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The primary objective was to describe predictors of physical, emotional and social quality of life (QoL) in children receiving active treatment for cancer. This Canadian multi-institutional cross-sectional study included children with cancer receiving any type of active treatment. The primary caregiver provided information on child physical, emotional and social QoL according to the PedsQL 4.0 Generic Core scales. Between November 2004 and February 2007, 376 families provided the data. In multiple regression, children with acute lymphoblastic leukemia had better physical health (OR: 0.37, 95% CI 0.23, 0.60; P<0.0001) while intensive chemotherapy treatment (OR: 2.34, 95% CI: 1.42, 3.85; P=0.0008) and having a sibling with a chronic condition (OR: 2.53, 95% CI: 1.54, 4.15; P=0.0002) were associated with poor physical QoL. Better emotional health was associated with good prognosis, less intensive chemotherapy treatment and greater household savings, whereas female children and those with a sibling with a chronic condition had poor social QoL. Physical, emotional and social QoL are influenced by demographic, diagnostic and treatment variables. Sibling and household characteristics are associated with QoL. This information will help to identify children at higher risk of poor QoL during treatment for cancer. [ABSTRACT FROM AUTHOR]

A sound and comprehensive knowledge base about symptoms in children experiencing cancer is necessary if health care professionals hope to effectively manage their symptoms. To date, there is still much to be discovered about how children with cancer and their families experience childhood cancer symptoms. Accordingly, a longitudinal qualitative study was undertaken between July 1998 and December 2000 to explore and describe the childhood cancer symptom course from the perspectives of children and their families. The study was conducted in three settings: the participants' homes and both an inpatient and outpatient pediatric cancer unit located in Western Canada. Thirty-nine children (4 1/2- to 18-year-old males and females) with mixed cancer diagnoses and their families (parents and siblings) participated in the study. The majority of the children were diagnosed with either leukemia or lymphoma (72%), had siblings (87%), and two parents (87.2%), and remained in remission at the completion of the study (90%). All the children received chemotherapy either alone (56%) or in combination with surgery (18%), radiation (5%), radiation and bone marrow transplant (8%), radiation and surgery (10%), and surgery, radiation, and bone marrow transplant (3%). Multiple methods of data collection were used including open-ended formal interviewing and participant observation. Interview and participant observation data were analyzed by the constant comparative method of data analysis. The creation of illness narratives added to the understanding of children's and families' experiences. In addition to providing a description of how the symptoms affected children's and families' daily living, findings related to how to health professionals can better understand and approach children's cancer symptoms emerged. When families, physicians, nurses, and other health professionals approached children's symptoms solely as side effects (e.g., nausea) or singular physical and psychological states, children provided minimal description of what they were actually experiencing. However, a greater understanding was achieved when the symptoms were approached as dynamic multidimensional experiences that occurred within a particular context. Children experienced symptoms as feeling states. Critical to children's feeling states were the meanings that children and their families assigned to the symptoms. Viewing cancer symptoms in the context of assigned meanings has implications for how symptoms are assessed and managed. The need to develop a children's symptom assessment tool based on assigned meanings is recommended. [ABSTRACT FROM AUTHOR]

