Search

Implication Statement: COVID-19 pandemic restrictions abruptly changed the way interviews for medical school admissions have been conducted. This study is unique as it highlights the first successful virtual synchronous multiple mini interview (MMI) in Canada. Our low technical incident rate, troubleshooting strategies and approach may reassure other medical schools considering conducting a virtual MMI. Success was achieved with collaboration, a strong organizational and communication strategy, learning along the way and a priori contingency plans. Virtual interviewing in academic medicine is likely here to stay, and future work to highlight the impact on applicants will help to build on the diversity mission in undergraduate medicine admissions., Énoncé des implications de la recherche : Les restrictions liées à la pandémie de la COVID-19 ont brusquement changé la façon de mener les entrevues dans les processus d'admission aux programmes de doctorat en médecine. Notre étude est unique dans la mesure où elle présente la réussite, pour la première fois au Canada, d'une mini-entrevue multiple (MMI) en mode virtuel synchrone. Notre faible taux d'incidents techniques, nos stratégies de dépannage et notre approche peuvent rassurer les facultés de médecine qui envisagent d'effectuer des MEM virtuelles. Ce succès a été obtenu grâce à la collaboration, à une solide stratégie d'organisation et de communication, à l'apprentissage en cours de route et à la préparation de plans d'urgence. L'entrevue virtuelle n'est pas près de disparaître des programmes de doctorat en médecine, et les travaux futurs visant à mettre en évidence son impact sur les candidats contribueront à renforcer la promotion de la diversité dans le processus d'admission.

Rationale Prescribed opioids are major contributors to the international public health opioid crisis. Such widespread iatrogenic harms usually result from collective decision failures of healthcare organizations rather than solely of individual organizations or professionals. Findings from a system-wide safety analysis of the iatrogenic opioid crisis that includes roles of pertinent healthcare organizations may help avoid or mitigate similar future iatrogenic consequences. In this retrospective exploratory study, we report such an analysis. Methods The study population encompassed the entire age spectrum and included those in whom opioids prescribed for chronic pain (unrelated to malignancy) were associated with death or morbidity. Root cause analysis, incorporating recent suggestions for improvement, was used to identify possible contributory factors from the literature. Based on their mandated roles and potential influences to prevent or mitigate the iatrogenic crisis, relevant organizations were grouped and stratified from most to least influential. Results The analysis identified a chain of multiple interrelated causal factors within and between organizations. The most influential organizations were pharmaceutical, political, and drug regulatory; next: experts and their related societies, and publications. Less influential: accreditation, professional licensing and regulatory, academic and healthcare funding bodies. Collectively, their views and decisions influenced prescribing practices of frontline healthcare professionals and advocacy groups. Financial associations between pharmaceutical and most other organizations/groups were common. Ultimately, patients were adversely affected. There was a complex association with psychosocial variables. Limitations The analysis suggests associations not causality. Conclusion The iatrogenic crisis has multiple intricately linked roots. The major catalyst: pervasive pharma-linked financial conflicts of interest (CoIs) involving most other healthcare organizations. These extensive financial CoIs were likely triggers for a cascade of erroneous decisions and actions that adversely affected patients. The actions and decisions of pharma ranged from unethical to illegal. The iatrogenic opioid crisis may exemplify 'institutional corruption of pharmaceuticals'.

Rationale Prescribed opioids are major contributors to the current international public health opioid crisis. Such iatrogenic calamities usually result from collective decision failures of healthcare organizations rather than solely of individual organizations or professionals. Findings from a system-wide safety analysis of the iatrogenic opioid crisis that includes roles of pertinent healthcare organizations may help avoid or mitigate similar future tragedies. In this exploratory study, we report on such an analysis. Methods Root cause analysis, incorporating recent suggestions for improvement, was used to retrospectively identify possible causal factors from the literature. Based on their mandated roles and potential influences to prevent or mitigate the iatrogenic crisis, relevant organizations were grouped and stratified from most to least influential. Results The analysis identified a chain of multiple interrelated causal factors within and between organizations. The most influential organizations were: pharmaceutical, political and drug regulatory; next: experts and their related societies, and publications. Less influential: accreditation, professional licensing and regulatory, academic and healthcare funding bodies. Collectively, their views and decisions influenced prescribing practices of frontline healthcare professionals and advocacy groups. Financial associations between pharmaceutical and all other organizations/groups were common. Ultimately, patients were adversely affected. There was a complex association with psychosocial variables. Limitations Our analysis suggests associations not causality. Conclusions The iatrogenic crisis has multiple intricately linked interacting roots. The major catalyst: pervasive pharma-linked financial conflicts of interest (CoIs) involving most of the other healthcare organizations. These extensive financial CoIs were likely triggers for a cascade of erroneous decisions and actions that adversely affected patients. The actions and decisions of pharma ranged from unethical to illegal. The iatrogenic opioid crisis exemplifies widespread “institutional corruption of pharmaceuticals.”

