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Papers by David Dix

The Journal of Pediatric Pharmacology and Therapeutics, 2005

Although enoxaparin is used to treat thromboembolism in children, current treatment guidelines ar... more Although enoxaparin is used to treat thromboembolism in children, current treatment guidelines are largely extrapolated from adults. The objectives of this study were to determine: i) correlation between enoxaparin dose and anti-factor Xa (anti-Xa) level, ii) intra-patient variability, and iii) whether dose or anti-Xa level is a predictor of outcomes. A retrospective chart review was conducted on all hospitalized patients receiving enoxaparin in a tertiary care pediatric institution. Simple linear regression, coefficient of variation (CV), and Student's t-test were used to analyze the objectives. Eighty treatment courses with interpretable anti-Xa levels were analyzed. Mean patient age was 6.5 years. Mean enoxaparin dose was 1.10 mg/kg q12h. Correlation between initial dosing and anti-Xa level was poor; R2 = 0.0307 and 0.0237 for patients > 2 months with and without cardiac or renal diseases, respectively. Four out of seven patients ≤ 2 months of age compared to 4/32 patients...

Journal of the National Comprehensive Cancer Network, 2022

cal significance of pulmonary nodules detected by CT and not CXR in patients treated for favorabl... more cal significance of pulmonary nodules detected by CT and not CXR in patients treated for favorable histology Wilms tumor on national Wilms tumor studies-4 and-5: a report from the Children's Oncology Group. Pediatr Blood Cancer 2012;59:631-635. 4. Dix DB, Fernandez CV, Chi YY, et al. Augmentation of therapy for combined loss of heterozygosity of chromosomes 1p and 16q in favorable histology Wilms tumor: a Children's Oncology Group AREN0532 and

Cold Spring Harbor molecular case studies, 2018

Children with papillary thyroid carcinoma (PTC) may relapse despite response to radioactive iodin... more Children with papillary thyroid carcinoma (PTC) may relapse despite response to radioactive iodine (RAI). Two children with multiply relapsed PTC underwent whole-genome and transcriptome sequencing. A fusion was identified in one tumor, with outlier expression compared to the TCGA thyroid cancer compendium and to Illumina BodyMap normal thyroid. This patient demonstrated resolution of multiple pulmonary nodules without toxicity on oral TRK inhibitor therapy. A fusion was identified in the second tumor, another potentially actionable finding. Identification of oncogenic drivers in recurrent pediatric PTC may facilitate targeted therapy while avoiding repeated RAI.

Journal of Pediatric Surgery, 2012

The incidence of Clostridium difficile-associated disease (CDAD) in the adult population doubled ... more The incidence of Clostridium difficile-associated disease (CDAD) in the adult population doubled in the past decade, with increasing morbidity and mortality; however, little research has been performed in the pediatric population. We characterized C difficile infection in the pediatric population, with emphasis on the surgical population. Methods: At a university-based children's hospital, we reviewed 231 patient (birth to 18 years of age) records containing a diagnosis of CDAD between January 1, 2002, and December 31, 2008. Results: Clostridium difficile-associated disease incidence increased from 250 per 100,000 hospitalizations in 2002 to 580 per 100,000 hospitalizations in 2008. No fatalities or surgical interventions were attributable to CDAD. Eighty-seven percent of patients received antibiotics within 2 months of diagnosis. Fifty-two percent of patients underwent operative intervention within 2 months of diagnosis; of these, 89% percent received previous antibiotic therapy and 57% were immunosuppressed. The most common antecedent procedures were bone marrow biopsy and line placement for myelodysplastic diseases (40%), followed by renal transplant (11%). Conclusions: Pediatric CDAD incidence doubled during the study period but was not associated with death or operative intervention. A substantial number of CDAD cases were associated with previous operative procedures, particularly in immunosuppressed patients and those who received prior antibiotics.

