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Objective: To compare the impact of active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) and standard CPR on the outcomes of in-hospital and prehospital victims of cardiac arrest.Design: Randomized controlled trial with blinding of allocation using a sealed container.Settings: (1) Emergency departments, wards, and intensive care units of 5 university hospitals and (2) all locations outside hospitals in 2 midsized cities.Patients: A total of 1784 adults who had cardiac arrest.Intervention: Patients received either standard or ACD CPR throughout resuscitation.Main Outcome Measures: Survival for 1 hour and to hospital discharge and the modified Mini-Mental State Examination (MMSE).Results: All characteristics were similar in the standard and ACD CPR groups for the 773 in-hospital patients and the 1011 prehospital patients. For in-hospital patients, there were no significant differences between the standard (n = 368) and ACD (n = 405) CPR groups in survival for 1 hour (35.1% vs 34.6%; P = .89), in survival until hospital discharge (11.4% vs 10.4%; P = .64), or in the median MMSE score of survivors (37 in both groups). For patients who collapsed outside the hospital, there were also no significant differences between the standard (n = 510) and ACD (n = 501) CPR groups in survival for 1 hour (16.5% vs 18.2%; P = .48), in survival to hospital discharge (3.7% vs 4.6%; P = .49), or in the median MMSE score of survivors (35 in both groups). Exploration of clinically important subgroups failed to identify any patients who appeared to benefit from ACD CPR.Conclusions: ACD CPR did not improve survival or neurologic outcomes in any group of patients with cardiac arrest. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of a restrictive and a liberal red blood cell (RBC) transfusion strategy on mortality and morbidity in critically ill patients.Study Design: Multicenter, prospective, randomized clinical trial.Patient Population: Sixty-nine normovolemic critically ill patients admitted to one of five tertiary level intensive care units with hemoglobin values less than 90 g/L within 72 hours of admission.Interventions: Patients were randomly allocated to one of two RBC transfusion strategies. Hemoglobin values were maintained between 100 and 120 g/L in the liberal transfusion group and between 70 and 90 g/L in the restrictive group.Results: Primary diagnosis and mean +/- SD age (58.6 +/- 15 vs 59.0 +/- 21 years and Acute Physiology and Chronic Health Evaluation II score (20 +/- 6.2 vs 21 +/- 7.2) were similar in the restrictive and liberal groups, respectively. Daily hemoglobin values averaged 90 g/L in the restrictive group vs 109 g/L in the liberal group (P < .001). The restrictive group received 2.5 U per patient compared with 4.8 U per patient in the liberal group. This represents a 48% relative decrease (P < .001) in RBC units transfused per patient. The 30-day mortality rate was 24% in the restrictive group compared with 25% in the liberal group; the 95% confidence interval around the absolute difference was -19% to 21%. Similar observations were noted for intensive care unit mortality (P = .76) and 120-day mortality (P > .99). In addition, survival analysis comparing time until death in both groups did not reveal any significant difference (P = .93) between groups. Organ dysfunction scores were also similar (P = .44).Conclusion: In this small randomized trial, neither mortality nor the development of organ dysfunction was affected by the transfusion strategy, which suggests that a more restrictive approach to the transfusion of RBCs may be safe in critically ill patients. However, the study lacked power to detect small but clinically significant differences. Therefore, further investigations of RBC transfusion strategies are warranted. [ABSTRACT FROM AUTHOR]

Objectives: It is unknown whether more frequent screening of invasively ventilated patients, identifies patients earlier for a spontaneous breathing trial, and shortens the duration of ventilation. We assessed the feasibility of conducting a large trial to evaluate screening frequency in critically ill adults in the North American context., Design: We conducted two contemporaneous, multicenter, pilot, randomized controlled trials (the LibeRation from MEchanicaL VEntilAtion and ScrEening Frequency [RELEASE] and Screening Elderly PatieNts For InclusiOn in a Weaning [SENIOR] trials) to address concerns regarding the potential for higher enrollment, fewer adverse events, and better outcomes in younger patients., Setting: Ten and 11 ICUs in Canada, respectively., Patients: Parallel trials of younger (RELEASE < 65 yr) and older (SENIOR ≥ 65 yr) critically ill adults invasively ventilated for at least 24 hours., Interventions: Each trial compared once daily screening to "at least twice daily" screening led by respiratory therapists., Measurements and Main Results: In both trials, we evaluated recruitment (aim: 1-2 patients/month/ICU) and consent rates, reasons for trial exclusion, protocol adherence (target: ≥ 80%), crossovers (aim: ≤ 10%), and the effect of the alternative screening frequencies on adverse events and clinical outcomes. We included 155 patients (53 patients [23 once daily, 30 at least twice daily] in RELEASE and 102 patients [54 once daily, 48 at least twice daily] in SENIOR). Between trials, we found similar recruitment rates (1.32 and 1.26 patients/month/ICU) and reasons for trial exclusion, high consent and protocol adherence rates (> 92%), infrequent crossovers, and few adverse events. Although underpowered, at least twice daily screening was associated with a nonsignificantly faster time to successful extubation and more successful extubations but significantly increased use of noninvasive ventilation in both trials combined., Conclusions: Similar recruitment and consent rates, few adverse events, and comparable outcomes in younger and older patients support conduct of a single large trial in North American ICUs assessing the net clinical benefits associated with more frequent screening.

