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Derek C Angus

Publications and source records attributed to Derek C Angus.

At least 73 records · Page 4Linked to original sources
PubMed2004

Pharmacoeconomic implications of new therapies in sepsis.

Severe sepsis is a major healthcare problem, characterised by a high incidence, mortality and cost. New breakthroughs in treatment are quite diverse, including: (i) more effective regimens for generic, inexpensive broad anti-inflammatory agents (corticosteroids); (ii) a recombinant protein (drotrecogin-alfa [activated]); and (iii) a protocol-based treatment approach (early goal-directed therapy). Economic analyses of new sepsis agents should adopt the societal perspective, which requires prolonging the time horizon beyond that currently typically studied in sepsis trials, so that patient-centred outcomes can be more fully captured. Sepsis affects a very diverse group of patients, and if findings are to be generalisable, careful attention must be paid to study entry criteria and differences in effects and costs across different patient subgroups. Existing care patterns for sepsis are also quite diverse, with the consequence that the incremental effects on costs and outcomes could vary widely by practice pattern, again affecting generalisability. Furthermore, many sepsis patients receive multiple other therapies, which together with therapies under study may have varied and unintended, potentially costly or dangerous adverse effects, which could have a large influence on cost-effectiveness estimates. Finally, there are a number of large yet potentially hidden costs of sepsis, such as the long-term costs of managing patients who develop sepsis or the costs of introducing different interventions into clinical practice. Such costs must also be addressed in economic analyses. The search for new anti-sepsis strategies remains vigorous and exciting. We recommend wider incorporation of economic analyses into the study of potential new therapies, with appropriate attention to the caveats discussed above. Clinical demand to use new agents must be balanced against the economic consequences of their use.

Anti-Inflammatory Agents↗
PubMed2003

Drotrecogin alfa (activated) treatment of older patients with severe sepsis.

The incidence of severe sepsis increases dramatically with advanced age, with a mortality rate that approaches 50%. The main purpose of this investigation was to determine both short- and long-term survival outcomes among 386 patients aged >or=75 years who were enrolled in the Protein C Worldwide Evaluation of Severe Sepsis (PROWESS) trial. Subjects who were treated with drotrecogin alfa (activated; DAA) had absolute risk reductions in 28-day and in-hospital mortality of 15.5% and 15.6%, respectively (P=.002 for both), compared with placebo recipients. The relative risk (RR) for 28-day mortality was 0.68 (95% confidence interval [CI], 0.54-0.87), and the in-hospital RR was 0.70 (95% CI, 0.56-0.88). Resource use and patient disposition for DAA-treated patients compared favorably with those for placebo recipients. In addition, long-term follow-up data were available for 375 subjects (97.2%), and survival rates for DAA recipients were significantly higher over a 2-year period (P=.02). The incidences of serious adverse bleeding during the 28-day study period in the DAA and placebo groups were 3.9% and 2.2%, respectively (P=.34). There was no interaction between age and bleeding rates (P=.97). In conclusion, older patients with severe sepsis have higher short- and long-term survival rates when treated with DAA than when treated with placebo but an increased risk of serious bleeding that is not aged related.

Aged↗
PubMed2003

Pneumonia: still the old man's friend?

BACKGROUND: Hospital mortality of patients admitted with community-acquired pneumonia (CAP) has been well described. However, the long-term survival of those discharged alive is less clear. We sought to determine long-term survival of patients hospitalized with CAP and compare the outcome with controls hospitalized for reasons other than CAP. METHODS: We performed a matched case-control analysis using the Medicare hospital discharge database from the first quarter of 1997. We compared all Medicare recipients 65 years or older hospitalized with CAP and controls matched for age, sex, and race hospitalized for reasons other than CAP. We measured 1-year mortality determined from the Medicare Beneficiary Entitlement file and the Social Security Administration. RESULTS: We identified 158 960 CAP patients and 794 333 hospitalized controls. Hospital mortality rates for the CAP cohort and hospitalized controls were 11.0% and 5.5%, respectively (P<.001). One-year mortality rates for the CAP cohort and hospitalized controls were 40.9% and 29.1%, respectively (P<.001). One-year mortality rates in hospital survivors of the CAP and control cohorts were 33.6% and 24.9%, respectively (P<.001). The difference in mortality between the CAP and control cohorts was not explained by underlying disease. Standardized against the general population, the risk of death for both cohorts decreased monthly but was still elevated 1 year after hospital discharge. The standardized mortality ratio was 2.69 (95% confidence interval, 2.47-2.93) for CAP patients and 1.93 (95% confidence interval, 1.79-2.08) for hospital controls. CONCLUSIONS: Almost half of all elderly patients admitted for CAP die in the subsequent year, with most deaths occurring after hospital discharge. The mortality is considerably higher than that of either the general population or a control population hospitalized for reasons other than CAP.

