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Introduction: Social prescribing offers a formal pathway of connecting patients in the health system with sources of support within the community to help improve their health and well‐being. Since its launch in March 2022, the Canadian Institute for Social Prescribing has acted as a collective impact network to identify, connect and build upon established social prescribing initiatives using a co‐design methodology. The institute received input from a participant advisory council, co‐design partners and several communities of interest groups. This study aimed to describe the perceptions of the Canadian Institute for Social Prescribing's role in advancing social prescribing using a co‐design approach and the barriers and facilitators to implementing social prescribing in Canada. Methods: We used a qualitative descriptive study design, document analysis, participant observation and semi‐structured individual interviews (n = 7) with members of the Canadian Institute for Social Prescribing co‐design group and the institute's leadership. We also analysed documents, field notes and transcripts using codebook thematic analysis. Results: Four themes were developed representing the facilitators of implementing the Canadian Institute for Social Prescribing to support social prescribing: Creating relational mechanisms (i.e., partnerships and connections), Bringing awareness to social prescribing and contributing to the evidence (i.e., values and beliefs), Addressing systemic conditions (i.e., having a common language for social prescribing and organizing the community health sector) and Enabling funding and policy to drive social prescribing initiatives (i.e., shifting evidence into policy and securing sustainable funding). Conclusion: Participants' reflections on the co‐design process demonstrated that the Canadian Institute for Social Prescribing development provided networking opportunities and shared resources relevant to social prescribing. Co‐design efforts also fostered relational and informational support, which laid the necessary groundwork in Canada to overcome the complex interplay between the macro‐ and micro‐level settings in which social prescribing is practiced. Patient or Public Contribution: The interviews and observations involved participants with lived experience of delivering, receiving or advocating for social prescribing. [ABSTRACT FROM AUTHOR]

This is the protocol for an evidence and gap map. The objectives are as follows: This EGM aims to map available evidence on the effects of in‐person interventions to reduce social isolation and/or loneliness across all age groups in all settings. [ABSTRACT FROM AUTHOR]

Background: Frailty, social isolation, loneliness, and poverty may render older adults vulnerable to social or health stressors. It is imperative to identify effective interventions to address them especially in the context of COVID‐19 pandemic. Objective: To identify effective community‐based interventions to address frailty, social isolation, loneliness, and poverty among community‐dwelling older adults. Design: Umbrella review. Data Source: We systematically searched PubMed, Ovid MEDLINE, Embase, Cochrane CENTRAL, EBM‐Reviews, CINAHL via EBSCO, and APA PsycInfo via Ovid from January 2009 to December 2022. Eligibility Criteria: We included systematic reviews or quantitative reviews of non‐pharmacologic interventions targeting community‐dwelling older adults. Data Selection, Extraction, and Management: Two review authors independently screened the titles and abstracts, performed data extraction and appraised the methodological quality of the reviews. We used a narrative synthesis approach to summarize and interpret the findings. We assessed the methodological quality of the studies using AMSTAR 2.0 tool. Results: We identified 27 reviews incorporating 372 unique primary studies that met our inclusion criteria. Ten of the reviews included studies conducted in low‐middle‐income countries. Twelve reviews (46%, 12/26) included interventions that addressed frailty. Seventeen reviews (65%, 17/26) included interventions that addressed either social isolation or loneliness. Eighteen reviews included studies with single component interventions, while 23 reviews included studies with multi‐component interventions. Interventions including protein supplementation combined with physical activity may improve outcomes including frailty status, grip strength, and body weight. Physical activity alone or in combination with diet may prevent frailty. Additionally, physical activity may improve social functioning and interventions using digital technologies may decrease social isolation and loneliness. We did not find any review of interventions addressing poverty among older adults. We also noted that few reviews addressed multiple vulnerabilities within the same study, specifically addressed vulnerability among ethnic and sexual minority groups, or examined interventions that engaged communities and adapted programs to local needs. Conclusion: Evidence from reviews support diets, physical activity, and digital technologies to improve frailty, social isolation or loneliness. However, interventions examined were primarily conducted under optimal conditions. There is a need for further interventions in community settings and conducted under real world settings in older adults living with multiple vulnerabilities. [ABSTRACT FROM AUTHOR]