Background: Several new trials evaluating transfusion strategies in patients with cardiovascular disease have recently been published, increasing the number of enrolled patients by over 30%. The objective was to evaluate transfusion thresholds in patients with cardiovascular disease., Methods: We conducted an updated systematic review of randomized trials that compared patients assigned to maintain a lower (restrictive transfusion strategy) or higher (liberal transfusion strategy) hemoglobin concentration. We focused on new trial data in patients with cardiovascular disease. The primary outcome was 30-day mortality. Specific subgroups were patients undergoing cardiac surgery and with acute myocardial infarction., Results: A total of 37 trials that enrolled 19,049 patients were appraised. In cardiac surgery, mortality at 30days was comparable between groups (risk ratio 0.99; 95% confidence interval 0.74-1.33). In 2 small trials (n=154) in patients with myocardial infarction, the point estimate for the mortality risk ratio was 3.88 (95% CI, 0.83-18.13) favoring the liberal strategy. Overall, from 26 trials enrolling 15,681 patients, 30-day mortality was not different between restrictive and liberal transfusion strategies (risk ratio 1.0, 95% CI, 0.86-1.16). Overall and in the cardiovascular disease subgroup, there were no significant differences observed across a range of secondary outcomes., Conclusions: New trials in patients undergoing cardiac surgery establish that a restrictive transfusion strategy of 7 to 8g/dL is safe and decreased red cell use by 24%. Further research is needed to define the optimal transfusion threshold in patients with acute myocardial infarction., (Copyright © 2018. Published by Elsevier Inc.)

Purpose Patient safety remains a top priority in healthcare. Many organizations have developed systems to monitor and prevent harm, and have invested in different approaches to quality improvement. Despite these organizational efforts to better detect adverse events, efficient resolution of safety problems remains a significant challenge. The authors developed and implemented a comprehensive multimodal patient safety improvement program called SafetyLEAP. The term "LEAP" is an acronym that highlights the three facets of the program including: a Leadership and Engagement approach; Audit and feedback; and a Planned improvement intervention. The purpose of this paper is to evaluate the implementation of the SafetyLEAP program in the intensive care units (ICUs) of three large hospitals. Design/methodology/approach A comparative case study approach was used to compare and contrast the adherence to each component of the SafetyLEAP program. The study was conducted using a convenience sample of three ( n=3) ICUs from two provinces. Two reviewers independently evaluated major adherence metrics of the SafetyLEAP program for their completeness. Analysis was performed for each individual case, and across cases. Findings A total of 257 patients were included in the study. Overall, the proportion of the SafetyLEAP tasks completed was 64.47, 100, and 26.32 percent, respectively. ICU nos 1 and 2 were able to identify opportunities for improvement, follow a quality improvement process and demonstrate positive changes in patient safety. The main factors influencing adherence were the engagement of a local champion, competing priorities, and the identification of appropriate resources. Practical implications The SafetyLEAP program allowed for the identification of processes that could result in patient harm in the ICUs. However, the success in improving patient safety was dependent on the engagement of the care teams. Originality/value The authors developed an evidence-based approach to systematically and prospectively detect, improve, and evaluate actions related to patient safety.

