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The clinical consequences of red blood cell storage age for critically ill pediatric patients have not been examined in a large, randomized clinical trial.To determine if the transfusion of fresh red blood cells (stored ≤7 days) reduced new or progressive multiple organ dysfunction syndrome compared with the use of standard-issue red blood cells in critically ill children.The Age of Transfused Blood in Critically-Ill Children trial was an international, multicenter, blinded, randomized clinical trial, performed between February 2014 and November 2018 in 50 tertiary care centers. Pediatric patients between the ages of 3 days and 16 years were eligible if the first red blood cell transfusion was administered within 7 days of intensive care unit admission. A total of 15 568 patients were screened, and 13 308 were excluded.Patients were randomized to receive either fresh or standard-issue red blood cells. A total of 1538 patients were randomized with 768 patients in the fresh red blood cell group and 770 in the standard-issue group.The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured for 28 days or to discharge or death.Among 1538 patients who were randomized, 1461 patients (95%) were included in the primary analysis (median age, 1.8 years; 47.3% girls), in which there were 728 patients randomized to the fresh red blood cell group and 733 to the standard-issue group. The median storage duration was 5 days (interquartile range [IQR], 4-6 days) in the fresh group vs 18 days (IQR, 12-25 days) in the standard-issue group (P .001). There were no significant differences in new or progressive multiple organ dysfunction syndrome between fresh (147 of 728 [20.2%]) and standard-issue red blood cell groups (133 of 732 [18.2%]), with an unadjusted absolute risk difference of 2.0% (95% CI, -2.0% to 6.1%; P = .33). The prevalence of sepsis was 25.8% (160 of 619) in the fresh group and 25.3% (154 of 608) in the standard-issue group. The prevalence of acute respiratory distress syndrome was 6.6% (41 of 619) in the fresh group and 4.8% (29 of 608) in the standard-issue group. Intensive care unit mortality was 4.5% (33 of 728) in the fresh group vs 3.5 % (26 of 732) in the standard-issue group (P = .34).Among critically ill pediatric patients, the use of fresh red blood cells did not reduce the incidence of new or progressive multiple organ dysfunction syndrome (including mortality) compared with standard-issue red blood cells.ClinicalTrials.gov Identifier: NCT01977547.

Accurate prognostic information in patients with severe traumatic brain injury remains limited, but mortality following the withdrawal of life-sustaining therapies is high and variable across centers. We designed a survey to understand attitudes of physicians caring for patients with severe traumatic brain injury toward the determination of prognosis and clinical decision making on the level of care.We conducted a cross-sectional study of intensivists, neurosurgeons, and neurologists that participate in the care of patients with severe traumatic brain injury at all Canadian level 1 and level 2 trauma centers.None.The main outcome measure was physicians' perceptions of prognosis and recommendations on the level of care.Our response rate was 64% (455/712). Most respondents (65%) reported that an accurate prediction of prognosis would be most helpful during the first 7 days. Most respondents (80%) identified bedside monitoring, clinical exam, and imaging to be useful for evaluating prognosis, whereas fewer considered electrophysiology tests (60%) and biomarkers (15%). In a case-based scenario, approximately one-third of respondents agreed, one-third were neutral, and one-third disagreed that the patient prognosis would be unfavorable at one year. About 10% were comfortable recommending withdrawal of life-sustaining therapies.A significant variation in perceptions of neurologic prognosis and in clinical decision making on the level of care was found among Canadian intensivists, neurosurgeons, and neurologists. Improved understanding of the factors that can accurately predict prognosis for patients with traumatic brain injury is urgently needed.

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.

BACKGROUNDThe optimal approach to titrate vasopressor therapy is unclear. Recent sepsis guidelines recommend a mean arterial pressure (MAP) target of 65 mmHg and higher for chronic hypertensive patients. As data emerge from clinical trials comparing blood pressure targets for vasopressor therapy, an accurate description of usual care is required to interpret study results. Our aim was to measure MAP values during vasopressor therapy in Canadian intensive care units (ICUs) and to compare these with stated practices and guidelines.METHODIn a multicenter prospective cohort study of critically ill adults with severe hypotension, we recorded MAP and vasopressor doses hourly. We investigated variability across patients and centres using multivariable regression models and Analysis of variance (ANOVA), respectively.RESULTSWe included data from 56 patients treated in 6 centers. The mean (standard deviation [SD]) age and Acute Physiology and Chronic Health Evaluation (APACHE) II score were 64 (14) and 25 (8). Half (28 of 56) of the patients were at least 65 years old, and half had chronic hypertension. The patient-averaged MAP while receiving vasopressors was 75 mm Hg (6) and the median (1st quartile, 3rd quartile) duration of vasopressor therapy was 43 hours (23, 84). MAP achieved was not associated with history of underlying hypertension (p = 0.46) but did vary by center (pCONCLUSIONSIn this multicenter, prospective observational study, the patient-level average MAP while receiving vasopressors for severe hypotension was 75 mmHg, approximately 10 mmHg above current recommendations and stated practices. Moreover, our results do not support the notion that clinicians tailor vasopressor therapy to individual patient characteristics such as underlying chronic hypertension but MAP achieved while receiving vasopressors varied by site.

Nurses have an obligation to disclose an error when one occurs. This study explored 1180 nurses' perceptions of error disclosure in the nursing home setting. Nurse respondents found disclosure to be a difficult process. Registered nurse respondents and nurses who had prior experience disclosing a serious error were more likely to disclose a serious error. The study has implications to improve nursing education, policy, and patient safety culture in the nursing home setting.

Objective To discuss the characteristics of incidents reported to the Medical Safety in Community Practice (MSCP) safety learning system. Methods Members of family physician offices in the Alberta Health Services—Calgary zone, confidentially reported patient safety incidents via web or fax from September 2007 to August 2010. The incident reporting form contained both open-ended and closed questions. Incidents were reviewed for their characteristics. Results A total of 19 family practices participated in MSCP. A total of 264 useable reports were collected. Reporting was higher when practices first joined and then decreased. There was an average of 1.4 reports per month. Physicians submitted the majority of reports. Physicians and nurses were more likely to report an incident than office staff. The vast majority of reported incidents were judged to have ‘ virtually certain evidence of preventability’ (93%). Harm was associated with 50% of incidents. Only 1% of the incidents had a severe impact. The top four types of incidents reported were documentation (41.4%), medication (29.7%), clinical administration (18.7%) and clinical process (17.5%). Conclusion MSCP has developed and implemented the first safety learning system in Canada for family practice. All clinic members were encouraged to submit reports, but most of the incidents were reported by physicians. The vast majority of incidents reported were preventable with limited severity. The most frequently reported types of incidents fell into the categories of documentation and medication. The low reporting rates suggest that for family practices incident reporting may not be the most effective method to determine the types and frequency of incidents in family medicine.

