Faculty Bibliography

CONTEXT/BACKGROUND:Even though red blood cells (RBCs) are lifesaving in neonatal intensive care, transfusing older RBCs may result in higher rates of organ dysfunction, nosocomial infection, and length of hospital stay. OBJECTIVE:To determine if RBCs stored for 7 days or less compared with usual standards decreased rates of major nosocomial infection and organ dysfunction in neonatal intensive care unit patients requiring at least 1 RBC transfusion. DESIGN, SETTING, AND PARTICIPANTS/METHODS:Double-blind, randomized controlled trial in 377 premature infants with birth weights less than 1250 g admitted to 6 Canadian tertiary neonatal intensive care units between May 2006 and June 2011. INTERVENTION/METHODS:Patients were randomly assigned to receive transfusion of RBCs stored 7 days or less (n = 188) vs standard-issue RBCs in accordance with standard blood bank practice (n = 189). MAIN OUTCOME MEASURES/METHODS:The primary outcome was a composite measure of major neonatal morbidities, including necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia, and intraventricular hemorrhage, as well as death. The primary outcome was measured within the entire period of neonatal intensive care unit stay up to 90 days after randomization. The rate of nosocomial infection was a secondary outcome. RESULTS:The mean age of transfused blood was 5.1 (SD, 2.0) days in the fresh RBC group and 14.6 (SD, 8.3) days in the standard group. Among neonates in the fresh RBC group, 99 (52.7%) had the primary outcome compared with 100 (52.9%) in the standard RBC group (relative risk, 1.00; 95% CI, 0.82-1.21). The rate of clinically suspected infection in the fresh RBC group was 77.7% (n = 146) compared with 77.2% (n = 146) in the standard RBC group (relative risk, 1.01; 95% CI, 0.90-1.12), and the rate of positive cultures was 67.5% (n = 127) in the fresh RBC group compared with 64.0% (n = 121) in the standard RBC group (relative risk, 1.06; 95% CI, 0.91-1.22). CONCLUSION/CONCLUSIONS:In this trial, the use of fresh RBCs compared with standard blood bank practice did not improve outcomes in premature, very low-birth-weight infants requiring a transfusion. TRIAL REGISTRATION/BACKGROUND:clinicaltrials.gov Identifier: NCT00326924; Current Controlled Trials Identifier: ISRCTN65939658.

Blood component transfusion is an integral part of the care of children with oncologic and hematologic conditions. The complexity of transfusion medicine may however lead to challenges for pediatric hematologists/oncologists. In this review, three commonly encountered areas of transfusion medicine are explored. The approach to the investigation and management of suspected platelet refractoriness is reviewed. The unique transfusion related challenges encountered by children undergoing stem cell transplantation are also discussed. Finally, issues arising out of the care of children with hemoglobinopathies are explored, with an emphasis on the incidence of allo- and autoimmunization.

Pathology is an unpopular residency choice for medical students worldwide. In some countries, this has contributed to a crisis in pathologist human resources that has affected the quality of clinical laboratories. Several previous studies have used information from junior medical students and from residents to suggest ways of improving pathology recruitment. There are, however, no published studies of pathology residency choice that focus on the senior medical students who must be recruited. This study uses focus groups of senior medical students to explore both general and pathology-specific influences on residency choice. Several general influences are identified, including students' expectations for their future clinical practices, their own clinical rotation experiences, influences from other people including mentors, and their choice to reject certain fields. Several specific antipathology influences are also revealed, including negative stereotypes about pathologists, a perceived incompatibility of personality between most medical students (extroverted) and pathologists (introverted), and perceptions of pathologists as being in some ways nonmedical. The most important antipathology influence was that, from the students' perspective, pathology was utterly invisible in clinical practice. Most students did not consider and then reject a pathology residency: instead, pathology was completely ignored. Given the importance of clerkship electives in influencing medical student career choice, promoting clerkship experiences in pathology may improve recruitment. However, departments of pathology must first make pathology visible to students and teach them how pathologists contribute to clinical care.

Red blood cell morphology (RBC-M) reporting is a routine requirement for hospital laboratories when reporting complete blood counts. However, there is little evidence that RBC-M reporting is useful to pediatric clinicians. We surveyed pediatric hematology specialists and nonspecialists at the BC Children's Hospital (Vancouver, Canada), to evaluate the perceived clinical utility of this reporting. Although a large majority of pediatric clinicians refer to RBC-M reports in their clinical practice, less than half consider these reports to be clinically useful. Hematology specialists were more likely than nonspecialists to identify individual RBC-M descriptions as clinically useful. Some RBC-M descriptions, such as anisocytosis, were considered not useful by specialists and by nonspecialists. A large proportion of nonspecialist respondents noted that they did not know the clinical significance of some of the RBC-M terms. Educational initiatives to inform nonspecialists about the clinical significance of some RBC-M descriptions should be considered. A few RBC-M descriptions are not clinically useful to either specialists or nonspecialists, and these could be omitted from RBC-M reports as a step toward improved hematology laboratory reporting.

