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Biomedical subjects

D C Angus

Publications and source records attributed to D C Angus.

At least 19 recordsLinked to original sources
PubMed2005

Cost effectiveness of drotrecogin alfa (activated) for the treatment of severe sepsis in the United Kingdom.

Drotrecogin alfa (activated) is licensed in Europe for the treatment of severe sepsis in patients with multiple organ failure. We constructed a model to assess the cost effectiveness of drotrecogin alfa (activated) from the perspective of the UK National Health Service when used in adult intensive care units. Patient outcomes from a 28-day international clinical trial (PROWESS) and a subsequent follow-up study (EVBI) were supplemented with UK data. Cost effectiveness was assessed as incremental cost per life year and per quality adjusted life year saved compared to placebo alongside best usual care. Applying the 28-day mortality outcomes of the PROWESS study, the model produced a cost per life year saved of 4608 UK pounds and cost per quality adjusted life year saved of 6679 UK pounds. Equivalent results using actual hospital outcomes were 7625 UK pounds per life year and 11,051 UK pounds per quality adjusted life year. Drotrecogin alfa (activated) appears cost effective in treating severe sepsis in UK intensive care units.

Adult↗
PubMed2004

Incidence and definition of sepsis and associated organ dysfunction.

AIMS: To discuss the incidence, outcome and predisposing factors to systemic inflammatory response syndrome (SIRS), sepsis, and multiple organ failure. METHODS: A qualitative review of the literature. RESULTS: Case definitions of sepsis and severe sepsis, though clarified recently, are still arbitrary. It seems, however, that SIRS is not useful in identifying severe sepsis while organ failure has become a cornerstone for this definition. Incidence of severe sepsis appears to be approximately 10% of all ICU admissions, totaling nearly one million cases annually in the U.S. alone, and rising. Mortality associated with these events is still high, especially among ICU patients. Recent studies have been demonstrating an association between a variety of genetic polymorphisms and progression to and dying from sepsis. CONCLUSION: Recently there has been an increasing amount of information enabling characterization of the epidemiology of sepsis, which may help to direct appropriate care in the coming years.

Biomarkers↗
PubMed2003

Genetic variation and risk of sepsis.

Sepsis is the leading cause of death in non-coronary intensive care unit patients. Sepsis is caused by the immune response to infection and is manifest by pain, fever and edema as the result of the activation of coagulation and inflammatory responses. In severe cases, sepsis leads to organ dysfunction and failure. Sepsis affects more than 750,000 people each year in the US alone, with a mortality rate of over 35 percent making it one of the leading causes of death in developed countries. In addition many patients that die of other diseases have their hospital courses complicated by sepsis. Most patients with infection do not develop severe sepsis and septic shock and yet those that do have a significantly increased risk of death. Genetic and environmental variables may influence why one patient with infection gets sicker than the next. For example, people may be programmed to respond to infection in different ways; some with aggressive immune responses that may be able to wipe out infection before it manifests itself in physical symptoms, while others may have less aggressive immune systems that allow them to get sick more often. The discovery of various common genetic polymorphisms in genes that control the inflammatory response (e.g. tumor necrosis factor) has lent credence to this hypothesis. Yet discovery of the actual relationship between risks of infection / severe sepsis and individual genotypes will require larger, more rigorously designed studies.

Animals↗
PubMed2001

Epidemiology of neonatal respiratory failure in the United States: projections from California and New York.

We wanted to determine the incidence, cost, outcome, and patterns of care for neonates requiring mechanical ventilation (MV) in the United States. Using 1994 state hospital discharge data from California and New York, we conducted an observational study of all neonatal hospitalizations (n = 16,405) with MV, comparing outcomes at centers of different technological capability, and generating national projections using census and natality reports. The MV rate was 18 per 1,000 live births. Although the incidence was much higher in lower birth weight (BW) babies, one-third had normal BW. The incidence was higher in boys (20 versus 15.6 per 1,000) and in blacks (29 per 1,000). Hospital mortality was 11.1%, higher in minority groups, and associated with low BW, congenital anomalies, and major hemorrhage. Mean hospital length of stay and costs were 31.1 d and $51,700. Half of all deaths occurred at lower level centers. There are 80,000 cases per year in the United States with 8,500 deaths and total hospital costs of $4.4 billion. We conclude neonatal respiratory failure is common, expensive, and frequently fatal. There are a surprisingly large number of normal BW cases and there are large racial differences.