Background/aims: The role of ustekinumab therapeutic drug monitoring in patients with Crohn's disease (CD) remains ambiguous. Examination of the association serum ustekinumab concentrations and endoscopic outcomes has yielded inconsistent results. Our study examined whether serum ustekinumab concentrations were associated with endoscopic healing in patients with moderate-to-severe CD., Methods: This was a cross-sectional study of adult patients with CD on maintenance ustekinumab. Patients were included if they had serum ustekinumab concentrations and endoscopic evaluation taken within 4 months of each other. Endoscopic healing was defined as absence of ulceration on endoscopy or Simplified Endoscopic Score for Crohn's disease (SES-CD) < 3. Quartile analysis of drug levels was performed, and receiver operating characteristic curve was calculated. Multivariate logistic regression assessed for the probability of endoscopic healing based on serum ustekinumab concentration., Results: Seventy-four patients were included in the final analysis. The mean serum ustekinumab concentration of the population was 6.10 mcg/mL. Serum ustekinumab concentration did not predict endoscopic remission based on either the absence of ulceration or SES-CD < 3. There was no difference in the frequency of ulceration at increasing serum ustekinumab concentrations. There was no threshold serum ustekinumab concentration associated with the absence of ulceration (area under the curve [AUC] = 0.50) or SES-CD < 3 (AUC = 0.49)., Conclusions: Our study found no association between serum ustekinumab concentrations and endoscopic remission in patients with CD. Exploration of mechanisms accounting for this lack of association is warranted., Competing Interests: D.M.P.D.F., B.A., R.Y., Y.A., P.G., A.B., and G.W. have no COI to declare. W.A. served as speaker, advisory board member, and/or clinical investigator for Abbvie, Amgen, BMS, Dynacare, Eli-Lilly, Janssen, Merck, Novartis, Pfizer, Prometheus, Sandoz, Sanofi, and Takeda. P.L.L. has been a speaker and/or advisory board member: AbbVie, Amgen, BioJamp, Bristol Myers Squibb, Fresenius Kabi, Genetech, Gilead, Janssen, Merck, Mylan, Organon, Pendopharm, Pfizer, Roche, Sandoz, Takeda, Tillots, and Viatris, and has received unrestricted research grant: AbbVie, Gilead, Takeda, and Pfizer. T.B. acted as a speaker or advisor for Abbvie, Alimentiv, Amgen, Bristol-Myers-Squibb, Eli Lilly, Ferring, Fresenius Kabi, Gilead, Iterative Scopes, Janssen, Pendopharm, Merck, Pentax, Pfizer, Roche, Sandoz, Takeda, and Viatris., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn's & Colitis Foundation.)