Background: There is considerable uncertainty regarding the optimal haemoglobin threshold for the use of red blood cell (RBC) transfusions in anaemic patients. Blood is a scarce resource, and in some countries, transfusions are less safe than others because of a lack of testing for viral pathogens. Therefore, reducing the number and volume of transfusions would benefit patients., Objectives: The aim of this review was to compare 30-day mortality and other clinical outcomes in participants randomized to restrictive versus liberal red blood cell (RBC) transfusion thresholds (triggers) for all conditions. The restrictive transfusion threshold uses a lower haemoglobin level to trigger transfusion (most commonly 7 g/dL or 8 g/dL), and the liberal transfusion threshold uses a higher haemoglobin level to trigger transfusion (most commonly 9 g/dL to 10 g/dL)., Search Methods: We identified trials by searching CENTRAL (2016, Issue 4), MEDLINE (1946 to May 2016), Embase (1974 to May 2016), the Transfusion Evidence Library (1950 to May 2016), the Web of Science Conference Proceedings Citation Index (1990 to May 2016), and ongoing trial registries (27 May 2016). We also checked reference lists of other published reviews and relevant papers to identify any additional trials., Selection Criteria: We included randomized trials where intervention groups were assigned on the basis of a clear transfusion 'trigger', described as a haemoglobin (Hb) or haematocrit (Hct) level below which a red blood cell (RBC) transfusion was to be administered., Data Collection and Analysis: We pooled risk ratios of clinical outcomes across trials using a random-effects model. Two people extracted the data and assessed the risk of bias. We conducted predefined analyses by clinical subgroups. We defined participants randomly allocated to the lower transfusion threshold as 'restrictive transfusion' and to the higher transfusion threshold as 'liberal transfusion'., Main Results: A total of 31 trials, involving 12,587 participants, across a range of clinical specialities (e.g. surgery, critical care) met the eligibility criteria. The trial interventions were split fairly equally with regard to the haemoglobin concentration used to define the restrictive transfusion group. About half of them used a 7 g/dL threshold, and the other half used a restrictive transfusion threshold of 8 g/dL to 9 g/dL. The trials were generally at low risk of bias .Some items of methodological quality were unclear, including definitions and blinding for secondary outcomes.Restrictive transfusion strategies reduced the risk of receiving a RBC transfusion by 43% across a broad range of clinical specialties (risk ratio (RR) 0.57, 95% confidence interval (CI) 0.49 to 0.65; 12,587 participants, 31 trials; high-quality evidence), with a large amount of heterogeneity between trials (I² = 97%). Overall, restrictive transfusion strategies did not increase or decrease the risk of 30-day mortality compared with liberal transfusion strategies (RR 0.97, 95% CI 0.81 to 1.16, I² = 37%; N = 10,537; 23 trials; moderate-quality evidence) or any of the other outcomes assessed (i.e. cardiac events (low-quality evidence), myocardial infarction, stroke, thromboembolism (high-quality evidence)). Liberal transfusion did not affect the risk of infection (pneumonia, wound, or bacteraemia)., Authors' Conclusions: Transfusing at a restrictive haemoglobin concentration of between 7 g/dL to 8 g/dL decreased the proportion of participants exposed to RBC transfusion by 43% across a broad range of clinical specialities. There was no evidence that a restrictive transfusion strategy impacts 30-day mortality or morbidity (i.e. mortality at other points, cardiac events, myocardial infarction, stroke, pneumonia, thromboembolism, infection) compared with a liberal transfusion strategy. There were insufficient data to inform the safety of transfusion policies in certain clinical subgroups, including acute coronary syndrome, myocardial infarction, neurological injury/traumatic brain injury, acute neurological disorders, stroke, thrombocytopenia, cancer, haematological malignancies, and bone marrow failure. The findings provide good evidence that transfusions with allogeneic RBCs can be avoided in most patients with haemoglobin thresholds above 7 g/dL to 8 g/dL.

Background: Most clinical practice guidelines recommend restrictive red cell transfusion practices, with the goal of minimising exposure to allogeneic blood. The purpose of this review is to compare clinical outcomes in patients randomised to restrictive versus liberal transfusion thresholds (triggers)., Objectives: To examine the evidence for the effect of transfusion thresholds on the use of allogeneic and/or autologous red cell transfusion, and the evidence for any effect on clinical outcomes., Search Methods: We identified trials by searching; The Cochrane Injuries Group Specialised Register (searched 01 Feb 2011), Cochrane Central Register of Controlled Trials 2011, issue 1 (The Cochrane Library), MEDLINE (Ovid) 1948 to January Week 3 2011, EMBASE (Ovid) 1980 to 2011 (Week 04), ISI Web of Science: Science Citation Index Expanded (1970 to Feb 2011), ISI Web of Science: Conference Proceedings Citation Index- Science (1990 to Feb 2011). We checked reference lists of other published reviews and relevant papers to identify any additional trials., Selection Criteria: Controlled trials in which patients were randomised to an intervention group or to a control group. Trials were included where intervention groups were assigned on the basis of a clear transfusion 'trigger', described as a haemoglobin (Hb) or haematocrit (Hct) level below which a red blood cell (RBC) transfusion was to be administered., Data Collection and Analysis: Risk ratios of requiring allogeneic blood transfusion, transfused blood volumes and other clinical outcomes were pooled across trials, using a random effects model. Data extraction and assessment of the risk of bias was performed by two people., Main Results: Nineteen trials involving a total of 6264 patients were identified, and were similar enough that the results could be combined. Restrictive transfusion strategies reduced the risk of receiving a RBC transfusion by 39% (RR 0.61, 95% CI 0.52 to 0.72). This equates to an average absolute risk reduction (ARR) of 34% (95% CI 24% to 45%). The volume of RBCs transfused was reduced on average by 1.19 units (95% CI 0.53 to 1.85 units). However, heterogeneity between trials was statistically significant (P<0.00001; I(2)≥93%) for these outcomes. Restrictive transfusion strategies did not appear to impact the rate of adverse events compared to liberal transfusion strategies (i.e. mortality, cardiac events, myocardial infarction, stroke, pneumonia and thromboembolism). Restrictive transfusion strategies were associated with a statistically significant reduction in hospital mortality (RR 0.77, 95% CI 0.62-0.95) but not 30 day mortality (RR 0.85, 95% CI 0.70 to 1.03). The use of restrictive transfusion strategies did not reduce functional recovery, hospital or intensive care length of stay. The majority of patients randomised were included in good quality trials, but some items of methodological quality were unclear. There are no trials in patients with acute coronary syndrome., Authors' Conclusions: The existing evidence supports the use of restrictive transfusion triggers in most patients including those with pre-existing cardiovascular disease. As there are no trials, the effects of restrictive transfusion triggers in high risk groups such as acute coronary syndrome need to be tested in further large clinical trials. In countries with inadequate screening of donor blood, the data may constitute a stronger basis for avoiding transfusion with allogeneic red cells.

