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Biomedical subjects

Derek C Angus

Publications and source records attributed to Derek C Angus.

At least 37 records · Page 2Linked to original sources
PubMed2006

Bench-to-bedside review: critical illness-associated cognitive dysfunction--mechanisms, markers, and emerging therapeutics.

Cognitive dysfunction is common in critically ill patients, not only during the acute illness but also long after its resolution. A large number of pathophysiologic mechanisms are thought to underlie critical illness-associated cognitive dysfunction, including neuro-transmitter abnormalities and occult diffuse brain injury. Markers that could be used to evaluate the influence of specific mechanisms in individual patients include serum anticholinergic activity, certain brain proteins, and tissue sodium concentration determination via high-resolution three-dimensional magnetic resonance imaging. Although recent therapeutic advances in this area are exciting, they are still too immature to influence patient care. Additional research is needed if we are to understand better the relative contributions of specific mechanisms to the development of critical illness-associated cognitive dysfunction and to determine whether these mechanisms might be amenable to treatment or prevention.

Biomarkers↗
PubMed2006

Severe sepsis in community-acquired pneumonia: when does it happen, and do systemic inflammatory response syndrome criteria help predict course?

STUDY OBJECTIVES: Most natural history studies of severe sepsis are limited to ICU populations. We describe the onset and timing of severe sepsis during the hospital course for patients hospitalized with community-acquired pneumonia (CAP). We also determine the ability of the systemic inflammatory response syndrome (SIRS) and other proposed risk stratification scores measured at emergency department (ED) presentation to predict progression to severe sepsis, septic shock, or death. DESIGN: Retrospective analysis of a prospective observational outcome study from the Pneumonia Patient Outcomes Research Team (PORT). SETTING: Four academic medical centers in the United States and Canada between October 1991 and March 1994. PARTICIPANTS: The 1,339 patients hospitalized for CAP in the PORT study cohort, and a random subset of 686 patients for whom we had information for SIRS criteria. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: All subjects had infection (CAP). Severe sepsis was defined as new-onset acute organ dysfunction in this cohort, using consensus criteria. Severe sepsis developed in one half of the patients (n = 639, 48%), nonpulmonary organ dysfunction developed in 520 patients (39%), and septic shock developed in 61 subjects (4.5%). Severe sepsis and septic shock were present at ED presentation in 457 patients (71% of severe sepsis cases) and 27 patients (44% of septic shock cases), respectively. While SIRS was common at presentation (82% of the subset of 686 had two SIRS criteria), it was not associated with increased odds for progression to severe sepsis (odds ratios [ORs], 0.65 and 0.89 for two or more SIRS criteria and three or more SIRS criteria, respectively), septic shock (ORs, 0.80 and 0.55), or death (ORs, 0.65 and 0.39), with poor discrimination (all receiver operating characteristic [ROC] areas under the curve < 0.5). The pneumonia severity index was associated with severe sepsis (p < 0.001) with moderate discrimination (ROC, 0.63). CONCLUSIONS: Severe sepsis is common in hospitalized CAP patients, occurring early in the hospital course. SIRS criteria do not appear to be useful predictors for progression to severe sepsis in CAP.

Cohort Studies↗
PubMed2006

Epidemiology of severe sepsis around the world.

Severe sepsis is an ongoing challenge for clinicians and health-care administrators mainly because is associated with a high incidence, mortality rate and costs. In recent years, several epidemiological studies about the incidence of sepsis have come out in different and prestigious journals. However, it is not advisable to draw direct conclusions from those studies considering methodological flaws or even different approaches. Hence, we have to be familiar with those obstacles and know how to overcome them. This review paper highlights the methods which have been used in these studies and depicts the results of occurrence rate or incidence of sepsis in countries and in intensive care units.

Epidemiologic Methods↗
PubMed2005

Cost-effectiveness of fixed-dose combination of isosorbide dinitrate and hydralazine therapy for blacks with heart failure.