Background & Aims: Clinical and radiologic variables associated with perianal fistula (PAF) outcomes are poorly understood. We developed prediction models for anti-tumor necrosis factor (TNF) treatment failure in patients with Crohn's disease-related PAF., Methods: In a multicenter retrospective study between 2005 and 2022 we included biologic-naive adults (>17 years) who initiated their first anti-TNF therapy for PAF after pelvic magnetic resonance imaging (MRI). Pretreatment MRI studies were prospectively reread centrally by blinded radiologists. We developed and internally validated a prediction model based on clinical and radiologic parameters to predict the likelihood of anti-TNF treatment failure, clinically, at 6 months. We compared our model and a simplified version of MRI parameters alone with existing imaging-based PAF activity indices (MAGNIFI-CD and modified Van Assche MRI scores) by De Long statistical test., Results: We included 221 patients: 32 ± 14 years, 60% males, 76% complex fistulas; 68% treated with infliximab and 32% treated with adalimumab. Treatment failure occurred in 102 (46%) patients. Our prediction model included age at PAF diagnosis, time to initiate anti-TNF treatment, and smoking and 8 MRI characteristics (supra/extrasphincteric anatomy, fistula length >4.3 cm, primary tracts >1, secondary tracts >1, external openings >1, tract hyperintensity on T1-weighted imaging, horseshoe anatomy, and collections >1.3 cm). Our full and simplified MRI models had fair discriminatory capacity for anti-TNF treatment failure (concordance statistic, 0.67 and 0.65, respectively) and outperformed MAGNIFI-CD (P = .002 and < .0005) and modified Van Assche MRI scores (P < .0001 and < .0001), respectively., Conclusions: Our risk prediction models consisting of clinical and/or radiologic variables accurately predict treatment failure in patients with PAF., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether the use of proton pump inhibitors (PPIs) compared with the use of histamine-2 receptor antagonists (H2RAs) is associated with an increased risk of inflammatory bowel disease (IBD)., Design: Population-based cohort study designed to address the impact of protopathic bias., Setting: General practices contributing data to the UK Clinical Practice Research Datalink GOLD., Participants: 1 498 416 initiators of PPIs and 322 474 initiators of H2RAs from 1 January 1990 to 31 December 2018, with follow-up until 31 December 2019. Patients were analysed according to the timing of the IBD diagnosis after treatment initiation (early vs late)., Main Outcome Measures: Standardised morbidity ratio weighted Cox proportional hazards models were used to estimate marginal HRs and 95% CIs. In the early-event analysis, IBD diagnoses were assessed within the first 2 years of treatment initiation, an analysis subject to potential protopathic bias. In the late-event analysis, all exposures were lagged by 2 years to account for latency and minimise protopathic bias., Results: In the early-event analysis, the use of PPIs was associated with an increased risk of IBD within the first 2 years of treatment initiation, compared with H2RAs (HR 1.39, 95% CI 1.14 to 1.69). In contrast, the use of PPIs was not associated with an increased risk of IBD in the late-event analysis (HR 1.05, 95% CI 0.90 to 1.22). The results remained consistent in several sensitivity analyses., Conclusions: Compared with H2RAs, PPIs were not associated with an increased risk of IBD, after accounting for protopathic bias., Competing Interests: Competing interests: RP, HY, RY and EGM have no conflicts of interest to disclose. DA is now employed by Pfizer. AB has been a member of Advisory Boards for Abbvie, Pfizer, Takeda, Janssen and Merck, and has received speaker fees from Abbvie, Janssen, Takeda, Pfizer. LA has received consulting and speaking fees from Janssen, Pfizer and Roche for work unrelated to this study., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The natural history of perianal Crohn disease (PCD) after fecal diversion in the era of biologics is poorly understood. We assessed clinical and surgical outcomes after fecal diversion for medically refractory PCD and determined the impact of biologics., Methods: We performed a retrospective, multicenter study from 1999 to 2020. Patients who underwent fecal diversion for refractory PCD were stratified by diversion type (ostomy with or without proctectomy). Times to clinical and surgical outcomes were estimated using Kaplan-Meier methods, and the association with biologics was assessed using multivariable Cox proportional hazards models., Results: Eighty-two patients, from 3 academic institutions, underwent a total of 97 fecal diversions: 68 diversions without proctectomy and 29 diversions with proctectomy. Perianal healing occurred more commonly after diversion with proctectomy than after diversion without proctectomy (83% vs 53%; P = 0.021). Among the patients who had 68 diversions without proctectomy, with a median follow-up of 4.9 years post-diversion (interquartile range, 1.66-10.19), 37% had sustained healing, 31% underwent surgery to restore bowel continuity, and 22% underwent proctectomy. Ostomy-free survival occurred in 21% of patients. Biologics were independently associated with avoidance of proctectomy (hazard ratio, 0.32; 95% confidence interval, 0.11-0.98) and surgery to restore bowel continuity (hazard ratio, 3.10; 95% confidence interval, 1.02-9.37), but not fistula healing., Conclusions: In this multicenter study, biologics were associated with bowel restoration and avoidance of proctectomy after fecal diversion without proctectomy for PCD; however, a minority of patients achieved sustained fistula healing after initial fecal diversion or after bowel restoration. These results highlight the refractory nature of PCD., (© 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Purpose: Unstable carotid plaques are a common cause of ischemic strokes. Identifying markers that reflect/contribute to plaque instability has become a prominent focus in cardiovascular research. The adipokines, resistin and chemerin, and ChemR23 (chemerin receptor), may play a role in carotid atherosclerosis, making them potential candidates to assess plaque instability. However, the expression and interrelationship of resistin and chemerin (and ChemR23) protein and mRNA within the carotid atherosclerotic plaque remains elusive. Thus, we investigated herein, the association between plaque mRNA and protein expression of resistin and chemerin (and ChemR23) and carotid plaque instability in humans, and whether sex differences exist in the relationship between these adipokines and plaque instability., Methods: Human carotid plaques were processed for immunohistochemical/mRNA analysis of resistin, chemerin, and ChemR23. Plaque instability was assessed by gold-standard histological classifications. A semi-quantitative scoring system was used to determine the intensity of adipokine expression on macrophages/foam cells, as well as the percentage of inflammatory cells stained positive. Plaque adipokine protein expression was also digitally quantified and mRNA expression was assessed by qRT-PCR., Results: Resistin and chemerin mRNA expression was 80% and 32% lower, respectively, in unstable versus stable plaques (P<0.05), while no difference in ChemR23 mRNA expression was observed. In contrast, greater resistin staining intensity and percentage of cells stained positive were detected in unstable versus stable plaques (P<0.01). Similarly, chemerin and ChemR23 staining intensity and percentage of cells stained were positively associated with plaque instability (P<0.05). No strong sex-specific relationship was observed between adipokines and plaque instability., Conclusions: This study examined the relationship between resistin, chemerin, and ChemR23, and carotid plaque instability, with a specific analysis at the plaque level. We reported a positive association between plaque instability and protein levels of resistin, chemerin, and ChemR23 but a negative association with resistin and chemerin mRNA expression. This suggests these adipokines exert proinflammatory roles in the process of carotid atherosclerosis and may be regulated via a negative feedback regulatory mechanism.