A novel model for measuring the strength of perfluoroalkyl acid (PFAA) binding to human serum albumin (HSA) by use of the protein's native fluorescence is described. The model is derived from published properties of HSA and its interactions with other surfactants; it is consistent with these properties and experimental observations. The model's validity has been tested with both medium- to long-chain PFAAs (perfluoroheptanoate, perfluorooctanoate, perfluorononanoate, perfluorodecanoate, perfluoroundecanoate, perfluorohexanesulfonate, and perfluorooctanesulfonate) and short-chain PFAAs (perfluorohexanoate and perfluorobutanesulfonate). These experiments confirm the model as a valid description for the binding of medium- to long-chain PFAAs to HSA. Results indicate at least 2-3 PFAAs bind to each protein with affinity on the order of 10(4) M(-1). These binding strengths exhibit a dependence on protein concentration. Measured PFAA binding constants are approximately 10% of those values reported for fatty acids of similar chain length; correcting for protein concentration suggests the binding strengths may be as low as 2-3% of the corresponding fatty acids' affinities. Like fatty acids, the carboxylate PFAAs exhibit a trend of generally increasing binding strength with increased chain length. The model does not appear valid for the binding of short-chain PFAAs to HSA. Hill binding coefficients, fluorescence intensity measurements, and wavelengths of maximum emission suggest short-chain PFAAs associate with HSA differently and fail to promote the same conformational changes in the protein's tertiary structure as the medium- to long-chain PFAAs.

Perfluorochemicals are globally pervasive contaminants that are persistent, bioaccumulative, and toxic. Perfluorocarboxylic acids (PFCAs) with 8-13 carbons accumulate in the liver and blood of aquatic organisms; PFCA-protein interactions may explain this accumulation pattern. Here, the interactions between PFCAs with 8-11 carbons and serum albumin are examined using three experimental approaches: surface tension titrations, (19)F NMR spectroscopy, and fluorescence spectroscopy. Surface tension titrations indicate complex formation at high (mM) PFCA concentrations. Secondary association constants ranging from 10(2) to 10(4) M(-1) were determined from (19)F NMR titrations at high PFCA:albumin mole ratios. Fluorescence measurements indicate that PFCA-albumin interactions alter the protein conformation at low PFCA:albumin mole ratios (up to 5:1) and suggest two binding classes with association constants around 10(5) and 10(2) M(-1). While (19)F NMR and fluorescence provide both qualitative and quantitative information about PFCA-albumin interactions, surface tension provides only qualitative information. Limitations associated with instrumentation and methods require high PFCA concentrations in both surface tension and (19)F NMR experiments; in contrast, fluorescence allows for analysis of a wider range of PFCA concentrations and PFCA:albumin mole ratios. Results from this study indicate that fluorescence, though an indirect method, offers a more comprehensive picture of the nature of PFCA-albumin interactions.

Background: As critical care practice increases in scope, size, and complexity, enrollment of critically ill patients into clinical studies is increasing., Objective: To understand the experiences, beliefs, and practices of the Canadian Critical Care Trials Group and Australian and New Zealand Intensive Care Society Clinical Trials Group regarding enrollment of critically ill children and adults into clinical studies., Methods: Survey items generated by the research team were formatted in four domains: experiences, beliefs, practices, and demographics. Five research coordinators and five physicians pretested the survey, providing feedback on clarity and completeness. Intrarater reliability (16 participants, 2 wks apart) was very good., Results: The response rate was 284 of 322 (88.2%). Respondents worked in intensive care units with a mean of 20.5 (SD 10) beds, caring for adults (72.2%), pediatric (18.8%), and both groups (9%) of critically ill patients. Clinical research was considered key to the future of improved clinical care. To enhance recruitment efficiency, respondents widely endorsed the effectiveness of increasing participating centers, after-hours, and weekend enrollment (all 3 scores 7 [6-7[sqb], reflecting median [interquartile range] on 1-7 scale). Overall, the effectiveness (6 [4-7]), feasibility (5 [4-6]) and ethics (5 [4-7]) of coenrollment into more than one randomized trial was endorsed. Half of respondents have adopted coenrollment with scientific and psychosocial provisos. Alternative designs, such as factorial and cluster randomized trials, were considered when suitable. Modifications to consent approaches (deferred consent (7 [6-7]), waived consent (7 [6-7]), or consent from two physicians in the absence of a substitute decision maker (6 [5-7])) were considered effective, but beliefs about the feasibility and ethics of some of these approaches varied., Conclusions: Clinical research is highly valued by these intensive care unit communities. Strategies to increase capacity involve enhancing recruitment efficiencies, considering alternative study designs and expanding consent procedures. Thoughtfully implementing these strategies may advance the care of critically ill adults and children.