BACKGROUND: It is important to determine the optimal hemoglobin (Hb) concentration for red blood cell (RBC) transfusion for patients undergoing cardiac surgery because increased mortality has been associated with the severity of anemia and exposure to RBCs. Because a definitive trial will require thousands of patients, and because there is variability in transfusion practices, a pilot study was undertaken to determine adherence to proposed strategies. STUDY DESIGN AND METHODS: A single-center parallel randomized controlled pilot trial was conducted in high-risk cardiac patients to assess adherence to two transfusion strategies. Fifty patients were randomly assigned either to a “restrictive” transfusion strategy (RBCs if their Hb concentration was 70 g/L or less intraoperatively during cardiopulmonary bypass [CPB] and 75 g/L or less postoperatively) or a “liberal” transfusion strategy (RBCs if their Hb concentration was 95 g/L or less during CPB and less than 100 g/L postoperatively). RESULTS: The percentage of adherence overall was 84% in the restrictive arm and 41% in the liberal arm. Twenty-two (88%) patients were transfused 99 units of RBCs in the liberal group compared to 13 patients who were transfused 50 units in the restrictive group (p

Background Heart failure (HF) is an increasing problem for the aging population, specifically among women. The etiology of HF influences both the selection and outcome of the treatment. There are variations between genders in morbidity and mortality in different studies, possibly reflecting etiology. The objective of this study was to examine the strength of evidence available for gender differences in the etiology of chronic heart failure. Methods Computer-assisted searches from 19802009 for gender differences in the etiology of heart failure were performed (Medline, EMBASE and PubMed). From 2347 abstracts reviewed based on inclusion criteria, 35 original articles were chosen for review. Data extraction was based on observational studies (prospective/retrospective cohort or cross sectional) with a mean follow up of 3 months. There was no interrater variability between the 2 reviewers on data-extraction. Results Ventricular systolic dysfunction being more associated with male sex, but female sex was more reported to be associated with preserved left ventricular function. Ischemic etiology and associated coronary heart disease were strongly correlated with male sex. The risk for HF was dramatically more elevated for women with systolic hypertension but the association for diabetes mellitus as the etiology of HF was somewhat equal between males and females. Conclusions One of the limitations in reaching conclusions about gender differences in cardiovascular disease is that many major clinical trials do not include a gender analysis nor they are powered to do so as women are under-represented in most of the HF studies. The need remains for a well designed prospective study of sufficient numbers of male and female patients with and without heart failure and analyzing etiology and risk factors based on the sex differences. J Geriatr Cardiol 2011; 8: 1523. doi: 10.3724/SP.J.1263.2011.00015

Adrenal insufficiency is a clinical condition associated with fluid- and catecholamine-resistant hypotension.The objectives of this study were to determine the prevalence of adrenal insufficiency, risk factors and potential mechanisms for its development, and its association with clinically important outcomes in critically ill children.A prospective, cohort study was conducted from 2005 to 2008 in seven tertiary-care, pediatric intensive care units in Canada on patients up to 17 years of age with existing vascular access. Adrenocorticotropic hormone stimulation tests (1 microg) were performed and adrenocorticotropic hormone levels measured in all participants.A total of 381 patients had adrenal testing on admission. The prevalence of adrenal insufficiency was 30.2% (95% confidence interval, 25.9-35.1). Patients with adrenal insufficiency had higher baseline cortisol levels (28.6 microg/dl vs. 16.7 microg/dl, P0.001) and were significantly older (11.5 yr vs. 2.3 yr, P0.001) than those without adrenal insufficiency. Adrenal insufficiency was associated with an increased need for catecholamines (P0.001) and more fluid boluses (P = 0.026). The sensitivity and specificity of the low-dose adrenocorticotropic hormone stimulation test were 100% and 84%, respectively.Adrenal insufficiency occurs in many disease conditions in critically ill children and is associated with an increased use of catecholamines and fluid boluses. It is likely multifactorial in etiology and is associated with high baseline cortisol levels. Further research is necessary to determine which of these critically ill children are truly cortisol deficient before any treatment recommendations can be made.

The objectives of our study were (1) to explore the link between joint contractures acquired in the ICU and the ambulatory status of patients at discharge home, to determine (2) when and how many patients received physiotherapy services in ICU and on the hospital ward, and (3) the differences in the use of hospital resources in the presence or absence of joint contractures.Data on ICU joint contractures were extracted from an existing contracture database containing information on 155 Canadian patients with a tertiary ICU stay of 14 days or more.Of 155 patients, 115 (74.2%) received a range of motion assessment in the ICU. The assessment took place a median of 7 days (IQR 0-36) after ICU admission. Significantly fewer patients with joint contractures than without joint contractures were mobilized on the hospital ward (21/38 [55.3%] vs. 27/34 [79.4%], P = 0.03). At discharge home, more patients with joint contractures had a low ambulatory status (38 [64.4%]) compared with patients without joint contractures (26 [51.0%]; P = 0.002).The median delay of 7 days before musculoskeletal assessment in the ICU together with failure to assess 26% of patients may have allowed the development of contractures, which affected the patients' ambulatory status at discharge from hospital.

BACKGROUND: The objective was to determine if there is an association between red blood cell (RBC) storage time and development of new or progressive multiple organ dysfunction syndrome (MODS) in critically ill children. STUDY DESIGN AND METHODS: This was an analytic cohort analysis of patients enrolled in a randomized controlled trial, TRIPICU (Transfusion Requirements in Pediatric Intensive Care Units; ISRCTN37246456), in which stable critically ill children were randomly assigned to a restrictive or liberal strategy. Transfused patients were analyzed using three different sliding time cutoffs (7, 14, and 21 days). Storage time for multiply transfused patients was defined according to the oldest unit transfused. RESULTS: A total of 455 patients were retained (liberal, 310; restrictive, 145). Multivariate logistic regression was performed to determine independent associations. In the restrictive group, a maximum RBC storage time of more than 21 days was independently associated with new or progressive MODS (adjusted odds ratio [OR], 3.29; 95% confidence interval [CI], 1.21-9.04). The same association was found in the liberal group for a storage time of more than 14 days (adjusted OR, 2.50; 95% CI, 1.12-5.58). When the two groups were combined in a meta-analysis, a storage time of more than 14 days was independently associated with increased MODS (adjusted OR, 2.23; 95% CI, 1.20-4.15) and more than 21 days was associated with increased Pediatric Logistic Organ Dysfunction (PELOD) scores (adjusted mean difference, 4.26; 95% CI, 1.99-6.53) and higher mortality (9.2% vs. 3.8%). CONCLUSION: Stable critically ill children who receive RBC units with storage times longer than 2 to 3 weeks may be at greater risk of developing new or progressive MODS.

INTRODUCTION The benefits, harms and feasibility of intensive insulin therapy in critically ill patients remain unclear. Several single center studies have attempted to demonstrate the benefit of intensive insulin therapy in critically ill patients with variable results. OBJECTIVES We conducted a pilot randomized trial to assess the feasibility, safety and clinical outcomes of preprinted glucose management algorithms before the initiation of a large multicenter trial. PATIENTS AND METHODS Within 48 hours of admission to the intensive care unit, we randomized mechanically ventilated patients to either the "high" group (target serum glucose concentration 9-11 mmol/l) or the "low" group (target serum glucose concentration 5-7 mmol/l). To assess feasibility we measured the time to reach target glucose range, time in target range, morning glucose concentrations, average daily glucose concentrations, and number of crossovers. To assess safety, we measured the number of hypoglycemic events (serum glucose