A tool can function as a body part yet not feel like one: Putting down a fork after dinner does not feel like losing a hand. However, studies show fake body-parts are embodied and experienced as parts of oneself. Typically, embodiment illusions have only been reported when the fake body-part visually resembles the real one. Here we reveal that participants can experience an illusion that a mechanical grabber, which looks scarcely like a hand, is part of their body. We found changes in three signatures of embodiment: the real hand's perceived location, the feeling that the grabber belonged to the body, and autonomic responses to visible threats to the grabber. These findings show that artificial objects can become embodied even though they bear little visual resemblance to the hand.

Background: Bariatric surgery is an effective treatment for severe obesity; however, high rates of psychiatric comorbidity complicate bariatric surgery care. As a result, importance has been placed on the need for ongoing psychiatric support in patients undergoing bariatric surgery. Given the lack of conclusive presurgery psychosocial predictors of postoperative mental health outcomes, studies have now shifted their focus to understand the long-term psychosocial sequalae that arise after surgery. Increasing evidence has demonstrated the potential for psychiatric care to stabilize psychiatric symptoms and minimize patient distress., Objective: To review psychopharmacological and psychological interventions for patients undergoing bariatric surgery and their impact on mental health and weight outcomes after surgery., Methods: We performed a comprehensive literature search in Ovid MEDLINE for studies examining the impact of psychopharmacological and psychological treatments on bariatric patients' postoperative mental health and weight outcomes., Results: Overall, 37 studies were included in the review. Preliminary evidence suggests that psychiatric medications do not negatively impact weight loss or health-related quality of life in the short term; however, more rigorous research designs are needed. There are insufficient data on specific psychiatric medications and long-term impact on weight loss and psychosocial outcomes. Postoperative psychological interventions have evidence for improving eating psychopathology, anxiety, and depressive symptoms; however, effects on weight loss remain unclear., Conclusion: Evidence for psychopharmacological and psychological treatments remains preliminary. Consideration should be given to integrated, stepped-care models to provide personalized psychiatric interventions after surgery. Future research on expanding current psychiatric interventions, timing of delivery, and predictors of response is needed., (Copyright © 2020 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: We aimed to describe the rates of psychiatric medication use in bariatric surgery candidates and factors associated with psychiatric medication use., Methods: Patients from the Toronto Western Hospital Bariatric Surgery Program were recruited from 2011 to 2014. Data extracted included demographics, clinical factors (e.g., mood disorder, anxiety disorder, eating disorder, Patient Health Questionnaire-9, Generalized Anxiety Disorder 7), and psychiatric medication use. Logistic regression analyses were used to examine the relationship between demographic variables, clinical factors, and psychiatric medication use. Multiple logistic regression was conducted to determine the predictors of clinical factors from demographic variables with psychiatric medication use., Results: A total of 262 (35.1%) patients were taking at least 1 psychiatric medication and 105 patients (14.1%) were taking more than 1 psychiatric medication. Antidepressants were the most common psychiatric medication reported. The majority of patients taking a psychiatric medication had a psychiatric illness, with 16.0% not having a lifetime diagnosis of a mental illness. Being male and being employed significantly predicted lower odds of being on a psychiatric medication. Older age significantly predicted higher odds of being on a psychiatric medication. Psychiatric disorders were significantly associated with psychiatric medication use independent of demographic variables., Conclusion: Our study provides insights into clinical and demographic factors related to psychiatric medication use in bariatric surgery patients. The findings support careful screening and clarification of psychiatric medications, especially in patients without a formal psychiatric diagnosis., (Copyright © 2018 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Germline SAMD9 and SAMD9L mutations cause a spectrum of multisystem disorders that carry a markedly increased risk of developing myeloid malignancies with somatic monosomy 7. Here, we describe 16 siblings, the majority of which were phenotypically normal, from 5 families diagnosed with myelodysplasia and leukemia syndrome with monosomy 7 (MLSM7; OMIM 252270) who primarily had onset of hematologic abnormalities during the first decade of life. Molecular analyses uncovered germline SAMD9L (n = 4) or SAMD9 (n = 1) mutations in these families. Affected individuals had a highly variable clinical course that ranged from mild and transient dyspoietic changes in the bone marrow to a rapid progression of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with monosomy 7. Expression of these gain-of-function SAMD9 and SAMD9L mutations reduces cell cycle progression, and deep sequencing demonstrated selective pressure favoring the outgrowth of clones that have either lost the mutant allele or acquired revertant mutations. The myeloid malignancies of affected siblings acquired cooperating mutations in genes that are also altered in sporadic cases of AML characterized by monosomy 7. These data have implications for understanding how SAMD9 and SAMD9L mutations contribute to myeloid transformation and for recognizing, counseling, and treating affected families.

