Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An analysis of risks and benefits is an important component of patient care. Drotrecogin alfa (activated), the first approved cogin (a class of recombinant human coagulation inhibitors), provides a clear example of a treatment that requires a careful risk-benefit analysis. Treatment with this novel compound has been shown to reduce significantly the risk of death in patients with sepsis and acute organ dysfunction (severe sepsis). However, the drug is a natural antithrombotic that can increase the risk of bleeding in recipients. We will discuss bleeding and other potential risks associated with drotrecogin alfa (activated) treatment, as well as the survival benefits seen with the use of this therapy in patients with severe sepsis.
 ...
PMID:Risk-benefit analysis for drotrecogin alfa (activated). 1252 15

A number of management issues confront the clinician treating a critically ill patient with drotrecogin alfa (activated) (Xigris; Eli Lilly and Company, Indianapolis, IN), a compound documented to significantly reduce the risk of 28-day all-cause mortality in patients with severe sepsis. The management issues that will be discussed include differentiating drug effect from the hemostatic changes of sepsis, prevention and management of bleeding during drotrecogin alfa (activated) infusion, treatment considerations in the patient with thrombocytopenia or disseminated intravascular coagulation, thromboprophylaxis in drug-treated patients, and the use of drotrecogin alfa (activated) in patients requiring renal replacement therapy. Proper adherence to principles described in this article can facilitate patient management and reduce the risk of bleeding.
 ...
PMID:Management of patients with severe sepsis, treated by drotrecogin alfa (activated). 1252 16

Sepsis with acute organ dysfunction is common, frequently fatal, and expensive. The critical care nurse is involved in the continuous bedside care of the critically ill patient; consequently, he or she has the opportunity to prevent sepsis through infection control practices and general nursing care, to identify patients at risk for the disease, to monitor these patients for the clinical signs of sepsis, and to detect developing organ dysfunction as a manifestation of severe sepsis. In addition, the nurse is responsible for monitoring the patient's response to organ support measures and specific antisepsis interventions. The role of the critical care nurse in the assessment and management of severe sepsis is significant and can greatly improve outcomes for the patient with this disease. Drotrecogin alfa (activated) is a promising new therapy in the treatment of severe sepsis. Nurses caring for patients with this disease need to understand the issues related to the administration of drotrecogin alfa (activated) and the monitoring of patients receiving this drug to promote optimal and appropriate use of this innovative therapy.
 ...
PMID:The role of the critical care nurse in the assessment and management of the patient with severe sepsis. 1259 37

Severe sepsis in immunosuppressed recipients of solid-organ transplants is associated with a high mortality. Conventional management of sepsis in this patient population has not specifically attempted to treat the underlying inflammatory or procoagulant responses that contribute to the development of multisystem organ failure. Drotrecogin alfa (activated, human activated protein C) has been shown to be a safe and effective adjuvant in the treatment of severe sepsis; however, experience in recipients of solid-organ transplants has not been addressed. The treatments and outcomes of three solid-organ transplant recipients (liver, kidney, and kidney-pancreas) who experienced episodes of severe sepsis are presented and demonstrate initial success with the use of drotrecogin alfa (activated).
 ...
PMID:Solid-organ transplant recipients treated with drotrecogin alfa (activated) for severe sepsis. 1266 May 22

(1) Severe sepsis is fatal in 30-50% of cases, despite antibiotic therapy and intensive care. (2) The first specific treatment to be marketed in France was HA-IA monoclonal antibodies, in 1991. However, marketing approval was granted precipitously, on the basis of a single, controversial comparative trial, and the product was withdrawn after a second trial gave negative results. (3) Marketing authorization for drotrecogin alfa (recombinant activated protein C) was granted in 2002 for this indication. (4) The product was approved after a single comparative double-blind placebo-controlled trial in 1 690 patients. The protocol was modified during the trial, to exclude patients at high risk of death from causes unrelated to sepsis. The manufacturing process was also changed, making it difficult to interpret the results of this trial. (5) The trial found that drotrecogin alfa reduced mortality (by 6% in absolute values: 25% versus 31%), but also increased the risk of severe haemorrhage, the main adverse effect (3.5% versus 2%). (6) Retrospective subgroup analyses identified patients most likely to benefit from drotrecogin alfa, and also patients who would be needlessly exposed to an additional risk. (7) Drotrecogin alfa is a very expensive drug. (8) In practice, this clinical trial should be considered preliminary. Other, strictly designed and conducted trials are therefore required.
 ...
PMID:Drotrecogin alfa: new preparation. For some cases of severe sepsis? 1267 16

Human recombinant activated protein C (Xigris) represents a new concept in adjuvant therapy for patients with severe sepsis. In the large randomized controlled trial on which the registration is based, 28 day mortality was significantly reduced by 6.1% from 30.8% in the placebo group to 24.7% in the treatment group. Treatment benefit seemed to be restricted to those patients with the most severe disease. Side effects in terms of intracerebral hemorrhage and procedure related bleeding were seen during the 4 day infusion period. Until further data becomes available from ongoing studies, we recommend that treatment be restricted to those patients for whom benefit has been shown in the clinical trial, i.e. adult patients with septic shock and at least one additional sign of organ dysfunction as defined in the study. Patients with septic organ dysfunctions with a longer duration than 24 h were not evaluated in the study.
 ...
PMID:[Activated protein C--recent addition to therapy of sepsis]. 1287 74