Canadian Medical Association Journal, 2012

CMAJ • One in twenty women of child-bearing age in Canada has inadequate levels of vitamin B 12. ... more CMAJ • One in twenty women of child-bearing age in Canada has inadequate levels of vitamin B 12. • Infant B 12 sufficiency is related to maternal levels via neonatal stores at birth and the amount in breast milk. • Vitamin B 12 deficiency in infants, although rare, is important to recognize because treatment can prevent severe developmental delay and neurologic sequelae. • Prevention includes dietary supplementation for mothers and their breastfed infants who are at risk of vitamin B 12 deficiency.

BMC Cancer, 2017

Background: Primary objective was to describe the proportion of children newly diagnosed with can... more Background: Primary objective was to describe the proportion of children newly diagnosed with cancer enrolled on a therapeutic clinical trial. Secondary objectives were to describe reasons for non-enrollment and factors associated with enrollment on trials. Methods: In this retrospective cohort study, we included children newly diagnosed with cancer between 0 and 14 years of age and diagnosed from 2001 to 2012. We used data from the Cancer in Young People in Canada (CYP-C) national pediatric cancer population-based database. CYP-C captures all cases of pediatric cancer (0-14 years) diagnosed and treated at one of the 17 tertiary pediatric oncology centers in Canada. Non-enrollment was evaluated using univariate and multiple logistic regression analysis. Results: There were 9204 children with cancer included, of whom 2533 (27.5%) were enrolled on a clinical trial. The most common reasons cited for non-enrollment were lack of an available trial (52.2%) and physician choice (11.2%). In multiple regression, Asian and Arab/west Asian race were associated with lower enrollment (P = 0.006 and P = 0.032 respectively). All cancer diagnoses were more likely to be enrolled compared to astrocytoma and children with acute lymphoblastic leukemia had an almost 18-fold increased odds of enrollment compared to astrocytoma (P < 0.0001). Greater distance from the tertiary care center was independently associated with non-enrollment (P < 0.0001). Conclusions: In Canada, 27.5% of children with cancer are enrolled onto therapeutic clinical trials and lack of an available trial is the most common reason contributing to non-enrollment. Future research should better understand reasons for lack of trial availability and physician preferences to not offer trials.

Journal of the National Comprehensive Cancer Network, 2021

Refinements in surgery, radiation therapy, and chemotherapy since the mid-20th century have resul... more Refinements in surgery, radiation therapy, and chemotherapy since the mid-20th century have resulted in a survival rate exceeding 90% for patients with Wilms tumor (WT). Although this figure is remarkable, a significant proportion of patients continue to have event-free survival (EFS) estimates of <75%, and nearly 25% of survivors experience severe chronic medical conditions. The first-generation Children’s Oncology Group (COG) renal tumor trials (AREN ‘0’), which opened to enrollment in 2006, focused on augmenting treatment regimens for WT subgroups with predicted EFS <75% to 80%, including those with the adverse prognostic marker of combined loss of heterozygosity (LOH) at chromosomes 1p/16q, pulmonary metastasis with incomplete lung nodule response after 6 weeks of chemotherapy, bilateral disease, and anaplastic histology. Conversely, therapy was reduced for patient subgroups with good outcomes and potential for long-term toxicity, such as those with lung metastasis with co...

Journal of Clinical Oncology, 2019

PURPOSE In National Wilms Tumor Study 5 (NWTS-5), tumor-specific combined loss of heterozygosity ... more PURPOSE In National Wilms Tumor Study 5 (NWTS-5), tumor-specific combined loss of heterozygosity of chromosomes 1p and 16q (LOH1p/16q) was associated with adverse outcomes in patients with favorable histology Wilms tumor. The AREN0533/AREN0532 studies assessed whether augmenting therapy improved event-free survival (EFS) for these patients. Patients with stage I/II disease received regimen DD4A (vincristine, dactinomycin and doxorubicin) but no radiation therapy. Patients with stage III/IV disease received regimen M (vincristine, dactinomycin, and doxorubicin alternating with cyclophosphamide and etoposide) and radiation therapy. METHODS Patients were enrolled through the AREN03B2 Biology study between October 2006 and October 2013; all underwent central review of pathology, surgical reports, and imaging. Tumors were evaluated for LOH1p/16q by microsatellite testing. EFS and overall survival were compared using the log-rank test between NWTS-5 and current studies. RESULTS LOH1p/16q ...