While change is acknowledged as integral to all action research, literature linking the theories of change theoretically merits exploration. Are some theories of change more congruent to principles of action research than others? Does congruence depend on which type of action research and which change theory are being compared? During the implementation of a four-cycle community-based participatory action research (CBPR) project in nursing education in Ghana, such questions arose. This paper is an attempt to grapple with those questions. While Kotter’s eight-step theory of organizational change was chosen to guide this study, it became obvious that various elements of change theories were integrated in the study as it progressed. For Kotter’s organizational change theory to serve as an effective guide for the implementation cycles in the CBPR project, it must be conducted through the lens of critical social theory and a perspective on social and cultural change.

Introduction Although patient safety has improved steadily, harm remains a substantial global challenge. Additionally, safety needs to be ensured not only in hospitals but also across the continuum of care. Better understanding of the complex cognitive factors influencing health care–related decisions and organizational cultures could lead to more rational approaches, and thereby to further improvement. Hypothesis A model integrating the concepts underlying Reason's Swiss cheese theory and the cognitive-affective biases plus cascade could advance the understanding of cognitive-affective processes that underlie decisions and organizational cultures across the continuum of care. Methods Thematic analysis, qualitative information from several sources being used to support argumentation. Discussion Complex covert cognitive phenomena underlie decisions influencing health care. In the integrated model, the Swiss cheese slices represent dynamic cognitive-affective (mental) gates: Reason's successive layers of defence. Like firewalls and antivirus programs, cognitive-affective gates normally allow the passage of rational decisions but block or counter unsounds ones. Gates can be breached (ie, holes created) at one or more levels of organizations, teams, and individuals, by (1) any element of cognitive-affective biases plus (conflicts of interest and cognitive biases being the best studied) and (2) other potential error-provoking factors. Conversely, flawed decisions can be blocked and consequences minimized; for example, by addressing cognitive biases plus and error-provoking factors, and being constantly mindful. Informed shared decision making is a neglected but critical layer of defence (cognitive-affective gate). The integrated model can be custom tailored to specific situations, and the underlying principles applied to all methods for improving safety. The model may also provide a framework for developing and evaluating strategies to optimize organizational cultures and decisions. Limitations The concept is abstract, the model is virtual, and the best supportive evidence is qualitative and indirect. Conclusions The proposed model may help enhance rational decision making across the continuum of care, thereby improving patient safety globally.

OBJECTIVES There are only a few descriptive reports on the implementation of distributed medical education (DME) and these provide accounts of successful implementation from the senior leadership perspective. In Saskatchewan, over a period of 4 years (2010-2014), four family medicine residency sites were established and two additional sites could not be developed. The aim of this study was to identify challenges, success factors and pitfalls in DME implementation based upon experiences of multiple stakeholders with both successful and unsuccessful outcomes. METHODS Data were obtained through document analysis (n = 64, spanning 2009-2016; perspectives of government, senior leadership, management and learners), focus groups of management and operations personnel (n = 10) and interviews of senior leaders (n = 4). Challenges and success factors were ascertained through categorisation. Iterative coding guided by three sensitising frameworks was used to determine themes in organisational dynamics. RESULTS Both challenges and success factors included contextual variables, governance, inter- and intra-organisational relationships (most common success factor), resources (most common challenge), the learning environment and pedagogy. Management and operations were only a challenge. Organisational themes affecting the outcome and the pitfalls included the pace of development across multiple sites, collaborative governance, continuity in senior leadership, operations alignment and reconciliation of competing goals. CONCLUSIONS Emerging opportunities for DME can be leveraged through collaborative governance, aligned operations and resolution of competing goals, even in constrained contexts, to translate political will into success; however, there are pitfalls that need to be avoided. Our findings based upon multi-stakeholder perspectives add to the body of knowledge on deployment, carefully considering the conditions for success and associated pitfalls.

Little is known about the impact of enrollment on therapeutic clinical trials on adverse event rates. Primary objective was to describe the impact of clinical trial registration on sterile site microbiologically documented infection for children with newly diagnosed acute myeloid leukemia (AML). We conducted a multicenter cohort study that included children aged ≤18 years with de novo AML. Primary outcome was microbiologically documented sterile site infection. Infection rates were compared between those registered and not registered on clinical trials. Five hundred seventy-four children with AML were included of which 198 (34.5%) were registered on a therapeutic clinical trial. Overall, 400 (69.7%) had at least one sterile site microbiologically documented infection. In multiple regression, registration on clinical trials was independently associated with a higher risk of microbiologically documented sterile site infection [adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 1.01-1.53; p = 0.040] and viridans group streptococcal infection (OR 1.46, 95% CI 1.08-1.98; p = 0.015). Registration on trials was not associated with Gram-negative or invasive fungal infections. Children with newly diagnosed AML enrolled on clinical trials have a higher risk of microbiologically documented sterile site infection. This information may impact on supportive care practices in pediatric AML.