Aged↗
PubMed2003

Surviving intensive care: a report from the 2002 Brussels Roundtable.

The traditional goal of intensive care has been to decrease short-term mortality. While worthy, this goal fails to address the issue of what it means to survive intensive care. Key questions include whether intensive care survivors have optimal long-term outcomes and whether ICU care decisions would change if we knew more about these outcomes. The 2002 Brussels Roundtable, "Surviving Intensive care", highlighted these issues, summarizing the available evidence on natural history and risk factors for critical illness and outlining future directions for care and research. Critical illness is associated with a wide array of serious and concerning long-term sequelae that interfere with optimal patient-centered outcomes. Although traditional short-term outcomes, such as hospital mortality, remain extremely important, they are not likely to be adequate surrogates for subsequent patient-centered outcomes. As such, it is important to focus specifically on how critical illness and intensive care affects a patient's and relatives' long-term health and well-being. There are a large number of potential pre-, intra-, and post-ICU factors that may improve or worsen these outcomes, and these factors are subjects for future research. In addition, future clinical trials of ICU therapies should include long-term follow-up of survival, quality of life, morbidity, functional status, and costs of care. Follow-up ought to be for at least six months. The SF-36 and EuroQOL EQ-5D are the best-suited instruments for measuring quality of life in multicenter critical care trials though further methodologic research and instrument design is encouraged. There are also opportunities today to improve care. Key to taking advantage of such opportunities is the need for a global awareness of critical illness as an entity that begins and ends outside the ICU 'box'. Specific interventions that show promise for improving care include ICU discharge screening tools and ICU follow-up clinics.

Belgium↗
PubMed2003

Community-acquired pneumonia in the elderly.

CAP is traditionally considered a medical disease, and is managed with intravenous fluids and antibiotics on medical floors. Recent cost-containment efforts have shifted the provision of care to the outpatient settings, and only those with most severe disease and multiple comorbid illnesses are admitted to hospitals. Therefore, the proportion of hospitalized patients with severe CAP that need intensive care and life support is increasing. Furthermore, the incidence of severe CAP is also rising due to disproportionate growth of the elderly population that is most vulnerable to this deadly disease. Many of these elderly patients have advanced underlying diseases, and CAP might often be a terminal event superimposed on an underlying chronic debilitating illness. As ICU physicians, we need to be familiar with this disease, its complications, and its prognosis to provide intensive care in a timely and rational fashion in some patients, and refrain from life support in others. Just as prior efforts have sought to improve and standardize criteria for hospital admission, future efforts should aim to improve and standardize decisions regarding intensive care and life support in these very sick elderly patients. Future efforts in the management of CAP need to consider the postdischarge period where most deaths occur. Prevention is an important issue especially for those at high risk for CAP.

Aged↗
PubMed2003

Cost-effectiveness of drotrecogin alfa (activated) in the treatment of severe sepsis.