Background: Given the increasing use of intravenous immunoglobulin (IVIG) for various neurologic conditions and uncertainty pertaining to its benefits and harms, a systematic review was conducted of randomized controlled trials (RCTs) evaluating IVIG for all neurologic indications for which there was at least one published trial., Study Design and Methods: For this systematic review, a systematic search strategy was applied to MEDLINE (1966-June 2003) and the Cochrane Register of Controlled Trials (June 2003) to identify potentially eligible RCTs comparing IVIG to placebo or an active control. All dosage regimens were considered. Abstracts were excluded, and no restriction was placed on language of publication. Two investigators independently performed data extraction with a standardized form. Measures of effect were calculated for each trial independently, and studies were pooled based on clinical and methodologic judgment as to its appropriateness. Where pooling of trials was inappropriate, a qualitative discussion of findings is provided., Results and Conclusions: Thirty-seven trials representing 14 conditions were identified. IVIG is more effective than placebo for treatment of relapsing-remitting multiple sclerosis and idiopathic chronic inflammatory demyelinating polyneuropathy. There is also potential benefit for treatment of multifocal motor neuropathy, myasthenia gravis, dermatomyositis, stiff-person syndrome, and Lambert-Eaton myasthenic syndrome. There was insufficient evidence to determine whether IVIG therapy was more effective than plasma exchange for Guillain-Barré syndrome. There was also insufficient evidence regarding paraprotein-associated polyneuropathy. No evidence of benefit was observed for secondary progressive multiple sclerosis or inclusion body myositis.

Background and Objective: The quality and integrity of information is pivotal to the validity and reliability of inferences drawn in research. The aim of this study is to demonstrate that standardized medical records can be used as a data abstraction training tool and a quality control measure to assess the validity of medical record data abstraction., Methods: Sixteen hospitals participating in a large multicenter study completed standardized data abstraction forms for three representative patient charts, one in each of the clinical areas of postoperative critical care and trauma, cardiac surgery, and repair of hip fracture. The completed forms were then compared to an established gold standard., Results: The mean level of accuracy of the completed data abstraction forms in each of the above three clinical areas were 91.8, 77.5, and 91.5%, respectively. Missing data accounted for 19% of all discrepancies between the abstracted information and the gold standard. If queries and amendments were made by the study's coordinating center, the mean level of accuracy increased to 94.5, 82.5, and 92.9%, respectively., Conclusion: The present study stressed the need for quality control measures in abstracting information from medical records to ensure the accuracy and completeness of the data abstracted.

Background: An analysis from the prospective multicenter randomized controlled trial (Transfusion Requirements in Critical Care Trial) compared the use of restrictive and liberal transfusion strategies with resuscitated critically ill trauma patients., Methods: Critically ill trauma patients with a hemoglobin concentration less than 90 g/L within 72 hours of admission to the intensive care unit were randomized to a restrictive (hemoglobin concentration, 70 g/L) or liberal (hemoglobin concentration, 100 g/L) red blood cell transfusion strategy., Results: The baseline characteristics in the restrictive (n = 100) and liberal (n = 103) transfusion groups were comparable. The average hemoglobin concentrations (82.7 +/- 6.2 g/L vs. 104.3 +/- 12.2 g/L; p < 0.0001) and the red blood cell units transfused per patient (2.3 +/- 4.4 vs. 5.4 +/- 4.3; p < 0.0001) were significantly lower in the restrictive group than in the liberal group. The 30-day all-cause mortality rates in the restrictive group were 10%, as compared with 9% in the liberal group (p = 0.81). The presence of multiple organ dysfunction (9.2 +/- 6.3 vs. 9.0 +/- 6.0; p = 0.81), the changes in multiple organ dysfunction from baseline scores adjusted for death (1.2 +/- 6.1 vs. 1.9 +/- 5.7; p = 0.44), and the length of stay in the intensive care unit (9.8 +/- 8.1 vs. 10.2 +/- 8.7 days; p = 0.73) and hospital (31.4 +/- 17.1 vs. 33.7 +/- 17.7 days; p = 0.34) also were similar between the restrictive and liberal transfusion groups., Conclusions: A restrictive red blood cell transfusion strategy appears to be safe for critically ill multiple-trauma patients. A randomized controlled trial would provide the appropriate level of evidence with regard to the daily use of blood in this population of patients.