Background With current emphasis on leadership in medicine, this study explores Goleman’s leadership styles of medical education leaders at different hierarchical levels and gain insight into factors that contribute to the appropriateness of practices. Methods Forty two leaders (28 first-level with limited formal authority, eight middle-level with wider program responsibility and six senior- level with higher organizational authority) rank ordered their preferred Goleman’s styles and provided comments. Eight additional senior leaders were interviewed in-depth. Differences in ranked styles within groups were determined by Friedman tests and Wilcoxon tests. Based upon style descriptions, confirmatory template analysis was used to identify Goleman’s styles for each interviewed participant. Content analysis was used to identify themes that affected leadership styles. Results There were differences in the repertoire and preferred styles at different leadership levels. As a group, first-level leaders preferred democratic, middle-level used coaching while the senior leaders did not have one preferred style and used multiple styles. Women and men preferred democratic and coaching styles respectively. The varied use of styles reflected leadership conceptualizations, leader accountabilities, contextual adaptations, the situation and its evolution, leaders’ awareness of how they themselves were situated, and personal preferences and discomfort with styles. The not uncommon use of pace-setting and commanding styles by senior leaders, who were interviewed, was linked to working with physicians and delivering quickly on outcomes. Conclusions Leaders at different levels in medical education draw from a repertoire of styles. Leadership development should incorporate learning of different leadership styles, especially at first- and mid-level positions. Electronic supplementary material The online version of this article (10.1186/s12909-017-0995-z) contains supplementary material, which is available to authorized users.

BACKGROUND The prevalence and severity of Clostridium difficile infection (CDI) has increased over time in adult patients, but little is known about CDI in pediatric cancer. The primary objectives were to describe the incidence and characteristics of CDI in children with de novo acute myeloid leukemia (AML). The secondary objective was to describe factors associated with CDI. METHOD We performed a multicenter, retrospective cohort study of children with de novo AML and evaluated CDI. Recurrence, sepsis and infection-related death were examined. Factors associated with CDI were also evaluated. RESULTS Forty-three CDI occurred in 37 of 341 (10.9%) patients during 42 of 1277 (3.3%) courses of chemotherapy. There were 6 children with multiple episodes of CDI. Three infections were associated with sepsis, and no children died of CDI. Only 2 children had an associated enterocolitis. Both days of broad-spectrum antibiotics (odds ratio 1.03, 95% confidence interval: 1.01 to 1.06; P = 0.003) and at least 1 microbiologically documented sterile site infection (odds ratio 10.81, 95% confidence interval: 5.88 to 19.89; P < 0.0001) were independently associated with CDI. CONCLUSIONS CDI occurred in 11% of children receiving intensive chemotherapy for AML, and outcomes were not severe. CDI is not a prominent issue in pediatric AML in terms of prevalence, incidence or associated outcomes.

Summary Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in paediatric acute myeloid leukaemia (AML). This study describes risk factors for IFI and IFI-related sepsis in this population. We conducted a population-based, retrospective cohort study of children with AML in Canada. IFIs during chemotherapy and prior to haematopoietic stem cell transplantation, relapse, persistent disease or death were identified. Risk factors for proven or probable IFI were examined. Among courses complicated by IFI, risk factors for sepsis were also evaluated. There were 341 children with AML included of which 41 (12.0%) experienced 46 different episodes of IFI. Candida species accounted for 23 (50.0%) of IFIs and Aspergillus spp. accounted for 14 (30.4%). Days of broad-spectrum antibiotics, days of corticosteroids and neutropenia at start of the course were independently associated with IFI. Only days of fever were independently associated with IFI-related sepsis. Invasive fungal infections occurred in 12.0% of paediatric AML patients. Risk factors for IFI and IFI-related sepsis were identified. This knowledge may help to consider targeted strategies.

In Canada, CNS tumors accounted for nearly 22% of the new childhood cancer diagnoses during 1995–2000 in the ≤15 year age group. The study’s objective was to describe children and youth (age

There is a paucity of published literature on the epidemiology of childhood acute leukemias and lymphomas in Canada. This study was designed to describe children and youth (age20 years) diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL) in Alberta, Canada, during 22 fiscal years. The Alberta Cancer Registry was used to extract data all ALL, AML, HL, and NHL cases diagnosed between April 1, 1982, and March 31, 2004. Population data for Alberta were also obtained. Descriptive statistics and cluster detection tests were used. During 22 years, 525, 117, 257, and 111 children (total = 1010) were diagnosed with ALL, AML, HL, and NHL, respectively. The median ages at diagnosis were 4, 11, 16, and 12 years for ALL, AML, HL, and NHL, respectively. The majority were male for ALL (287/525, 55%), AML (64/117, 55%), and NHL (81/111, 73%), and female for HL (133/257, 52%). The crude rates per 100,000 children were variable, without significant trends, over time and for each diagnosis; the median annual rates, per 100,000 children, were 3.00 (ranging from 1.87 to 3.75) for ALL, 0.62 (ranging from 0.26 to 1.27) for AML, 1.42 (ranging from 0.76 to 2.67) for HL, and 0.54 (ranging from 0.24 to 1.40) for NHL. A few potential spatiotemporal clusters were identified. They are likely due to small number of cases and plausibly clinically insignificant. Overall, childhood leukemia and lymphoma rates in Alberta have remained relatively stable, with no clear epidemiological trends and no significant spatiotemporal clustering. Further investigations are warranted to see if such stability continues and if spatiotemporal patterns arise from longer studies and studies in larger geographic regions with a larger sample size, whilst analyzing for other causal/associated factors, individual susceptibilities, and disease outcomes.

