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1.  The Initiative to Maximize Progress in Adolescent and Young Adult Cancer Therapy (IMPACT) Cohort Study: a population-based cohort of young Canadians with cancer 
BMC Cancer  2014;14(1):805.
Background
Cancer is the leading cause of disease-related death in adolescents and young adults (AYA). Annual improvements in AYA cancer survival have been inferior to those observed in children and older adults. Prior studies of AYA with cancer have been limited by their focus on patients from select treatment centres, reducing generalizability, or by being population-based but lacking diagnostic and treatment details. There is a critical need to conduct population-based studies that capture detailed patient, disease, treatment and system-level data on all AYA regardless of treatment location.
Methods/Design
We will create a cohort of all AYA (aged 15–21 years) at the time of diagnosis with any malignancy between 1992 and 2011 in Ontario, Canada (n = 5,394). Subjects will be identified through the Ontario Cancer Registry and the final cohort will be expanded to include 2012 diagnoses, as these data become available. Detailed diagnostic, treatment and outcome data for those patients treated at a pediatric cancer centre will be provided by a population-based pediatric cancer registry (n = 1,030). For 15–18 year olds treated at adult centres (n = 923) and all 19–21 year olds (n = 3396), trained abstractors will collect the comparable data elements from medical records. We will link these data to population-based administrative health data that include physician billings, hospitalizations and emergency room visits. This will allow descriptions of health care access and use prior to cancer diagnosis, and during and after treatment.
Discussion
The IMPACT cohort will serve as a platform for addressing questions that span the AYA cancer journey. These will include determining which factors influence where AYA receive care, the impact of locus of care on the types and intensity of cancer therapy, appropriateness of surveillance for disease recurrence, access to clinical trials, and receipt of palliative and survivor care. Findings using the IMPACT cohort have the potential to lead to changes in practice and cancer policy, reduce mortality, and improve quality of life for AYA with cancer. The IMPACT data platform will be a permanent resource, accessible to researchers across Canada.
doi:10.1186/1471-2407-14-805
PMCID: PMC4228075  PMID: 25367402
Adolescents; Young adults; Cancer; Treatment; Recurrence; Survival; Cohort; Population-based
2.  Antenatal Steroid Therapy for Fetal Lung Maturation and the Subsequent Risk of Childhood Asthma: A Longitudinal Analysis 
Journal of Pregnancy  2010;2010:789748.
This study was designed to test the hypothesis that fetal exposure to corticosteroids in the antenatal period is an independent risk factor for the development of asthma in early childhood with little or no effect in later childhood. A population-based cohort study of all pregnant women who resided in Nova Scotia, Canada, and gave birth to a singleton fetus between 1989 and 1998 was undertaken. After a priori specified exclusions, 80,448 infants were available for analysis. Using linked health care utilization records, incident asthma cases developed after 36 months of age were identified. Extended Cox proportional hazards models were used to estimate hazard ratios while controlling for confounders. Exposure to corticosteroids during pregnancy was associated with a risk of asthma in childhood between 3–5 years of age: adjusted hazard ratio of 1.19 (95% confidence interval: 1.03, 1.39), with no association noted after 5 years of age: adjusted hazard ratio for 5–7 years was 1.06 (95% confidence interval: 0.86, 1.30) and for 8 or greater years was 0.74 (95% confidence interval: 0.54, 1.03). Antenatal steroid therapy appears to be an independent risk factor for the development of asthma between 3 and 5 years of age.
doi:10.1155/2010/789748
PMCID: PMC3065803  PMID: 21490744
3.  Lack of treatment-related mortality definitions in clinical trials of children, adolescents and young adults with lymphomas, solid tumors and brain tumors: a systematic review 
BMC Cancer  2014;14(1):612.
Background
There is a lack of standardized definition for treatment-related mortality (TRM), which represents an important endpoint in cancer. Our objective was to describe TRM definitions used in studies of children, adolescents and young adults with lymphomas, solid tumors and brain tumors.
Methods
We conducted a systematic review of studies enrolling children, adolescents and young adults with lymphomas, solid tumors and brain tumors in which an anti-cancer intervention was randomized, or all study designs in which TRM was a primary or secondary outcome. We searched Ovid MEDLINE, EMBASE and Evidence-Based Medicine Reviews from 1980 to June 2013. Two reviewers evaluated study eligibility and abstracted data.
Results
In total, 67 studies were included and consisted of 62 randomized therapeutic trials and 5 TRM studies. None of the studies (0/67) provided a definition for TRM. Only one randomized trial of rhabdomyosarcoma provided a definition of early death.
