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Objective: To characterize empiric antibiotic use in patients with suspected nosocomial ICU-acquired infections (NI), and determine the impact of prolonged therapy in the absence of infection.Design and Setting: Multicenter prospective cohort, with eight medical-surgical ICUs in North America and Europe.Patients: 195 patients with suspected NI.Methods: The diagnosis of NI was adjudicated by a blinded Clinical Evaluation Committee using retrospective review of clinical, radiological, and culture data.Results: Empiric antibiotics were prescribed for 143 of 195 (73.3%) patients with suspected NI; only 39 of 195 (20.0%) were adjudicated as being infected. Infection rates were similar in patients who did (26 of 143, 18.2%), or did not (13 of 52, 25.0%) receive empiric therapy (p = 0.3). Empiric antibiotics were continued for more than 4 days in 56 of 95 (59.0%) patients without adjudicated NI. Factors associated with continued empiric therapy were increased age (p = 0.02), ongoing SIRS (p = 0.03), and hospital (p = 0.004). Patients without NI who received empiric antibiotics for longer than 4 days had increased 28-day mortality (18 of 56, 32.1%), compared with those whose antibiotics were discontinued (3 of 39, 7.7%; OR = 5.7, 95% CI 1.5-20.9, p = 0.005). When the influence of age, admission diagnosis, vasopressor use, and multiple organ dysfunction was controlled by multivariable analysis, prolonged empiric therapy was not independently associated with mortality (OR = 3.8, 95% CI 0.9-15.5, p = 0.07).Conclusions: Empiric antibiotics were initiated four times more often than NI was confirmed, and frequently continued in the absence of infection. We found no evidence that prolonged use of empiric antibiotics improved outcome for ICU patients, but rather a suggestion that the practice may be harmful. [ABSTRACT FROM AUTHOR]

Climate is changing across a range of scales, from local to global, but ecological consequences remain difficult to understand and predict. Such projections are complicated by change in the connectivity of resources, particularly water, nutrients, and propagules, that influences the way ecological responses scale from local to regional and from regional to continental. This paper describes ecological responses to expected changes in four key meso-scale drivers that influence the ecosystems of the North American continental interior: drought, warming, snowpack disappearance, and altered fire regimes. Changes in these drivers will affect, for example, atmospheric smoke, dust, and reactive nitrogen concentrations; stream discharge; nitrate concentrations; sediment loads; and the vector-borne spread of invasive species and infectious diseases. A continental network of sensors and simulation models is required to detect changes in the transport vectors - atmospheric, hydrologic, and mechanized - that connect spatial scales. Knowledge of these downwind, downstream, and down-corridor effects will be critical if we are to understand and forecast responses to climate change at regional to continental scales. [ABSTRACT FROM AUTHOR]

The epidemiology of irritable bowel syndrome (IBS) in Europe and North America was analyzed from published material. The percentage of the population of Western civilisation with IBS symptoms is between 10 and 15% in most studies. The proportion of a Western population visiting a doctor for IBS symptoms is around 5%. The prevalence of IBS and the proportion of consulters do not seem to depend on age in an adult population. The female-to-male ratio of IBS in the population is close to 2. It is higher in IBS consulters in primary care and may be as high as 3 or 4 in tertiary referral centers. At least in patients from these centers, the number of physician visits and colonoscopies is considerable. Most of the consulters get a drug prescription.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Data from 72 Douglas-fir (Pseudotsuga menziesii var. glauca (Beissn.) Franco) plots across the Interior Northwest were used to determine whether (i) increased intercepted photosynthetically active radiation(%IPAR), effective leaf area index (LAIe), and stemwood volume production (cubic metres stemwood per hectare per year) could still be detected 7 or 8 years after nitrogen fertilization and (ii) fertilization would increase the efficiency by which light is converted into stemwood volume. Projected LAIe varied from 1.82 to 6.07 m27m-2 on the control plots. The fertilized plots intercepted 9-11% more light than the control plots (P < 0.001); they also had 22-25% higher LAIe than the control plots (P < 0.001). Stemwood volume production increased by 25-29% relative to the control (P < 0.001) andincreased exponentially with %IPAR across all study plots (R2 = 0.57). Stemwood growth efficiency averaged 12.0 1 0.4 (mean +/- SE), 13.5 +/- 0.4, and 13.7 +/- 0.4 m37ha-17a-1 per IPAR for the control, low fertilization, and high fertilization plots, respectively (P < 0.01). Fertilization thus induced increases in both light interception and the efficiency with whichintercepted light was converted to stemwood across the region. [ABSTRACT FROM AUTHOR]