Cancer medicine, 2018

Objectives were to describe any bothersome symptom and severely bothersome symptoms in inpatient ... more Objectives were to describe any bothersome symptom and severely bothersome symptoms in inpatient children with cancer and hematopoietic stem cell transplant (HSCT) recipients. We included children 8-18 years of age with cancer or HSCT recipients who were receiving active treatment for cancer, admitted to hospital, and expected to be in hospital 3 days later. We administered the self-report Symptom Screening in Pediatrics Tool (SSPedi). We described those who identified any degree of symptom bother (at least "a little") and those who rated the degree of bother as severe ("a lot" or "extremely"). Factors associated with severe symptoms and total SSPedi scores were examined using multiple logistic and linear regression. Among the 302 patients, 298 (98.7%) reported having any bothersome symptom and 181 (59.9%) had at least one severely bothersome symptom. In multiple regression, older children were significantly more likely to have at least one severely bot...

Open Forum Infectious Diseases, 2018

Background. This study investigated the genetic structure of Streptococcus pneumoniae isolates fr... more Background. This study investigated the genetic structure of Streptococcus pneumoniae isolates from invasive pneumococcal disease (IPD) in Korean children after national immunization program (NIP) of extended-valency pneumococcal conjugate vaccines (PCVs) in Korea from 2014 to 2017. Methods. Invasive isolates were collected from 23 hospitals throughout Korea. IPD cases were identified by isolating pneumococci from normally sterile sites. Each isolate was analyzed using standard microbiological techniques, Quellung reaction, multilocus sequence typing, and antimicrobial susceptibility testing. eBURST v3 software was used to estimate the relationships among the isolates and to assign the strains to a clonal complex (CC). Results. Ninety-two pneumococcal isolates were analyzed. The source of isolates were blood (77), cerebrospinal fluid (7), pleural fluid (2), joint fluid (2), deep tissue abscess (2), and peritoneal fluid (2). A total of 38 STs and 17 singletons were assigned. Ten clonal complexes were identified:

Journal of the Pediatric Infectious Diseases Society, Jan 24, 2018

Among 235 children with acute myeloid leukemia, 17 experienced 19 perianal infections. Among 12 e... more Among 235 children with acute myeloid leukemia, 17 experienced 19 perianal infections. Among 12 episodes with definite abscess, 75% were severely neutropenic. Sixteen diagnostic imaging evaluations were performed; diagnostic yield was similar between computerized tomography of pelvis (5 of 10) and ultrasound (3 of 5). Consistent management approaches to perianal infection should be developed.

Cancer, 2018

BACKGROUND: It is questionable whether enrollment on clinical trials offers any survival advantag... more BACKGROUND: It is questionable whether enrollment on clinical trials offers any survival advantage at the population level over standard-of-care treatment. The objectives of this study were to describe the impact of trial enrollment on event-free survival and overall survival in pediatric acute myeloid leukemia (AML) using the Cancer in Young People in Canada (CYP-C) database. METHODS: Children were included if they had had AML newly diagnosed between ages birth and 14 years from 2001 to 2012. CYP-C is a national pediatric cancer population-based database that includes all cases of pediatric cancer diagnosed and treated at 1 of the 17 tertiary pediatric oncology centers in Canada. Univariate and Cox proportional hazards models were used to evaluate the impact of initial trial enrollment on survival. RESULTS: In total, 397 eligible children with AML were included in the analysis, of whom 94 (23.7%) were enrolled on a clinical trial at initial diagnosis. The most common reason for non-enrollment was that no trial was available. The eventfree survival rate at 5 years was 57.8% ± 5.2% for those enrolled versus 54.8% ± 2.9% for those not enrolled (P = .75). The overall survival rate at 5 years was 70.1% ± 4.9% for those enrolled versus 66.3% ± 2.8% for those not enrolled (P = .58). Enrollment on a trial was not associated with improved event-free or overall survival in multiple regression analyses. CONCLUSIONS: Enrollment on a clinical trial was not associated with improved survival for children with AML in a population-based cohort. Rationale for trial enrollment should not include the likelihood of benefit compared with non-enrollment.