Background: The incidence of isolated testicular relapse (ITR) of acute lymphoblastic leukemia (ALL) has decreased with contemporary treatment strategies, but outcomes are suboptimal with a 58% 5-year overall survival (OS). This study aimed to improve outcome in patients with ITR of B-cell ALL (B-ALL) occurring after 18 months of first clinical remission using intensive systemic chemotherapy and to decrease long-term sequelae by limiting use of testicular radiation., Procedure: Forty patients in first ITR of B-ALL were enrolled. Induction (dexamethasone, vincristine, daunorubicin, and intrathecal triple therapy) was preceded by one dose of high-dose methotrexate (MTX, 5 g/m 2 ). Following induction, 25 of 26 patients who had persistent testicular enlargement underwent testicular biopsy. Eleven had biopsy-proven disease and received bilateral testicular radiation (24 Gy), whereas twenty-nine did not., Results: Overall 5-year event-free survival (EFS)/OS was 65.0 ± 8.8%/73.1 ± 8.3%, with 5-year EFS 62.1 ± 11.0% vs. 72.7 ± 14.4% for patients who did not receive radiation therapy (XRT) (n = 29) compared with those who did (n = 11), respectively (P = 0.64). There were six second bone marrow relapses and six second ITRs. The proportion of second relapses was similar in the patients that received testicular radiation and those who did not. However, the 5-year OS was similar for patients who did not receive XRT (72.6 ± 10.2%) compared with those who did (72.7 ± 14.4%) (P = 0.85)., Conclusions: A 5-year OS rate of 73.1 ± 8.3% was obtained in children with first ITR of B-ALL occurring after 18 months of CR1 (length of first clinical remission) using intensive chemotherapy and limiting testicular radiation., (© 2017 Wiley Periodicals, Inc.)