Pathology has been frequently identified in the literature as an unpopular choice for medical students. For many years, there have been predictions that this unpopularity would lead to inadequate pathologist numbers, which would in turn contribute to poor quality patient care. In Canada, the predicted crisis has become a reality: after a high-profile failure of laboratory quality, a public inquiry reported that poor pathology recruitment was partially responsible and recommended that medical schools take steps to make pathology more attractive to medical students. There are several published studies into pathology recruitment, but none has asked nonpathology residents why they did not choose pathology. This study uses qualitative techniques to investigate why pathology residents chose to specialize in pathology and why clinical residents rejected a pathology career. Pathology residents across Canada were surveyed, as were clinical (nonpathology) residents in every residency training program at the University of British Columbia in Vancouver, Canada. Pathology residents overwhelmingly cited various attractive features of pathology practice, including its academic nature, the opportunity to explore basic pathogenesis, and its interesting and varied daily work. Most clinical residents rejected pathology because they preferred direct patient contact; however, a sizable minority blamed insufficient or inadequate medical school experiences in pathology. Clinical residents also cited several misconceptions and stereotypes about pathology, including misunderstandings about the role of pathologists and the nature of pathology practice. The reasons why clinical residents rejected pathology careers may provide guidance in improving pathology recruitment of medical students.

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.

OBJECTIVE:To provide recommendations to physicians, midwives, genetic counsellors, and clinical laboratory scientists involved in pre-conceptional or prenatal care regarding carrier screening for thalassemia and hemoglobinopathies (e.g., sickle cell anemia and other qualitative hemoglobin disorders). OUTCOMES/RESULTS:To determine the populations to be screened and the appropriate tests to offer to minimize practice variations across Canada. EVIDENCE/METHODS:The Medline database was searched for relevant articles published between 1986 and 2007 on carrier screening for thalassemia and hemoglobinopathies. Key textbooks were also reviewed. Recommendations were quantified using the Evaluation of Evidence guidelines developed by the Canadian Task Force on Preventive Health Care. VALUES/METHODS:The evidence collected from the Medline search was reviewed by the Prenatal Diagnosis Committee of the Canadian College of Medical Geneticists (CCMG) and the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC). BENEFITS, HARMS, AND COSTS/RESULTS:Screening of individuals at increased risk of being carriers for thalassemia and hemoglobinopathies can identify couples with a 25% risk of having a pregnancy with a significant genetic disorder for which prenatal diagnosis is possible. Ideally, screening should be done pre-conceptionally. However, for a significant proportion of patients, the screening will occur during the pregnancy, and the time constraint for obtaining screening results may result in psychological distress. This guideline does not include a cost analysis. RECOMMENDATIONS/CONCLUSIONS:1. Carrier screening for thalassemia and hemoglobinopathies should be offered to a woman if she and/or her partner are identified as belonging to an ethnic population whose members are at higher risk of being carriers. Ideally, this screening should be done pre-conceptionally or as early as possible in the pregnancy. (II-2A) 2. Screening should consist of a complete blood count, as well as hemoglobin electrophoresis or hemoglobin high performance liquid chromatography. This investigation should include quantitation of HbA2 and HbF. In addition, if there is microcytosis(mean cellular volume < 80 fL) and/or hypochromia (mean cellular hemoglobin < 27 pg) in the presence of a normal hemoglobin electrophoresis or high performance liquid chromatography the patient should be investigated with a brilliant cresyl blue stained blood smear to identify H bodies. A serum ferritin (to exclude iron deficiency anemia) should be performed simultaneously. (III-A) 3. If a woman's initial screening is abnormal (e.g., showing microcytosis or hypochromia with or without an elevated HbA2, or a variant Hb on electrophoresis or high performance liquid chromatography) then screening of the partner should be performed. This would include a complete blood count as well as hemoglobin electrophoresis or HPLC, HbA2 and HbF quantitation,and H body staining. (III-A) 4. If both partners are found to be carriers of thalassemia or an Hb variant, or of a combination of thalassemia and a hemoglobin variant, they should be referred for genetic counselling. Ideally,this should be prior to conception, or as early as possible in the pregnancy. Additional molecular studies may be required to clarify the carrier status of the parents and thus the risk to the fetus. (II-3A) 5. Prenatal diagnosis should be offered to the pregnant woman/couple at risk for having a fetus affected with a clinically significant thalassemia or hemoglobinopathy. Prenatal diagnosis should be performed with the patient's informed consent. If prenatal diagnosis is declined, testing of the child should be done to allow early diagnosis and referral to a pediatric hematology centre, if indicated. (II-3A) 6. Prenatal diagnosis by DNA analysis can be performed using cells obtained by chorionic villus sampling or amniocentesis. Alternatively for those who decline invasive testing and are at risk of hemoglobin Bart's hydrops fetalis (four-gene deletion alpha-thalassemia), serial detailed fetal ultrasound for assessment of the fetal cardiothoracic ratio (normal < 0.5) should be done in a centre that has experience conducting these assessments for early identification of an affected fetus. If an abnormality is detected, a referral to a tertiary care centre is recommended for further assessment and counselling. Confirmatory studies by DNA analysis of amniocytes should be done if a termination of pregnancy is being considered. (II-3A) 7. The finding of hydrops fetalis on ultrasound in the second or third trimester in women with an ethnic background that has an increased risk of alpha-thalassemia should prompt immediate investigation of the pregnant patient and her partner to determine their carrier status for alpha-thalassemia. (III-A) VALIDATION: This guideline has been prepared by the Prenatal Diagnosis Committee of the Canadian College of Medical Geneticists (CCMG) and the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and approved by the Board of Directors of the CCMG and the Executive and Council of the SOGC.

