Elizabeth Yetisir

A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group.

BACKGROUND To determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produced equivalent results in critically ill patients, we compared the rates of death from all causes at 30 days and the severity of organ dysfunction. METHODS We enrolled 838 critically ill patients with euvolemia after initial treatment who had hemoglobin concentrations of less than 9.0 g per deciliter within 72 hours after admission to the intensive care unit and randomly assigned 418 patients to a restrictive strategy of transfusion, in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g per deciliter and hemoglobin concentrations were maintained at 7.0 to 9.0 g per deciliter, and 420 patients to a liberal strategy, in which transfusions were given when the hemoglobin concentration fell below 10.0 g per deciliter and hemoglobin concentrations were maintained at 10.0 to 12.0 g per deciliter. RESULTS Overall, 30-day mortality was similar in the two groups (18.7 percent vs. 23.3 percent, P= 0.11). However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill -- those with an Acute Physiology and Chronic Health Evaluation II score of < or =20 (8.7 percent in the restrictive-strategy group and 16.1 percent in the liberal-strategy group; P=0.03) -- and among patients who were less than 55 years of age (5.7 percent and 13.0 percent, respectively; P=0.02), but not among patients with clinically significant cardiac disease (20.5 percent and 22.9 percent, respectively; P=0.69). The mortality rate during hospitalization was significantly lower in the restrictive-strategy group (22.3 percent vs. 28.1 percent, P=0.05). CONCLUSIONS A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina.

Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases

ObjectiveTo compare a restrictive red blood cell transfusion strategy with a more liberal strategy in volume-resuscitated critically ill patients with cardiovascular disease. SettingTwenty-two academic and three community critical care units across Canada. Study Design Randomized controlled clinical trial. Study PopulationThree hundred fifty-seven critically ill patients with cardiovascular diseases from the Transfusion Requirements in Critical Care trial who had a hemoglobin concentration of <90 g/L within 72 hrs of admission to the intensive care unit. InterventionsPatients were randomized to a restrictive strategy to receive allogeneic red blood cell transfusions at a hemoglobin concentration of 70 g/L (and maintained between 70 and 90 g/L) or a liberal strategy to receive red blood cells at 100 g/L (and maintained between 100 and 120 g/L). ResultsBaseline characteristics in the restrictive (n = 160) and the liberal group (n = 197) were comparable, except for the use of cardiac and anesthetic drugs (p < .02). Average hemoglobin concentrations (85 ± 6.2 vs. 103 ± 6.7 g/L;p < .01) and red blood cell units transfused (2.4 ± 4.1 vs. 5.2 ± 5.0 red blood cell units;p < .01) were significantly lower in the restrictive compared with the liberal group. Overall, all mortality rates were similar in both study groups, including 30-day (23% vs. 23%;p = 1.00), 60-day, hospital, and intensive care unit rates. Changes in multiple organ dysfunction from baseline scores were significantly less in the restrictive transfusion group overall (0.2 ± 4.2 vs. 1.3 ± 4.4;p = .02). In the 257 patients with severe ischemic heart disease, there were no statistically significant differences in all survival measures, but this is the only subgroup where the restrictive group had lower but nonsignificant absolute survival rates compared with the patients in the liberal group. ConclusionA restrictive red blood cell transfusion strategy generally appears to be safe in most critically ill patients with cardiovascular disease, with the possible exception of patients with acute myocardial infarcts and unstable angina.

Effect of a liberal versus restrictive transfusion strategy on mortality in patients with moderate to severe head injury

ObjectiveTo 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).MethodsThis 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).ResultsBaseline 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.ConclusionsWe 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.

Cardiac resynchronization therapy: a meta-analysis of randomized controlled trials