CONTEXT: Clinical diagnosis of pediatric meningitis is fundamental; therefore, familiarity with evidence underscoring clinical features suggestive of meningitis is important. OBJECTIVE: To seek evidence supporting accuracy of clinical features of pediatric bacterial meningitis. METHODS: A review of Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, Web of Science, and PubMed was conducted for all articles of relevance. Articles contained prospective data of clinical features in children with laboratory-confirmed bacterial meningitis and in comparison groups of those without it. Two authors independently assessed quality and extracted data to calculate accuracy data of clinical features. RESULTS: Of 14 145 references initially identified, 10 met our inclusion criteria. On history, a report of bulging fontanel (likelihood ratio [LR]: 8.00 [95% confidence interval (CI): 2.4–26]), neck stiffness (7.70 [3.2–19]), seizures (outside febrile-convulsion age range) (4.40 [3.0–6.4]), or reduced feeds (2.00 [1.2–3.4]) raised concern about the presence of meningitis. On examination, jaundice (LR: 5.90 [95% CI: 1.8–19]), being toxic or moribund (5.80 [3.0–11]), meningeal signs (4.50 [2.4–8.3]), neck stiffness (4.00 [2.6–6.3]), bulging fontanel (3.50 [2.0–6.0]), Kernig sign (3.50 [2.1–5.7]), tone up (3.20 [2.2–4.5]), fever of >40°C (2.90 [1.6–5.5]), and Brudzinski sign (2.50 [1.8–3.6]) independently raised the likelihood of meningitis. The absence of meningeal signs (LR: 0.41 [95% CI: 0.30–0.57]) and an abnormal cry (0.30 [0.16–0.57]) independently lowered the likelihood of meningitis. The absence of fever did not rule out meningitis (LR: 0.70 [95% CI: 0.53–0.92]). CONCLUSIONS: Evidence for several useful clinical features that influence the likelihood of pediatric meningitis exists. No isolated clinical feature is diagnostic, and the most accurate diagnostic combination is unclear.

Objectives The objective of this study was to describe children and youth

Background Sickle cell disease is a genetically inherited red blood cell disorder which features pain as a predominant manifestation. Objectives To review the evidence within Cochrane systematic reviews on the management of pain associated with vaso-occlusive crises and priapism secondary to sickle cell disease in paediatric populations. Methods The Cochrane Library of Systematic Reviews was searched for all reviews that addressed interventions to relieve pain associated with sickle cell disease. Reviews that primarily addressed the reduction of sickle cell crises were excluded. Data were extracted from included reviews. Results Three reviews were included. One review examined pharmacological interventions to relieve pain associated with vaso-occlusive pain crises. One trial in children reported a significant reduction in VAS scores associated with ketorolac administration versus pethidine, but another trial performed in adults showed no significant reduction in VAS scores when ketorolac was compared to placebo. Two trials found that parenterally delivered corticosteroids reduced the length of analgesic therapy compared to placebo, and another trial found that there was no difference in the pain scores of children when morphine was delivered either parenterally or orally. Two trials reported on long-term psychological interventions to manage pain. One found that coping skills training in children resulted in a reduction in the tendency to report pain, while the other trial found that cognitive behavioural therapy in adolescents and adults resulted in a decrease in the emotional component of pain but not the sensory component. One review addressed the treatment of stuttering priapism in boys and men using stilboestrol, but included an insufficient number of patients to draw a conclusion. Authors' Conclusions Pharmacological interventions to treat vaso-occlusive pain crises show mixed results in the use of ketorolac and no difference between parenteral versus oral administration of morphine. Psychological interventions for vaso-occlusive crises demonstrated benefit in improving some components of pain. Evidence regarding treatment of priapism was weak. Further studies should employ multi-centre trials and begin to address generalisability concerns by more focus in Africa, where the majority of patients with sickle cell disease reside. Copyright © 2008 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration

Little is known about the impact of enrollment on therapeutic clinical trials on adverse event rates. Primary objective was to describe the impact of clinical trial registration on sterile site microbiologically documented infection for children with newly diagnosed acute myeloid leukemia (AML). We conducted a multicenter cohort study that included children aged ≤18 years with de novo AML. Primary outcome was microbiologically documented sterile site infection. Infection rates were compared between those registered and not registered on clinical trials. Five hundred seventy-four children with AML were included of which 198 (34.5%) were registered on a therapeutic clinical trial. Overall, 400 (69.7%) had at least one sterile site microbiologically documented infection. In multiple regression, registration on clinical trials was independently associated with a higher risk of microbiologically documented sterile site infection [adjusted odds ratio (OR) 1.24, 95% confidence interval (CI) 1.01-1.53; p = 0.040] and viridans group streptococcal infection (OR 1.46, 95% CI 1.08-1.98; p = 0.015). Registration on trials was not associated with Gram-negative or invasive fungal infections. Children with newly diagnosed AML enrolled on clinical trials have a higher risk of microbiologically documented sterile site infection. This information may impact on supportive care practices in pediatric AML.

Summary. Haemophilia care is effective but therapy is expensive. Despite concentrates being available in some areas for more than 30 years, many scientific questions concerning the management of haemophilia, such as what doses and duration of factor are required for different bleeding episodes or for surgical procedures, remain inadequately answered. Modern rigorous methods of assessment of the evidence both assist in determining what facts are available, how reliable the evidence is, and also help to define what studies need to be done. Cochrane methodology can be applied to haemophilia, and an assessment of prophylaxis provides an example. International collaborative studies would be valuable and require enthusiastic participants.

