To explore this mechanism further, Ficoll-Hypaque--separated peripheral blood lymphocytes (PBL) from four anemic untreated patients with DBS, or from normals were cocultured with control marrow in vitro and the growth of erythropoietin-responsive stem cell colonies (CFU-E) was dermined. CFU-E numbers obtained from cultures with added normal PBL were not significantly different from the number without PBL. Similarly, CFU-E from cultures with added DBS PBL were not significantly different from the number without PBL (215 versus 220, 229 versus 220 and 84 versus 60, 74 versus 94/10(5) cells, respectively). Mixing marrows from a control and one DBS patient in ratios of 2:1, 1:1, or 1:2 prior to culture failed to disclose a decrease of colony growth. We could not show cellular inhibition of erythropoiesis in these patients with DBS. The mechanism of anemia in this disorder remains an open question.     

Neurological symptoms in children with intussusception

Aim:  The classical combination of abdominal pain, vomiting, rectal blood loss and a palpable abdominal mass is only present in a minority of children with intussusception. Neurological signs and symptoms have been described, but are not a well understood phenomenon. We performed a retrospective study to ascertain the frequency and nature of these symptoms and to describe the characteristics of the patients presenting in this atypical way.
Methods:  The records of 58 children presenting with intussusception from 2003 to 2008 were reviewed for abdominal and neurological signs and symptoms, duration of symptoms and effectiveness of treatment.
Results:  In 10 out of 58 patients (17%), one or more neurological symptoms were recorded at presentation, with lethargy being the most frequent, followed by hypotonia and fluctuating consciousness. The patients with neurological abnormalities were significantly younger and presented with a shorter duration of symptoms. Therapy was more invasive, although not statistically significant, in this patient category.
Conclusion:  Intussusception should be considered in the differential diagnosis in young children presenting with lethargy, hypotonia and/or sudden alterations of consciousness even in the absence of the classical symptoms of intussusception.