TA-TMA is a post-hematopoietic stem cell transplant complication with clinical features of hemolytic anemia and thrombocytopenia. A 26-month-old child who had had an allogeneic transplant for treatment of DBA developed severe TA-TMA with heavy red blood cell and platelet transfusion dependence. Incidentally, he was found to have a lung sequestration. TA-TMA resolved and transfusion dependence resolved after resection of the sequestration. The finding suggests the malformation vasculature was selectively vulnerable to the trigger of TA-TMA-raising perhaps a clue to basic pathophysiology of TA-TMA and/or vascular malformations., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Given the prevalence and morbidity associated with delirium, there is a need for effective and efficient institutional approaches to delirium training in health care settings. Novel education methods, specifically the "flipped classroom" (FC) and "train-the-trainer" (TTT), have the potential to address these delirium training gaps. This study evaluates the effect of a TTT FC interprofessional delirium training program on participants' perceived ability to manage delirium, delirium knowledge, and clinicians' delirium assessment behaviors., Methods: FC Delirium TTT sessions were implemented in a large four-hospital network and consisted of presession online work and a 3-hour in-session component. The 156 TTT interprofessional participants who attended the sessions (ie, trainers) were expected to then deliver delirium training to their patient care units. Delirium care self-efficacy and knowledge test scores were measured before, after, and 6 months after the training session. Clinician delirium assessment rates were measured by chart audits before and 3 months after trainer's implementation of delirium training sessions., Results: Delirium knowledge test scores (7.8 ± 1.6 versus 9.7 ± 1.2, P < .001) and delirium care self-efficacy were significantly higher immediately after the TTT session compared with those of presession and these differences remained significant at 6-month after the TTT session. Trainer sessions significantly improved clinician delirium assessment rates from 53% for pretraining to 66% for posttraining., Discussion: Our data suggest that a TTT FC delirium training approach can improve participants' perceived delirium care skills and confidence, and delirium knowledge up to 6 months after the session. This approach provides a model for implementing hospitalwide delirium education that can change delirium assessment behavior while minimizing time and personnel requirements.

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., (© 2015 UICC.)

Purpose: The multiple late-effects experienced by survivors of childhood brain tumors, are not only a source of great distress for survivors, but also for their parents and siblings. The aim of this review is to systematically identify and synthesize qualitative evidence on how survivors of childhood brain tumors and their parents experience life after surviving childhood brain tumors., Methods: Based on literature search in seven databases, 10 qualitative studies, published between 2004 and 2014 were included., Results: Surviving a childhood brain tumor was experienced as paradox for survivors and their parents. While parents and survivors celebrated making it through the cancer experience, they nonetheless encountered a world with loss and new challenges. In short, the experience of survival was a bittersweet experience for survivors and their parents. Survivors and their parents experienced change that included living with uncertainty, intensification of the parenting role, a changing social world, a different way of being, and the need for additional help., Conclusion: Results from this synthesis reinforce that surviving a childhood brain tumor should be viewed as a point on a continuum of living with a brain tumor. Psychosocial effects of surviving brain cancer affect the entire family unit. A need for psychosocial support is evident, although development of such supports necessitates a more full understanding of challenges face by the child affected, their parents, and siblings. The limitations noted in this synthesis reinforce that more qualitative research is needed in this subject area., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusions: 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: 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.

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.

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.

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.

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.

Background: The impact of pandemic H1N1 influenza (pH1N1) virus in pediatric cancer is uncertain. The objectives of this study were to characterize the clinical course of pH1N1 and identify factors associated with severe outcomes., Methods: We conducted a Canadian multicenter retrospective review of children with cancer and stem cell transplant (SCT) recipients who were diagnosed with laboratory-confirmed pH1N1 infection between May 1, 2009 and January 31, 2010., Results: We identified 100 (19 in wave 1 and 81 in wave 2) cases of pH1N1 infection. Median age was 8.7 years. 71% had a hematologic malignancy, and 20% received SCT. Median duration of fever and illness was 2 and 12.5 days, respectively. 51 (51.5%) were hospitalized for a median of 5 days, with no deaths and only 1 requiring admission to the intensive care unit. Radiologically confirmed pneumonia was diagnosed in 10 (10%). Interruption of chemotherapy or conditioning occurred in 43 patients. In multivariable analyses, age <5 years (relative to ≥ 10 years) and neutropenia were associated with hospitalization while neutropenia was associated with pneumonia. Despite oseltamivir use in 89%, viral shedding was prolonged (median, 46 days) and often persisted after symptom resolution. However, an extended treatment course (>5 days) correlated with shortened duration of viral shedding (P=0.041)., Conclusions: pH1N1 infection in pediatric cancer and SCT patients infrequently caused complications but commonly interrupted cancer treatment. Persistent shedding of virus after illness resolution was common. Further research is needed to verify this finding as it could have implications for treatment guidelines and infection control practices., (© 2012 Blackwell Publishing Ltd.)