OBJECTIVE: Vasopressin and corticosteroids are often added to support cardiovascular dysfunction in patients who have septic shock that is nonresponsive to fluid resuscitation and norepinephrine infusion. However, it is unknown whether vasopressin treatment interacts with corticosteroid treatment. DESIGN: Post hoc substudy of a multicenter randomized blinded controlled trial of vasopressin vs. norepinephrine in septic shock. SETTING: Twenty-seven Intensive Care Units in Canada, Australia, and the United States. PATIENTS: : Seven hundred and seventy-nine patients who had septic shock and were ongoing hypotension requiring at least 5 microg/min of norepinephrine infusion for 6 hours. INTERVENTIONS: Patients were randomized to blinded vasopressin (0.01-0.03 units/min) or norepinephrine (5-15 microg/min) infusion added to open-label vasopressors. Corticosteroids were given according to clinical judgment at any time in the 28-day postrandomization period. MEASUREMENTS: The primary end point was 28-day mortality. We tested for interaction between vasopressin treatment and corticosteroid treatment using logistic regression. Secondary end points were organ dysfunction, use of open-label vasopressors and vasopressin levels. MAIN RESULTS: There was a statistically significant interaction between vasopressin infusion and corticosteroid treatment (p = 0.008). In patients who had septic shock and were also treated with corticosteroids, vasopressin, compared to norepinephrine, was associated with significantly decreased mortality (35.9% vs. 44.7%, respectively, p = 0.03). In contrast, in patients who did not receive corticosteroids, vasopressin was associated with increased mortality compared with norepinephrine (33.7% vs. 21.3%, respectively, p = 0.06). In patients who received vasopressin infusion, use of corticosteroids significantly increased plasma vasopressin levels by 33% at 6 hours (p = 0.006) to 67% at 24 hours (p = 0.025) compared with patients who did not receive corticosteroids. CONCLUSIONS: There is a statistically significant interaction between vasopressin and corticosteroids. The combination of low-dose vasopressin and corticosteroids was associated with decreased mortality and organ dysfunction compared with norepinephrine and corticosteroids.

Despite recent trends in decreasing transfusion thresholds and the development of technologies designed to avoid allogeneic exposure, allogeneic red blood cell (RBC) transfusions remain an important supportive and life-saving measure for neonatal intensive care patients experiencing illness and anemia. Reluctantly, a number of laboratory and observational studies have indicated that the amount of time RBCs are stored can affect oxygen delivery to tissues. Consequently, older RBCs may result in higher rates of organ dysfunction, nosocomial infection, and lengths of stay. Because of such harmful effects, an evaluation of the association between age of blood and nosocomial infection and organ dysfunction is warranted. The aim of the study was to determine if RBCs stored for 7 days or less (fresh RBCs) compared to current standard transfusion practice decreases major nosocomial infection and organ dysfunction in neonates admitted to the neonatal intensive care unit and requiring at least one RBC transfusion. This study is a double-blind, multicenter, randomized controlled trial design. The trial will be an effectiveness study evaluating the effectiveness of stored vs fresh RBCs in neonates requiring transfusion. Neonatal patients requiring at least one unit of RBCs will be randomized to receive either (1) RBCs stored no longer than 7 days or (2) standard practice. The study was conducted in Canadian university-affiliated level III (tertiary) neonatal intensive care units. The primary outcome for this study will be a composite measure of major neonatal morbidities (necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage, and mortality). Secondary outcomes include individual items of the composite measure and nosocomial infection (bacteremia, septic shock, and pneumonia). The sample size calculations have been estimated based on the formula for 2 independent proportions using an alpha of .05, a (1-beta) of .80, and a 10% noncompliance factor. The baseline rate for our composite measure is estimated to be 65% as indicated by the literature. Assuming a 15% absolute risk reduction with the use of RBCs stored 7 days or less, our estimated total sample size required will be 450 (225 patients per treatment arm). The Age of Red Blood Cells in Premature Infants (ARIPI) trial is registered at the US National Institutes of Health (ClinicalTrials.gov) no. NCT00326924 and current controlled trials ISRCTN65939658.

It is unknown whether fluid resuscitation with colloid or crystalloid in patients with severe sepsis or septic shock is associated with an improvement in clinical outcome. This randomized controlled trial determined the feasibility of conducting a large trial testing resuscitation with pentastarch vs normal saline in early septic shock, powered for a difference in mortality.At three Canadian and one New Zealand academic centre, 40 patients with early septic shock defined by at least two systemic inflammatory response syndrome criteria, infectious source, and persistent hypotension afteror= 1 L of crystalloid fluid were recruited. Feasibility measures were patient recruitment, blinding of the study fluids, and acceptability of the goal directed algorithms. Boluses of blinded normal saline or pentastarch (500 mL - maximum 3 L or 28 mL x kg(-1)) were administered within goal directed care for the first 12 hr.Of 161 patients screened, 121 were excluded and 40 patients were enrolled, for a recruitment rate of 0.75 patients/site/month. Only 57% of physicians and 54% of nurses correctly guessed the study fluid (P = 0.46 and P = 0.67, respectively). The goal directed algorithms were acceptable to 97% of physicians.The ability to recruit patients in this pilot randomized controlled trial was below expectations. Blinding of study fluids was adequate, and resuscitation algorithms were acceptable to most physicians. Methods to improve recruitment are required to enhance the feasibility of conducting a multicentre fluid resuscitation trial in early septic shock.

As critical care practice increases in scope, size, and complexity, enrollment of critically ill patients into clinical studies is increasing.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.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.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.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.

Antifibrinolytic agents are commonly used during cardiac surgery to minimize bleeding and to reduce exposure to blood products. We sought to determine whether aprotinin was superior to either tranexamic acid or aminocaproic acid in decreasing massive postoperative bleeding and other clinically important consequences.In this multicenter, blinded trial, we randomly assigned 2331 high-risk cardiac surgical patients to one of three groups: 781 received aprotinin, 770 received tranexamic acid, and 780 received aminocaproic acid. The primary outcome was massive postoperative bleeding. Secondary outcomes included death from any cause at 30 days.The trial was terminated early because of a higher rate of death in patients receiving aprotinin. A total of 74 patients (9.5%) in the aprotinin group had massive bleeding, as compared with 93 (12.1%) in the tranexamic acid group and 94 (12.1%) in the aminocaproic acid group (relative risk in the aprotinin group for both comparisons, 0.79; 95% confidence interval [CI], 0.59 to 1.05). At 30 days, the rate of death from any cause was 6.0% in the aprotinin group, as compared with 3.9% in the tranexamic acid group (relative risk, 1.55; 95% CI, 0.99 to 2.42) and 4.0% in the aminocaproic acid group (relative risk, 1.52; 95% CI, 0.98 to 2.36). The relative risk of death in the aprotinin group, as compared with that in both groups receiving lysine analogues, was 1.53 (95% CI, 1.06 to 2.22).Despite the possibility of a modest reduction in the risk of massive bleeding, the strong and consistent negative mortality trend associated with aprotinin, as compared with the lysine analogues, precludes its use in high-risk cardiac surgery. (Current Controlled Trials number, ISRCTN15166455 [controlled-trials.com].).

