Abstract:
OBJECTIVE:To elucidate sources of variability in the estimate of treatment effects in a successful phase 3 trial in severe sepsis and to assess their implications on the design of future clinical trials. DESIGN:Retrospective evaluation of prospectively defined subgroups from a large phase 3, placebo-controlled clinical trial (PROWESS). SETTING:The study involved 164 medical centers. PATIENTS:Patients were 1,690 patients with severe sepsis. INTERVENTIONS:Drotrecogin alfa (activated) (Xigris) 24 microg/kg/hr for 96 hrs, or placebo. MEASUREMENTS AND MAIN RESULTS:All prospectively defined subgroups were examined to identify treatment effects that potentially differed across subgroup strata (assessed by Breslow-Day p < .10). Potential interactions were identified for subgroups defined by a) presence vs. absence of a significant protocol violation (p = .07); b) original vs. amended protocol (p = .08); and c) Acute Physiology and Chronic Health Evaluation (APACHE) II quartile at baseline (p = .09). No treatment benefit was observed in patients having a protocol violation, regardless of type. There appeared to be less treatment effect in patients enrolled under the original vs. amended protocol. The risk ratio exceeded 1.0 for patients in the lowest APACHE II score quartile. A highly significant correlation was observed between the sequence of enrollment at a site, the frequency of protocol violations, and the observed treatment effect. As enrollment increased, frequency of protocol violations decreased (p < .0001) and the treatment effect improved. The correlation between the sequence of enrollment and improvement in treatment effect remained even after removal of patients with protocol violations. Removal of the first block of patients at each site from the analysis reduced the extent of interaction by protocol version and APACHE II score. CONCLUSIONS:A learning curve appeared to be present within the PROWESS trial such that the ability to demonstrate efficacy improved with increasing site experience. This potential learning curve may have implications for design of future trials. Investigational sites may need to require a minimum level of protocol-specific experience to appropriately implement a given trial. This experience should be an important consideration in designing trials and analysis plans. Diligence by coordinating centers, site investigators, study coordinators, and sponsors is necessary to ensure that the protocol is executed as designed such that a treatment benefit, if present, will be evident.
journal_name
Crit Care Medjournal_title
Critical care medicineauthors
Macias WL,Vallet B,Bernard GR,Vincent JL,Laterre PF,Nelson DR,Derchak PA,Dhainaut JFdoi
10.1097/01.ccm.0000147440.71142.acsubject
Has Abstractpub_date
2004-12-01 00:00:00pages
2385-91issue
12eissn
0090-3493issn
1530-0293pii
00003246-200412000-00003journal_volume
32pub_type
临床试验,杂志文章,多中心研究,随机对照试验abstract:OBJECTIVE:Our objective was to quantify the association between intensive care unit-acquired dysglycemia (hyperglycemia, hypoglycemia, and high variability) and in-hospital mortality. DESIGN:Retrospective, observational study. SETTING:eICU Research Institute participating hospitals with an active tele-ICU program bet...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0b013e3182656ae5
更新日期:2012-12-01 00:00:00
abstract:OBJECTIVES:The American College of Critical Care Medicine provided 2002 and 2007 guidelines for hemodynamic support of newborn and pediatric septic shock. Provide the 2014 update of the 2007 American College of Critical Care Medicine "Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shoc...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000002425
更新日期:2017-06-01 00:00:00
abstract:OBJECTIVE:The Acute Respiratory Distress Syndrome Network protocol recommends limiting tidal volume and plateau pressure; it also recommends increasing respiratory rate to prevent hypercapnia. We tested a strategy that combines the low tidal volume with lower respiratory rates and minimally invasive CO2 removal. SUBJE...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000000312
更新日期:2014-06-01 00:00:00
abstract:OBJECTIVES:Ethicists advise that life-sustaining treatment decisions should be made in keeping with patient preferences. Until recently, there has been little systematic study of the impact of patient preferences on the use of various life-sustaining treatments or the consequent cost of hospital care. This prospective ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199611000-00009
更新日期:1996-11-01 00:00:00
abstract:OBJECTIVE:Procalcitonin, the precursor peptide of calcitonin, has been shown to be a serum marker of the severity and mortality of several systemic inflammatory response syndromes. This study addressed the correlation of serum procalcitonin with the course of classic (nonexertional) heatstroke. DESIGN:Serum samples we...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199708000-00024
更新日期:1997-08-01 00:00:00
abstract::Hypersensitivity reactions are defined as immunologically based adverse reactions to chemicals or medicinal agents. These reactions are common in the intensive care unit and can present as a simple, mildly symptomatic rash or as life-threatening anaphylactic reactions. Hypersensitivity reactions have traditionally bee...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/CCM.0b013e3181de0c99
