Sarah Burrow

Canadian Study of Determinants of Endometabolic Health in ChIlDrEn (CanDECIDE study): a cohort study protocol examining the mechanisms of obesity in survivors of childhood brain tumours

Background Childhood obesity has reached epidemic proportions and is impacting childrens health globally. In adults, obesity is associated with chronic low-grade inflammation that leads to insulin resistance, which is one of the important mechanisms through which dysregulation of metabolism occurs. There is limited information available about the contribution of inflammation to metabolic health in obese children, and how individual and lifestyle factors impact this risk. One of the paediatric groups at risk of higher rates of obesity includes the survivors of childhood brain tumours. The aim of this study was to evaluate the mechanisms that contribute to inflammation in obese survivors of childhood brain tumours. Methods and analysis This is a prospective cohort study. We will recruit lean and obese survivors of childhood brain tumours, and a control group composed of lean and obese children with no history of tumours. We will measure circulating and urinary cytokine levels and cytokine gene expression in monocytes. In addition, the methylation patterns of cytokine genes and that of toll-like receptor genes will be evaluated. These will be correlated with individual and lifestyle factors including age, sex, ethnicity, puberty, body mass index, fasting lipid levels, insulin sensitivity, diet, exercise, sleep, stress and built environment. The sample size calculation showed that we need 25 participants per arm Ethics and dissemination This study has received ethics approval from the institutional review board. Once completed, we will publish this work in peer-reviewed journals and share the findings in presentations and posters in meetings. Discussion This study will permit the interrogation of inflammation as a contributor to obesity and its complications in obese survivors of childhood brain tumours and compare them with lean survivors and lean and obese controls with no history of tumours, which may help identify therapeutic and preventative interventions to combat the rising tide of obesity.

Hip Arthroscopy in Trauma: A Systematic Review of Indications, Efficacy, and Complications

PURPOSE This systematic review explored the indications, efficacy, and complications of hip arthroscopy in the setting of trauma. METHODS Databases (PubMed, Medline, Embase, and Web of Science) were searched from database inception to March 2015 for studies using hip arthroscopy in trauma treatment. Systematic screening of eligible studies was undertaken in duplicate. The inclusion criteria included studies pertaining to arthroscopic intervention of all traumatic hip injuries. Abstracted data were organized in table format with descriptive statistics presented. RESULTS From an initial search yield of 2,809 studies, 32 studies (25 case reports and 7 case series) satisfied the criteria for inclusion. A total of 144 patients (age range, 10 to 53 years) underwent hip arthroscopy for 6 indications associated with trauma: 8 patients for bullet extraction, 6 for femoral head fixation, 82 for loose body removal, 6 for acetabular fracture fixation, 20 for labral intervention, and 23 for ligamentum teres debridement. Patients were followed up postoperatively for a mean of 2.9 years (range, 8 days to 16 years). Successful surgery was achieved in 96% of patients. The rate of major complications (i.e., pulmonary embolism and abdominal compartment syndrome) was 1.4% (2 of 144); avascular necrosis, 1.4% (2 of 144); and nerve palsy, 0.7% (1 of 144). CONCLUSIONS Hip arthroscopy appears effective and safe in the setting of trauma. These data should be interpreted with caution because of the low-quality evidence of the included studies. Surgeons should be aware of the potential complications such as abdominal compartment syndrome and thromboembolic events when performing hip arthroscopy in the setting of trauma. LEVEL OF EVIDENCE Level IV, systematic review of Level IV studies.

Overweight, obesity and adiposity in survivors of childhood brain tumours: a systematic review and meta-analysis: Overweight, obesity, adiposity in SCBT

Survivors of childhood brain tumours (SCBT) have increased cardiometabolic risks, but the determinants of these risks are unclear. This systematic review aims to compare the prevalence of overweight and obesity as well as adiposity measures between SCBT and non‐cancer controls. The PubMed, EMBASE, MEDLINE, CINAHL and the Cochrane Library databases were searched. The primary outcomes were the prevalence of overweight and obesity based on body mass index. The secondary outcomes were adiposity measures including percent fat mass, waist‐to‐hip and waist‐to‐height ratios. Forty‐one studies were included in the meta‐analysis. The prevalence of overweight and obesity combined was similar between overall SCBT, SCBT excluding craniopharyngioma and non‐cancer controls (42.6%, 95% CI 30.1–55.1 vs. 31.7%, 95% CI 20.4–43.0 vs. 40.4%, 95% CI 34.0–46.8). We also found that SCBT have higher percent fat mass (mean difference 4.1%, 95% CI 2.0–6.1), waist‐to‐hip ratio (mean difference 0.07, 95% CI 0.02–0.13) and waist‐to‐height ratio (mean difference 0.06, 95% CI 0.01–0.10) than non‐cancer controls. We conclude that SCBT have similar overweight and obesity distribution but higher adiposity than non‐cancer controls. More studies were needed to explore the determinants of adiposity and its contribution to cardiometabolic outcomes in SCBT.