Background: Residents of long-term care homes (LTCH) often experience unnecessary and non-beneficial hospitalizations and interventions near the end-of-life. Advance care directives aim to ensure that end-of-life care respects resident needs and wishes.Methods: In this retrospective cohort study, we used multistate models to examine the health trajectories associated with Do-Not-Resuscitate (DNR) and Do-Not-Hospitalize (DNH) directives of residents admitted to LTCH in Ontario, Alberta, and British Columbia, Canada. We adjusted for baseline frailty-related health instability. We considered three possible end states: change in health, hospitalization, or death. For measurements, we used standardized RAI-MDS 2.0 LTCH assessments linked to hospital records from 2010 to 2015.Results: We report on 123,003 LTCH residents. The prevalence of DNR and DNH directives was 71 and 26% respectively. Both directives were associated with increased odds of transitioning to a state of greater health instability and death, and decreased odds of hospitalization. The odds of hospitalization in the presence of a DNH directive were lowered, but not eliminated, with odds of 0.67 (95% confidence interval 0.65-0.69), 0.63 (0.61-0.65), and 0.47 (0.43-0.52) for residents with low, moderate and high health instability, respectively.Conclusion: Even though both DNR and DNH orders are associated with serious health outcomes, DNH directives were not frequently used and often overturned. We suggest that policies recommending DNH directives be re-evaluated, with greater emphasis on advance care planning that better reflects resident values and wishes. [ABSTRACT FROM AUTHOR]

Background: An increased risk of complications, including death, has been associated with stored red blood cell (RBC) units in observational studies but not in randomized trials. We aimed to evaluate for volume-dependent effects attributable to length of RBC storage in a secondary analysis of the Age of Blood Evaluation (ABLE) trial.Study Design and Methods: In the 2510 critically ill adults from the ABLE trial randomized to receive RBC units stored not more than 7 days or the oldest compatible RBC units, we estimated the hazard ratio (HR) for death by intensive care unit (ICU) and hospital discharge and by days 28, 90, and 180, within subgroups defined by the number of RBC units received. Extended Cox proportional hazards regression was used to model the HR.Results: A volume-dependent effect of storage age on survival was present for death by 90 and 180 days, but not earlier endpoints. The HR for death by 90 days was 0.55 (95% confidence interval [CI], 0.11-0.98, fresh vs standard) after transfusion of 6 RBC units but 1.45 (95% CI, 1.06-1.98) after transfusion of 1 RBC unit.Conclusion: In this exploratory analysis, volume-dependent effects related to RBC storage were documented in the ABLE trial. The harms associated with small volumes of fresh RBC units and large volumes of older RBC units should be further explored. [ABSTRACT FROM AUTHOR]

Importance: The clinical consequences of red blood cell storage age for critically ill pediatric patients have not been examined in a large, randomized clinical trial.Objective: 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.Design, Setting, and Participants: 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.Interventions: 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.Main Outcomes and Measures: The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured for 28 days or to discharge or death.Results: 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).Conclusions and Relevance: 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.Trial Registration: ClinicalTrials.gov Identifier: NCT01977547. [ABSTRACT FROM AUTHOR]

Introduction Home care clients are increasingly medically complex, have limited access to effective chronic disease management and have very high emergency department (ED) visitation rates. There is a need for more appropriate and targeted supportive chronic disease management for home care clients. We aim to evaluate the effectiveness and preliminary cost effectiveness of a targeted, person-centred cardiorespiratory management model. Methods and analysis The Detection of Indicators and Vulnerabilities of Emergency Room Trips (DIVERT) — Collaboration Action Research and Evaluation (CARE) trial is a pragmatic, cluster-randomised, multicentre superiority trial of a flexible multicomponent cardiorespiratory management model based on the best practice guidelines. The trial will be conducted in partnership with three regional, public-sector, home care providers across Canada. The primary outcome of the trial is the difference in time to first unplanned ED visit (hazard rate) within 6 months. Additional secondary outcomes are to identify changes in patient activation, changes in cardiorespiratory symptom frequencies and cost effectiveness over 6 months. We will also investigate the difference in the number of unplanned ED visits, number of inpatient hospitalisations and changes in health-related quality of life. Multilevel proportional hazard and generalised linear models will be used to test the primary and secondary hypotheses. Sample size simulations indicate that enrolling 1100 home care clients across 36 clusters (home care caseloads) will yield a power of 81% given an HR of 0.75. Ethics and dissemination Ethics approval was obtained from the Hamilton Integrated Research Ethics Board as well as each participating site’s ethics board. Results will be submitted for publication in peer-reviewed journals and for presentation at relevant conferences. Home care service partners will also be informed of the study’s results. The results will be used to inform future support strategies for older adults receiving home care services. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Many aging adults undergo progressive loss of autonomy, develop increasingly complex medical needs and experience multiple care transitions. We sought to determine the degree of variation in rates of transfer from home care services and long-term care in several Canadian jurisdictions. Methods: In this retrospective cohort study, we examined transitions from home care services and long-term care to different possible end states: change in health stability (getting better or worse), transfer to hospital, transfer to another care setting or death. We used standardized interRAI assessments from long-term care and home care linked to hospital records (data from the Discharge Abstract Database and National Ambulatory Care Reporting System) from 2010 to 2016. Multistate modelling was used to adjust for patients with complex health status and transitions in care. Results: We report data for 254 664 patients in home care programs and 162 045 residents in long-term care. Compared with patients in Ontario, patients requiring home care services in Alberta and British Columbia had increased odds of being admitted to hospital regardless of the underlying severity of illness (the adjusted odds ratios [OR] ranged from 2.08 to 3.77 in Alberta and from 1.28 to 1.46 in BC). Residents in long-term care in Alberta and BC had less than half the odds of being transferred to hospital, independent of all other factors, when compared with long-term care residents in Ontario (the adjusted OR ranged from 0.38 to 0.39 in Alberta and from 0.33 to 0.44 in BC). Interpretation: Significant variations in transfer rates were observed between provinces, even after controlling for individual patient characteristics. These results suggest that transfers to hospital are largely driven by health care policies, health care professional practice patterns and available infrastructure rather than individual patient needs. [ABSTRACT FROM AUTHOR]