BACKGROUND: Fixed-dose combination of isosorbide dinitrate/hydralazine (ISDN/HYD) improved clinical outcomes in the African-American Heart Failure Trial (A-HeFT). We assessed the resource use, costs of care, and cost-effectiveness of ISDN/HYD therapy in the A-HeFT trial population. METHODS AND RESULTS: We obtained resource use data from A-HeFT, assigning costs through the use of US federal sources. Excluding indirect costs, we summarized the within-trial experience and modeled cost-effectiveness over extended time horizons, including a US societal lifetime reference case. During the mean trial follow-up of 12.8 months, the ISDN/HYD group incurred fewer heart failure-related hospitalizations (0.33 versus 0.47 per subject; P=0.002) and shorter mean hospital stays (6.7 versus 7.9 days; P=0.006). When study drug costs were excluded, both heart failure-related and total healthcare costs were lower in the ISDN/HYD group (mean per-subject heart failure-related costs, 5997 dollars versus 9144 dollars; P=0.04; mean per-subject total healthcare costs, 15,384 dollars versus 19,728 dollars; P=0.03). With an average daily drug cost of 6.38 dollars, ISDN/HYD therapy was dominant (reduced costs and improved outcomes) over the trial duration. Assuming that no additional benefits accrue beyond the trial, we project the cost-effectiveness of ISDN/HYD therapy using heart failure-related costs to be 16,600 dollars/life-year at 2 years after enrollment, 37,100 dollars/life-year at 5 years, and 41,800 dollars/life-year over lifetime (reference case). CONCLUSIONS: ISDN/HYD therapy, previously shown to improve clinical outcomes, also reduced resource use and costs in A-HeFT, primarily because of a large reduction in hospitalizations. Long-term use of ISDN/HYD therapy should be associated with a favorable cost-effectiveness profile in this population.

Black People↗
PubMed2005

Critical care medicine training and certification for emergency physicians.

Demand for critical care services is increasing. Unless the supply of intensivists increases, critically ill patients will not have access to intensivists. Recent critical care society recommendations include increased graduate medical education support and expansion of the J-1 visa waiver program for foreign medical graduates. This article proposes additional recommendations, based on strengthening the relationship between emergency medicine and critical care medicine. Critical care is a continuum that includes out-of-hospital, emergency department (ED), and ICU care teams. Both emergency medicine and critical care medicine require expertise in treating life-threatening acute illness, with many critically ill patients often presenting first to the ED. Increased patient volumes and acuity have resulted in longer ED lengths of stay and more critical care delivery in the ED. However, the majority of critical care medicine fellowships do not accept emergency medicine residents, and those who do successfully complete a fellowship do not have access to a US certification examination in critical care medicine. Despite these barriers, interest in critical care medicine training among emergency physicians is increasing. Dual emergency medicine- and critical care medicine-trained physicians will not only help alleviate the intensivist shortage but also strengthen critical care delivery in the ED and facilitate coordination at the ED-ICU interface. We therefore propose that all accreditation bodies work cooperatively to create a route to critical care medicine certification for emergency physicians who complete a critical care fellowship.

Certification↗
PubMed2005

The future of critical care.

Critical care has become an important part of the health care system; however, it still is provided in a heterogeneous, and likely suboptimal, fashion. Future challenges will include providing an adequate workforce; ensuring critical care is delivered to the right patients at the right time; converting advances in our understanding of the biology of critical illness into improved care and outcomes; and partnering successfully with patients, families, and society in forging the critical care of the future.

Critical Care↗
PubMed2005

Haloperidol use is associated with lower hospital mortality in mechanically ventilated patients.

OBJECTIVE: To determine whether haloperidol use is associated with lower mortality in mechanically ventilated patients. DESIGN: Retrospective cohort analysis. SETTING: A large tertiary care academic medical center. PATIENTS: A total of 989 patients mechanically ventilated for >48 hrs. MEASUREMENTS AND MAIN RESULTS: We compared differences in hospital mortality between patients who received haloperidol within 2 days of initiation of mechanical ventilation and those who never received haloperidol. Despite similar baseline characteristics, patients treated with haloperidol had significantly lower hospital mortality compared with those who never received haloperidol (20.5% vs. 36.1%; p = .004). The lower associated mortality persisted after adjusting for age, comorbidity, severity of illness, degree of organ dysfunction, admitting diagnosis, and other potential confounders. CONCLUSIONS: Haloperidol was associated with significantly lower hospital mortality. These findings could have enormous implications for critically ill patients. Because of their observational nature and the potential risks associated with haloperidol use, they require confirmation in a randomized, controlled trial before being applied to routine patient care.