Objective: Atrial fibrillation is a common problem associated with morbidity and mortality in critically ill patients; however, evidence-based treatment recommendations are lacking. The objective of this systematic review was to evaluate the efficacy of pharmacologic rhythm control of new-onset atrial fibrillation in noncardiac, critically ill adults. Data Source: Citations identified from an electronic search of Medline, the Cochrane register of controlled trials, and Embase databases (1966 to August 2006) were independently reviewed by two investigators. Study Selection: All prospective randomized controlled trials evaluating pharmacologic rhythm conversion regimens for newonset atrial fibrillation in (noncardiac surgery) critically ill adult patients were included. The primary end point was atrial fibrillation resolution. Data Extraction: Using a standardized data extraction form, data related to study design, population characteristics, pharmacologic intervention, and outcome measures were collected. Data Synthesis: Four trials met inclusion criteria from 1995 citations screened. Of the 143 evaluable patients in these trials 89 (76%) had atrial fibrillation while the remaining ones had other atrial tachyarrhythmias. Drugs evaluated for rhythm conversion included amiodarone (n 26), procainamide (n 14), magnesium (n 18), flecainide (n 15), esmolol (n 28), verapamil (n 15), and diltiazem (n 27). The definition of treatment success ranged from conversion within 1 hr to conversion within 24 hrs. No study evaluated maintenance of conversion, and one study included hemodynamically unstable patients. Lack of methodologic homogeneity prevented any pooled analysis. Conclusions: Using the current published literature, we cannot recommend a standard treatment for atrial fibrillation in noncardiac critically ill adult patients. Clinical trials evaluating rhythm conversion in critically ill populations outside of cardiac surgery are lacking. Further trials that address goals of care in hemodynamically stable and unstable patients and utilize standardized definitions of successful cardioversion are required. (Crit Care Med 2008; 36:1620‐1624)

Background: Prolonged immobility during a critical illness may predispose patients to the development of joint contracture. We sought to document the incidence of, the risk factors for and the reversibility of joint contractures among patients who stayed in a tertiary intensive care unit (ICU) for 2 weeks or longer. Methods: We conducted a chart review to collect data on the presence of and risk factors for joint contractures in the shoulders, elbows, hips, knees and ankles among patients admitted to the ICU between January 2003 and March 2005. Results: At the time of transfer out of the ICU, at least 1 joint contracture was recorded in 61 (39%) of 155 patients; 52 (34%) of the patients had joint contractures of an extent documented to impair function. Time spent in the ICU was a significant risk factor for contracture: a stay of 8 weeks or longer was associated with a significantly greater risk of any joint contracture than a stay of 2 to 3 weeks (adjusted odds ratio [OR] 7.09, 95% confidence interval (CI) 1.29–38.9; p = 0.02). Among the variables tested, only the use of steroids conferred a protective effect against joint contractures (adjusted OR 0.35, 95% CI 0.14–0.83; p = 0.02). At the time of discharge to home, which occurred a median of 6.6 weeks after transfer out of intensive care, 50 (34%) of the 147 patients not lost to follow-up still had 1 or more joint contractures, and 34 (23%) of the patients had at least 1 functionally significant joint contracture. Interpretation: Following a prolonged stay in the ICU, a functionally significant contracture of a major joint occurred in more than one-third of patients, and most of these contractures persisted until the time of discharge to home.

Enterobacter sakazakii infections often involve debilitated neonates consuming contaminated reconstituted powdered infant formula. There is the possibility that expressed human breast milk can become contaminated with E. sakazakii in the hospital or home setting and through the use of contaminated breast milk fortifiers. In addition, although breast milk has been shown to have some antimicrobial effects, this has not been extensively researched in regards to E. sakazakii. Thus, we examined the survival and growth of 9 strains of E. sakazakii in breast milk, human breast milk with fortifiers and powdered infant formula at 10, 23 and 37 degrees C. The average generation times for clinical, food and environmental isolates in breast milk were 0.94+/-0.04, 0.75+/-0.04 and 0.84+/-0.04 h at 23 degrees C; and 0.51+/-0.03, 0.33+/-0.03 and 0.42+/-0.03 h at 37 degrees C, respectively. E. sakazakii was able to survive up to 12 days in breast milk with fortifiers at 10 degrees C. However, its average generation times among replicates and isolate sources ranged from 11.97+/-3.82 to 27.08+/-4.54 h in breast milk at 10 degrees C. Interestingly, average generation times in breast milk with fortifiers at 23 degrees C (0.83+/-0.05, 0.93+/-0.06 and 0.96+/-0.06 h) and 37 degrees C (0.41+/-0.04, 0.51+/-0.05 and 0.54+/-0.05 h) were longer than in powdered infant formula and breast milk at the same temperatures, indicating that human breast milk fortifiers may have an inhibitory effect on the growth of E. sakazakii. However, the intrinsically ascribed antimicrobial properties of breast milk do not appear to inhibit the growth of this foodborne pathogen in-vitro.

Fluid resuscitation is a key factor in restoring hemodynamic stability and tissue perfusion in patients with severe sepsis. We sought to examine associations of the quantity and type of fluid administered in the first six hours after identification of severe sepsis and hospital mortality, intensive care unit (ICU) mortality, and organ failure. A retrospective, multicentre cohort study was undertaken at five Canadian tertiary care ICUs. We identified patients with severe sepsis admitted to the ICU between July 1, 2000, and June 30, 2002, using both administrative and clinical databases. Patients were included if they were hypotensive, had an infectious source, and at least two systemic inflammatory response syndrome criteria. We recorded total quantity and type of fluid administered for the first six hours after severe sepsis was identified. The first episode of hypotension defined the starting point for collection of fluid data. Multivariable regression analyses were performed to examine associations between quantity and type of fluid administered and hospital/ICU mortality, and organ failure. Of 2,026 potentially eligible patient charts identified, 496 patients met eligibility criteria. The mean age and Acute Physiology and Chronic Health Evaluation score (APACHE II) were 61.8 ± 16.5 yr and 29.0 ± 8.0, respectively. No associations between quantity or type of fluid administered and hospital mortality or ICU mortality were identified, and there were no statistically significant associations between quantity or type of fluid administered and organ failure. However, more fluid resuscitation was associated with an increased risk of cardiovascular failure [odds ratio (OR) and 95% confidence interval (CI)] for 2-4 L 1.67 (1.03-2.70) and > 4 L 2.34 (1.23-4.44) and a reduced risk of renal failure [OR, 95% CI for 2-4 L 0.48 (0.28-0.83) and > 4 L 0.45 (0.22-0.92)] in the first 24 hr of severe sepsis. Administration of colloid and crystalloid fluid as compared to crystalloid fluid alone was associated with a lower risk of renal failure [OR, 95% CI 0.45 (0.26 to 0.76)]. An association between hospital mortality and quantity or type of fluid administered in the first six hours after the diagnosis of severe sepsis was not identifiable. These findings should be considered as hypothesis-generating and warrant confirmation or refutation by randomized controlled trials. La reanimation liquidienne est un facteur crucial pour restaurer la stabilite hemodynamique et la perfusion tissulaire chez les patients en septicemie severe. Nous avons cherche a examiner les liens entre la quantite et le type de liquide administre durant les six premieres heures suivant le diagnostic d’une septicemie severe et la mortalite hospitaliere, la mortalite aux soins intensifs et la defaillance systemique. Une etude de cohorte retrospective et multi-centrique a ete entreprise dans cinq unites de soins intensifs de soins tertiaires au Canada. Nous avons identifie les patients atteints de septicemie severe admis aux soins intensifs entre le 1er juillet 2000 et le 30 juin 2002, en se fondant sur des bases de donnees administratives et cliniques. Les criteres d’inclusion comprenaient: l’hypotension, la presence d’une source infectieuse, et au minimum deux criteres du syndrome de reponse inflammatoire systemique. Nous avons enregistre la quantite totale et le type de liquide administre durant les six premieres heures suivant le diagnostic d’une septicemie severe. Le premier episode d’hypotension a defini le point de depart pour la recolte des donnees concernant les liquides administres. Des analyses de regression multivariees ont ete menees afin d’examiner les liens entre la quantite et le type de liquide administre et la mortalite a l’hopital/aux soins intensifs, ainsi que la defaillance systemique. Parmi les 2 026 dossiers de patients potentiellement eligibles, 496 patients ont presente les criteres d’admissibilite. L’âge moyen et le score APACHE II (Acute Physiology and Chronic Health Evaluation) etaient de 61,8 ± 16,5 ans et 29,0 ± 8,0, respective-ment. Aucun lien entre la quantite ou le type de liquide administre et la mortalite a l’hopital ou aux soins intensifs n’a ete identifie, et nous n’avons pas trouve de liens statistiquement significatifs entre la quantite ou le type de liquide administre et la defaillance systemi-que. Toutefois, davantage de reanimation liquidienne a ete associee a un risque accru de defaillance cardiovasculaire [rapport de cote (OR) et intervalle de confiance (CI) de 95 %] pour 2-4 L 1,67 (1,03-2,70) et> 4L 2,34 (1,23-4,44) ainsi qu’un risque reduit de defaillance renale [OR, CI 95 % pour 2-4 L 0,48 (0,28-0,83) et> 4L 0,45 (0,22-0,92)] durant les premieres 24 h de septice-mie severe. L’administration simultanee de colloide et cristalloide, comparativement a du cristalloide seul, a ete associee a un risque moindre de defaillance renale [OR, CI 95 % 0,45 (0,26 a 0,76)]. Aucune association entre la mortalite a l’hopital et la quantite ou le type de liquide administre durant les six premieres heures suivant le diagnostic d’une septicemie severe n’a pu etre identifiee. Ces donnees devraient etre considerees comme generatrices d’hypotheses et exigent leur confirmation ou, au contraire, leur refutation, par des etudes randomisees controlees.