Background: Blood transfusion is common in the resuscitation of patients with traumatic injury. However, the clinical impact of the length of storage of transfused blood is unclear in this population.Study Design and Methods: We undertook a prespecified nested analysis of 372 trauma victims of the 2510 critically ill patients from 64 centers treated as part of the Age of Blood Evaluation (ABLE) randomized controlled trial. Patients were randomized according to their trauma status to receive either a transfusion of fresh blood stored not more than 7 days or standard-issue blood. Our primary outcome was 90-day all-cause mortality.Results: Overall, 186 trauma patients received fresh blood and 186 received standard-issue blood. Adherence to transfusion protocol was 94% (915/971) for all fresh blood transfused and 100% (753/753) for all standard-issue blood transfused. Mean ± SD blood storage duration was 5.6 ± 3.8 days in the fresh group and 22.7 ± 8.4 days in the standard-issue group (p < 0.001). Ninety-day mortality in the fresh group was 21% (38/185), compared to 16% (29/184) in the standard-issue group, with an unadjusted absolute risk difference of 5% (95% confidence interval [CI], -3.1 to 12.6) and an adjusted absolute risk difference of 2% (95% CI, -3.5 to 6.8).Conclusion: In critically ill trauma patients, transfusion of fresh blood did not decrease 90-day mortality or secondary outcomes, a finding similar to the overall population of the ABLE trial. [ABSTRACT FROM AUTHOR]

Background: Social isolation and loneliness affect one in four older adults in many regions around the world. Social isolation and loneliness are shown to be associated with declines in physical and mental health. Intersecting social determinants of health influence both the risk of being socially isolated and lonely as well as the access and uptake of interventions. Our objective is to evaluate what evidence is available within systematic reviews on how to mitigate inequities in access to and effectiveness of interventions.Methods: We performed an overview of reviews following methods of the Cochrane Handbook for Overviews of Reviews. We selected systematic reviews of effectiveness of interventions aimed at mitigating social isolation and loneliness in older adults (aged 60 or above) published in the last 10 years. In addition, we assessed all primary studies from the most recent systematic review with a broad intervention focus. We searched MEDLINE, EMBASE, PsycINFO, CINAHL, and Scopus in collaboration with a librarian scientist. We used a structured framework called PROGRESS-Plus to assess the reporting and consideration of equity. PROGRESS-Plus stands for place of residence, race/ethnicity/culture/language, occupation, gender or sex, religion, education, socioeconomic status (SES), social capital, while "plus" stands for additional factors associated with discrimination and exclusion such as age, disability, and sexual orientation. We assessed whether PROGRESS-Plus factors were reported in description of the population, examination of differential effects, or discussion of applicability or limitations.Results: We identified and assessed 17 eligible systematic reviews. We assessed all 23 primary studies from the most recent systematic review with a broad intervention focus. All systematic reviews and primary studies described the population by one or more PROGRESS-Plus factor, most commonly across place of residence and age, respectively. None of the reviews and five primary studies examined differential effects across one or more PROGRESS-Plus dimension. Nine reviews and four primary studies discussed applicability or limitations of their findings by at least one PROGRESS-Plus factor.Conclusions: Although we know that social isolation and loneliness are worse for the poorest and most socially disadvantaged older adults, the existing evidence base lacks details on how to tailor interventions for these socially disadvantaged older people. [ABSTRACT FROM AUTHOR]

While it is known that the use of health care resources increases at the end of life in patients admitted to the Intensive Care Unit (ICU), the allocation of blood products at the end of life has not been described. The objective of this study was to describe overall transfusion patterns in the ICU, and specifically in patients who die in hospital. We conducted a retrospective cohort study of adult patients admitted to the ICU of a university-affiliated hospital, who were discharged or died between November 1, 2006 and June 30, 2012. During the study period, 10,642 patients were admitted at least once to the ICU. Of these patients, 4079 (38.3%) received red blood cells (RBCs), plasma or platelets in the ICU. The ICU mortality rate was 28.1% and in-hospital mortality rate was 32.3%. Among 39,591 blood product units transfused over the course of the study in the ICU (18,144 RBC units, 16,920 plasma units and 4527 platelet units), 46.2% were administered to patients who later died within the same hospitalization (41.2% of RBCs, 50.4% of plasma and 50.8% of platelets). Of all blood product units (RBCs, plasma and platelets) administered in the ICU over the study period, 11% were given within the last 24 hours before death. A large proportion of blood products used in the ICU are administered to patients who ultimately succumb to their illness in hospital, and many of these blood units are given in close proximity to death. [ABSTRACT FROM AUTHOR]