OBJECTIVE: To assess the cost-effectiveness of drotrecogin alfa (activated) therapy, which was recently shown to reduce mortality in severe sepsis. DESIGN: Estimates of effectiveness and resource use were based on data collected prospectively as part of a multicenter international trial. Estimates of hospital costs were based on a subset of the patients treated in the United States (33% of all enrolled patients). Lifetime projections were modeled from published sources and tested in sensitivity analyses. Analyses were conducted from the United States societal perspective, limited to healthcare costs, and using a 3% annual discount rate. SETTING: A total of 164 medical institutions in 11 countries. PATIENTS: Adults > or = 18 yrs of age with severe sepsis INTERVENTIONS: Eligible patients were randomly assigned to receive a 96-hr intravenous infusion of drotrecogin alfa (activated) at 24 microg/kg/hr (n = 850) or placebo (n = 840). MEASUREMENTS AND MAIN RESULTS: Base Case: incremental short-term (days 1-28) healthcare costs per day-28 survivor; Panel on Cost-Effectiveness in Health and Medicine Reference Case: incremental lifetime healthcare costs per quality-adjusted life-year. Over the first 28 days (short-term Base Case), drotrecogin alfa (activated) increased the costs of care by $9,800 and survival by 0.061 lives saved per treated patient. Thus, drotrecogin alfa (activated) cost $160,000 per life saved (with 84.7% probability that ratio is <$250,000 per life saved). Projected to lifetime (lifetime Reference Case), drotrecogin alfa (activated) increased the costs of care by $16,000 and quality-adjusted survival by 0.33 quality-adjusted life-years per treated patient. Thus, drotrecogin alfa (activated) cost $48,800 per quality-adjusted life-year (with 82% probability that ratio is <$100,000 per quality-adjusted life-year). Estimates were generally robust to sensitivity analyses, although cost-effectiveness deteriorated to >$100,000 per quality-adjusted life-year if survivors lived <4.6 yrs on average. Drotrecogin alfa (activated) cost $27,400 per quality-adjusted life-year when limited to patients with an Acute Physiology and Chronic Health Evaluation II score > or = 25 and was cost-ineffective when limited to patients with a score <25. CONCLUSIONS: Drotrecogin alfa has a cost-effectiveness profile similar to that of many well-accepted healthcare strategies and below commonly quoted thresholds.

Adult↗
PubMed2003

Drotrecogin alfa (activated) administration across clinically important subgroups of patients with severe sepsis.

OBJECTIVE: To assess the effects of drotrecogin alfa (activated) therapy, a recombinant human activated protein C, across clinically relevant subpopulations in a randomized, phase 3, placebo-controlled study of patients with severe sepsis (recombinant human activated protein C worldwide evaluation in severe sepsis [PROWESS]). DESIGN: Univariate and multivariable analysis of prospectively defined subgroups from the PROWESS study. SETTING: A total of 164 medical centers in 11 countries. PATIENTS: A total of 1,690 patients with severe sepsis. MEASUREMENTS AND MAIN RESULTS: We report observed 28-day mortality rates for drotrecogin alfa (activated) and placebo patients for subgroups prospectively defined by demographic data, surgical status, type and site of infection, and clinical and biochemical measures of disease severity. We performed subgroup analyses to explore the consistency of the mortality benefit observed in the overall population and performed tests for both quantitative and qualitative interactions. To examine the magnitude of the treatment benefit with drotrecogin alfa (activated) across the underlying predicted risk of mortality spectrum, we used stepwise logistic regression on PROWESS placebo patients to generate a predicted risk of mortality model that simultaneously included many clinical and biochemical markers of mortality risk. Because drotrecogin alfa (activated) has anticoagulant properties, we also present analyses of bleeding and thrombotic events. Actual mortality rates were lower with drotrecogin alfa (activated) compared with placebo for nearly all prospectively defined subgroups. Both univariate and multivariable regression analyses showed a consistent relative risk reduction in 28-day mortality rates for drotrecogin alfa (activated). Larger absolute risk reductions were found with drotrecogin alfa (activated) in patients with a higher baseline predicted risk of mortality, and actual mortality rates were lower with drotrecogin alfa (activated) in all subgroups defined by disease severity measures where a > or = 20% placebo mortality was observed. Although discriminatory power was limited by few observed events, the increased absolute risk of experiencing a serious bleeding event with treatment did not seem to vary according to the baseline predicted risk of mortality. CONCLUSIONS: The administration of drotrecogin alfa (activated) to patients with severe sepsis was associated with a significant survival benefit that tended to increase with higher baseline likelihood of death. Current data suggest that the increased risk of bleeding does not vary according to likelihood of death.