Background: A 2010 study of preceptorship as a clinical teaching model in Ghana revealed weaknesses related to high student-preceptor ratios and inadequate support from faculty in the educational institution. A four-cycle community-based participatory action research study was designed to further delineate clinical teaching and learning issues and partner with Ghanaian stakeholders in critical analysis of possibilities for positive change in clinical nursing education. The purpose of this paper, taken from Cycle One of the study, is to provide understanding of the challenges of the current clinical teaching model(s) used in the study institution from the perspectives of students and faculty. Early engagement of external stakeholders is described.Methods: Each university target group was invited to complete a semi-structured questionnaire. Interviews were conducted with representatives from the Ministry of Health, the Nursing and Midwifery Council of Ghana, and the Ghana Registered Nurses’ and Midwives’ Association. Clinical documents were examined.Results: Clinical teaching and learning issues identified included the need for: a) more effective clinical teaching and supervision; b) adequate equipment for practice; c) meaningful evaluation of performance; d) enhanced collaboration between the school and clinical settings; and, e) reduced travel time to clinical opportunities. External stakeholders became aware and supportive of the research endeavour.Conclusions: Participants acknowledged changes are needed in order to improve clinical nursing education in Ghana. Clinical teaching and learning issues were identified and formed a baseline from which more in-depth discussion of resources, constraints and possibilities for change could ensue in subsequent cycles of the study.

Several influential national/international bodies including The Bologna Accord, The Carnegie Foundation and The Future of Medical Education in Canada (FMEC) have called for increased coordination across the medical education continuum. FMEC recognizes accreditation as a ‘‘powerful lever’’ and encourages the alignment of undergraduate and postgraduate standards. The Carnegie Foundation includes a similar call for the creation of a more coherent accreditation system. As a first step, using the Canadian context, we present a methodological approach that assesses the example of how well LCME/CACMS undergraduate accreditation standards align with the Royal College of Physician and Surgeons of Canada (RCPSC) postgraduate training standards. We analyzed how closely the 132 LCME/CACMS Medical School accreditation standards aligned with the 155 post-graduate standards from the RCPSC accreditation General Standards (A and B). This comparative evaluation demonstrates that the standards do not align closely. Gaps, redundancies and key differences are highlighted. These results are the first step in understanding how accreditation needs to be adapted and re-aligned across the education continuum to provide consistent and coordinated training and these methods could easily be applied to other contexts and jurisdictions.

Background Children with Down syndrome (DS) are at high risk of infectious toxicity when treated with acute lymphoblastic leukemia chemotherapy protocols optimized in children without DS. Our objective was to determine if children with DS and acute myeloid leukemia (AML) have a different risk of infection when treated with chemotherapy protocols developed for children with DS compared to AML treatment protocols developed for children without DS. Methods We conducted a retrospective, population-based cohort study that included DS children ≤ 18 years of age with de novo, non-M3 AML diagnosed between January 1995 and December 2004, and treated at 15 Canadian centers. Patients were monitored for infection from initiation of AML treatment until recovery from the last cycle of chemotherapy, conditioning for hematopoietic stem cell transplantation, relapse, persistent disease or death (whichever occurred first). Trained research associates abstracted all information from each site. Results There were 31 children with DS included; median age was 1.7 (range 0.1-11.1) years. Eleven were treated according to a DS-specific protocol while 20 were treated with non-DS specific protocols. A total of 157 courses of chemotherapy were delivered. Microbiologically documented sterile site infection occurred in 11.9% and 14.3% of DS-specific and non-DS specific AML treatment courses respectively. Sepsis was rare and there were no infection-related deaths. In multiple regression, treatment with a DS-specific protocol was independently associated with a reduction in microbiologically documented sterile site infection (adjusted odds ratio (OR) 0.65, 95% confidence interval (CI) 0.42-0.99; P = 0.044), and clinically documented infection (adjusted OR 0.36, 95% CI 0.14-0.91; P = 0.031) but not bacteremia (adjusted OR 0.73, 95% CI 0.44-1.22; P = 0.231). Conclusions Our study suggests that children with DS do not experience excessive infectious toxicity during treatment for AML compared to children without DS. Incorporation of DS-specific AML treatment protocols is associated with a more favorable infection profile for children with DS-AML.

Viridans group streptococci (VGS) cause significant morbidity in children treated for acute myeloid leukemia (AML). Our goals were to determine the occurrence and impact of these infections in children treated for AML and to understand the factors that increase the risk of VGS infections and viridans streptococcal shock syndrome (VSSS) in this population.We conducted a retrospective, population-based cohort study that included children ≤18 years of age with de novo AML treated at 15 Canadian centers. We evaluated factors related to VGS infection and VSSS.Among 341 children with AML, VGS occurred in 78 (22.9%) children over the entire course of therapy and 16 had recurrent episodes. VGS infection occurred in 97 of 1277 courses of chemotherapy (7.6%). VSSS occurred in 19.6% of these episodes and included 11 patients who required intensive care services with 2 VGS infections resulting in death. In multiple regression analysis, factors independently related to VGS included treatment on a Medical Research Council-based protocol (odds ratio (OR) 2.87, 95% confidence interval (CI) 1.53-5.39; P = 0.001), cytarabine dose per gram/m² (OR 1.04, 95% CI 1.01-1.07; P = 0.002) and prolonged neutropenia (OR 1.58, 95% CI: 0.97-2.56; P = 0.06). None of the evaluated factors were predictive of VSSS.VGS infections occur in 7.6% of chemotherapy courses and remain an important cause of morbidity and even mortality in children being treated for AML. Interventions to reduce VGS need to be identified.