California↗
PubMed2001

Predicting hospital mortality for patients in the intensive care unit: a comparison of artificial neural networks with logistic regression models.

OBJECTIVE: Logistic regression (LR), commonly used for hospital mortality prediction, has limitations. Artificial neural networks (ANNs) have been proposed as an alternative. We compared the performance of these approaches by using stepwise reductions in sample size. DESIGN: Prospective cohort study. SETTING: Seven intensive care units (ICU) at one tertiary care center. PATIENTS: Patients were 1,647 ICU admissions for whom first-day Acute Physiology and Chronic Health Evaluation III variables were collected. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We constructed LR and ANN models on a random set of 1,200 admissions (development set) and used the remaining 447 as the validation set. We repeated model construction on progressively smaller development sets (800, 400, and 200 admissions) and retested on the original validation set (n = 447). For each development set, we constructed models from two LR and two ANN architectures, organizing the independent variables differently. With the 1,200-admission development set, all models had good fit and discrimination on the validation set, where fit was assessed by the Hosmer-Lemeshow C statistic (range, 10.6-15.3; p > or = .05) and standardized mortality ratio (SMR) (range, 0.93 [95% confidence interval, 0.79-1.15] to 1.09 [95% confidence interval, 0.89-1.38]), and discrimination was assessed by the area under the receiver operating characteristic curve (range, 0.80-0.84). As development set sample size decreased, model performance on the validation set deteriorated rapidly, although the ANNs retained marginally better fit at 800 (best C statistic was 26.3 [p = .0009] and 13.1 [p = .11] for the LR and ANN models). Below 800, fit was poor with both approaches, with high C statistics (ranging from 22.8 [p <.004] to 633 [p <.0001]) and highly biased SMRs (seven of the eight models below 800 had SMRs of <0.85, with an upper confidence interval of <1). Discrimination ranged from 0.74 to 0.84 below 800. CONCLUSIONS: When sample size is adequate, LR and ANN models have similar performance. However, development sets of < or = 800 were generally inadequate. This is concerning, given typical sample sizes used for individual ICU mortality prediction.

APACHE↗
PubMed2001

Economics of end-of-life care in the intensive care unit.

End-of life care is in need of improvement, yet little is known about the effectiveness or cost of various end-of-life therapies. Economic analyses are used to help make decisions between two or more therapies when resources are constrained. In this chapter, we review the various types of economic analyses, the costs of dying, and how healthcare reform has impacted these costs. Finally, we discuss the unique issues associated with cost-effectiveness studies of palliative therapy, with emphasis on the problem of calculating a cost-effectiveness ratio when there is no good measurement for valuing the quality of death. It is likely that methods for conducting a cost-effectiveness analyses for end-of-life care will need to evolve or alternative strategies such as cost-benefit analysis or distributive justice will be needed to inform resource allocation decisions. As the national debate about healthcare costs, access, and quality continues, we will increasingly turn to economic analyses to help make resource allocation decisions. Cost-effectiveness analysis will continue to be the most popular form of economic analysis because it combines the results (effectiveness of treatment) with the costs of achieving the results. We must be aware of the limitations of cost-effectiveness analyses and the need for value judgments when using cost-effectiveness analyses to inform healthcare decisions.

Attitude to Death↗
PubMed2001

Intensivists...

Explore the source record for details and available documents.

Critical Care↗
PubMed2001

Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care.