APACHE↗
PubMed2003

Economic evaluation of new therapies in critical illness.

The recent Food and Drug Administration approval of drotrecogin alfa (activated) and the potential of several other new therapies may represent the beginning of a breakthrough in the management of critical illness in the intensive care unit. However, their use in clinical practice will likely be dependent on a rigorous appraisal not only of their effects, but also of their costs. Novel therapies can no longer be judged simply by their effectiveness in treating illness, but must also be evaluated on an institutional and societal level on the basis of their cost. These considerations have important implications for the practicing intensivist, who will need to better understand the conduct and design of economic evaluations, including their strengths and weaknesses. In this article, we review the rationale behind economic evaluations of new therapies and the alternative economic approaches available. We then discuss in more detail the elements contained in a cost-effectiveness analysis, the preferred approach to pharmacoeconomic evaluation today.

Cost-Benefit Analysis↗
PubMed2003

Effects of drotrecogin alfa (activated) on organ dysfunction in the PROWESS trial.

OBJECTIVE: To assess morbidity in patients with severe sepsis managed with and without drotrecogin alfa (activated). DESIGN: Analysis of secondary end points in a prospective, randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (PROWESS). SETTING: A total of 164 medical institutions in 11 countries. PATIENTS: A total of 1,690 consecutive adult patients with severe sepsis. INTERVENTIONS: A 96-hr infusion of drotrecogin alfa (activated) (human recombinant activated protein C) or placebo. MEASUREMENTS AND MAIN RESULTS: Sequential Organ Failure Assessment (SOFA) scores for cardiovascular, respiratory, renal, hematologic, and hepatic organ systems were measured for 28 days. Mean cardiovascular SOFA scores were significantly lower for patients treated with drotrecogin alfa (activated) compared with placebo patients over this time period (p = .022). Drotrecogin alfa (activated)-treated patients also showed significantly faster resolution of cardiovascular (p = .009) and respiratory (p = .009) dysfunction and significantly slower onset of hematologic organ dysfunction (p = .041) compared with placebo patients for days 1 to 7. No significant differences in morbidity were observed between treatment groups among 28-day survivors. CONCLUSION: Drotrecogin alfa (activated) demonstrated significant improvements in organ function compared with placebo in a large phase 3 clinical trial that has shown a mortality benefit in patients with severe sepsis.

APACHE↗
PubMed2003

Improving clinical trial design in acute lung injury.

If future trials of acute lung injury/acute respiratory distress syndrome are to be rigorous, informative, and successful, a number of key design issues need to be considered. First, appropriate sample size and entry criteria must be selected. The present definitions of acute lung injury/acute respiratory distress syndrome are arbitrary and select a broad, heterogeneous patient population in which treatment effects may often be small, requiring much larger sample sizes than those of previous trials. The alternative approach, selecting a subset of patients in whom a larger benefit is anticipated, is potentially hazardous because the subset selection criteria are unproven. Second, it must be ensured that the therapy is tested against current best methods of care. To ensure that a study is considered current at completion, investigators should anticipate that recent evidence at study commencement will be considered standard at study completion. Up-to-date evidence-based medicine should therefore be encouraged for all enrolled patients and, probably, protocolized in unblinded studies. Multiple novel therapies can also be tested, but care must be paid to the particular study design choice. Third, appropriate outcomes must be chosen. The traditional end point of 28-day mortality is too short and too crude to capture all relevant patient and societal outcomes. Thus, consideration of survival over a longer duration, coupled with assessment of quality of life, functional status, and morbidity, is essential. Fourth, the study must comply with new standards for the protection of human subjects. Protecting human subjects' rights and ensuring patient safety in subjects who are critically ill and who are rarely able to provide fully informed consent is a significant challenge. However, it is essential that new studies comply with required standards without becoming so burdensome that they cannot reasonably be completed.

Clinical Trials as Topic↗
PubMed2003

Hospital costs in patients receiving prolonged mechanical ventilation: does age have an impact?