Background It is not known whether children with acute promyelocytic leukemia (APL) have an infection risk similar to non- APL acute myeloid leukemia. The objective was to describe infectious risk in children with newly diagnosed APL and to describe factors associated with these infections. Methods We conducted a retrospective, population-based cohort study that included children ≤ 18 years of age with de novo APL treated at 15 Canadian centers. Thirty-three children with APL were included; 78.8% were treated with APL -specific protocols. Results Bacterial sterile site infection occurred in 12 (36.4%) and fungal sterile site infection occurred in 2 (6.1%) children. Of the 127 chemotherapy courses, 101 (79.5%) were classified as intensive and among these, the proportion in which a sterile site microbiologically documented infection occurred was 14/101 (13.9%). There was one infection-related death. Conclusions One third of children with APL experienced at least one sterile site bacterial infection throughout treatment and 14% of intensive chemotherapy courses were associated with a microbiologically documented sterile site infection. Infection rates in pediatric APL may be lower compared to non- APL acute myeloid leukemia although these children may still benefit from aggressive supportive care during intensive chemotherapy.

Reason for withdrawal from publication Withdraw To view the published versions of this article, please click the 'Other versions' tab.

Background:The primary objective was to describe infectious complications in children with acute myeloid leukemia from presentation to the healthcare system to initiation of chemotherapy and to describe how these infections differ depending on neutropenia.Methods:We conducted a retrospective, population-based cohort study that included children and adolescents with acute myeloid leukemia diagnosed and treated at 15 Canadian centers. We evaluated infections that occurred between presentation to the healthcare system (for symptoms that led to the diagnosis of acute myeloid leukemia) until initiation of chemotherapy.Results:Among 328 children, 92 (28.0%) were neutropenic at presentation. Eleven (3.4%) had sterile-site microbiologically documented infection and four had bacteremia (only one Gram negative). Infection rate was not influenced by neutropenia. No child died from an infectious cause prior to chemotherapy initiation.Conclusion:It may be reasonable to withhold empiric antibiotics in febrile non-neutropenic children with newly diagnosed acute myeloid leukemia until initiation of chemotherapy as long as they appear well without a clinical focus of infection. Future work could examine biomarkers or a clinical score to identify children presenting with leukemia and fever who are more likely to have an invasive infection. © 2013 Portwine et al.

HEPARIN-INDUCED thrombocytopenia (HIT) is an infrequent complication of heparin therapy. 1 A unique problem arises in patients with HIT who need anticoagulation, especially if urgent cardiac surgery is planned. We report a case of HIT in an infant in which Argatroban (GlaxoSmithKline, Middlesex, UK) was used as anticoagulant during cardiopulmonary bypass (CPB) and the unsuccessful use of recombinant activated factor VII (rF-VIIa) to reverse the anticoagulant effects postoperatively.

Background. Infection continues to be a major problem for children with acute myeloid leukemia (AML). Objectives were to identify factors associated with infection, sepsis, and infectious deaths in children with newly diagnosed AML.Methods. We conducted a retrospective, population-based cohort study that included children ≤18 years of age with de novo, non-M3 AML diagnosed between January 1995 and December 2004, treated at 15 Canadian centers. Patients were monitored for infection from initiation of AML treatment until recovery from the last cycle of chemotherapy, conditioning for hematopoietic stem cell transplantation, relapse, persistent disease, or death (whichever occurred first). Consistent trained research associates abstracted all information from each site.Results. 341 patients were included. Median age was 7.1 years (interquartile range [IQR], 2.0-13.5) and 29 (8.5%) had Down syndrome. In sum, 26 (7.6%) experienced death as a first event. There were 1277 courses of chemotherapy administered in which sterile site microbiologically documented infection occurred in 313 courses (24.5%). Sepsis and infectious death occurred in 97 (7.6%) and 16 (1.3%) courses, respectively. The median days of corticosteroid administration was 2 per course (IQR, 0-6). In multiple regression analysis, duration of corticosteroid exposure was significantly associated with more microbiologically documented sterile site infection, bacteremia, fungal infection, and sepsis. The only factor significantly associated with infectious death was days of corticosteroid exposure (odds ratio, 1.05; 95% confidence interval, 1.02-1.08; P =. 001).Conclusions. In pediatric AML, infection, sepsis, and infectious death were associated with duration of corticosteroid exposure. Corticosteroids should be avoided when possible for this population. © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