Background: Mortality associated with colorectal cancer can be reduced by early detection. However, the participation of eligible people in colorectal cancer screening is thought to be inadequate. We examined the frequency of colorectal cancer screening in 4 Canadian provinces and the influence of patient contact with a family physician on the uptake of cancer screening. Methods: We performed analyses using data from the 2003 Canadian Community Health Survey. The study population included 12 776 people at average risk for colon cancer living in British Columbia, Saskatchewan, Ontario, and Newfoundland and Labrador who were aged 50 years or older and who were eligible for colorectal cancer screening. We assessed the proportion of respondents who reported having previous colorectal cancer screening tests and the degree of contact with a family physician. Results: The provincial response rates for the survey were 78.5%–87.0%. The proportion of respondents who reported any history of colorectal cancer screening was 23.5%. This value dropped to 17.6% when only up-to-date screening was considered (screening within the time frame recommended in guidelines). The proportion of people with up-to-date colorectal cancer screening varied significantly among provinces, but it was low in all provinces sampled. Contact with a family physician was associated with increased colorectal cancer screening. Compared with no physician contact, the odds of screening associated with 1–2 physician contacts in the 12 months before the survey was 1.97 (95% confidence interval [CI] 1.56–2.48], and the odds of screening associated with more than 4 contacts was 2.75 (95% CI 2.14–3.53). Interpretation: Self-reported colorectal cancer screening falls well below acceptable levels. People with increased contact with a family physician are more likely than those without contact to report a history of up-to-date colorectal cancer screening.

Background and Objective Identifying factors that can predict adults at high risk of receiving red blood cell transfusion during coronary artery bypass graft (CABG) surgery may aid in more efficient blood banking practices and may tailor blood conservation strategies for these adult patients. The objective was to identify clinical factors associated with increased red cell transfusion in adults undergoing CABG surgery. Methods A systematic review of the MEDLINE and HealthSTAR databases from 1966 to December 2005 was conducted. Citations containing the medical subject heading or textwords ‘coronary artery bypass graft’, ‘CABG’ and ‘cardiovascular surgery’ were combined with the medical subject headings or textwords ‘transfusion’ and ‘blood transfusion’. Results A total of 2461 abstracts were retrieved. Twenty-one studies met the inclusion/exclusion criteria. Transfusion rates ranged from 7 to 97%. Several variables were identified that were associated with increased red cell transfusion rates including older age, female sex, low haemoglobin concentration or haematocrit value, renal insufficiency and urgent/emergent surgery. The strongest risk factor was the urgency of surgery (urgent or emergent surgery), which was associated with a 4× to 8× increase in transfusion rates compared to elective surgery. Increasing age and female sex increased the likelihood of transfusion by 1× to 3× and 2×, respectively. Conclusions Increasing patient age, female sex, lower preoperative haemoglobin levels, as well as the urgency of the CABG surgery were associated with higher transfusion rates. Identifying risk factors for transfusion may allow for targeted use of blood conservation strategies, improved efficiency in blood utilization and informing adults at risk of transfusion.

Hemoglobin concentrations were maintained at a mean (±SD) level that was 2.1±0.2 g per deciliter lower in the restrictive-strategy group than in the liberal-strategy group (lowest average levels, 8.7±0.4 and 10.8±0.5 g per deciliter, respectively; P

Marshall SC, Gray D, Wilson KG, Yelle J-D, Hebert P, O'Rourke K, Jamshidi M: A prospective study to validate an impairment questionnaire for major trauma survivors. Am J Phys Med Rehabil 2007 ;86:114-124. Objective: To develop and validate an impairment questionnaire that will provide an estimate of whole-person impairment in patients who have suffered major trauma. Design: This was a multicenter prospective study involving a convenience sample of 43 volunteer participants who had sustained major trauma within 1 yr of study commencement. Patients were recruited from two trauma centers in Ontario, Canada. The impairment questionnaire was developed as a self-administered questionnaire based on the American Medical Association's Guides to the Evaluation of Permanent Impairment, Fourth Edition. Results: Clinician assessments of whole-person impairment showed adequate interrater (r ≥ 0.55, P ≤ 0.03) and intrarater (r ≥0.62, P ≤ 0.055) reliabilities across dimensions. The impairment questionnaire correlated significantly with clinician assessments at the initial visit (r ≥ 0.57, P 0.60, P< 0.001). Comparison of the physical and emotional subcategories of the impairment questionnaire, whole-person impairment ratings by physicians, and the Short Form 36 demonstrated good convergent and divergent validity of the impairment questionnaire. Conclusions: The impairment questionnaire is a reliable and valid self-administered tool that can be used to evaluate physical impairment after major trauma.

Background Surgeons, other healthcare professionals, and patients may identify different health-related concerns related to the quality of life of patients undergoing major surgery. Methods Semistructured interviews were conducted with surgeons (n =14), other healthcare professionals (n =19), and patients undergoing major elective surgery (n = 52). Themes were extracted by content analysis and organized into major domains. The frequencies with which specific themes were mentioned were compared among groups. Results A total of 85 themes were extracted from the interviews, 15 of which were mentioned by 50% or more of participants in each group, representing 5 of the 6 domains. The greatest differences were observed in the domains of social well-being, wherein 5 themes were mentioned less often by surgeons than other groups, and spiritual well-being, wherein 2 themes were mentioned more often by patients than other groups. Differences in the physical, emotional, cognitive preparation, and concern about quality of care domains were minimal. Conclusions Surgeons, other healthcare professionals, and patients identified many similar concerns related to the well-being of patients undergoing major surgery. However, the importance of social and spiritual themes to patients may be underestimated by surgeons.