Objective: Aggressive glycemic control improves mortality and morbidity in critically ill adults, however implementation of such a strategy can be logistically difficult. This study evaluates the efficiency and safety of a nurse-managed insulin protocol in critically ill adults., Design: Combined retrospective-prospective before-after cohort study., Setting: Twenty-one bed, medical/surgical ICU in a tertiary care hospital., Patients: Two cohorts of 50 consecutive ICU patients requiring insulin infusions., Intervention: Patients in the control cohort received insulin infusions titrated according to target blood glucose ranges and sliding scales at the physician's discretion. Patients in the interventional cohort received an insulin infusion adjusted using a standardized protocol targeting a blood glucose of 4.5-6.1 mmol/l (81-110 mg/dl)., Measurements and Main Results: Efficiency was measured by comparing the time to reach, and the time spent within, the target range between cohorts. Safety was assessed by comparing the incidence of severe hypoglycemia, the frequency of rescue dextrose administration and the cumulative time that the infusion was held for hypoglycemia between cohorts. Patients in the interventional cohort reached their target more rapidly (11.3+/-7.9 vs 16.4+/-12.6 h; p=0.028) and maintained their blood glucose within the target range longer (11.5+/-3.7 vs 7.1+/-5.0 h/day; p<0.001) than controls. The standardized protocol yielded a four-fold reduction in the incidence of severe hypoglycemia (4 vs 16%; p=0.046) and reduced the median frequency of dextrose rescue therapy (0 [0-0.91] vs 0.17 [0-1.2] episodes/patient per day; p=0.01) as compared to controls., Conclusion: Standardization of intensive insulin therapy improves the efficiency and safety of glycemic control in critically ill adults.

Background: Most clinical practice guidelines recommend restrictive red cell transfusion practices with the goal of minimising exposure to allogeneic blood (from an unrelated donor). The purpose of this review is to compare clinical outcomes in patients randomised to restrictive versus liberal transfusion thresholds (triggers)., Objectives: To examine the evidence on the effect of transfusion thresholds, on the use of allogeneic and/or autologous blood, and the evidence for any effect on clinical outcomes., Search Strategy: Trials were identified by: computer searches of OVID Medline (1966 to December 2000), Current Contents (1993 to Week 48 2000), and the Cochrane Controlled Trials Register (2000 Issue 4). References in identified trials and review articles were checked and authors contacted to identify any additional studies., Selection Criteria: Controlled trials in which patients were randomised to an intervention group or to a control group. Trials were included where the intervention groups were assigned on the basis of a clear transfusion "trigger", described as a haemoglobin (Hb) or haematocrit (Hct) level below which a RBC transfusion was to be administered., Data Collection and Analysis: Trial quality was assessed using criteria proposed by Schulz et al. (1995). Relative risks of requiring allogeneic blood transfusion, transfused blood volumes and other clinical outcomes were pooled across trials using a random effects model., Main Results: Ten trials were identified that reported outcomes for a total of 1780 patients. Restrictive transfusion strategies reduced the risk of receiving a red blood cell (RBC) transfusion by a relative 42% (RR=0.58: 95%CI=0.47,0.71). This equates to an average absolute risk reduction (ARR) of 40% (95%CI=24% to 56%). The volume of RBCs transfused was reduced on average by 0.93 units (95%CI=0.36,1.5 units). However, heterogeneity between these trials was statistically significant (p<0.00001) for these outcomes. Mortality, rates of cardiac events, morbidity, and length of hospital stay were unaffected. Trials were of poor methodological quality., Reviewer's Conclusions: The limited published evidence supports the use of restrictive transfusion triggers in patients who are free of serious cardiac disease. However, most of the data on clinical outcomes were generated by a single trial. The effects of conservative transfusion triggers on functional status, morbidity and mortality, particularly in patients with cardiac disease, need to be tested in further large clinical trials. In countries with inadequate screening of donor blood the data may constitute a stronger basis for avoiding transfusion with allogeneic red cells.

We developed a rapid in vitro antibiotic susceptibility test to screen double- and triple-antibiotic combinations for bactericidal activity against 75 multiresistant Pseudomonas aeruginosa isolates referred from 44 cystic fibrosis (CF) patients. When used alone, the most effective intravenous antibiotic, meropenem, was bactericidal against only 44% of the isolates. High-dose tobramycin (200 microg/ml; concentrations achievable by aerosol administration) was bactericidal against 72% of isolates. Adding a second antibiotic significantly improved bactericidal activity. The most effective double-antibiotic combinations contained high-dose tobramycin plus meropenem, piperacillin/tazobactam, or ciprofloxacin, and were bactericidal against 88 to 94% of the isolates. Excluding high-dose tobramycin, the most effective intravenous double-antibiotic combinations contained meropenem plus ciprofloxacin, tobramycin (4 microg/ml), or cefipime, and were bactericidal against 85%, 71%, and 70% of isolates, respectively. Adding a third antibiotic did not significantly improve inhibition in vitro. We conclude that double-antibiotic combinations containing meropenem or high-dose tobramycin show the best bactericidal activity in vitro against multiresistant strains of P. aeruginosa. Addition of a third antibiotic to these double-antibiotic combinations may be unnecessary.