Background Studies of cardiac resynchronization therapy in addition to an implantable cardioverter defibrillator in patients with mild to moderate congestive heart failure had not been shown to reduce mortality until the recent RAFT trial (Resynchronization/Defibrillation for Ambulatory Heart Failure Trial). We performed a meta-analysis including the RAFT trial to determine the effect of cardiac resynchronization therapy with or without an implantable defibrillator on mortality. Methods We searched electronic databases and other sources for reports of randomized trials using a parallel or crossover design. We included studies involving patients with heart failure receiving optimal medical therapy that compared cardiac resynchronization therapy with optimal medical therapy alone, or cardiac resynchronization therapy plus an implantable defibrillator with a standard implantable defibrillator. The primary outcome was mortality. The optimum information size was considered to assess the minimum amount of information required in the literature to reach reliable conclusions about cardiac resynchronization therapy. Results Of 3071 reports identified, 12 studies (n = 7538) were included in our meta-analysis. Compared with optimal medical therapy alone, cardiac resynchronization therapy plus optimal medical therapy significantly reduced mortality (relative risk [RR] 0.73, 95% confidence interval [CI] 0.62–0.85). Compared with an implantable defibrillator alone, cardiac resynchronization therapy plus an implantable defibrillator significantly reduced mortality (RR 0.83, 95% CI 0.72–0.96). This last finding remained significant among patients with New York Heart Association (NYHA) class I or II disease (RR 0.80, 95% CI 0.67–0.96) but not among those with class III or IV disease (RR 0.84, 95% CI 0.69–1.07). Analysis of the optimum information size showed that the sequential monitoring boundary was crossed, which suggests no need for further clinical trials. Interpretation The cumulative evidence is now conclusive that the addition of cardiac resynchronization to optimal medical therapy or defibrillator therapy significantly reduces mortality among patients with heart failure.

Risk of hemolytic uremic syndrome after sporadic Escherichia coli O157:H7 infection: Results of a Canadian collaborative study

OBJECTIVES The objectives of this study were to better estimate the age-specific risks of hemolytic uremic syndrome (HUS) and hemolytic anemia after Escherichia coli O157:H7 infection among a representative cohort of both referred and nonreferred children with documented illness from the province of Alberta and to compare this with the rates in children evaluated at referral centers in the rest of Canada. STUDY DESIGN Children with HUS or E. coli O157:H7 gastroenteritis were eligible if they were < 15 years of age. Hemoglobin, blood smear, urinalysis, and serum creatinine were obtained 8 to 10 days after the onset of diarrhea to ascertain for hemolysis, anemia, thrombocytopenia, and renal injury. Subjects were monitored for 1 month. RESULTS From June 1991 to March 1994, HUS was diagnosed in 205 children. Of these 77% had evidence of E. coli O157:H7 infection. A further 582 children had E. coli O157:H7 gastroenteritis, of whom 18 had hemolytic anemia. The risk of HUS after E. coli O157:H7 infection in Alberta was 8.1% (95% confidence interval, 5.3 to 11.6) compared with 31.4% in referral centers in the rest of Canada. In Alberta the highest age-specific risk of HUS/hemolytic anemia was 12.9% in those < 5 years of age. CONCLUSIONS These data will help guide clinical care and provide a basis for estimating the sample sizes required in future treatment trials for the secondary prevention of HUS.

Cardiac Resynchronization Therapy in Patients with Permanent Atrial Fibrillation: Results from the Resynchronization for Ambulatory Heart Failure Trial (RAFT)

Background—Cardiac resynchronization (CRT) prolongs survival in patients with systolic heart failure and QRS prolongation. However, most trials excluded patients with permanent atrial fibrillation. Methods and Results—The Resynchronization for Ambulatory Heart Failure Trial (RAFT) randomized patients to an implantable cardioverter defibrillator (ICD) or ICD+CRT, stratified by the presence of permanent atrial fibrillation. Patients with permanent atrial fibrillation were randomized to CRT-ICD (n=114) or ICD (n=115). Patients receiving a CRT-ICD were similar to those receiving an ICD: age (71.6±7.3 versus 70.4±7.7 years), left ventricular ejection fraction (22.9±5.3% versus 22.3±5.1%), and QRS duration (151.0±23.6 versus 153.4±24.7 ms). There was no difference in the primary outcome of death or heart failure hospitalization between those assigned to CRT-ICD versus ICD (hazard ratio, 0.96; 95% CI, 0.65–1.41; P=0.82). Cardiovascular death was similar between treatment arms (hazard ratio, 0.97; 95% CI, 0.55–1.71; P=0.91); however, there was a trend for fewer heart failure hospitalizations with CRT-ICD (hazard ratio, 0.58; 95% CI, 0.38–1.01; P=0.052). The change in 6-minute hall walk duration between baseline and 12 months was not different between treatment arms (CRT-ICD: 19±84 m versus ICD: 16±76 m; P=0.88). Patients treated with CRT-ICD showed a trend for a greater improvement in Minnesota Living with Heart Failure score between baseline and 6 months (CRT-ICD: 41±21 to 31±21; ICD: 33±20 to 28±20; P=0.057). Conclusions—Patients with permanent atrial fibrillation who are otherwise CRT candidates appear to gain minimal benefit from CRT-ICD compared with a standard ICD. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00251251.Background— Cardiac resynchronization (CRT) prolongs survival in patients with systolic heart failure and QRS prolongation. However, most trials excluded patients with permanent atrial fibrillation. Methods and Results— The Resynchronization for Ambulatory Heart Failure Trial (RAFT) randomized patients to an implantable cardioverter defibrillator (ICD) or ICD+CRT, stratified by the presence of permanent atrial fibrillation. Patients with permanent atrial fibrillation were randomized to CRT-ICD (n=114) or ICD (n=115). Patients receiving a CRT-ICD were similar to those receiving an ICD: age (71.6±7.3 versus 70.4±7.7 years), left ventricular ejection fraction (22.9±5.3% versus 22.3±5.1%), and QRS duration (151.0±23.6 versus 153.4±24.7 ms). There was no difference in the primary outcome of death or heart failure hospitalization between those assigned to CRT-ICD versus ICD (hazard ratio, 0.96; 95% CI, 0.65–1.41; P =0.82). Cardiovascular death was similar between treatment arms (hazard ratio, 0.97; 95% CI, 0.55–1.71; P =0.91); however, there was a trend for fewer heart failure hospitalizations with CRT-ICD (hazard ratio, 0.58; 95% CI, 0.38–1.01; P =0.052). The change in 6-minute hall walk duration between baseline and 12 months was not different between treatment arms (CRT-ICD: 19±84 m versus ICD: 16±76 m; P =0.88). Patients treated with CRT-ICD showed a trend for a greater improvement in Minnesota Living with Heart Failure score between baseline and 6 months (CRT-ICD: 41±21 to 31±21; ICD: 33±20 to 28±20; P =0.057). Conclusions— Patients with permanent atrial fibrillation who are otherwise CRT candidates appear to gain minimal benefit from CRT-ICD compared with a standard ICD. Clinical Trial Registration— URL: . Unique identifier: [NCT00251251][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00251251&atom=%2Fcirchf%2F5%2F5%2F566.atom