BACKGROUND: Patient autonomy is a fundamental, yet challenging, principle of professional medical ethics. The idea that individual patients should have the freedom to make choices about their lives, including medical matters, has become increasingly prominent in current literature. However, this has not always been the case, especially in communist countries where paternalistic attitudes have been interwoven into all relationships including medical ones. Patients' expectations and the role of the doctor in the patient-physician relationship are changing. Croatia, as a transitional country, is currently undergoing this particular process. ----- METHODS: Qualitative research was conducted by means of six focus group discussions held in the years 2012 and 2013 in Croatia. Focus groups were held separately with each of the following: first year and final (6(th)) year medical students, physicians engaged in medical ethics education, physicians practicing in a clinical hospital, family medicine residents and individuals representing patients with chronic disease. This research specifically addresses issues related to patient autonomy, in particular, the principles of truth telling, confidentiality, and informed consent. All focus group discussions were audio taped and then transcribed verbatim and systematized according to acknowledged qualitative analysis methods. ----- RESULTS AND DISCUSSION: Patient autonomy is much more than a simple notion defined as the patient's right to make treatment decisions independently. It has to be understood in context of the broader socio-cultural setting. At present, both patients and medical doctors in Croatia are increasingly appreciating the importance of promoting the principle of autonomy in medical decision-making. However, the current views of medical students, physicians and patients reveal inconsistencies. ----- CONCLUSIONS: Knowing how to respect the various facets of patients' autonomy should be part of physician's professional duties, and also be reflected in his or her core clinical competencies. For this reason greater importance should be dedicated to patient autonomy issues in medical education in Croatia.

International audience; A boy with X-linked agammaglobulinemia experienced progressive global motor decline, cerebellar syndrome, and epilepsy. All standard polymerase chain reactions for neurotropic viruses were negative on cerebrospinal fluid and brain biopsy. Next-generation sequencing allowed fast identification of a new astrovirus strain (HAstV-VA1/HMO-C-PA), which led to tailor the patient's treatment, with encouraging clinical monitoring over 1 year.

Red blood cell units are stored up to 42 days post-collection. The standard policy of blood banks is to deliver the oldest units in order to limit blood wastage. Many caregivers believe that giving fresh rather than old units can improve the outcome of their transfused patients. The ABLE study aims to check if the transfusion of red blood cell units stored seven days or less (fresh arm) improve the outcome of transfused critically ill adults compared to patients who received units delivered according to the standard delivery policy (control arm). From March 2009 to May 2014, 1211 patients were allocated to the fresh arm, 1219 to the control arm (length of storage: 6.1 ± 4.9 and 22.0 ± 8.4 days respectively, P0.001). The primary outcome measure was 90-day all-cause mortality post-randomisation: there were 448 deaths (37.0%) in the fresh arm and 430 (35.3%) in the control arm (absolute risk difference: 1.7%; 95% confidence interval: -2.1% to 5.5%). In a survival analysis, the risk of death was higher in the fresh arm (hazard ratio: 1.1; 95%CI: 0.9 to 1.2), but the difference was not statistically significant (P=0.38). The same trend against the fresh arm was observed with all but one secondary outcome measures. The conclusion is that the transfusion of red blood cell units stored seven days or less does not improve the outcome of critically ill adults compared to the transfusion of units stored about three weeks (22.0 ± 8.4 days).

Background and objective How patients respond to being notified of a large-scale adverse event (LSAE), such as improper sterilisation of medical equipment that exposes them to bloodborne pathogens, is not well known. The objective of this study was to determine, using administrative data, the intended and unintended consequences of patient notification following a LSAE. Methods We examined five LSAEs where patients may have been inadvertently exposed to hepatitis C virus (HCV), HIV, and hepatitis B virus (HBV). A total of 9638 cases were identified at five Department of Veteran Affairs (VA) medical facilities between 2009 and 2012. We identified controls at the same facility prior to the exposure period and at neighbouring facilities (n=45 274). Difference-in-differences models were used with Veterans Health Administration (VHA) and Medicare data to examine infectious disease testing rates and subsequent utilisation patterns. Results Receipt of a LSAE notification was associated with a 73.2, 76.8 and 77.1 adjusted percentage point increase for HCV, HIV and HBV testing, respectively (all p

Transfusion of red blood cells in the trauma patient can be lifesaving. The question is how much and when? It is important to weigh the risks and benefits of red blood cell transfusions, as well alternatives to transfusion as these products are not benign.We explore the evidence, and provide the rationale for current and future red blood cell transfusion strategies within a framework of prehospital and hospital care of the trauma patient. We also describe how red blood cell transfusion trends are changing in trauma, discuss alternatives to red blood cell transfusion and present evidence from randomized controlled trials that support a lower transfusion trigger.Optimal transfusion practice and use of alternatives in trauma is a rapidly expanding and important area of research. Strong clinical evidence derived by future randomized controlled trials in the area of transfusion triggers as well as transfusion alternatives is required to determine their roles in clinical practice.

The debate about mechanisms underlying the evolution of host specialization by herbivorous insects remains open. Natural selection may act locally and lead to different patterns of geographic variation in life history traits of polyphagous herbivores. The hypothesis of genetically-based trade-offs in offspring performance on different hosts has been proposed but this has rarely been demonstrated. Under laboratory conditions, the biological performance of two populations of the hemlock looper Lambdina fiscellaria (Guenée), a highly polyphagous lepidopteran, was compared when reared on three different tree host species: balsam fir, eastern hemlock and sugar maple. One population originated from Anticosti Island, Québec, Canada, where the insect has evolved without having access to two of the three tree species tested, the other being from the mainland where all tree species are present. When reared on balsam fir foliage, which was naturally available to each population, larvae from Anticosti Island underwent four instars compared with five for the mainland population, indicating the existence of geographic biotypes in L. fiscellaria. When reared on the foliage of non-naturally available host trees, larvae from Anticosti Island had a higher incidence of supernumerary instars. This is a unique example where local adaptation to environmental conditions of an insect herbivore is expressed through a differential number of larval instars. Moreover, the Anticosti Island population showed a higher growth related index on the host available to both populations indicating that a fitness trade-off was the evolutionary process underlying the local adaptation of this population on balsam fir.

The transfusion transmission of hepatitis C and HIV to thousands of Canadian blood recipients was one of this country's largest public health catastrophes. In response to this crisis, and in an effort to prevent such a tragedy from occurring again, the Canadian blood system has undergone substantial reform. Variant Creutzfeldt–Jakob (vCJD) disease was the first infectious threat faced by the blood system since undergoing reform. The response at the time to this risk provides insights into the Canadian blood system's new approach to infectious threats. Our analysis of the decision-making concerning vCJD identifies two dominant themes characterizing the new blood system's approach to safety: (1) the adoption of a precautionary approach to new risks which involves taking action in advance of definitive evidence, and (2) risk aversion amongst policy makers, which has contributed to the adoption of safety measures with comparatively high cost-effectiveness ratios. Overall the principles governing the new blood system have contributed to the system both providing protection against emerging infectious risks and regaining the confidence of the public and recipients. However, the current set of policy factors will likely contribute to increasingly risk-averse policy making that will contribute to continued increases in the cost of the blood system. The challenge the blood system now faces is to find the appropriate balance between maximizing safety and ensuring the system remains affordable.

Background A high proportion of patients having cardiac bypass surgery receive erythrocyte transfusions. Decisions about when to transfuse patients having surgery for coronary artery disease may impact on erythrocyte utilization and patient morbidity and mortality. There are no published data about the factors that influence physicians' decisions to transfuse erythrocytes to these patients. The objectives of this study were to determine the hemoglobin concentration for transfusion and the factors that influence physicians' perioperative transfusion decisions for coronary artery bypass patients. Methods The authors conducted a cross-sectional study using pretested, self-administered, mailed questionnaires sent in 2004 to all cardiac surgeons and anesthesiologists in Canada who participate in coronary artery bypass surgery. The questionnaire included four intraoperative and four postoperative vignettes. Factors assessed included patient age, sex, cardiac index, and myocardial ischemia. Results The response rates were 70% (345 of 489) for the intraoperative and 61% (297 of 489) for the postoperative case scenarios. The mean hemoglobin concentrations for transfusion were 7.0 g/dl for the intraoperative case scenarios and 7.2 g/dl for the postoperative case scenarios. Older age, the presence of myocardial ischemia, and a low cardiac index were factors that increased the hemoglobin concentration for transfusion (P < 0.0001). Physicians ranked myocardial ischemia as the most significant factor affecting their transfusion decisions. Conclusions Factors such as the presence of a low cardiac index, myocardial ischemia, and older age increase the hemoglobin concentrations at which physicians transfuse coronary bypass surgery patients. Future studies are required to elucidate whether transfusions based on these variables affect patient morbidity and mortality.