更新日期:2010-06-01 00:00:00
abstract:OBJECTIVE:To evaluate the relationship between the acute inflammatory response after surgical trauma and changes in hepatic cytochrome P450 3A4 activity, compare changes in cytochrome P450 3A4 activity after procedures with varying degrees of surgical stress, and to explore the time course of any potential drug-cytokin...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.CCM.0000063040.24541.49
更新日期:2003-05-01 00:00:00
abstract:OBJECTIVES:To perform a complete immunological characterization of compensatory anti-inflammatory response syndrome in patients with sepsis and to explore the relationship between these changes and clinical outcomes of 28-day mortality and secondary infections. DESIGN:Prospective single-center study conducted between ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000000100
更新日期:2014-04-01 00:00:00
abstract:OBJECTIVES:To determine the outcome of oxygen consumption (VO2) and energy expenditure after cessation of sedation in severe head-injured patients and to assess its usefulness as a predictor of neurologic severity. DESIGN:Prospective, descriptive study. SETTING:Neurosurgical intensive care unit (ICU) in a university ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199407000-00011
更新日期:1994-07-01 00:00:00
abstract:OBJECTIVE:We investigated whether serum levels of neuron-specific enolase (NSE) and S-100beta protein could be used to evaluate cerebral injury and to predict outcome in severe sepsis and severe septic shock. DESIGN:Prospective study. SETTING:University hospital. PATIENTS AND MEASUREMENTS:In 170 consecutively enroll...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.CCM.0000217218.51381.49
更新日期:2006-07-01 00:00:00
abstract:OBJECTIVES:Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia. In patients, thrombocytopenia is correlated with an adverse outcome of pneumonia. Platelets can modulate the host response to infection in several ways, that is, by facilitating clot formation, production of antim...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000000853
更新日期:2015-03-01 00:00:00
abstract:OBJECTIVES:To describe the unique perspective of pediatric intensivists caring for critically ill adults during the coronavirus disease 2019 pandemic. DESIGN:Observational study. SETTING:Academic medical center in New York City. PATIENTS:Coronavirus disease 2019 positive adults requiring admission to an ICU. INTERV...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000004543
更新日期:2020-11-01 00:00:00
abstract:OBJECTIVE:To compare compliance and end-expiratory lung volume during reexpansion of normal and surfactant-deficient ex vivo atelectatic lungs with either gas or total liquid ventilation. DESIGN:Controlled, animal study using an ex vivo lung preparation. SETTING:A research laboratory at a university medical center. ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199602000-00015
更新日期:1996-02-01 00:00:00
abstract::This study was performed to determine if particulate material within the pulmonary vascular bed could be sampled by aspirating blood from a wedged pulmonary artery catheter. 99mTechnetium-labeled albumin microspheres (20 micrometers) were injected and embolized into the precapillary pulmonary vasculature of 6 critical...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198304000-00001
更新日期:1983-04-01 00:00:00
abstract:OBJECTIVE:Catheter-associated infections are common, costly, and potentially lethal. The impact of catheter insertion site on infection risk remains controversial. We aimed to establish whether nontunneled central venous catheters inserted in the subclavian vein are associated with lower risk of catheter-associated inf...
journal_title:Critical care medicine
pub_type: 杂志文章,meta分析
doi:10.1097/CCM.0b013e31823e99cb
更新日期:2012-05-01 00:00:00
abstract:OBJECTIVES:To describe the variety of medications prescribed along with the doses administered and routes of administration, and to delineate the clarity of orders written and the accuracy of transcription of drugs used for sedation, anxiety, pain, and neuromuscular blockade in a surgical intensive care unit (ICU). DE...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199406000-00016
更新日期:1994-06-01 00:00:00
abstract:OBJECTIVE:To evaluate the reproducibility and accuracy of a new pulmonary artery catheter system that provides both right ventricular ejection fraction and continuous venous oxygen saturation monitoring. DESIGN:Criterion standard study. SETTING:University medical center. PATIENTS:A consecutive sample of ten patients...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199212000-00008
更新日期:1992-12-01 00:00:00
abstract::Little is known about the structure and objectives of various hospital ethics committees due to their need to preserve confidentiality, their reluctance to reveal internal hospital problems, and their concern about becoming involved in the developing debate about the appropriate role and value of such committees. The ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198211000-00018
更新日期:1982-11-01 00:00:00
abstract:OBJECTIVE:Critical care medicine trainees and faculty must acquire and maintain the skills necessary to provide state-of-the art clinical care to critically ill patients, to improve patient outcomes, optimize intensive care unit utilization, and continue to advance the theory and practice of critical care medicine. Thi...