Adult↗
PubMed2005

Critical care medicine training and certification for emergency physicians.

Demand for critical care services is increasing. Unless the supply of intensivists increases, critically ill patients will not have access to intensivists. Recent critical care society recommendations include increased graduate medical education support and expansion of the J-1 visa waiver program for foreign medical graduates. This article proposes additional recommendations, based on strengthening the relationship between emergency medicine and critical care medicine. Demand for critical care services is increasing. Unless the supply of intensivists increases, critically ill patients will not have access to intensivists. Recent critical care society recommendations include increased graduate medical education support and expansion of the J-1 visa waiver program for foreign medical graduates. This article proposes additional recommendations, based on strengthening the relationship between emergency medicine (EM) and critical care medicine (CCM). Critical care is a continuum that includes prehospital, emergency department (ED), and intensive care unit (ICU) care teams. Both EM and CCM require expertise in treating life-threatening acute illness, with many critically ill patients often presenting first to the ED. Increased patient volumes and acuity have resulted in longer ED lengths of stay and more critical care delivery in the ED. However, the majority of CCM fellowships do not accept EM residents, and those who successfully complete a fellowship do not have access to a U.S. certification exam in CCM. Despite these barriers, interest in CCM training among EM physicians is increasing. Dual EM/CCM-trained physicians not only will help alleviate the intensivist shortage but also will strengthen critical care delivery in the ED and facilitate coordination at the ED-ICU interface. We therefore propose that all accreditation bodies work cooperatively to create a route to CCM certification for emergency physicians who complete a critical care fellowship.

Certification↗
PubMed2005

Outcome measures for clinical research in sepsis: a report of the 2nd Cambridge Colloquium of the International Sepsis Forum.

BACKGROUND AND OBJECTIVES: Sepsis is the leading cause of morbidity and mortality for patients admitted to an intensive care unit. The evaluation of new therapies has been hampered by the underdevelopment of outcome measures used to detect biological activity and patient-centered benefit in a complex and highly heterogeneous patient population. We sought to evaluate existing approaches and to draw on insights from other disciplines to propose a comprehensive approach to outcome evaluation in sepsis clinical trials. METHODS: An expert colloquium organized by the International Sepsis Forum brought together sepsis researchers, clinical epidemiologists, and experts in the development and implementation of outcome measures in rheumatology, neurology, and oncology. RESULTS: The translation of an evolving understanding of the biology of sepsis into effective new therapies for critically ill patients requires a reevaluation of the end points used to determine response to intervention. These represent a continuum that measures biological activity against the target at one end and sustained improvement in survival or quality of life at the other. Early phase research should determine whether an intervention works in vivo, using measures that are responsive and informative to provide proof of principle, to aid in selecting optimal patient populations for study, and to gain insights into optimal dose and duration of therapy. After in vivo biology has been demonstrated and the possibility of efficacy inferred by plausible improvements in surrogate physiologic measures, definitive studies should seek robust evidence of benefit using end points that measure important, patient-centered benefit, including intermediate and longer term survival and health-related quality of life. Nonmortal measures of benefit assume particular importance for populations, such as children, whose mortality risk is low, or who have significant rates of comorbidities that independently limit survival. Composite measures that integrate morbidity and mortality effects may provide the most meaningful information about therapeutic efficacy. CONCLUSIONS: The development of explicit, hypothesis-driven, and iterative approaches to outcome measure development, patterned on approaches used in the fields of rheumatology and oncology, may improve the conduct of clinical studies in the critically ill.

Clinical Trials as Topic↗