The established technique of electron energy-loss spectrometry (EELS) in the electron microscope has surpassed the task of chemical microanalysis. Some aspects of EELS, such as low energy losses for optical studies, have a long tradition and we see them re-emerge after a long period of oblivion. Other aspects such as coherence of inelastically scattered electrons are now much better understood and can be used to advantage. Many applications of EELS can and will profit from the enormous progress in instrumentation and computing capacity. In this paper we discuss some unconventional examples of EELS beyond chemical microanalysis.

To assess red blood cell transfusion practices among Canadian anesthesiologists.A survey depicting three realistic clinical scenarios of elective surgical procedures with different risks of bleeding was administered to all Canadian practicing members (n = 2,100) of the Canadian Anesthesiologists' Society. Respondents were requested to choose hemoglobin thresholds for which they would transfuse red blood cells under various conditions within each scenario.We obtained a response rate of 47% (719/1,512). Transfusion thresholds differed significantly between baseline scenarios. A threshold above 70 g x L(-1) was chosen by 48% of respondents in the general surgery scenario compared to 56% in the orthopedic surgery scenario and 79% in the vascular surgery scenario (P0.001). A history of coronary artery disease was associated with a transfusion thresholdor= 100 g x L(-1) in a significant proportion of respondents ranging from 20% in the orthopedic surgery scenario to 31% in the general surgery scenario and to 49% in the vascular surgery scenario (P0.001). Conversely, changing the patient's age from 60 to 20 yr resulted in the adoption of a transfusion thresholdor= 60 g x L(-1) by30% of respondents in two scenarios (P0.001). The year of respondent graduation was strongly associated with these findings.There was significant variation in transfusion practices among Canadian anesthesiologists. The type of surgical procedure, patient's age and a history of coronary artery disease influenced reported transfusion threshold. Practice variation in specific subgroups would support the need for further research to identify optimal transfusion thresholds.

Background: The utility of a pretrial clinical evaluation or run-in phase prior to conducting trials of complex interventions such as hypothermia therapy following severe traumatic brain injury in children and adolescents has not been established. Methods: The primary objective of this study was to prospectively evaluate the ability of investigators to adhere to the clinical protocols of care including the cooling and rewarming procedures as well as management guidelines in patients with severe traumatic brain injury (Glasgow Coma Scale ≤8) treated with 24 h of hypothermia therapy. A secondary objective was to evaluate the ability of study research assistants to complete the study case report form using a procedures manual. The study was conducted at 18 sites in Canada, the United Kingdom and France prior to proceeding to a randomized controlled trial (RCT). After 2 patients were enrolled at each center, an independent clinical evaluation committee examined the process of care and the completeness of data collection. Centers were permitted to enroll patients in the RCT once they met pre-established adherence criteria. Results: Seventeen of the 18 centers completed the pretrial clinical evaluation phase demonstrating compliance with study procedures and proceeded to an RCT of hypothermia therapy. One center enrolled only 1 patient in the pretrial clinical evaluation phase due to small numbers of patients with traumatic brain injury, and therefore, did not proceed to the RCT. Three centers were required to enroll more than 2 patients in the pretrial clinical evaluation phase prior to proceeding to the RCT because of problems with adherence to the clinical protocols at two centers and the training of new study personnel at another center. Of the 39 patients enrolled during the pretrial clinical evaluation phase, 8 (20.5%) died and 22 (62.9%) had a good outcome defined as normal, mild or moderate disability assessed using the Pediatric Cerebral Performance Category score at 6 months following injury. Discussion: The pretrial clinical evaluation phase was useful to ensure compliance with complex hypothermia therapy and consensus-based clinical management guidelines of care successfully implemented across 17 of 18 centers. This study maneuver allowed us to complete a subsequent RCT in 225 children following severe traumatic brain injury.

Background: Glycemic control is increasingly being recognized as a priority in the treatment of critically ill patients. Titration and monitoring of insulin infusions involve frequent blood glucose measurement to achieve target glucose ranges and prevent adverse events related to hypoglycemia. Therefore, it is imperative that bedside glucose testing methods be safe and accurate. Objective: To determine the accuracy and clinical impact of three common methods of bedside point-of-care testing for glucose measurements in critically ill patients receiving insulin infusions. Design: Prospective observational study. Setting: A 21-bed mixed medical/surgical intensive care unit of a tertiary care teaching hospital. Patients: Thirty consecutive critically ill patients who were vasopressor-dependent (n = 10), had significant peripheral edema (n = 10), or were admitted following major surgery (n = 10). Measurements: Findings from three different methods of glucose measurement were compared with central laboratory measurements: (1) glucose meter analysis of capillary blood (finger-stick); (2) glucose meter analysis of arterial blood; and (3) blood gas/chemistry analysis of arterial blood. Patients were enrolled for a maximum of 3 days and had a maximum of nine sets of measurements determined during this time. Results: Clinical agreement with the central laboratory was significantly better with arterial blood analysis (69.9% and 76.5% for glucose meter and blood gas/chemistry analysis, respectively) than with capillary blood analysis (56.8%; p = .039 and .001, respectively). During hypoglycemia, clinical agreement was only 26.3% with capillary blood analysis and 55.6% and 64.9% for glucose meter and blood gas/chemistry analysis of arterial blood (p = .010 and

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-Barre 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.

To document variation of transfusion practice following repair of hip fracture or cardiac surgery, as well as those requiring intensive care following a surgical intervention or multiple trauma (high risk patients).We documented rates of allogeneic red cell transfusion in 41,568 patients admitted to 11 hospitals across Canada between August 1998 and August 2000 as part of a retrospective observational cohort study. In the subgroup of 7,552 patients receiving red cells, we also compared mean nadir hemoglobin concentrations from centre to centre.The overall rate of red cell transfusion was 38.7%, and ranged from 23.8% to 51.9% across centres among the 41,568 perioperative and critically ill patients. Women were more likely to be transfused (43.7% vs 35.3%, P0.0001), with higher rates of transfusion in eight of 11 centres. Compared to a chosen reference hospital having a crude transfusion rate near the median, the adjusted odds of transfusion ranged from 0.44 to 1.53 overall, from 0.42 to 1.22 in patients undergoing a hip fracture repair, from 0.72 to 3.17 in cardiac surgical patients undergoing cardiac surgery, and from 0.27 to 1.11 in critically ill and trauma patients. In the 7,552 transfused patients, the mean adjusted nadir hemoglobin was 74.0 +/- 4.83 g x L(-1) overall, and ranged from 66.9 +/- 1.7 g x L(-1) to 84.5 +/- 1.6 g x L(-1) across centres. Similar differences among centres were observed amongst hip fracture patients (71.2 +/- 2.9 g x L(-1) to 82.8 +/- 1.7 g x L(-1)), cardiac surgical patients (65.7 +/- 1.1 g x L(-1) to 77.3 +/- 1.0 g x L(-1)) and critically ill and trauma patients (66.1 +/- 3.04 g x L(-1) to 87.5 +/- 2.5 g x L(-1)).We noted significant differences in the rates of red cell transfusion and nadir hemoglobin concentrations in various surgical and critical care settings.