Shelter-based managed alcohol administration to chronically homeless people addicted to alcohol

Background: People who are homeless and chronically alcoholic have increased health problems, use of emergency services and police contact, with a low likelihood of rehabilitation. Harm reduction is a policy to decrease the adverse consequences of substance use without requiring abstinence. The shelter-based Managed Alcohol Project (MAP) was created to deliver health care to homeless adults with alcoholism and to minimize harm; its effect upon consumption of alcohol and use of crisis services is described as proof of principle. Methods: Subjects enrolled in MAP were dispensed alcohol on an hourly basis. Hospital charts were reviewed for all emergency department (ED) visits and admissions during the 3 years before and up to 2 years after program enrolment, and the police database was accessed for all encounters during the same periods. The results of blood tests were analyzed for trends. A questionnaire was administered to MAP participants and staff about alcohol use, health and activities of daily living before and during the program. Direct program costs were also recorded. Results: Seventeen adults with an average age of 51 years and a mean duration of alcoholism of 35 years were enrolled in MAP for an average of 16 months. Their monthly mean group total of ED visits decreased from 13.5 to 8 (p = 0.004); police encounters, from 18.1 to 8.8 (p = 0.018). Changes in blood test findings were nonsignificant. All program participants reported less alcohol consumption during MAP, and subjects and staff alike reported improved hygiene, compliance with medical care and health. Interpretation: A managed alcohol program for homeless people with chronic alcoholism can stabilize alcohol intake and significantly decrease ED visits and police encounters.

Sprint Fidelis Lead Fractures in Patients with Cardiac Resynchronization Therapy Devices: Insight from the Resynchronization/Defibrillation for Ambulatory Heart Failure (RAFT) Study