BACKGROUND: The aging of the population is one of the causes of the increase in healthcare costs in the past few decades. It is controversial whether chronological age alone should be used in making healthcare decisions. OBJECTIVE: To determine the association between age and hospital costs in patients receiving mechanical ventilation (MV). DESIGN: Prospective, observational study. SETTING: Intensive care units at a teaching hospital. PATIENTS: A total of 813 adults who received prolonged (> or =48 hrs) mechanical ventilation. INTERVENTION: None. MEASUREMENTS: Severity of illness, comorbidities, length of stay, hospital costs, and mortality. We evaluated the independent association of age with hospital costs using linear regression. RESULTS: Mean (+/-sd) age of patients was 60.4 +/- 18.8 yrs. Median Acute Physiology Chronic Health Evaluation III score and probability of hospital death at intensive care unit admission were 64 and 0.31, respectively. Hospital mortality was 36%. Median total hospital costs and daily costs were $ 56,056 and $2,655 US dollars, respectively. Older age was associated with lower total hospital costs after controlling for sex, intensive care unit type, severity of illness, length of stay, insurance type, resuscitation status, and survival. Hospital costs were significantly less in older patients in all cost departments examined, except for respiratory care and intensive care unit room costs. CONCLUSIONS: Daily and total hospital costs were lower in older patients. Decreased hospital resource use in older patients may be related to a preference for less aggressive care by older patients and their families or by healthcare providers.

APACHE↗
PubMed2003

Long-term mortality and medical care charges in patients with severe sepsis.

OBJECTIVE: To estimate long-term mortality and medical care charges among patients with severe sepsis. DESIGN: Retrospective cohort study. SETTING: Large, integrated, geographically diverse, U.S. health-insurance claims database covering three million lives annually. PATIENTS: All persons with bacterial or fungal infections and acute organ dysfunction (severe sepsis) who were hospitalized between January 1, 1991, and August 31, 2000. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients were followed from the date of hospitalization with severe sepsis (index admission) to August 31, 2000, disenrollment from the health plan, or death, whichever occurred first. Measures of interest included mortality and medical care charges and were estimated for the index admission, the 90- and 180-day periods following the index admission, and annually thereafter (up to 5 yrs), using techniques of survival analysis. A total of 16,019 patients were identified who met study entrance criteria. Most patients (81.2%) were >/=65 yrs of age; 53.4% were men. Mortality was 21.2% for the index admission, 51.4% at 1 yr, and 74.2% at 5 yrs. Mean cumulative total medical care charges were 44,600 US dollars for the index admission, 78,500 US dollars at 1 yr, and 118,800 US dollars at 5 yrs. Hospitalization accounted for the largest component of total medical care charges. CONCLUSIONS: Mortality and economic costs are high in patients with severe sepsis, during the period of acute illness as well as subsequently.

Adolescent↗
PubMed2003

Reassessing the value of short-term mortality in sepsis: comparing conventional approaches to modeling.

OBJECTIVE: Clinical trials of therapies for sepsis have been mostly unsuccessful in impacting mortality. This may be partly due to the use of insensitive mortality end points. We explored whether modeling survival was more sensitive than traditional end points in detecting mortality differences in cohorts of patients with sepsis. DESIGN: Patients were stratified into seven a priori defined paired subgroups that reflected high and low mortality risk according to known clinical risk factors. We fitted an exponential survival model to the high- and low-risk cohort of each subgroup, providing estimates of the rate of dying, long-term survival, and excess day 1 mortality. Mortality in the high- and low-risk cohorts in each subgroup was compared using model parameters, fixed-point mortality, and Kaplan-Meier survival analysis. SETTING: Eight intensive care units within a university teaching institution. PATIENTS: One hundred thirty patients with severe sepsis or suspected Gram-negative bacteremia. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Overall mortality of the cohort was 58.5% at 28 days. The survival of the entire cohort was well described by an exponential model (r2 =.99). Modeling identified differences in high- and low-risk cohorts in five of the seven paired subgroups, while conventional end-points only detected differences in 2. CONCLUSIONS: Modeling survival was more sensitive than conventional end-points in identifying survival differences between high- and low-risk subgroups. We encourage further evaluation of modeling in the search for more sensitive mortality end points.

APACHE↗