Adiposity in childhood brain tumors: A report from the Canadian Study of Determinants of Endometabolic Health in Children (CanDECIDE Study)

Children with brain tumors (CBT) are at high risk of cardiovascular diseases and type 2 diabetes compared to the general population. Recently, adiposity has been reported to be more informative for cardiometabolic risk stratification than body mass index (BMI) in the general population. The goal of this study is to describe the adiposity phenotype in CBT, and to establish adiposity determinants. We recruited CBT (n = 56) and non-cancer controls (n = 106). Percent body fat (%FM), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were measured to determine total and central adiposity, respectively. Regression analyses were used to evaluate adiposity determinants. CBT had higher total and central adiposity compared to non-cancer controls despite having similar BMI measurements. Those with tumors at the supratentorial region had increased total and central adiposity, while those who received radiotherapy had increased total adiposity. In conclusion, CBT have increased total and central adiposity in the presence of similar BMI levels when compared to non-cancer controls. Adiposity, especially central adiposity, is a potential cardiometabolic risk factor present relatively early in life in CBT. Defining interventions to target adiposity may improve long-term outcomes by preventing cardiometabolic disorders in CBT.

The effectiveness of interventions to treat hypothalamic obesity in survivors of childhood brain tumours: a systematic review

Survivors of childhood brain tumours (SCBT) are at risk of type 2 diabetes and cardiovascular diseases. Obesity is a major driver of cardiometabolic diseases in the general population, and interventions that tackle obesity may lower the risk of these chronic diseases. The goal of this systematic review was to summarize current evidence for the presence of interventions to manage obesity, including hypothalamic obesity, in SCBT.

The effectiveness of interventions to treat obesity in survivors of childhood brain tumors: a systematic review protocol

BackgroundPediatric brain tumors are the most common solid tumors in children. Advances in understanding the hallmarks of cancer biology and novel therapies have led to an increasing number of survivors of childhood brain tumors (SCBT). However, these survivors are at an increased risk of obesity and cardiometabolic disorders that affect their quality of life and lifespan. It is important to define effective strategies to treat and prevent obesity in this population. This systematic review aims to investigate the effectiveness of lifestyle interventions, pharmacotherapy, and bariatric surgery on treating obesity in SCBT.MethodsSearches will be conducted in PubMed, MEDLINE, EMBASE, PsycINFO, SPORTDiscus, CINAHL, Cochrane Database of Systematic Review, Cochrane Central Register of Controlled Trials (CENTRAL), and Database of Abstracts of Reviews of Effect (DARE). In addition, ClinicalTrials.gov and ProQuest Dissertations and Theses A&I will be searched to identify relevant gray literature. The reference lists of eligible articles will be searched for additional studies. All screening, quality assessment, and data abstraction will be done independently by two reviewers. We will perform meta-analysis if there are sufficient studies.DiscussionThis review will summarize evidence for the effectiveness of interventions used to reduce obesity risk in SCBT. This has significant implications for SCBT, as it can identify gaps in knowledge and provide insights into the development of new interventions to manage obesity in survivors, which may improve their outcomes.Systematic review registrationPROSPERO CRD42015025909

Recruitment feasibility to a cohort study of endocrine and metabolic health among survivors of childhood brain tumours: a report from the Canadian study of Determinants of Endometabolic Health in ChIlDrEn (CanDECIDE)

Objectives The aim of this study was to test the feasibility of recruitment and performance of study procedures of the Canadian Study of Determinants of Endometabolic Health in ChIlDrEn (CanDECIDE) study, which was designed to assess the determinants of endocrine and metabolic health in survivors of childhood brain tumours. Setting A single paediatric tertiary care centre in Hamilton, Ontario, Canada. Participants We included boys and girls, aged 5 years and older, who were lean (body mass index (BMI) below 85th centile for age and gender) or overweight/obese (BMI 85th centile or above for age and gender). We excluded children on steroids or immunosuppressant therapy, smokers and those who had an active infection for the 2 weeks prior to participation. Outcomes Feasibility targets included recruitment rate of at least 50%, the consenting of 80% of participants to provide biological samples, 90% questionnaire completion rate and the ability to process biological samples from at least 80% of participants. Results We approached 210 potential participants, and of the 112 (53%) who agreed to participate, 30 (26.8%) completed the study visit over 7 months. All participants agreed to fast, provide biological samples and complete the questionnaires. Sample collection was successful in 97% (29/30) of participants and laboratory procedures were feasible in 100% of collected samples. We also tested resources required for the conduct of the full study including personnel, space, laboratory equipment and procedures and determined that they are all feasible. Conclusions Recruitment and consenting of patients for the CanDECIDE study may be feasible. However, we are considering prolonging recruitment duration and collaboration with other centres to meet recruitment targets due to lower than expected recruitment rate. Completion of questionnaires and implementation of sample processing protocols are feasible.

Birth weight and body mass index z-score in childhood brain tumors: A cross-sectional study

Children with brain tumors (CBT) are at higher risk of cardiovascular disease and type 2 diabetes compared to the general population, in which birth weight is a risk factor for these diseases. However, this is not known in CBT. The primary aim of this study was to explore the association between birth weight and body mass measures in CBT, compared to non-cancer controls. This is a secondary data analysis using cross-sectional data from the CanDECIDE study (n = 78 CBT and n = 133 non-cancer controls). Age, sex, and birth weight (grams) were self-reported, and confirmed through examination of the medical records. Body mass index (BMI) was calculated from height and weight measures and reported as kg/m2. BMI z-scores were obtained for subjects under the age of 20 years. Multivariable linear regression was used to evaluate the relationship between birth weight and BMI and BMI z-score, adjusted for age, sex, puberty, and fat mass percentage. Higher birth weight was associated with higher BMI and BMI z-score among CBT and controls. In conclusion, birth weight is a risk factor for higher body mass during childhood in CBT, and this may help the identification of children at risk of future obesity and cardiometabolic risk.