This article was migrated. The article was not marked as recommended. Attendance at scheduled learning activities enhances medical students' education and demonstrates professionalism.This study explores the relationship between attendance and psychological distress in a cohort of medical learners.We recorded the attendance of pre-clinical students at compulsory activities over two years. Counselors in our learner support program were asked to anonymously indicate whether individual learners had sought assistance for psychological distress. The study protocol was approved by the University of Alberta's Research Ethics and Privacy Offices.One hundred and seventy students recorded 965 absences. The mean (SD) of absences per student was 5.68 (5.56). Twenty one (12%) students had significant psychological distress. There was a negative correlation (r = - 0.33) between absences and academic performance. The correlation between absences and psychological distress was moderate (r = 0.63). The mean (SD) number of absences among students without distress was 4.37 (3.46). Among those with distress, the mean (SD) number of absences was 14.95 (8.32). The difference was significant (p < 0.0001) with an effect size of Cohen's d = 3.06.In the culture of medical school, absences are often interpreted as a lack of moral fitness for the profession, and attendance policies are designed accordingly. However, absenteeism may be symptomatic of psychological distress. If so, institutional regulations could be modified to address this more effectively.

We evaluated single nucleotide polymorphisms (SNPs) associated with infection risk in children with newly diagnosed acute myeloid leukaemia (AML). We conducted a multicentre, prospective cohort study that included children aged ≤18 years with de novo AML. DNA was isolated from blood lymphocytes or buccal swabs, and candidate gene SNP analysis was conducted. Primary outcome was the occurrence of microbiologically documented sterile site infection during chemotherapy. Secondary outcomes were Gram-positive and -negative infections, viridans group streptococcal infection and proven/probable invasive fungal infection. Interpretation was guided by consistency in risk alleles and microbiologic agent with previous literature. Over the study period 254 children and adolescents with AML were enrolled. Overall, 190 (74.8%) had at least one sterile site microbiologically documented infection. Among the 172 with inferred European ancestry and DNA available, nine significant associations were observed; two were consistent with previous literature. Allele A at IL1B (rs16944) was associated with decreased microbiologically documented infection, and allele G at IL10 (rs1800896) was associated with increased risk of Gram-positive infection. We identified SNPs associated with infection risk in paediatric AML. Genotype may provide insight into mechanisms of infection risk that could be used for supportive-care novel treatments.

Objective: The goal was to determine whether young children and their parents prefer physicians wearing clear face shields or surgical masks. Methods: Eighty children (4–10 years of age) and their guardians were recruited from a pediatric emergency department. A survey and color photographs of the same male and female physicians wearing face shields and surgical masks were distributed. The parents were asked to decide which set of physicians they would prefer to care for their children and with which set of physicians they thought their children would be most comfortable. The children then were asked to decide which set of physicians they would prefer to take care of them and why. The children also were asked whether they found any of the physicians frightening and, if so, why. Results: Fifty-one percent of parents preferred the pictures of physicians wearing face shields, and 62% thought that their children would choose the physicians in the face shields because their faces were visible and therefore less frightening. However, 59% of children stated that either set of physicians would be fine and neither was frightening; if given a choice, 49% would choose physicians in face shields. Conclusions: Physicians and parents have a perception that surgical masks are frightening to all children. Our study has shown that this perception is not completely true. Face shields may be a better choice, however, because both parents and children would prefer this option.

Background:The onset of progressive cerebellar ataxia in early childhood is considered a key feature of ataxiatelangiectasia (A-T), accompanied by ocular apraxia, telangiectasias, immunodeficiency, cancer susceptibility and hypersensitivity to ionizing radiation.Methods:We describe the clinical features and course of three Mennonite children who were diagnosed with A-T following the completion of therapy for lymphoid malignancies.Results:Prior to cancer therapy, all had non-progressive atypical neurological abnormalities, with onset by age 30 months, including dysarthria, dyskinesia, hypotonia and/or dystonia, without telangiectasias. Cerebellar ataxia was noted in only one of the children and was mild until his death at age eight years. None had severe infections. All three children were “cured” of their lymphoid malignancies, but experienced severe adverse effects from the treatments administered. The two children who received cranial irradiation developed supratentorial primitive neuroectodermal tumors of the brain, an association not previously described, with fatal outcomes.Conclusions:The range of neurological presentations of A-T is broad. Ataxia and telangiectasias may be minimal or absent and the course seemingly non-progressive. The diagnosis of A-T should be considered in all children with neuromotor dysfunction or peripheral neuropathy, particularly those who develop lymphoid malignancies. The consequences of missing the diagnosis may be dire. Radiation therapy and radiomimetic drugs should be avoided in individuals with A-T.

A male patient with B-cell lymphoma was treated with chemotherapy and allogeneic bone marrow transplant, including preparatory total body irradiation. Ten years later, at age 15 years, the patient developed an autonomous thyroid nodule and an incidental papillary microcarcinoma. This is the first report of an autonomous thyroid nodule after total body irradiation for bone marrow transplant. The case is presented and the literature is reviewed.