OBJECTIVE: To determine the incidence, cost, and outcome of severe sepsis in the United States. DESIGN: Observational cohort study. SETTING: All nonfederal hospitals (n = 847) in seven U.S. states. PATIENTS: All patients (n = 192,980) meeting criteria for severe sepsis based on the International Classification of Diseases, Ninth Revision, Clinical Modification. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We linked all 1995 state hospital discharge records (n = 6,621,559) from seven large states with population and hospital data from the U.S. Census, the Centers for Disease Control, the Health Care Financing Administration, and the American Hospital Association. We defined severe sepsis as documented infection and acute organ dysfunction using criteria based on the International Classification of Diseases, Ninth Revision, Clinical Modification. We validated these criteria against prospective clinical and physiologic criteria in a subset of five hospitals. We generated national age- and gender-adjusted estimates of incidence, cost, and outcome. We identified 192,980 cases, yielding national estimates of 751,000 cases (3.0 cases per 1,000 population and 2.26 cases per 100 hospital discharges), of whom 383,000 (51.1%) received intensive care and an additional 130,000 (17.3%) were ventilated in an intermediate care unit or cared for in a coronary care unit. Incidence increased >100-fold with age (0.2/1,000 in children to 26.2/1,000 in those >85 yrs old). Mortality was 28.6%, or 215,000 deaths nationally, and also increased with age, from 10% in children to 38.4% in those >85 yrs old. Women had lower age-specific incidence and mortality, but the difference in mortality was explained by differences in underlying disease and the site of infection. The average costs per case were $22,100, with annual total costs of $16.7 billion nationally. Costs were higher in infants, nonsurvivors, intensive care unit patients, surgical patients, and patients with more organ failure. The incidence was projected to increase by 1.5% per annum. CONCLUSIONS: Severe sepsis is a common, expensive, and frequently fatal condition, with as many deaths annually as those from acute myocardial infarction. It is especially common in the elderly and is likely to increase substantially as the U.S. population ages.

Adolescent↗
PubMed2001

Epidemiology of sepsis: an update.

OBJECTIVE: We review the case definition, occurrence, and outcome of sepsis. We discuss whether the epidemiology of sepsis has changed over time and discuss issues important to our understanding of sepsis. DATA SOURCES: Literature review. DATA SUMMARY: Our understanding of the epidemiology of sepsis is hampered by the lack of a reliable case definition. Inconsistent application of sepsis definition criteria contributes to confusion and variability in the literature. Variability in the time course of sepsis also introduces difficulty. The Centers for Disease Control estimated an incidence of 73.6 per 100,000 population in 1979, rising to 175.9 per 100,000 in 1989. However, this study was of septicemia, not severe sepsis. There are several hospital-based studies of the occurrence of severe sepsis, defined using the American College of Chest Physicians/Society of Critical Care Medicine consensus criteria. These studies reported variable hospital and intensive care unit (ICU) occurrence rates, ranging from 2% to 11% of all hospital or ICU admissions. Most of these data are from academic, tertiary care centers, which limits generalizability. More population-based studies are required to better delineate the incidence and risk factors of sepsis in the general population. Hospital mortality from sepsis has ranged from 25% to 80% over the last few decades. Although mortality may be lower in recent years, sepsis is clearly still a very serious condition. Achieving a better understanding of whether the mortality rate for sepsis is falling, however, is confounded by the lack of a uniform definition. Risk factors for adverse outcome include the degree of physiologic derangement, organ dysfunction, underlying illness, site of infection, and microbiological etiology. We do not know, however, the factors that predict response to new therapies. This dilemma has led researchers to explore whether markers of the inflammatory cascade might be more specific for sepsis, more accurate for risk prediction, or more useful for predicting response to therapy. However, there as yet is no equivalent of the CPK-MB for acute myocardial infarction. Whether we will find such a marker as we develop a greater understanding of the genetic control of the inflammatory cascade is uncertain but promising. One might assume intuitively that the epidemiology of sepsis is changing. For example, the number of patients being treated in ICUs has increased over time, the technologies used in the ICU have changed, and the choice and the use of antibiotics have changed. Predisposing factors, such as chemotherapeutic regimens, have also changed, and there have been marked changes in antibiotic resistance. Furthermore, there have been wide changes in the microbiological etiologies of diseases such as pneumonia and acute exacerbations of chronic bronchitis. However, lacking good case definitions and true incidence studies, we can only make inferences about whether the epidemiology of sepsis is truly changing. CONCLUSION: Many studies have documented many aspects of the epidemiology of sepsis. However, the composite picture they provide, although rich in many aspects, remains incomplete and emphasizes the heterogeneity of the condition. Unfortunately, few population-based prospective cohort studies exist that allow us to accurately delineate the risk factors for sepsis, its course, and its outcome. To place new information, such as the role of genetic predisposition, in the correct context, it is essential that such studies be conducted.