Objective: To compare outcomes in blunt trauma by using Trauma and Injury Severity Score (TRISS) models derived from the Major Trauma Outcome Study (MTOS) and the Ontario Trauma Registry (OTR) as well as to evaluate the role of the Revised Trauma Score within the TRISS model., Methods: Consecutive blunt trauma cases from 11 Level I trauma centers over a 4-year period were identified from the OTR. Coefficients of the Revised Trauma Score were modified using the Ontario data and this score was tested by using the Hosmer-Lemeshow Goodness of Fit Test. Two Ontario-specific TRISS models were developed with revised coefficients. The first used the standard Revised Trauma Score and the second used the Revised Trauma Score with regenerated coefficients. The accuracy of mortality predictions for all models were compared by using a Hosmer-Lemeshow Goodness of Fit procedure. Additionally, each TRISS models performance characteristics and receiver operating characteristic (ROC) curves were used to evaluate their discriminative capabilities., Results: A total of 5,436 cases were incorporated in the analysis. Patients with all component TRISS variables had a significantly lower mortality compared to all blunt trauma patients (7.0% vs. 15.5%,p < 0.01). Use of the Revised Trauma Score led to the exclusion of 40% of cases because of absent data necessary to compute the score. The Hosmer-Lemeshow Goodness of Fit statistic for the Revised Trauma Score was 79.45 (p = 0.0001). The Hosmer-Lemeshow Goodness of Fit Statistic ranged from 11.42, p = 0.175 and 13.1, p = 0.125 for the Ontario TRISS models compared to 25.62, p < 0.005 for the MTOS TRISS model. Sensitivity of all three TRISS models ranged from 98% to 99% with specificity ranging from 24% to 35%. ROC curves were identical for all three TRISS models., Conclusions: TRISS demonstrated satisfactory performance in a Canadian blunt trauma population. Although revision of coefficients led to a better fit on the Hosmer-Lemeshow statistic, ROC curves demonstrated virtually identical performance of the MTOS and Ontario-based TRISS models. The poor performance of the Revised Trauma Score and the observation that its use led to the exclusion of 40% of cases with a higher mortality raises concerns regarding its use in the TRISS model.

In this article we will review how a reader should evaluate a screening study. A clinical problem involving screening mammography is presented. We then outline criteria to determine whether screening is appropriate for a given condition. A search for relevant articles is described followed by an outline of the steps used to appraise a screening study critically. An applicable study is examined in detail for such things as the quality of randomisation and outcomes measured. The results of this study are then applied to a patient considered for screening.

Objective: To generate hypotheses regarding the association of standard Advanced Cardiac Life Support (ACLS) drugs with human cardiac arrest survival., Methods: This observational cohort study was conducted over a two-year period in the wards, intensive care units, and EDs of two tertiary care hospitals. Included werc adult patients who suffered cardiac arrest either inside or outside the hospital and who required epinephrine according to standard ACLS guidelines. Six standard ACLS drugs (given while CPR was in progress) were assessed for association with survival from resuscitation to one hour and to hospital discharge by univariate and multivariate logistic regression analyses., Results: In the 529 patients studied, initial cardiac rhythm had no impact on the association between drug administration and survival. The time of drug administration (quartile of ACLS period) was associated with resuscitation for atropine (p < 0.05) and lidocaine (p < 0.01). The odds ratios (95% CIs) for successful resuscitation, after multivariate adjustment for potential confounders, were: a respiratory initiating cause, 3.7 (2.1 -6.4); each 5-minute increase in CPR-ACLS interval, 0.5 (0.4-0.7); each 5-minute duration of ACLS. 0.9 (()1.8- 1.0; atropine, 1.2 (1.0-1.3); bretylium. (0.4 (0.1-1.1); calcium 0.8 (0.2-2.4); lidocaine, 0.9 (0.7-1.1); procainamide. 21.0 (5.2-84.0) d sodium bicarbonate 1.2 (1.0-1.6). All other potential confounding variables entered into the model were not significantly associated with resuscitation., Conclusion: Initiating cause of arrest, time to ACLS, and duration of ACLS were important correlates of survival. Other than procainaimide, standard ACLS drugs had relatively little association with survival, but timing of administration may be an important factor. Further research using definitive large randomized controlled trials is warranted to assess the role of drug therapy in improving cardiac arrest survival.