The article reports on the risks of the antifibrinolytic agent aprotinin. Topics discussed include the reasons behind the withdrawal of the drug from the market in October 2007, criticisms leveled against the Blood Conservation Using Antifibrinolytics in a Randomized Trial (BART) which prompted the drug's withdrawal from the market and the arguments presented by BART authors to defend their claims on the risks of using aprotinin. Also discussed is Canada's decision to reintroduce aprotinin.

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. [ABSTRACT FROM AUTHOR]

Rationale: Adrenal insufficiency is a clinical condition associated with fluid- and catecholamine-resistant hypotension.Objectives: 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.Methods: 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.Measurements and Main Results: 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, P < 0.001) and were significantly older (11.5 yr vs. 2.3 yr, P < 0.001) than those without adrenal insufficiency. Adrenal insufficiency was associated with an increased need for catecholamines (P < 0.001) and more fluid boluses (P = 0.026). The sensitivity and specificity of the low-dose adrenocorticotropic hormone stimulation test were 100% and 84%, respectively.Conclusions: 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. [ABSTRACT FROM AUTHOR]

Several letters to the editor are presented in response to the article "The need for an Institute of Continuing Health Education," by Paul Hébert in the 2008 issue.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article examines some of the controversies surrounding the use of red blood cell (RBC) transfusion in the critically ill patient. Two cross sectional studies conducted in Europe and the U.S. observed that RBC transfusions were administered in approximately 40 percent of all patients studied. However, there were no convincing data to support the routine use of RBC transfusion to treat anemia in critically ill patients without evidence of acute bleeding.

Background: Intravenous immunoglobulin therapy has been proposed as an adjuvant treatment for sepsis. Yet, its benefit remains unclear, and its use is not currently recommended. Purpose: To evaluate the effect of polyclonal intravenous immunoglobulin therapy on death in critically ill adult patients with sepsis. Data Sources: MEDLINE (1966 to May 2006) and the Cochrane Central Register of Controlled Trials (May 2006 edition). Study Selection: All randomized, controlled trials of critically ill adult patients with sepsis, severe sepsis, or septic shock who received polyclonal intravenous immunoglobulin therapy or placebo or no intervention were selected. No restrictions were made for study language or type of publication. Data extraction: Data were independently extracted by 2 investigators using a standardized form. Data Synthesis: The literature search identified 4096 articles, of which 33 were deemed to be potentially eligible. Twenty trials (n = 2621) met eligibility criteria and were included in the analysis. Polyclonal intravenous immunoglobulin therapy was associated with an overall survival benefit (risk ratio, 0.74 [95% CI, 0.62 to 0.89]) compared with placebo or no intervention. In sensitivity analyses, documented survival improved when the analysis was limited to published, peer-reviewed trials (risk ratio, 0.72 [CI, 0.58 to 0.89]) (17 trials [n = 1865]) and blinded trials (risk ratio, 0.61 [CI, 0.40 to 0.93) (7 trials [n = 896]). Severe sepsis or septic shock (risk ratio, 0.64 [CI, 0.52 to 0.79]) (11 trials [n = 689]), receiving a total dose regimen of 1 gram or more per kilogram of body weight (risk ratio, 0.61 [CI, 0.40 to 0.94]) (7 trials [n = 560]), and receiving therapy for longer than 2 days (risk ratio, 0.66 [CI, 0.53 to 0.82]) (17 trials [n = 1847]) were strongly associated with this survival benefit. Limitations: Most trials were published before new developments modifying the care and outcome of critically ill patients with sepsis including early goal-directed therapy and activated protein C treatment, were introduced. Conclusions: A survival benefit was observed for patients with sepsis who received polyclonal intravenous immunoglobulin therapy compared with those who received placebo or no intervention. A large, randomized, controlled trial of polyclonal intravenous immunoglobulin therapy should be performed on the basis of the methodological limitations of the current literature, the potential benefit from this therapy in more severely ill patients, and the potential effect of dosage and duration of this therapy. [ABSTRACT FROM AUTHOR]