Centers for Disease Control and Prevention, U.S.↗
PubMed2001

Quality-adjusted survival in the first year after the acute respiratory distress syndrome.

There is little information on long-term outcome after acute respiratory distress syndrome (ARDS). We measured quality-adjusted survival in the first year after ARDS in a prospective cohort (n = 200). All patients met traditional criteria for ARDS. Patients with sepsis and acute nonpulmonary organ dysfunction at presentation were excluded. The cohort was healthy before onset of ARDS as evidenced by high functional status (mean Karnofsky Performance Status index: 82.2/100 where >/= 80 = able to perform normal activities independently) and minimal comorbid illness (mean Charlson-Deyo comorbidity score: 0.32/17 where 0 = absence of chronic illness). We determined quality-adjusted life-years (QALYs) using the Quality of Well-being (QWB) scale (0 to 1 scale where 1 = optimal well-being), measured at 6 and 12 mo. Survival was 69.5 +/- 5.0% at 1 month, fell to 55.7 +/- 3.7% at 6 mo, and did not change at 12 mo, yielding a survival of 59 life-years in the first year per 100 patients with ARDS. QWB was low at 6 and 12 mo (0.59 +/- 0.015 and 0.60 +/- 0.015), yielding a quality-adjusted survival of 36 QALYs per 100 patients (sensitivity range: 21 to 46 QALYs). We conclude that ARDS developing in previously healthy patients is associated with poor quality-adjusted survival. These data are important for cost-effectiveness analyses and long-term care.

APACHE↗
PubMed2000

Caring for the critically ill patient. Current and projected workforce requirements for care of the critically ill and patients with pulmonary disease: can we meet the requirements of an aging population?

CONTEXT: Two important areas of medicine, care of the critically ill and management of pulmonary disease, are likely to be influenced by the aging of the US population. OBJECTIVE: To estimate current and future requirements for adult critical care and pulmonary medicine physicians in the United States. DESIGN, SETTING, AND PARTICIPANTS: Analysis of existing population, patient, and hospital data sets and prospective, nationally representative surveys of intensive care unit (ICU) directors (n = 393) and critical care specialists (intensivists) and pulmonary specialists (pulmonologists) (n = 421), conducted from 1996 to 1999. MAIN OUTCOME MEASURES: Influence of patient, physician, regional, hospital, and payer characteristics on current practice patterns; forecasted future supply of and demand for specialist care through 2030. Separate models for critical care and pulmonary disease. Base-case projections with sensitivity analyses to estimate the impact of future changes in training and retirement, disease prevalence and management, and health care reform initiatives. RESULTS: In 1997, intensivists provided care to 36.8% of all ICU patients. Care in the ICU was provided more commonly by intensivists in regions with high managed care penetration. The current ratio of supply to demand is forecast to remain in rough equilibrium until 2007. Subsequently, demand will grow rapidly while supply will remain near constant, yielding a shortfall of specialist hours equal to 22% of demand by 2020 and 35% by 2030, primarily because of the aging of the US population. Sensitivity analyses suggest that the spread of current health care reform initiatives will either have no effect or worsen this shortfall. A shortfall of pulmonologist time will also occur before 2007 and increase to 35% by 2020 and 46% by 2030. CONCLUSIONS: We forecast that the proportion of care provided by intensivists and pulmonologists in the United States will decrease below current standards in less than 10 years. While current health care reform initiatives and modification of existing practice patterns may temporarily forestall this problem, most anticipated effects are minor in comparison with the growing disease burden created by the aging US population. JAMA. 2000;284:2762-2770.

Aged↗
PubMed2000

E5 murine monoclonal antiendotoxin antibody in gram-negative sepsis: a randomized controlled trial. E5 Study Investigators.