Conclusions
We were unable to identify any TRM definitions used in studies of children, adolescents and young adults with lymphomas, solid tumors and brain tumors. Given that a proportion of this patient population may receive intensive treatment, there is an urgent need for consensus-based definitions of TRM for use across clinical trials.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2407-14-612) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2407-14-612
PMCID: PMC4152582  PMID: 25155014
Treatment-related mortality; Toxic death; Cancer; Pediatric; Adolescents; Young adults; Systematic review
4.  Optic pathway gliomas in adolescence—time to challenge treatment choices? 
Neuro-Oncology  2013;15(3):391-400.
Background
Optimal management of optic pathway/hypothalamic glioma (OPHG) remains an ongoing challenge. Little is known about the natural history, management strategies, and outcomes in adolescents. Carboplatin-based chemotherapy is a useful modality in younger children, delaying radiation to their immature brains. National trials have focused on younger children and excluded adolescents from studies evaluating the role of chemotherapy.
Methods
This retrospective study describes clinical characteristics, treatment regimens, and outcomes in adolescents (aged ≥10 years) with OPHG (diagnosis during 1990–2006). Progression-free survival was compared with that in a cohort of younger children (aged <10 years).
Results
Thirty-three adolescents (19 females, 6 with neurofibromatosis type 1) with OPHG were identified within 2 Canadian pediatric oncology institutions. The majority presented with visual symptoms (82%). More than 55% (18 of 33) involved the posterior tract and/or hypothalamus (modified Dodge classification 3/4). Seventeen were initially observed; 8 remained progression free. Of the 25 of 33 adolescents who required active treatment, 9 (36%) needed second-line therapy. The progression-free survival for any first active treatment at age <10 years (52 of 102) or ≥10 years (25 of 33) was similar (46.9 vs 46.8 months; P = .60). In those who received chemotherapy as first-line treatment or after prior nonchemotherapy treatment failure, the progression-free survival trend was superior (62.9 vs 38.9 months) in those aged ≥10 years although not statistically significant (P = .16).
Conclusions
Chemotherapy is a valuable treatment modality for the achievement of disease control even in adolescents; their progression-free survival compares favorably with that in younger children. We propose that chemotherapy be considered as a first-line modality in adolescents, avoiding potential radiation-associated morbidities.
doi:10.1093/neuonc/nos312
PMCID: PMC3578487  PMID: 23295772
adolescents; chemotherapy; glioma; OPHG; optic pathway
5.  Low Socioeconomic Status Is Associated with Worse Survival in Children with Cancer: A Systematic Review 
PLoS ONE  2014;9(2):e89482.
Background
While low socioeconomic status (SES) has been associated with inferior cancer outcome among adults, its impact in pediatric oncology is unclear. Our objective was therefore to conduct a systematic review to determine the impact of SES upon outcome in children with cancer.
Methods
We searched Ovid Medline, EMBASE and CINAHL from inception to December 2012. Studies for which survival-related outcomes were reported by socioeconomic subgroups were eligible for inclusion. Two reviewers independently assessed articles and extracted data. Given anticipated heterogeneity, no quantitative meta-analyses were planned a priori.
Results
Of 7,737 publications, 527 in ten languages met criteria for full review; 36 studies met final inclusion criteria. In low- and middle-income countries (LMIC), lower SES was uniformly associated with inferior survival, regardless of the measure chosen. The majority of associations were statistically significant. Of 52 associations between socioeconomic variables and outcome among high-income country (HIC) children, 38 (73.1%) found low SES to be associated with worse survival, 15 of which were statistically significant. Of the remaining 14 (no association or high SES associated with worse survival), only one was statistically significant. Both HIC studies examining the effect of insurance found uninsured status to be statistically associated with inferior survival.
Conclusions
Socioeconomic gradients in which low SES is associated with inferior childhood cancer survival are ubiquitous in LMIC and common in HIC. Future studies should elucidate mechanisms underlying these gradients, allowing the design of interventions mediating socioeconomic effects. Targeting the effect of low SES will allow for further improvements in childhood cancer survival.
doi:10.1371/journal.pone.0089482
PMCID: PMC3935876  PMID: 24586813
6.  Validation of a registry-derived risk algorithm based on treatment protocol as a proxy for disease risk in childhood acute lymphoblastic leukemia 
Background
Administrative databases and cancer registries are frequently used to conduct population-based research, but often lack clinical data necessary for risk stratification. Our objective was to determine the criterion validity of a risk-stratification algorithm based on treatment characteristics available from a pediatric cancer registry as a proxy for disease risk, by comparing it to traditional biology-based risk classifications.