journal_title:Critical care medicine
pub_type: 指南,杂志文章,实务指引
doi:10.1097/01.CCM.0000104916.33769.9A
更新日期:2004-01-01 00:00:00
abstract:OBJECTIVE:The effect of levosimendan, a novel inotropic vasodilator (inodilator), on the microvascular gastric mucosal hemoglobin oxygenation (muHbo(2)) is unknown. A possible effect could thereby be selective for the splanchnic region or could primarily reflect changes in systemic oxygen transport (Do(2)) and/or oxyge...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.ccm.0000150653.89451.6f
更新日期:2005-01-01 00:00:00
abstract:OBJECTIVE:To examine the effects of mechanical ventilation with a tidal volume of 6 mL/kg compared with 12 mL/kg predicted body weight on hemodynamics, vasopressor use, fluid balance, diuretics, sedation, and neuromuscular blockade within 48 hrs in patients with acute lung injury and acute respiratory distress syndrome...
journal_title:Critical care medicine
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1097/01.ccm.0000149836.76063.71
更新日期:2005-01-01 00:00:00
abstract::Two new catecholamines, dopamine and dobutamine, have found widespread use for cardiovascular support. The relative efficacy of these drugs in aiding resuscitation from cardiopulmonary arrest is unknown. Dogs were subjected to either asphyxial or fibrillatory cardiac arrest. Resuscitation was attempted with artificial...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-198109000-00005
更新日期:1981-09-01 00:00:00
abstract:OBJECTIVES:To compare the frequency and preventability of adverse drug events and potential adverse drug events in intensive care units (ICUs) and non-ICUs. To evaluate systems factors involving the individual caregivers, care unit teams, and patients involved in each adverse drug event by comparing ICUs with non-ICUs ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199708000-00014
更新日期:1997-08-01 00:00:00
abstract:OBJECTIVES:Although highly active antiretroviral therapy has led to improved survival in HIV-infected individuals, outcomes for HIV-infected patients with sepsis in the post-highly active antiretroviral therapy era are conflicting. Access to highly active antiretroviral therapy and healthcare disparities continue to af...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000001003
更新日期:2015-08-01 00:00:00
abstract:OBJECTIVE:Pulmonary edema is a serious condition following brain injury of diverse etiologies, including large hemispheric infarctions. We have previously shown that treatment with hypertonic saline attenuates cerebral edema associated with experimental ischemic stroke. In a well-characterized animal model of large isc...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/01.ccm.0000150659.15558.23
更新日期:2005-01-01 00:00:00
abstract:OBJECTIVES:To investigate attitudes and practices regarding oxygen therapy in intensive care units (ICUs) and to devise quantitative descriptive indices. SETTING:Canadian university-affiliated adult ICUs. PARTICIPANTS:Fifty-two medical directors of ICUs in 48 institutions. INTERVENTION:Structured postal questionnair...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199912000-00033
更新日期:1999-12-01 00:00:00
abstract:OBJECTIVE:This article analyzes, from a legal perspective, a recent phenomenon involving a clash between the values of attending medical personnel and the instructions of surrogate decision-makers acting on behalf of incompetent patients. Some hospitals have gone to court to challenge decisions by surrogates to continu...
journal_title:Critical care medicine
pub_type: 杂志文章,评审
doi:10.1097/00003246-199605000-00026
更新日期:1996-05-01 00:00:00
abstract:OBJECTIVES:Conflict is common between physicians and surrogate decision makers around end-of-life care in ICU. Involving experts in conflict management improve outcomes, but little is known about what differences in conflict management styles may explain the benefit. We used simulation to examine potential differences ...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000001583
更新日期:2016-05-01 00:00:00
abstract:OBJECTIVE:To compare measurement of cardiac output by the CO2 rebreathing method vs. the thermodilution cardiac output technique in the setting of acute respiratory failure in patients with chronic obstructive pulmonary disease. DESIGN:Prospective, comparative study of two methods in a consecutive sample. SETTING:Int...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/00003246-199401000-00017
更新日期:1994-01-01 00:00:00
abstract:OBJECTIVES:Survivors of critical illness in early life are at risk of long-term-memory and attention impairments. However, their neurobiologic substrates remain largely unknown. DESIGN:A prospective follow-up study. SETTING:Erasmus MC-Sophia Children's Hospital, Rotterdam, the Netherlands. PATIENTS:Thirty-eight scho...
journal_title:Critical care medicine
pub_type: 杂志文章
doi:10.1097/CCM.0000000000002553
更新日期:2017-10-01 00:00:00