CURB-65, PSI, and APACHE II to assess mortality risk in patients with severe sepsis and community acquired pneumonia in PROWESS.

Background: Patients with community-acquired pneumonia (CAP) comprised 35.6% of the overall phase 3 Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study and 33.1% of the placebo arm.

A retrospective observational study of drotrecogin alfa (activated) in adults with severe sepsis: comparison with a controlled clinical trial.

Objective: To compare characteristics and outcomes of patients treated with drotrecogin alfa (activated) (DrotAA) in clinical practice to those treated in a phase III randomized controlled trial (PROWESS).

Design: Observational data were collected retrospectively from patients who received DrotAA as part of physician-directed treatment.

Setting: Intensive care units of five teaching institutions.

Growth hormone replacement therapy in adults with growth hormone deficiency improves maximal oxygen consumption independently of dosing regimen or physical activity.

Context: Several studies have demonstrated an improvement in aerobic exercise capacity with 6 months of GH replacement in adults with GH deficiency (GHD).

Objective: The objective of the study was to determine whether improvements in aerobic exercise capacity with GH treatment in adults with GHD are related to changes in physical activity or affected by the GH dosing regimen.

Design: This was a randomized, two-arm, parallel, open-label study.

Simplified pharmacoeconomics of critical care and severe sepsis.

Understanding pharmacoeconomic evaluation can empower clinicians to be stronger decision makers. However, cost-effectiveness analyses (CEAs) in critical care are sometimes not easy to understand and often not placed in context with other interventions. The purpose of this article is to clarify and simplify the CEA process using examples from critical care and severe sepsis.

From bench to bedside: a review of the clinical trial development plan of drotrecogin alfa (activated).

Objective: To provide a comprehensive overview of the various clinical trials of drotrecogin alfa (activated) (DrotAA) completed by Eli Lilly and Company over the past 10 years.

Methods: Eli Lilly and Company data from phase 1 through phase 4 trials, observational studies, and compassionate-use studies of DrotAA were reviewed. Safety, efficacy, and pharmacokinetic data were included.

Differences in follicle-stimulating hormone secretion between 45,X monosomy Turner syndrome and 45,X/46,XX mosaicism are evident at an early age.

Context: Little information exists regarding FSH values in very young girls with Turner syndrome (TS).

Objectives: The objective of the study was to evaluate the pattern, natural progression, and karyotype-related differences in FSH secretion in young, prepubertal girls with TS.

Study Design: FSH was measured at study entry and annually for 2 yr.

Application of a population-based severity scoring system to individual patients results in frequent misclassification.

Introduction: APACHE II (AP2) was developed to allow a systematic examination of intensive care unit outcomes in a risk adjusted manner. AP2 has been widely adopted in clinical trials to assure broad consistency amongst different groups. Although errors in calculating the true AP2 score may not be reducible below 15%, the self-canceling effect of random errors reduces the importance of such errors when applied to large populations.

Steroid use in PROWESS severe sepsis patients treated with drotrecogin alfa (activated).

Introduction: In a study conducted by Annane, patients with septic shock and unresponsive to adrenocorticotropic hormone stimulation receiving low-dose steroid therapy had prolonged survival but not significantly improved 28-day mortality. The present study examines intravenous steroid use in PROWESS (Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis) patients meeting the Annane enrollment criteria (AEC).

Methods: Adrenocorticotropic hormone stimulation tests were not done in PROWESS.

Static and dynamic assessment of biomarkers in surgical patients with severe sepsis.

Background: Severe sepsis, defined as a systemic inflammatory response to infection associated with acute organ dysfunction, is common among surgical patients and is a major cause of morbidity and mortality. Severe sepsis has been associated with changes in inflammatory and hemostatic biomarkers. In patients undergoing surgical procedures there may be additional stimulation of cytokine release and activation of the coagulation system.

Obesity does not alter the pharmacokinetics of drotrecogin alfa (activated) in severe sepsis.

Background: Drotrecogin alfa (activated) [DrotAA] is approved for the reduction of mortality in adults with severe sepsis (sepsis with acute organ dysfunction) and high risk of death. Patients whose actual body weight was >135 kg were excluded from the Phase III PROWESS trial.

Objective: To compare exposure to DrotAA in patients with severe sepsis weighing >135 kg with those weighing < or =135 kg in an open-label, Phase IV trial, and quantify the elimination half-life (t1/2) of DrotAA in these patients.

Hospitalized cancer patients with severe sepsis: analysis of incidence, mortality, and associated costs of care.

Introduction: Infection is an important complication in cancer patients, which frequently leads to or prolongs hospitalization, and can also lead to acute organ dysfunction (severe sepsis) and eventually death. While cancer patients are known to be at higher risk for infection and subsequent complications, there is no national estimate of the magnitude of this problem. Our objective was to identify cancer patients with severe sepsis and to project these numbers to national levels.

Benefit/risk profile of drotrecogin alfa (activated) in surgical patients with severe sepsis.

Background: The Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial examined the safety and efficacy of drotrecogin alfa (activated) (Xigris) in adult patients with severe sepsis. A clinical evaluation committee examined clinical data for each patient enrolled in PROWESS. However, there were no surgeons on the committee, and thus questions remained regarding the safety and efficacy of drotrecogin alfa (activated) in surgical patients.