Objectives. We compared the health statuses of the indigenous populations of New Zealand and the United States with those of the numerically dominant populations of these countries. Methods. Health indicators compared included health outcome measures, preventive care measures, modifiable risk factor prevalence, and treatment measures. Results. In the case of nearly every health status indicator assessed, disparities (both absolute and relative) were more pronounced for Maoris than for American Indians/Alaska Natives. Both indigenous populations suffered from disparities across a range of health indicators. However, no disparities were observed for American Indians/Alaska Natives in regard to immunization coverage. Conclusions. Ethnic health disparities appear to be more pronounced in New Zealand than in the United States. These disparities are not necessarily intractable. Although differences in national health sector responses exist, New Zealand may be well placed in the future to evaluate the effectiveness of new strategies to reduce these disparities given the extent and quality of Maori-specific health information available.

The "lone" clinical bioethicist working in a large, multisite hospital faces considerable challenges. While attempting to build ethics capacity and sustain a demanding range of responsibilities, he or she must also achieve an acceptable level of integration, sustainability, and accountability within a complex organisational structure. In an effort to address such inherent demands and to create a platform towards better evaluation and effectiveness, the Clinical Ethics Group at the Joint Centre for Bioethics at the University of Toronto is implementing the Hub and Spokes Strategy at seven hospitals. The goal of the Hub and Spokes Strategy is to foster an ethical climate and strengthen ethics capacity broadly throughout healthcare settings as well as create models in clinical bioethics that are excellent and effective.

SUMMARY Decisions concerning the use of allogeneic red blood cell (RBC) transfusion in the treatment of anemia and hemorrhage require a clear understanding of the risks and benefits of both the condition and its treatment. Although we have developed a much clearer appreciation for the infectious and immunomodulatory risks of RBC transfusion over the past two decades, the risks of anemia in many clinical settings and the benefits of RBC transfusion are still inadequately characterized. Only one large randomized controlled trial has examined red cell administration in the perioperative and in the critical care setting, and high-quality clinical evidence is not yet available for many decisions related to red cell transfusions. Several studies and initiatives to evaluate alternatives to RBC transfusions and to improve current understanding of transfusion practices are underway. It is anticipated that risks and benefits of red cells and alternatives will be elucidated in the coming years.

Medication errors are common and harm hospitalized patients. The authors designed and implemented an automated system to complement an existing computerized order entry system by detecting the administration of excessive doses of medication to adult in-patients with renal insufficiency. Its impact, in combination with feedback to prescribers, was evaluated in 3 participating nursing units and compared with the remainder of a tertiary care academic medical center. The baseline rate of excessive dosing was 23.2% of administered medications requiring adjustment for renal insufficiency given to patients with renal impairment on the participating units and 23.6% in the rest of the hospital. The rate fell to 17.3% with nurse feedback and 16.8% with pharmacist feedback in the participating units (P.05 for each, relative to baseline). The rates of excessive dosing for the same time periods were 26.1% and 24.8% in the rest of the hospital. Automated detection and routine feedback can reduce the rate of excessive administration of medication in hospitalized adults with renal insufficiency.

Hypertrophic pyloric stenosis is a common affection in infants aged 3-8 weeks and typically does not affect older children. We report a case of pyloric stenosis that occurred recurrently at the ages of 3 and 7 years in a boy with X-linked chronic granulomatous disease. We emphasize the inflammatory origin of such stenosis, whose progression was favorable thanks exclusively to drug treatment with corticosteroids. We note that chronic granulomatous disease can affect the entire digestive tract, similar to inflammatory bowel disease in children.

Despite the frequency of use of do-not-resuscitate orders, there is still uncertainty regarding their optimal use. We discuss a controversial issue concerning end-of-life care arising from two cases from the Office of the Chief Coroner for Ontario: What are the limits of medical therapy for patients

Background There is a dearth of information about the cost of allogenic red blood cells (RBCs) and RBC transfusion in Canada in the aftermath of the Canadian blood system reorganization and the introduction of various safety measures. The unit cost of allogenic RBCs and RBC transfusion in Canada in 1994 was estimated at 152.17 US dollars. The objective of this study was to determine the unit cost of allogenic RBC transfusion in Canada from a societal perspective. Study design and methods A cost-structure analysis using the cost information from 2001 through 2002 was used. Costs of blood collection, production, distribution, delivery (hospital transfusion service processing and patient administration), transfusion reaction management, and opportunity cost of donor's time were included in the analysis. Canadian Blood Services and Hema-Quebec supplied the data for collection, production, and distribution stages. Delivery and transfusion reaction costs were collected from eight hospitals across six Canadian provinces. In-patient costs were assessed for the intensive care unit, emergency, general medicine ward, and operating room. Results The aggregate mean societal unit cost of RBCs transfused on an inpatient basis in 2002 was 264.81 US dollars (95% confidence interval [CI], 256.29 dollars-275.65 dollars). The mean cost of blood collection, production, and distribution was 202.74 US dollars (95% CI, 199.63 dollars-204.31 dollars), the mean opportunity cost of donor time was 18.21 US dollars (95% CI, 17.11 dollars-21.63 dollars), the mean cost of hospital transfusion service processing was 16.65 US dollars (95% CI, 13.50 dollars-19.79 dollars), of RBC transfusion was 26.92 US dollars (95% CI, 25.33 dollars-28.52 dollars), and of transfusion reaction management was 0.29 US dollars(95% CI, 0.22 dollars-0.36 dollars). There were substantial variations in hospital transfusion service processing and RBC transfusion costs across hospitals. Conclusion The societal unit cost of RBC transfusion has doubled since 1994 to 1995. Further increases in unit costs would be expected as additional safety measures are introduced. This will have important financial implications for treating patient populations that require a high level of RBC transfusions.

Background: Research into adverse events (AEs) has highlighted the need to improve patient safety. AEs are unintended injuries or complications resulting in death, disability or prolonged hospital stay that arise from health care management. We estimated the incidence of AEs among patients in Canadian acute care hospitals. Methods: We randomly selected 1 teaching, 1 large community and 2 small community hospitals in each of 5 provinces (British Columbia, Alberta, Ontario, Quebec and Nova Scotia) and reviewed a random sample of charts for nonpsychiatric, nonobstetric adult patients in each hospital for the fiscal year 2000. Trained reviewers screened all eligible charts, and physicians reviewed the positively screened charts to identify AEs and determine their preventability. Results: At least 1 screening criterion was identified in 1527 (40.8%) of 3745 charts. The physician reviewers identified AEs in 255 of the charts. After adjustment for the sampling strategy, the AE rate was 7.5 per 100 hospital admissions (95% confidence interval [CI] 5.7– 9.3). Among the patients with AEs, events judged to be preventable occurred in 36.9% (95% CI 32.0%–41.8%) and death in 20.8% (95% CI 7.8%–33.8%). Physician reviewers estimated that 1521 additional hospital days were associated with AEs. Although men and women experienced equal rates of AEs, patients who had AEs were significantly older than those who did not (mean age [and standard deviation] 64.9 [16.7] v. 62.0 [18.4] years; p = 0.016). Interpretation: The overall incidence rate of AEs of 7.5% in our study suggests that, of the almost 2.5 million annual hospital admissions in Canada similar to the type studied, about 185 000 are associated with an AE and close to 70 000 of these are potentially preventable.