Drotrecogin alfa (activated) improved survival in patients with severe sepsis in PROWESS, a double-blind, study of 1690 adult patients randomized to drotrecogin alfa (activated) at 24 microg/kg/h (N=850) or placebo (N=840) infused for 96 hours. Pharmacodynamic effects of drotrecogin alfa (activated) were assessed with 15 prospectively defined systemic biomarkers of hemostasis, inflammation and endothelial injury. The last-observation-carried-forward (LOCF) method of imputation for missing observations was the prospectively defined statistical method. The results were also analyzed with only the observed values without imputation for missing data (repeated measures analysis). With both statistical methods, drotrecogin alfa (activated)-treated patients demonstrated antithrombotic (reduced markers of thrombin generation and accelerated normalization of anticoagulant factor, protein C and fibrinolytic factors) and anticoagulant (prolonged PT and APTT) effects compared with placebo. A profibrinolytic (reduction in plasminogen activator inhibitor-1) effect was significant only with the LOCF imputation method in observed case and percent change from baseline analyses. An anti-inflammatory (reduction in interleukin-6) effect was significant only with the LOCF imputation method in change from baseline and percent change from baseline analyses. Drotrecogin alfa (activated) is a new and promising agent for treatment of patients with severe sepsis. The extensive analysis of systemic biomarkers confirms the previously published antithrombotic effects. However, the present results using different statistical methods do not provide a strong basis for systemic anti-inflammatory or pro-fibrinolytic effects. These latter two effects may occur at the local or cellular level. The systemic biomarkers reported here might not be the most appropriate approach to demonstrate these potential effects of drotrecogin alfa (activated).
 ...
PMID:Drotrecogin alfa (activated) (recombinant human activated protein C) reduces host coagulopathy response in patients with severe sepsis. 1511 70

New technologies in the impatient prospective payment system are discussed. On December 21, 2000, Congress passed Public Law 106-554 that includes a requirement to establish a mechanism to more expeditiously incorporate the costs and establish qualifying criteria for payment of new services and technologies into the hospital inpatient prospective payment system. The final ruling of this law states that a new service or technology must demonstrate substantial improvement, be inadequately paid under the DRG system, and be "new." The intent of these criteria is to identify new technologies that offer substantial improvement over existing technologies and to provide supplemental payment that encourages physicians and hospitals to utilize the new technology. In November 2001, drotrecogin alfa (activated) received fast-track FDA approval because of the robust findings from the PROWESS trial. Drotrecogin alfa (activated) is the first agent proven to reduce mortality in patients suffering from severe sepsis associated with acute organ dysfunction who are at a high risk of death (i.e., APACHE II score > 24). In August 2002, drotrecogin alfa (activated) was one of four such new technologies and the first agent approved for new technology payment under the prospective payment system (PPS). This decision offers confidence that the PPS is effectively striving to incorporate new medical services and technologies at a pace similar to that of innovation. Providers may receive up to $3400 in additional reimbursement when drotrecogin alfa (activated) is administered in the Medicare population. Pharmacy and patient accounting personnel should develop a collaborative process to identify, document, and capture this new source of payment.
 ...
PMID:Hospital inpatient prospective payment system: incorporating new technology. 1461 29

Drotrecogin alfa (activated) (Xigris; Eli Lilly and Company, Indianapolis, IN) significantly reduced mortality in severe sepsis in the PROWESS trial. We evaluate the cost-effectiveness of drotrecogin alfa (activated) as an adjunct to standard therapy from the German healthcare payer's perspective with respect to patients with 1) severe sepsis and 2) severe sepsis and multiple organ failure the approved European indication. Hospital resource use based on PROWESS was valued using German unit costs. German life-tables and long-term survival assumptions determined life-years gained. European and German healthcare resource use data are examined in the sensitivity analysis. We assumed a unit price of euro;237.50 for drotrecogin alfa (activated). Per patient treated, drotrecogin alfa (activated) increased costs by euro;7,500, and hospital costs by euro;900 for all patients (euro;7,400 and euro;1,500 respectively for the approved indication) and survival by 0.59 life years (0.87 life years respectively for the approved indication). Thus drotrecogin alfa (activated) cost euro;14,100 (euro;17,700 discounting life years at 3%) per life year gained for all patients (euro;10,200 and euro;12,900, respectively, for the approved indication). Testing the unit cost of drotrecogin alfa (activated), pattern of resource use, and survival benefit, demonstrated that cost-effectiveness lies well within the range of other life saving interventions in Germany representing good economic value.
 ...
PMID:Cost-effectiveness of drotrecogin alfa (activated) for the treatment of severe sepsis in Germany. 1469 95

The authors observed the effect of drotrecogin alfa (activated) in a case of pediatric severe sepsis. A 4-month-old male infant with Serratia marcescens septic shock, multiple organ dysfunction syndrome (MODS), and consumptive coagulopathy was admitted. The safety and efficacy of drotrecogin alfa (activated) has not yet been established for patients younger than 18 years of age. This is the first published report of the use of drotrecogin alfa (activated) in an infant with severe sepsis. Within 6 hours of starting therapy, there was a significant improvement in hemodynamics, which was not maintained after the drotrecogin alfa (activated) infusion was temporarily discontinued. No significant bleeding complications occurred during the infusion. A brain MRI on day 22 after drotrecogin alfa (activated) infusion showed bilateral small occipital hemorrhages. Drotrecogin alfa (activated) in this infant was temporally related to significant improvement. It is unknown whether the MRI brain lesions are related to severe sepsis with disseminated intravascular coagulation or drotrecogin alfa (activated) infusion. The authors believe that drotrecogin alfa (activated) should be considered in select children with life-threatening severe sepsis.
 ...
PMID:Drotrecogin alfa (activated) in an infant with gram-negative septic shock. 1503 56


<< Previous 1 2 3 4 5 6 7 Next >>