We report the first case of multiple intracranial tumors ("chloromas") at diagnosis of Philadelphia chromosome positive acute lymphoblastic leukemia. The patient presented comatose with signs of cerebral herniation. Initial management of raised intracranial pressure and hyperleukocytosis followed by emergent whole brain radiation therapy reversed the life-threatening neurological signs. High-dose chemotherapy combined with daily imatinib mesylate induced a rapid and sustained bone marrow remission. Ongoing rehabilitation resulted in a near complete neurological recovery within 6 months of diagnosis. This outcome justifies aggressive early management of increased intracranial pressure and hyperleukocytosis in future similar presentations.

To address concerns about regional physician shortages within British Columbia, the University of British Columbia began distributing its undergraduate medical curriculum across multiple campuses (ie, urban Vancouver, small urban Victoria, and rural Prince George) in 2005. The distribution of the pathology curriculum required meeting 3 specific challenges: (i) implementation of high-quality technologies to facilitate distribution; (ii) recruitment of pathologists to teach; and (iii) creation of an electronic pathology learning center. Technological needs were met by a state-of-the-art audiovisual system allowing simultaneous interactive didactic sessions across all 3 sites, and by the use of a digital "virtual slide" system. Recruitment of pathologist educators proved challenging owing to comparatively limited staffing levels at the rural site. A physical and virtual pathology learning center was developed to assist students in self-directed study. Student performance on pathology examinations has proven to be essentially identical pre- and post-distribution, and is equivalent across all 3 sites. Quantitative and qualitative student survey data show that distributed pathology instruction is overwhelmingly well received by medical students at all sites, that pathologists' expertise is very important to students, and that pathology is one of the most popular components of the distributed curriculum. Pathology education continues to be a vital part of a distributed undergraduate medical program, and student grades and feedback demonstrate the value of the teaching and the technologies we have used. To be implemented successfully, the distribution of pathology education requires considerable financial and infrastructure investment, and ongoing commitment from pathologists and university administrators.

To address the critical problem of inadequate physician supply in rural British Columbia, The University of British Columbia (UBC) launched an innovative, expanded and distributed medical program in 2004-2005. Medical students engage in a common curriculum at three geographically distinct sites across B.C.: in Vancouver, Prince George and Victoria. The distribution of the core Histology course required a thorough revision of our instructional methodology. We here report our progress and address the question "How does one successfully distribute Histology teaching to remote sites while maintaining the highest of educational standards?" The experience at UBC points to three specific challenges in developing a distributed Histology curriculum: (i) ensuring equitable student access to high quality histological images, (ii) designing and implementing a reliable, state-of-the-art technological infrastructure that allows for real-time teaching and interactivity across geographically separate sites and (iii) ensuring continued student access to faculty content expertise. High quality images--available through any internet connection--are provided within a new virtual slide box library of 300 light microscopic and 190 electron microscopic images. Our technological needs are met through a robust and reliable videoconference system that allows for live, simultaneous communication of audio/visual materials across the three sites. This system also ensures student access to faculty content expertise during all didactic teaching sessions. Student examination results and surveys demonstrate that the distribution of our Histology curriculum has been successful.