Background— Using data from the Resynchronization/Defibrillation for Ambulatory Heart Failure (RAFT) study, we examined whether Fidelis lead failure was more common in patients with implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (ICD-CRT) than in patients with an ICD only. Methods and Results— All cases of patients who had a right ventricular defibrillation lead revision in the RAFT study were adjudicated for the presence of lead fracture. Criteria for fracture were at least 2 of the following: (1) Impedance rise (>50% or >500 &OHgr; in 1 week), (2) short interval count >10 times per day or 300 times per month, or (3) inappropriate shock caused by noise, verified by stored electrogram. A total of 1798 patients were enrolled into the RAFT study, with a mean follow-up of 40±20 months. There were 818 patients (45.5%) who received a Fidelis lead at the original implantation, 405 with an ICD only and 413 with an ICD-CRT. There were 47 confirmed defibrillation lead fractures; 45 were Fidelis leads (5.5% of Fidelis leads). The overall rate of fracture in the ICD group was 3.2% compared with 7.8% in the ICD-CRT group (P=0.006; hazard ratio, 2.42; 95% confidence interval, 1.27–4.61). Significant correlates of lead fracture in this population were undergoing an ICD-CRT implantation and having ≥2 leads. Conclusions— In this analysis of the RAFT study, patients with an ICD-CRT were found to have a significantly higher fracture rate than patients with an ICD. This finding needs to be considered when these patients are assessed for possible lead revision at the time of an elective generator replacement.Background— Using data from the Resynchronization/Defibrillation for Ambulatory Heart Failure (RAFT) study, we examined whether Fidelis lead failure was more common in patients with implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (ICD-CRT) than in patients with an ICD only. Methods and Results— All cases of patients who had a right ventricular defibrillation lead revision in the RAFT study were adjudicated for the presence of lead fracture. Criteria for fracture were at least 2 of the following: (1) Impedance rise (>50% or >500 Ω in 1 week), (2) short interval count >10 times per day or 300 times per month, or (3) inappropriate shock caused by noise, verified by stored electrogram. A total of 1798 patients were enrolled into the RAFT study, with a mean follow-up of 40±20 months. There were 818 patients (45.5%) who received a Fidelis lead at the original implantation, 405 with an ICD only and 413 with an ICD-CRT. There were 47 confirmed defibrillation lead fractures; 45 were Fidelis leads (5.5% of Fidelis leads). The overall rate of fracture in the ICD group was 3.2% compared with 7.8% in the ICD-CRT group ( P =0.006; hazard ratio, 2.42; 95% confidence interval, 1.27–4.61). Significant correlates of lead fracture in this population were undergoing an ICD-CRT implantation and having ≥2 leads. Conclusions— In this analysis of the RAFT study, patients with an ICD-CRT were found to have a significantly higher fracture rate than patients with an ICD. This finding needs to be considered when these patients are assessed for possible lead revision at the time of an elective generator replacement. # Clinical Perspective {#article-title-18}

Spatial abilities in an elective course of applied anatomy after a problem‐based learning curriculum

A concern on the level of anatomy knowledge reached after a problem‐based learning curriculum has been documented in the literature. Spatial anatomy, arguably the highest level in anatomy knowledge, has been related to spatial abilities. Our first objective was to test the hypothesis that residents are interested in a course of applied anatomy after a problem‐based learning curriculum. Our second objective was to test the hypothesis that the interest of residents is driven by innate higher spatial abilities. Fifty‐nine residents were invited to take an elective applied anatomy course in a prospective study. Spatial abilities were measured with a redrawn Vandenberg and Kuse Mental Rotations Test in two (MRT A) and three (MRT C) dimensions. A need for a greater knowledge in anatomy was expressed by 25 residents after a problem‐based learning curriculum. MRT A and C scores obtained by those choosing (n = 25) and not choosing (n = 34) applied anatomy was not different (P = 0.46 and P = 0.38, respectively). Percentage of residents in each residency program choosing applied anatomy was different [23 vs. 31 vs. 100 vs. 100% in Family Medicine, Internal Medicine, Surgery, and Anesthesia, respectively; P < 0.0001]. The interest of residents in applied anatomy was not driven by innate higher spatial abilities. Our applied anatomy course was chosen by many residents because of training needs rather than innate spatial abilities. Future research will need to assess the relationship of individual differences in spatial abilities to learning spatial anatomy. Anat Sci Ed 2:107–112, 2009.

Sex differences in spatial abilities of medical graduates entering residency programs.

Sex differences favoring males in spatial abilities have been known by cognitive psychologists for more than half a century. Spatial abilities have been related to three‐dimensional anatomy knowledge and the performance in technical skills. The issue of sex differences in spatial abilities has not been addressed formally in the medical field. The objective of this study was to test an a priori hypothesis of sex differences in spatial abilities in a group of medical graduates entering their residency programs over a five‐year period. A cohort of 214 medical graduates entering their specialist residency training programs was enrolled in a prospective study. Spatial abilities were measured with a redrawn Vandenberg and Kuse Mental Rotations Tests in two (MRTA) and three (MRTC) dimensions. Sex differences favoring males were identified in 131 (61.2%) female and 83 (38.8%) male medical graduates with the median (Q1, Q3) MRTA score [12 (8, 14) vs. 15 (12, 18), respectively; P < 0.0001] and MRTC score [7 (5, 9) vs. 9 (7, 12), respectively; P < 0.0001]. Sex differences in spatial abilities favoring males were demonstrated in the field of medical education, in a group of medical graduates entering their residency programs in a five‐year experiment. Caution should be exerted in applying our group finding to individuals because a particular female may have higher spatial abilities and a particular male may have lower spatial abilities. Anat Sci Educ 6: 368–375.