Red cell (RBC) transfusions are a potentially life-saving therapy employed during the care of many critically ill patients to replace losses in hemoglobin to maintain oxygen delivery to vital organs. During storage, RBCs undergo a series of biochemical and biomechanical changes that reduce their survival and function. Additionally, accumulation of other biologic by-products of RBC preservation may be detrimental to recipients of blood transfusions. Laboratory studies and an increasing number of observational studies have raised the possibility that prolonged RBC storage adversely affects clinical outcomes. In this article, the laboratory and animal experiments evaluating changes to RBCs during prolonged storage are reviewed. Subsequently, the clinical studies that have evaluated the clinical consequences of prolonged RBC storage are reviewed. These data suggest a possible detrimental clinical effect associated with the transfusion of stored RBCs; randomized clinical trials further evaluating the clinical consequences of transfusing older stored RBCs are required. [ABSTRACT FROM AUTHOR]

Objective: To compare a restrictive versus a liberal transfusion strategy in patients with moderate to severe closed head injury following multiple trauma in 13 Canadian intensive care units (ICUs).Methods: This is a subgroup analysis of a multicenter randomized controlled clinical trial involving sixty-seven critically ill patients from the Transfusion Requirements in the Critical Care trial who sustained a closed head injury. Patients had a hemoglobin concentration less than 9.0 g/dL within 72 hours of admission to the ICU. Patients were randomized to a restrictive allogeneic red blood cell transfusion strategy (hemoglobin 7.0 g/dL and maintained between 7.0 and 9.0 g/dL) or a liberal strategy (hemoglobin 10.0 g/dL and maintained between 10.0 and 12.0 g/dL).Results: Baseline characteristics in the restrictive ( n = 29) and the liberal ( n = 38) transfusion groups were comparable. Average hemoglobin concentrations and red blood cell units transfused per patient were significantly lower in the restrictive compared to the liberal group. The 30-day all-cause mortality rates in the restrictive group were 17% as compared to 13% in the liberal group (risk difference 4.1 with 95% confidence interval [CI], 13.4 to 21.5, p = 0.64). Presence of multiple organ dysfunction (12.1 +/- 6.4 versus 10.6 +/- 6.3, p = 0.35) and changes in multiple organ dysfunction from baseline scores adjusted for death (4.5 +/- 6.2 versus 3.4 +/- 6.2, p = 0.49) were similar between the restrictive and liberal transfusion groups, respectively. Median length of stay in ICU (10 days, interquartile range 5 to 21 days versus 8 days, interquartile range 5 to 11 days, p = 0.26) and hospital (27 days, interquartile range 14 to 39 days versus 30.5 days, interquartile range 17 to 47 days, p = 0.72) were similar between the restrictive and liberal transfusion groups.Conclusions: We were unable to detect significant improvements in mortality with a liberal as compared to restrictive transfusion strategy in critically ill trauma victims with moderate to severe head injury. [ABSTRACT FROM AUTHOR]

This study examined themes relevant to health-related quality of life as identified by patients undergoing major surgery and by health care providers. Semi-structured interviews were conducted with 52 patients undergoing major abdominal, cardiac, orthopedic, thoracic, or vascular surgical procedures and 33 health professionals from various disciplines. A total of 58 themes were identified by content analysis. These themes were categorized into 6 domains. These were: physical well-being (14 themes), emotional well-being (13 themes), concern about quality of care (12 themes), social well-being (12 themes), cognitive preparation (4 themes), and spiritual well-being (3 themes). In general, we found that most aspects of health-related quality of life were common across various major surgical procedures and between patients and health care providers. However, when we examined the coverage of these themes in seven commonly-used health-related quality of life instruments, we found that many of the most frequently mentioned themes were not assessed with the available measures. A new evaluative instrument tailored to patients undergoing major surgery may therefore be warranted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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Context: The benefits of therapeutic hypothermia as a treatment for traumatic brain injury (TBI) remain unclear. Objective: To explore the effects of depth, duration, and rate of rewarming after discontinuation of hypothermia on mortality and neurologic outcome in adults after TBI. Data Sources: An electronic search of MEDLINE (OVID), EMBASE, Current Contents, the Cochrane library and a hand search of key journals were performed. Corresponding authors of identified studies were contacted for additional unpublished or ongoing clinical trials. Study Selection: All randomized controlled trials of therapeutic hypothermia for at least 24 hours vs normothermia in adults with TBI. Data Extraction: Demographic and clinical data, hypothermia interventions and cointerventions, mortality and neurologic outcomes, and methodological quality were abstracted by 2 independent reviewers. Data Synthesis: Twelve trials met eligibility criteria and were included in the analysis. We also performed subanalyses by different hypothermia interventions (ie, depth, duration, and rapidity of rewarming after hypothermia) and methodological quality. Therapeutic hypothermia was associated with a 19% reduction in the risk of death (95% confidence interval [CI], 0.69-0.96) and a 22% reduction in the risk of poor neurologic outcome (95% CI, 0.63-0.98) compared with normothermia. Hypothermia longer than 48 hours was associated with a reduction in the risks of death and of poor neurologic outcome (relative risk [RR], 0.70; 95% CI, 0.56-0.87 and RR, 0.65; 95% CI, 0.48-0.89, respectively) compared with normothermia. Hypothermia to a target temperature between 32°C and 33°C, a duration of 24 hours, and rewarming within 24 hours were all associated with reduced risks of poor neurologic outcome compared with normothermia. Assessment of methodological quality did not reveal evidence of bias. Conclusions: Therapeutic hypothermia may reduce the risks of mortality and poor neurologic outcome in... [ABSTRACT FROM AUTHOR]