Background: Venous thromboembolism (VTE) is a common complication of critical illness with important clinical consequences. The Prophylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) is a multicenter, blinded, randomized controlled trial comparing the effectiveness of the two most common pharmocoprevention strategies, unfractionated heparin (UFH) and low molecular weight heparin (LMWH) dalteparin, in medical-surgical patients in the intensive care unit (ICU). E-PROTECT is a prospective and concurrent economic evaluation of the PROTECT trial., Methods/design: The primary objective of E-PROTECT is to identify and quantify the total (direct and indirect, variable and fixed) costs associated with the management of critically ill patients participating in the PROTECT trial, and, to combine costs and outcome results to determine the incremental cost-effectiveness of LMWH versus UFH, from the acute healthcare system perspective, over a data-rich time horizon of ICU admission and hospital admission. We derive baseline characteristics and probabilities of in-ICU and in-hospital events from all enrolled patients. Total costs are derived from centers, proportional to the numbers of patients enrolled in each country. Direct costs include medication, physician and other personnel costs, diagnostic radiology and laboratory testing, operative and non-operative procedures, costs associated with bleeding, transfusions and treatment-related complications. Indirect costs include ICU and hospital ward overhead costs. Outcomes are the ratio of incremental costs per incremental effects of LMWH versus UFH during hospitalization; incremental cost to prevent a thrombosis at any site (primary outcome); incremental cost to prevent a pulmonary embolism, deep vein thrombosis, major bleeding event or episode of heparin-induced thrombocytopenia (secondary outcomes) and incremental cost per life-year gained (tertiary outcome). Pre-specified subgroups and sensitivity analyses will be performed and confidence intervals for the estimates of incremental cost-effectiveness will be obtained using bootstrapping., Discussion: This economic evaluation employs a prospective costing methodology concurrent with a randomized controlled blinded clinical trial, with a pre-specified analytic plan, outcome measures, subgroup and sensitivity analyses. This economic evaluation has received only peer-reviewed funding and funders will not play a role in the generation, analysis or decision to submit the manuscripts for publication., Trial Registration: Clinicaltrials.gov Identifier: NCT00182143 . Date of registration: 10 September 2005.

Background: The Surviving Sepsis Campaign (SSC) was launched in 2002 as a collaborative initiative of the European Society of Intensive Care Medicine (ESICM), the International Sepsis Forum (ISF), and the Society of Critical Care Medicine (SCCM). Its objective was, through the development and promulgation of evidence-based guidelines that facilitated the application of knowledge derived from clinical trials to bedside practice, to effect a 25% reduction in the relative risk of death from severe sepsis and septic shock., Methods: The evolution and content of the SSC is summarized and the scientific basis of the conclusions is reviewed from the literature., Results: The SSC developed evidence-based management guidelines and undertook a broad educational program to implement them by integrating their recommendations into resuscitation and management bundles. The process engaged practitioners in North America, Europe, and South America and was supported by professional societies around the world. It also engendered controversy based on accusations of undue industry influence and some dissatisfaction among individuals who were antagonistic toward protocolization of care. By its conclusion, more than 22,000 patients with sepsis had been entered in the SSC database, and analysis of the results showed that participation in the SSC was associated with a 5.4% absolute survival benefit., Conclusions: The SSC has impacted the care of septic patients and catalyzed changes that are likely to persist and evolve.

A multidisciplinary research program on levels of care was conducted in 15 adult intensive care units in North America, Europe, and Australia. The program addressed advance directives for cardiopulmonary resuscitation, provision of advanced life support, and clinicians' discomfort with evolving treatment plans. The results indicated that the factors that determined the establishment of directives for advance life support differed from the factors that informed a decision to limit or withdraw support after admission to an intensive care unit. In addition, clinicians' prognoses were imprecise and often an underestimation of the probability of short-term survival. Finally, some degree of discomfort was common in care providers in the intensive care unit, most often because they thought interventions were excessive and not compatible with an acceptable future quality of life. The provision of advanced life support mandates explicit decision making about how life-support measures should be used.

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.