Objective: This study aimed to gain a better understanding of the fertility preservation services provided by Canadian fertility clinics to women with cancer., Methods: We invited a total of 76 fertility clinics across Canada to complete a mailed questionnaire related to the availability, accessibility, affordability, and utilization of fertility preservation services for oncology patients., Results: The total response rate was 59.2%: 72.4% for IVF clinics and 51.1% for fertility centres without on-site IVF. Not all the responding IVF centres accepted oncology referrals for women. Six clinics without on-site IVF accepted cancer patients for consultation. The medical consultation fees are covered by public health insurance in all provinces. The majority of respondents expedited the referrals to schedule an initial medical appointment within three days. Despite that, the referral volume reported by respondents was markedly low for all except two facilities. With over 4000 young women of reproductive age given a diagnosis of cancer each year in Canada, the findings suggest that cancer patients are severely under-served by fertility clinics., Conclusion: There is a need to develop a stronger partnership between the fields of oncology and reproductive medicine to further improve access of patients with cancer to fertility preservation services. Development of evidence-based practice guidelines covering medical, clinical, psychosocial, ethical, and legal aspects geared to the Canadian health care system would help to avoid ambiguity relating to the roles and responsibilities in the provision of fertility preservation services. Such processes would ensure optimization of services so that all young cancer patients would receive the best care in protecting their fertility.

Background: It is currently unknown how the intensive and often prolonged treatment of childhood cancer impacts on the lives of single parents. Our aims were to determine whether single parents differ from parents from two-parent families in terms of caregiver demand (the time and effort involved in caregiving), and health-related quality of life (HRQL)., Procedures: Forty single parents and 275 parents from two-parent families were recruited between November 2004 and February 2007 from five pediatric oncology centers in Canada. Parents were asked to complete a questionnaire booklet composed of items and scales to measure caregiver demand and HRQL (SF-36). The booklet also measured the following constructs: background and context factors, child factors, caregiving strain, intrapsychic factors, and coping factors., Results: Single parents did not differ from parents from two-parent families in caregiving demand and physical and psychosocial HRQL. Compared with Canadian population norms for the SF-36, both groups reported clinically important differences (i.e., worse health) in psychosocial HRQL (effect size ≥ -2.00), while scores for physical HRQL were within one standard deviation of population norms., Conclusion: Our findings suggest that the impact of caregiving on single parents, in terms of caregiving demand and HRQL is similar to that of parents from two-parent families., (Copyright © 2011 Wiley Periodicals, Inc.)

Research with parents of children with cancer has identified factors related to their adjustment and coping, but it is not fully understood why some parents do well and others do not. Guided by a stress process model, we examined the interrelationships among a comprehensive set of factors to identify the most important determinants of health-related quality of life (HRQoL) in parents of children in active treatment for cancer. A cross-sectional survey of 411 parents (80% response rate) of children receiving cancer treatment in Canada was conducted between November 2004 and February 2007. The following constructs were measured: background and context factors, child characteristics, family-centered service delivery, caregiver strain, intrapsychic factors, coping/supportive factors and parental HRQoL. The model was evaluated using structural equation modeling. Analysis was stratified by time since diagnosis (i.e., <12 months and ≥12 months). For those within 12 months of their child's diagnosis, family-centred service provision, caregiver strain, and self-perception accounted for 58% of the variation in psychosocial health, whereas caregiver strain and social support explained 50% of the variation in physical health. For parents in the >12 month group, caregiving strain was the only factor with a direct relationship with parental psychosocial and physical health, accounting for 66% and 55% of the variance in these constructs, respectively. Our findings reinforce the need for health professionals to be particularly attuned to family caregivers in the early stages of treatment and identify potential areas for interventions to promote parental health., (Copyright © 2010 UICC.)