$Research paper thumbnail of Impact of vertebral fractures and glucocorticoid exposure on height deficits in children during treatment for leukemia$

The Journal of clinical endocrinology and metabolism, Jan 20, 2018

To assess the impact of vertebral fractures (VF) and glucocorticoid (GC) exposure on height defic... more To assess the impact of vertebral fractures (VF) and glucocorticoid (GC) exposure on height deficits in children during treatment of acute lymphoblastic leukemia (ALL). Children with ALL treated without cranial radiation therapy (n = 160; median age 5.1 years; 58.1% male) were followed prospectively for six years. Spinal deformity index (SDI) was used to quantify VF status. Baseline height Z-score was 0.3 ± 1.2. It fell by 0.5 ± 0.4 in the first six months for boys and by 0.4 ± 0.4 in the first 12 months for girls (p < 0.01 for both), then subsequently recovered. The prevalence of VF peaked at one year (17.6%). Among those with VF, median SDI rose from 2 (interquartile range (IQR) 1, 7) at baseline to 8 (IQR 1, 8) at one year. A mixed model for repeated measures showed that height Z-score declined by 0.13 (95% CI, 0.02 to 0.24, p = 0.02) for each five-unit increase in SDI during the previous 12 months. Every 10 mg/m2 increase in average daily GC dose (prednisone equivalent) in th...

Journal of the National Cancer Institute, 2018

The objective was to evaluate the reliability and validity of the self-report Symptom Screening i... more The objective was to evaluate the reliability and validity of the self-report Symptom Screening in Pediatrics Tool (SSPedi) from the perspective of children with cancer and pediatric hematopoietic stem cell transplant (HSCT) recipients. In this multicenter study, respondents were children age eight to 18 years who had cancer or had received HSCT, and their parents. Two different child respondent populations were targeted. More symptomatic respondents were receiving active treatment for cancer, admitted to the hospital, and expected to be in the hospital three days later. Less symptomatic respondents were in maintenance therapy for acute lymphoblastic leukemia or had completed cancer therapy. Children completed SSPedi and then responded to validated self-report measures of mucositis, nausea, pain, and global quality of life. Children in the more symptomatic group repeated SSPedi and a global symptom change scale three days later. Parent proxy-report was optional. Reliability was eval...

Journal of pain and symptom management, 2018

Primary objectives were to evaluate the interrater reliability and validity of proxy-report Sympt... more Primary objectives were to evaluate the interrater reliability and validity of proxy-report Symptom Screening in Pediatrics Tool (SSPedi) in children with cancer and pediatric hematopoietic stem cell transplant (HSCT) recipients. Secondary objective was to describe the interrater reliability of each SSPedi item. Respondents were children aged eight to 18 years with cancer or HSCT recipients, and their parents or guardians. We enrolled two pediatric respondent groups. The more symptomatic group was receiving active treatment for cancer, admitted to hospital, and expected to be in a hospital three days later. The less symptomatic group either was in maintenance therapy for acute lymphoblastic leukemia or had completed cancer treatments. Convergent validity was evaluated by comparing proxy-reported mucositis, nausea and vomiting, pain, and total SSPedi scores, with child self-reported validated scales, and we hypothesized fair correlations. Discriminant validity was evaluated by compar...