The authors report the case of a 57-year-old man with a history of ischemic heart disease who presented to the emergency department with an acute myocardial infarction and hypotension. Despite aggressive pharmacotherapy, the patient's heart rate decreased, and he developed pulseless electrical activity within 15 minutes of his arrival. Cardiopulmonary resuscitation (CPR) was begun with an active compression-decompression (ACD) device, and the patient became agitated, making purposeful movements. When ACD-CPR was discontinued for a rhythm check, the patient had no pulse and became motionless. Agitation and purposeful movements occurred on two subsequent occasions with the initiation of ACD-CPR. The patient required physical restraints, sedation, and paralysis for personnel to perform endotracheal intubation and facilitate treatment. The implications of this case are discussed.

Whether systolic contractility or diastolic compliance changes soon after tumor necrosis factor-alpha (TNF-alpha) exposure is not known. Accordingly, we measured hemodynamics, left ventricular contractility using the slope of the end-systolic pressure-volume relationship, and diastolic pressure-volume relationships in six control dogs and in six dogs receiving 60 micrograms.kg-1.h-1 i.v. of TNF-alpha. Mean aortic pressure decreased by 22% 1 h after TNF-alpha infusion and remained decreased (P < 0.05). Cardiac output increased by 19% 1 h after TNF-alpha infusion and remained significantly greater than control values (P < 0.05). Left ventricular contractility decreased by 23% (P < 0.05) 1 h after TNF-alpha infusion and decreased by 52% (P < 0.01) 5 h after TNF-alpha infusion. The diastolic pressure-volume relationship did not change in the TNF-alpha group or the control group. Ejection fraction did not change after TNF-alpha infusion despite the decrease in contractility because afterload decreased. We conclude that TNF-alpha is important in causing the hypotensive, hyperdynamic circulation of sepsis. The new finding that left ventricular contractility is decreased shortly after TNF-alpha infusion suggests that TNF-alpha, or another mediator released very soon after TNF-alpha, is an important myocardial depressant factor.

A simple multiple system organ failure (MSOF) score may predict mortality of patients who have sepsis syndrome. Using an MSOF scoring system, we prospectively determined the presence or absence of respiratory, cardiovascular, renal, hepatic, gastrointestinal, hematologic, and neurologic organ failure on day 1 of sepsis syndrome in 154 consecutive patients who had sepsis syndrome in the ICU of a tertiary care, teaching hospital. We used 30-day hospital mortality as the primary outcome variable. Overall 30-day mortality was 34 percent. There was a strong linear association between number of organ system failures and 30-day mortality (p < 0.0001). Mortality was 20 percent in patients who had less than 3 organ system failures (n = 111) and 70 percent in patients who had 3 or more organ system failures (n = 43). Survival was assessed using the Cox proportional hazards model and was found to be significantly different (p < 0.01) between the two groups defined by the aforementioned dichotomy after adjustment for age and sex using time to death as the primary outcome. The increase in relative risk of death associated with 3 or more organ system failures was 2.77 (95 percent confidence interval, 2.74 to 2.83). Using logistic regression, the adjusted odds ratios (OR) for covariates most predictive of mortality were hematologic (OR = 6.2), neurologic (OR = 4.4), hepatic (OR = 3.4), cardiovascular (OR = 2.6), and age (1.05 per year). The logistic model using the seven organ system failures and age as covariates accurately predicted outcome 75 percent of the time with a sensitivity of 51 percent and specificity of 87 percent. In conclusion, a simple scoring system tabulating the number of organ system failures present on day 1 of sepsis syndrome predicts the mortality of patients who have sepsis syndrome with reasonable accuracy.

Background: Recent studies suggest that doses of epinephrine of 0.1 mg per kilogram of body weight or higher may improve myocardial and cerebral blood flow as well as survival in cardiac arrest. Such studies have called into question the traditional dose of epinephrine (0.007 to 0.014 mg per kilogram) recommended for advanced cardiac life support., Methods: We randomly assigned 650 patients who had had cardiac arrest either in or outside the hospital to receive up to five doses of high-dose (7 mg) or standard-dose (1 mg) epinephrine at five-minute intervals according to standard protocols for advanced cardiac life support. Patients who collapsed outside the hospital received no advanced-life-support measures other than defibrillation before reaching the hospital., Results: There was no significant difference between the high-dose group (n = 317) and the standard-dose group (n = 333) in the proportions of patients who survived for one hour (18 percent vs. 23 percent, respectively) or who survived until hospital discharge (3 percent vs. 5 percent). Among the survivors, there was no significant difference in the proportions who remained in the best category of cerebral performance (90 percent vs. 94 percent) and no significant difference in the median Mini-Mental State score (36 vs. 37). The exploration of clinically important subgroups, including those with out-of-hospital arrest (n = 335) and those with in-hospital arrest (n = 315), failed to identify any patients who appeared to benefit from high-dose epinephrine and suggested that some patients may have worse outcomes after high-dose epinephrine., Conclusion: High-dose epinephrine was not found to improve survival or neurologic outcomes in adult victims of cardiac arrest.