*Institute of Internal & Cardiovascular Medicine, University of Perugia, Perugia, Italy; Department of Paediatrics, University of Alberta,Edmonton, Canada; and Departments of Clinical Haematology and Molecular Diagnostics, Manchester Royal Infirmary, Manchester, UKTo cite this article: Iorio A, Stobart K, Bolton-Maggs P. Can evidence harm? Certainly not hemophilia treatment and community. J ThrombHaemost 2006; 4: 505–6.See also Mannucci PM. Need for randomized trials in hemophilia. This issue, pp 501–2; Aledort L, Ljung R, Blanchette V on behalf of theInternational Prophylaxis Study Group. Are randomized clinical trials the only truth? Not always. This issue, pp 503–4; Srivastava A; Konkle B;Blanchette V; Makris M. Uncertain times for research on hemophilia and allied disorders. This issue, pp 680–3.

Introduction: One of the current approaches to managing persons with hemophilia entails the use of prophylactic treatment with clotting factor concentrates (CFC) to prevent bleeds and bleeding related complications. However, this process is not practiced in all countries, or is based on the synthesis of evidence from data of all trials. Objective: To conduct a systematic review/meta-analysis (SR/MA) regarding the effectiveness of clotting factor concentrate prophylaxis in the management of people with hemophilia A or B. Methods: We conducted a SR of all randomized controlled trials (RCTs) that studied the effect of prophylactic CFCs in people with hemophilia A or B. We searched all major electronic databases (MEDLINE, LILACS, EMBASE, and the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Controlled Trials Register) as well as performing handsearches of journals and relevant meeting abstract books. We included RCTs that that compared the use of prophylactic CFCs to a control group. Results: We identified 29 studies, of which four (including 37 participants) were eligible for inclusion. Three studies evaluated hemophilia A; one showed a decrease in frequency of joint bleeds with prophylaxis compared to placebo (non-physiological dose), with a rate difference (RD) −10.80 (95% confidence interval (CI) −16.33 to −5.27) bleeds per year. The remaining two studies evaluating hemophilia A compared two prophylaxis regimens, one study showed no difference in joint bleed frequency, RD −5.04 (95%CI −17.02 to 6.94) bleeds per year and another failed to demonstrate an advantage of factor VIII dosing based on individual pharmacokinetic data over the standard prophylaxis regimen with RD −0.14 (95% CI −1.34 to 1.05) bleeds per year. The fourth study evaluated hemophilia B and showed fewer joint bleeds with weekly (15 IU/kg) versus bi-weekly (7.5 IU/kg) prophylaxis, RD −3.30 (95% CI −5.50 to − 1.10) bleeds per year. Conclusion: There is insufficient evidence to determine whether prophylactic clotting factor concentrates decrease bleeding and bleeding-related complications in hemophilia A or B, compared to placebo, on-demand treatment, or prophylaxis based on pharmacokinetic data from individuals. Well-designed RCTs are needed to assess the effectiveness of prophylactic clotting factor concentrates.

Background The hallmark of severe hemophilia is recurrent bleeding into joints and soft tissues with progressive joint damage, notwithstanding on-demand treatment. Prophylaxis has long been used but not universally adopted because of medical, psychosocial, and cost controversies. Objectives To determine the effectiveness of clotting factor concentrate prophylaxis in the management of people with hemophilia A or B. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register. In addition, we searched major electronic databases (MEDLINE, EMBASE, CENTRAL), handsearched relevant journals and abstract books and reference lists of relevant articles. Last search of Group's Coagulopathies Trials Register: 07 April 2011. Selection criteria Randomised controlled trials and quasi-randomised controlled trials evaluating people with severe hemophilia A or hemophilia B receiving prophylactic clotting factor concentrates. Data collection and analysis Two authors independently reviewed studies for eligibility, assessed risk of bias and extracted data. Main results Six studies (including 142 participants) were eligible for inclusion. Two compared three-times-a-week prophylactic administration with on-demand treatment in children with hemophilia. Pooled results from these two studies showed a rate ratio of 0.30 (95% confidence interval; 0.12 to 0.76) for all bleedings and 0.22 (95% confidence interval 0.08 to 0.63) for joint bleedings favouring prophylaxis. Results on the number of patients with preserved joints after three to seven years of follow-up were not pooled due to significant heterogeneity. Three of the remaining four studies evaluated hemophilia A; one showed a statistically significant decrease in frequency of joint bleeds with prophylaxis compared to placebo, with a rate difference of -10.73 (95% confidence interval -16.55 to -4.91) bleeds per year. Two studies compared two prophylaxis regimens, failing to demonstrate an advantage of one regimen over the other in terms of bleeding frequency. The fourth study evaluated hemophilia B and showed fewer joint bleeds with weekly (15 IU/kg) versus bi-weekly (7.5 IU/kg) prophylaxis, rate difference -3.30 (95% confidence interval -5.50 to -1.10) bleeds per year. Non-significant increases in both inhibitor and infectious complications were observed in patients on prophylaxis, which occurred more often when using long-term venous access. Authors' conclusions There is strong evidence from randomised controlled trials and observational trials that prophylaxis preserves joint function in children with hemophilia as compared to on-demand treatment. There is insufficient evidence from randomised controlled trials to confirm the observational evidence that prophylaxis decreases bleeding and related complications in patients with existing joint damage. Well-designed randomised controlled trials and prospective observational controlled studies are needed to establish the best prophylactic regimen and to assess the effectiveness of prophylactic clotting factor concentrates in adult patients.