Methods
We identified all children with acute lymphoblastic leukemia diagnosed at a single institution between January 2000 and June 2011, and linked them to a population-based cancer registry. Several risk algorithms were then constructed using disease risk variables collected through chart review by a pediatric oncologist, and compared to a risk algorithm based on treatment protocol name and age, available from the registry.
Results
Of 596 patients identified, 579 (97.1%) met inclusion criteria and were successfully linked. The registry-based algorithm showed almost perfect agreement with a biology-based algorithm based on age, initial white blood cell count, immunophenotype and cytogenetics (kappa=0.85, 95th confidence interval 0.81-0.90). Discrepant cases were often due to the presence of unusual high risk features not captured by standard disease-risk variables but reflected in clinicians’ choices of higher intensity treatment protocols.
Conclusions
Protocol name represents a valid proxy of disease risk, allowing for risk stratification while conducting comparative effectiveness research using cancer registries and health services data. Future studies should examine the validity of treatment-based risk algorithms in other malignancies and using other treatment characteristics commonly found in health services data, such as the receipt of specific chemotherapeutic agents.
doi:10.1186/1471-2288-13-68
PMCID: PMC3679990  PMID: 23721155
Acute lymphoblastic leukemia; Administrative data; Health services research; Registries; Validation
7.  Sun Exposure, Vitamin D Receptor Polymorphisms FokI and BsmI and Risk of Multiple Primary Melanoma 
Cancer epidemiology  2011;35(6):e105-e110.
Sunlight exposure increases risk of melanoma. Sunlight also potentiates cutaneous synthesis of vitamin D, which can inhibit melanoma cell growth and promote apoptosis. Vitamin D effects are mediated through the vitamin D receptor (VDR). We hypothesized that genetic variation in VDR affects the relationship of sun exposure to risk of a further melanoma in people who have already had one.
We investigated the interaction between VDR polymorphisms and sun exposure in a population-based multinational study comparing 1138 patients with a multiple (second or subsequent) primary melanoma (cases) to 2151 patients with a first primary melanoma (controls); essentially a case-control study of melanoma in a population of melanoma survivors. Sun exposure was assessed using a questionnaire and interview, and was shown to be associated with multiple primary melanoma. VDR was genotyped at the FokI and BsmI loci and the main effects of variants at these loci and their interactions with sun exposure were analyzed.
Only the BsmI variant was associated with multiple primary melanoma (OR = 1.27, 95% CI 0.99-1.62 for the homozygous variant genotype). Joint effects analyses showed highest ORs in the high exposure, homozygous variant BsmI genotype category for each sun exposure variable. Stratified analyses showed somewhat higher ORs for the homozygous BsmI variant genotype in people with high sun exposure than with low sun exposure. P values for interaction, however, were high.
These results suggest that risk of multiple primary melanoma is increased in people who have the BsmI variant of VDR.
doi:10.1016/j.canep.2011.03.003
PMCID: PMC3182291  PMID: 21612999
melanoma; FokI; BsmI; sun exposure
8.  Health profile of deaf Canadians 
Canadian Family Physician  2007;53(12):2140-2141.
OBJECTIVE
To profile the health of deaf and hard-of-hearing Canadians inrelation to the population as a whole.
DESIGN
Using data from the Canada Community Health Survey 1.1, across-sectional survey conducted by Statistics Canada with a total of 131 535 respondents, a series of logistic regression models was fitted to estimate the odds, compared with the general population, of respondents classified as having hearing problems reporting the presence of various chronic health outcomes; of their utilizing the health care system; of their engaging in certain health promotion activities; and of their reporting certain perceptions about their overall health. For each odds ratio, 95% confidence intervals are provided. All analyses were adjusted for age and sex with some analyses being restricted to appropriate age ranges or having further adjustments made, depending on the outcomes.
MAIN OUTCOME MEASURES
In addition to indications of deafness or hearing loss, this study examined health care utilization, several commonly accepted health outcomes, engagement in health promotion activities, and perceptions of overall health.
RESULTS
Approximately 4% of respondents in the cross-sectional survey were considered to have hearing problems. The prevalence of hearing problems increased withage, with males having a slightly higher prevalence of hearing problems compared with females (4.52% versus 3.53%). Respondents classified as having hearing problems, whether hearing loss or deafness, were more likely to report adverse health conditions and low levels of physical activity, and to experience higher rates of depression. Respondents classified as having hearing problems were not more likely to smoke or to drink excessively.
CONCLUSION
Communication is essential to both health promotion and health care delivery. Deafness—both the disability and the culture—creates barriers to communication. Individual practitioners can and should consider the communication needs of individual patients with hearing loss or deafness to avoid barriers to optimal health.
PMCID: PMC2231554  PMID: 18077753

Results 1-8 (8)