CONTEXT: Knowledge and understanding of gram-negative sepsis have grown over the past 20 years, but the ability to treat severe sepsis successfully has not. OBJECTIVE: To assess the efficacy and safety of E5 in the treatment of patients with severe gram-negative sepsis. DESIGN: A multicenter, double-blind, randomized, placebo-controlled trial conducted at 136 US medical centers from April 1993 to April 1997, designed with 90% power to detect a 25% relative risk reduction, incorporating 2 planned interim analyses. SETTING: Intensive care units at university medical centers, Veterans Affairs medical centers, and community hospitals. PATIENTS: Adults aged 18 years or older, with signs and symptoms consistent with severe sepsis and documented or probable gram-negative infection. INTERVENTION: Patients were assigned to receive 2 doses of either E5, a murine monoclonal antibody directed against endotoxin (n = 550; 2 mg/kg per day by intravenous infusion 24 hours apart) or placebo (n = 552). MAIN OUTCOME MEASURES: The primary end point was mortality at day 14; secondary end points were mortality at day 28, adverse event rates, and 14-day and 28-day mortality in the subgroup without shock at presentation. RESULTS: The trial was stopped after the second interim analysis. A total of 1090 patients received study medication and 915 had gram-negative infection confirmed by culture. There were no statistically significant differences in mortality between the E5 and placebo groups at either day 14 (29.7% vs 31.1%; P = .67) or day 28 (38.5% vs 40.3%; P = .56). Patients presenting without shock had a slightly lower mortality when treated with E5 but the difference was not significant (28.9% vs 33.0% for the E5 and placebo groups, respectively, at day 28; P = .32). There was a similar profile of adverse event rates between E5 and placebo. CONCLUSIONS: Despite adequate sample size and high enrollment of patients with confirmed gram-negative sepsis, E5 did not improve short-term survival. Current study rationale and designs should be carefully reviewed before further large-scale studies of patients with sepsis are conducted.

Antibodies, Monoclonal↗
PubMed2000

Short-term and long-term outcome prediction with the Acute Physiology and Chronic Health Evaluation II system after orthotopic liver transplantation.

OBJECTIVE: To evaluate the relationship between the postoperative Acute Physiology and Chronic Health Evaluation (APACHE) II score and mortality at hospital discharge and at 1 yr in liver transplant recipients. POPULATION: Adult orthotopic liver transplant (OLTX) recipients (n = 599) admitted to the intensive care unit postoperatively at a university hospital. METHODS: The cohort was split randomly into development and validation sets. Three models were compared for each end point: a) the original APACHE II slope with the original APACHE II postgastrointestinal surgery intercept; b) the original APACHE II slope with an OLTX-specific intercept generated from the development set; and c) an OLTX-specific slope and intercept generated from the development set. Goodness-of-fit and calibration were assessed by the Hosmer-Lemeshow C statistic (where p>.05 suggests good fit) and standardized mortality ratios. Discrimination was assessed by receiver operator characteristic area under the curve analysis. MEASUREMENTS AND MAIN RESULTS: Hospital and 1-yr mortality rates were 9.9% and 15.9%, respectively. The APACHE II score was strongly associated with mortality (chi-square, p<.0001), but when used with the original equation, it significantly overestimated hospital mortality (standardized mortality ratio, 0.73 [confidence interval, 0.58-0.99]). Using the OLTX-specific approaches, goodness-of-fit for both hospital and 1-yr mortality was good (p = .2-.57) but discrimination was only moderate (receiver operator characteristic area under the curve, 0.675-0.723). CONCLUSIONS: APACHE II is a good predictor of short- and long-term mortality after liver transplantation, especially when using OLTX-specific coefficients. Because fit and calibration were better than discrimination, APACHE II will be most useful in the prediction of risk for groups of patients (e.g., in clinical trials or institutional comparisons) rather than for individuals. This study raises the possibility that APACHE II may be useful for long-term mortality prediction in other critically ill populations. The overestimation of mortality using the original equation suggests that orthotopic liver transplantation, by reversing the underlying pathophysiology, may modify risk.

APACHE↗
PubMed1999

Using large-scale databases to measure outcomes in critical care.

The major intent of this article is to describe the availability and potential use of large-scale databases; however, it is first essential to know and understand the basic principles involved in the conduct and interpretation of observational outcomes studies. In this article, the authors briefly overview the design of observational outcomes studies as applied to critical care medicine. Then, criteria for evaluating data sources and for in-depth reviewing of the available data sources from which these observational studies can be conducted are discussed.

Critical Care↗