Context: Leukocytes present in stored blood products can have a variety of biological effects, including depression of immune function, thereby increasing nosocomial infections and possibly resulting in organ failure and death. Premature infants, given their immature immune state, may be uniquely predisposed to the effects of transfused leukocytes. Objective: To evaluate the clinical outcomes following implementation of a universal prestorage red blood cell (RBC) leukoreduction program in premature infants admitted to neonatal intensive care units (NICUs). Design and Setting: Retrospective before-and-after study conducted in 3 Canadian tertiary care NICUs from January 1998 to December 2000. Patients: A total of 515 premature infants weighing less than 1250 g who were admitted to the NICU, received at least 1 RBC transfusion, and survived at least 48 hours were enrolled. The intervention group consisted of infants admitted in the 18-month period following the introduction of universal leukoreduction (n = 247) and the control group consisted of infants admitted during the 18 months prior to the introduction of universal leukoreduction (n = 268). Main Outcome Measures: Primary outcomes were nosocomial bacteremia and NICU mortality, compared before and after implementation of universal leukoreduction using multivariate regression. Secondary outcomes included bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and intraventricular hemorrhage. Results: The proportion of infants who acquired bacteremia after an RBC transfusion was 79/267 (29.6%) in the nonleukoreduction period and 63/246 (25.6%) in the leukoreduction period. For NICU mortality, there were 45 deaths (16.8%) in the nonleukoreduction period and 44 deaths (17.8%) in the leukoreduction period. The adjusted odds ratio (OR) for bacteremia was 0.59 (95% confidence interval [CI], 0.34-1.01) and for mortality was 1.22 (95% CI, 0.59-2.50). The adjusted ORs for bronchopulmonary... [ABSTRACT FROM AUTHOR]

Context: A number of countries have implemented a policy of universal leukoreduction of their blood supply, but the potential role of leukoreduction in decreasing postoperative mortality and infection is unclear. Objective: To evaluate clinical outcomes following adoption of a national universal prestorage leukoreduction program for blood transfusions. Design, Setting, and Population: Retrospective before-and-after cohort study conducted from August 1998 to August 2000 in 23 academic and community hospitals throughout Canada, enrolling 14 786 patients who received red blood cell transfusions following cardiac surgery or repair of hip fracture, or who required intensive care following a surgical intervention or multiple trauma. Intervention: Universal prestorage leukoreduction program introduced by 2 Canadian blood agencies. A total of 6982 patients were enrolled during the control period and 7804 patients were enrolled following prestorage leukoreduction. Main Outcome Measures: All-cause in-hospital mortality and serious nosocomial infections (pneumonia, bacteremia, septic shock, all surgical site infections) occurring after first transfusion and at least 2 days after index procedure or intensive care unit admission. Secondary outcomes included rates of posttransfusion fever and antibiotic use. Results: Unadjusted in-hospital mortality rates were significantly lower following the introduction of leukoreduction compared with the control period (6.19% vs 7.03%, respectively; P = .04). Compared with the control period, the adjusted odds of death following leukoreduction were reduced (odds ratio [OR], 0.87; 95% confidence interval [CI], 0.75-0.99), but serious nosocomial infections did not decrease (adjusted OR, 0.97; 95% CI, 0.87-1.09). The frequency of posttransfusion fevers decreased significantly following leukoreduction (adjusted OR, 0.86; 95% CI, 0.79-0.94), as did antibiotic use (adjusted OR, 0.90; 95% CI, 0.82-0.99). Conclusion: A national universal... [ABSTRACT FROM AUTHOR]

There are a number of difficulties in the conduct of randomized trials in the critically ill. These include difficulties in the definition of diseases and syndromes, a heterogenous population of patients undergoing a variety of therapeutic interventions, and outcomes that may not be able to discriminate between beneficial and risky therapies. Following a brief description of different randomized clinical trials (RCTs) and design philosophies, we outline the effects of different design choices in the complex critical care environment. Once the study topic has been determined to be relevant and important, then the potential investigator must establish whether efficacy or effectiveness will be the focus of the RCT. If an effectiveness design philosophy is chosen, then broad representation of study sites, liberal eligibility criteria, easily implemented intervention study protocols, and patient-centered outcomes should be chosen. The potential investigator wishing to establish efficacy will conduct the study in the centers of excellence and adopt stringent eligibility criteria, rigorous study protocols, and opt for outcomes that will be sensitive to change. In conclusion, we describe some of the major challenges and possible solutions to help a potential investigator through the myriad of difficulties in initiating an RCT in a complex environment. [ABSTRACT FROM AUTHOR]