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Jan 22, 2018

Osteoporotic fractures are a significant cause of morbidity in acute lymphoblastic leukemia (ALL)... more Osteoporotic fractures are a significant cause of morbidity in acute lymphoblastic leukemia (ALL). Our objective was to determine the incidence and predictors of fractures and recovery from osteoporosis in pediatric ALL over 6 years following glucocorticoid initiation. Vertebral fractures (VF) and vertebral body reshaping were assessed on annual spine radiographs, low-trauma non-VF were recorded at regular intervals and spine bone mineral density (BMD) was captured every 6 months for 4 years and then annually. A total of 186 children with ALL were enrolled (median age 5.3 years; range, 1.3 to 17.0 years). The cumulative fracture incidence was 32.5% for VF and 23.0% for non-VF; 39.0% of children with VF were asymptomatic. No fractures occurred in the sixth year and 71.3% of incident fractures occurred in the first 2 years. Baseline VF, cumulative glucocorticoid dose, and baseline lumbar spine (LS) BMD Z-score predicted both VF and non-VF. Vertebral body reshaping following VF was inc...

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 16, 2018

Purpose The National Wilms Tumor Study (NWTS) treatment of favorable histology Wilms tumor with l... more Purpose The National Wilms Tumor Study (NWTS) treatment of favorable histology Wilms tumor with lung metastases was vincristine/dactinomycin/doxorubicin (DD4A) and lung radiation therapy (RT). The AREN0533 study applied a new risk stratification and treatment strategy to improve event-free survival (EFS) while reducing exposure to lung RT. Methods Patients with favorable histology Wilms tumor and isolated lung metastases showing complete lung nodule response (CR) after 6 weeks of DD4A continued receiving chemotherapy without lung RT. Patients with incomplete response (IR) or loss of heterozygosity at chromosomes 1p/16q received lung RT and four cycles of cyclophosphamide/etoposide in addition to DD4A drugs (Regimen M). AREN0533 was designed to preserve a 4-year EFS of 85% for lung nodule CR and improve 4-year EFS from 75% to 85% for lung nodule IR. Results Among 292 assessable patients, 133 had CR and 159 had IR. For patients with CR, 4-year EFS and overall survival (OS) estimates w...

International journal of cancer. Journal international du cancer, Jan 29, 2015

Little is known about the impact of enrollment on therapeutic clinical trials on adverse event ra... more 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 multi-center 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 (...

British journal of cancer, Jan 13, 2009

The primary objective was to describe predictors of physical, emotional and social quality of lif... more 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...

Health Expectations, 2014

Purpose To develop and validate scales to measure constructs that survivors of childhood cancer r... more Purpose To develop and validate scales to measure constructs that survivors of childhood cancer report as barriers and/or facilitators to the process of transitioning from paediatric to adult-oriented long-term follow-up (LTFU) care. Methods Qualitative interviews provided a dataset that were used to develop items for three new scales that measure cancer worry, selfmanagement skills and expectations about adult care. These scales were field-tested in a sample of 250 survivors aged 15-26 years recruited from three Canadian hospitals between July 2011 and January 2012. Rasch Measurement Theory (RMT) analysis was used to identify the items that represent the best indicators of each scale using tests of validity (i.e. thresholds for item response options, item fit statistics, item locations, differential item function) and reliability (Person Separation Index). Traditional psychometric tests of measurement performance were also conducted. Results RMT led to the refinement of a 6-item Cancer Worry scale (focused on worry about cancer-related issues such as late effects), a 15-item Self-Management Skills scale (focused on skills an adolescent needs to acquire to manage their own health care), and a 12item Expectations scale (about the nature of adult LTFU care). Our study provides preliminary evidence about the reliability and validity of these new scales (e.g. Person Separation Index ≥ 0.81; Cronbach's a ≥ 0.81; test-retest reliability ≥ 0.85). Conclusion There is limited knowledge about the transition experience of childhood cancer survivors. These scales can be used to investigate barriers survivors face in the process of transition from paediatric to adult care.