There are a number of difficulties in the conduct of randomized trials in the critically ill. These include difficulties in the definition of diseases and syndromes, a heterogenous population of patients undergoing a variety of therapeutic interventions, and outcomes that may not be able to discriminate between beneficial and risky therapies. Following a brief description of different randomized clinical trials (RCTs) and design philosophies, we outline the effects of different design choices in the complex critical care environment. Once the study topic has been determined to be relevant and important, then the potential investigator must establish whether efficacy or effectiveness will be the focus of the RCT. If an effectiveness design philosophy is chosen, then broad representation of study sites, liberal eligibility criteria, easily implemented intervention study protocols, and patient-centered outcomes should be chosen. The potential investigator wishing to establish efficacy will conduct the study in the centers of excellence and adopt stringent eligibility criteria, rigorous study protocols, and opt for outcomes that wit be sensitive to change. In conclusion, we describe some of the major challenges and possible solutions to help a potential investigator through the myriad of difficulties in initiating an RCT in a complex environment. [ABSTRACT FROM AUTHOR]

Study objective: To determine whether currently available measurement tools can be used to obtain valid measurements of short-term changes in dyspnea and disease-specific quality of life (QOL) in outpatients with an acute COPD exacerbation. Design: Prospective cohort study. Methods: Sixty-six patients with an acute COPD exacerbation who presented to the emergency department completed the chronic respiratory disease index questionnaire (CRQ) and the baseline dyspnea index (BDI) and were discharged home receiving 10 days of medical therapy. Reassessment with the CRQ and the transitional dyspnea index (TDI) occurred within 48 h of relapse (defined as an urgent hospital revisit within 10 days because of worsening respiratory symptoms), or 10 days later if relapse did not occur. Results: Patients who did not relapse (n = 49) showed moderate-to-large improvements in disease-specific QOL across all four CRQ domains (improvements in each domain of 1.4 to 1.0 U; p < 0.001 for all domains) and large positive changes in the TDI (total TDI score, + 5.02 ± 0.55 U; p = 0.0001). In contrast, patients who had a relapse (n = 17) did not have improved CRQ or TDI scores (mean negative change in three of four CRQ domains, total TDI score -3.06 ± 1.14 U; p = 0.02). Changes in the CRQ dyspnea score and TDI correlated with each other (r = 0.78; p = 0.0001) and with changes in FEV[sub 1] (CRQ, r = 0.48 and p = 0.0001; TDI, r = 0.46 and p = 0.0002). Ten control patients with stable COPD showed no changes in the CRQ or TDI over 10 days. Conclusion: The CRQ and BDI/TDI can be used to obtain valid, responsive measures of acute changes in QOL and dyspnea associated with a COPD exacerbation. The direction and magnitude of change in these scores was highly correlated with clinical outcome and with other health measures. Most outpatients treated for a COPD exacerbation experience significant short-term improvements in QOL and dyspnea, with the exception of patients who have a... [ABSTRACT FROM AUTHOR]

Background: The presence of WBCs in RBCs is thought to be associated with a number of significant adverse effects in recipients. In adults, WBC reduction has been shown to reduce the frequency of HLA alloimmunization, CMV and HTLV infections, and febrile nonhemolytic transfusion reactions. However, neonates are unique, given that they have an immature immune system and are frequently transfused with RBCs. Thus, the aims of this systematic review were to determine whether WBC reduction of RBCs transfused to neonates decreases the transmission of CMV, reduces the ability to develop HLA antibodies, or reduces the risk of immunomodulation. In addition, nosocomial infection, mortality, and duration of stay were identified and analyzed.Study Design and Methods: All studies of WBC reduction were identified by a systematic review of the literature. Studies meeting the inclusion criteria were grouped based on study outcome. Where appropriate, studies were pooled to obtain an overall measure of effect.Results: Nine eligible studies were identified from the systematic literature search, and six were deemed evaluable. Two studies evaluated WBC reduction and the development of CMV, with different results. The pooled OR was 0.19 (95% Cl, 0.01-3.41), suggesting a clinical but nonsignificant effect. Two studies evaluated WBC reduction and HLA antibody development. As with CMV, the two studies were not congruent in their results. The pooled OR was 0.17 (95% Cl, 0.01-2.43). As for immunomodulation, two small studies presented evidence of a statistically significant change in lymphocyte subsets. No studies were identified with a primary objective of evaluating the impact of WBC reduction on nosocomial infection, mortality, or duration of stay.Conclusion: Current evidence suggests that WBC reduction may be effective in neonates; however, further studies are needed. The lack of convincing data and the significant cost of WBC reduction mandate evaluations to determine the clinical and economic impact. [ABSTRACT FROM AUTHOR]

Background: Correcting the decrease in oxygen delivery from anemia using allogeneic RBC transfusions has been hypothesized to help with increased oxygen demands during weaning from mechanical ventilation. However, it is also possible that transfusions hinder the process because RBCs may not be able to adequately increase oxygen delivery. In this study, we determined whether a liberal RBC transfusion strategy improved outcomes related to mechanical ventilation. Methods: Seven hundred thirteen patients receiving mechanical ventilation, representing a subgroup of patients from a larger trial, were randomized to either a restrictive transfusion strategy, receiving allogeneic RBC transfusions at a hemoglobin concentration of 7.0 g/dL (and maintained between 7.0 g/dL and to 9.0 g/dL), or to a liberal transfusion strategy, receiving RBCs at 10.0 g/dL (and maintained between 10.0 g/dL and 12.0 g/dL). The larger trial was designed to evaluate transfusion practice rather than weaning per se. Results: Baseline characteristics in the restrictive-strategy group (n = 357) and the liberalstrategy group (n = 356) were comparable. The average durations of mechanical ventilation were 8.3 ± 8.1 days and 8.3 ± 8.1 days (95% confidence interval [CI] around difference, -0.79 to 1.68; p = 0.48), while ventilator-free days were 17.5 ± 10.9 days and 16.1 ± 11.4 days (95% CI around difference, -3.07 to 0.21; p = 0.09) in the restrictive-strategy group vs the liberal-strategy group, respectively. Eighty-two percent of the patients in the restrictive-strategy group were considered successfully weaned and extubated for at least 24 h, compared to 78% for the liberal-strategy group (p = 0.19). The relative risk (RR) of extubation success in the restrictivestrategy group compared to the liberal-strategy group, adjusted for the confounding effects of age, APACHE (acute physiology and chronic health evaluation) II score, and comorbid illness, was 1.07 (95% CI, 0.96... [ABSTRACT FROM AUTHOR]

SUMMARY Transfusion of red blood cells (RBC) continues to be an important therapy for treatment of anemia in intensive care settings. The critically ill are a heterogeneous population affected by a variety of pathophysiological processes and are, therefore, predisposed to the - adverse outcomes of anemia. As such, the risks imposed on this population when transfusion therapy is prescribed are of great interest. Over the past decade there has been a shift in transfusion practice with guidelines being developed that promote more conservative and safer use of blood. The Transfusion Requirements in Critical Care (TRICC) trial clearly established the safety of a restrictive transfusion strategy, thereby suggesting that physicians could easily minimize exposure to allogeneic RBCs by lowering their transfusion threshold. Further research will add to the generalizability of this study as well as explore the possible mechanism to explain why red cell transfusions did not improve outcomes in the critically ill. [ABSTRACT FROM AUTHOR]

Background. Uncontrolled studies have found that high‐flux haemodialysis favourably modifies homocysteine and lipid profiles. We sought to confirm these findings by carrying out a randomized prospective comparison of high‐flux and low‐flux polysulphone in chronic, stable dialysis patients. [ABSTRACT FROM PUBLISHER]

The objective of this study was to determine stable estimates of the incidence, case fatality, and epidemiologic features of adult epiglottitis, and risk factors for intubation. The authors designed a retrospective cohort combined with a nested casecontrol study, followed by detailed analysis of cases from two tertiary care institutions. Among 813 cases, the incidence was 2.02 cases/105 population per year. Ten recorded deaths constituted a case fatality rate of 1.2% (95% confidence interval [CI]: 0.5% to 1.9%). The eight fully documented deaths indicated no sudden episodes of catastrophic upper airway obstructions without previous dyspnea. A detailed review of 51 cases revealed that 18% of patients underwent expeditious intubation. Patients managed without initially requiring intubation did not need emergency airway interventions. Only the presence of dyspnea (noted in 29% of patients) at the time of admission ( P < 0.001) predicted the need for intubation. A low case fatality rate in a conservatively managed cohort and the absence of sudden upper airway catastrophes in patients without dyspnea suggest that prophylactic intubation and intensive care unit monitoring is not warranted in all patients. An early complaint of dyspnea may safely discriminate between patients requiring invasive airway management and close observation. [ABSTRACT FROM AUTHOR]

This article discusses a study that reviews physiologic evidence regarding an optimum hemoglobin concentration in anemic patients or in patients with specific diseases. From the brief review of physiologic principles and the strong consensus in the literature, it is evident that cardiac function must be a central consideration in decisions about transfusion in anemia, because of the critical role it plays in assuring adequate O2 supply to all vital tissues.