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BackgroundResearch has demonstrated that increases in palliative homecare nursing are associated with a reduction in the rate of subsequent hospitalizations. However, little evidence is available about the cost-savings potential of palliative nursing when accounting for both increased nursing costs and potentially reduced hospital costs.MethodsOur retrospective cohort study included cancer decedents from British Columbia, Ontario, and Nova Scotia who received any palliative nursing in the last 6 months of life. A Poisson regression analysis was used to determine the association of increased nursing costs (in 2-week blocks) on the relative average hospital costs in the subsequent 2-week block and on the overall total cost (hospital costs plus nursing costs in the preceding 2-week block).ResultsThe cohort included 58,022 cancer decedents. Results of the analysis for the last month of life showed an association between increased nursing costs and decreased relative hospital costs in comparisons with a reference group (>0 to 1 hour nursing in the block): the maximum decrease was 55% for Ontario, 31% for British Columbia, and 38% for Nova Scotia. Also, increased nursing costs in the last month were almost always associated with lower total costs in comparison with the reference. For example, cost savings per person-block ranged from $376 (>10 nursing hours) to $1,124 (>4 to 6 nursing hours) in British Columbia.ConclusionsIn the last month of life, increased palliative nursing costs (compared with costs for >0 to 1 hour of nursing in the block) were associated with lower relative hospital costs and a lower total cost in a subsequent block. Our research suggests a cost-savings potential associated with increased community-based palliative nursing.

Background Breast-conserving surgery (BCS) is the preferred surgical approach for most patients with early-stage breast cancer. Frequently, concerns arise about the pathologic margin status, resulting in an average reoperation rate of 23% in Canada. No consensus has been reached about the ideal reoperation rate, although 10% has been suggested as a target. Upon undergoing reoperation, many patients choose mastectomy and breast reconstruction, which add to the morbidity and cost of patient care. We attempted to identify the cost of reoperation after BCS, and the effect that a reduction in the reoperation rate could have on the B.C. health care system. Methods A decision tree was constructed to estimate the average cost per patient undergoing initial BCS with two reoperation frequency scenarios: 23% and 10%. The model included the direct medical costs from the perspective of the B.C. health care system for the most common surgical treatment options, including breast reconstruction and postoperative radiation therapy. Results Costs ranged from a low of $8,225 per patient with definitive BCS [95% confidence interval (CI): $8,061 to $8,383] to a high of $26,026 for reoperation with mastectomy and delayed reconstruction (95% CI: $23,991 to $28,122). If the reoperation rate could be reduced to 10%, the average saving would be $1,055 per patient undergoing attempted BCS (95% CI: $959 to $1,156). If the lower rate were to be achieved in British Columbia, it would translate into a savings of $1.9 million annually. Summary The implementation of initiatives to reduce reoperation after BCS could result in significant savings to the health care system, while potentially improving the quality of patient care. [ABSTRACT FROM AUTHOR]

Background The use of systemic therapy near the end of life can expose cancer patients to severe toxicity for minimal survival gain and comes with a high cost. Early palliative care is recommended, but there is evidence that aggressive care remains common. To better understand those patterns, the present study set out to describe trends in systemic therapy use and cost for cancer patients in the last year of life. Methods Using the BC Cancer Registry, a retrospective population-based cohort of cancer decedents (2002-2007) was identified and linked to systemic therapy records. The outcomes of interest were any systemic therapy use and total systemic therapy costs during the last year of life. Multiple logistic regression (systemic therapy use) and generalized linear regression (costs) were conducted, adjusting for age, sex, and survival. Subgroup analyses were performed for patients with primary colorectal, lung, prostate, or breast cancer. Results From 2002 to 2007, use of systemic therapy in the last 12-4 months of life increased by 21% (95% CI: 10% to 33%); no significant change in use in the last 3 months of life was observed. Costs for both periods increased over time, by 48% (95% CI: 36% to 63%) and by 33% (95% CI: 19% to 49%) respectively. The trends varied across cancer sites, with the greatest increases being observed for lung and colorectal cancer patients. Conclusions The use and costs of systemic therapy have generally been increasing, putting pressure on health care providers and payers, but the quality-of-life implications for patients must be better understood. [ABSTRACT FROM AUTHOR]

Objective: SHAPE (Simple Hysterectomy And PElvic node assessment) was an international phase III trial demonstrating that simple hysterectomy was non-inferior to radical hysterectomy for pelvic recurrence risk, but superior for quality of life and sexual health. The objective was to conduct a cost-effectiveness analysis comparing simple vs. radical hysterectomy for low-risk early-stage cervical cancer., Methods: Markov model compared the costs and benefits of simple vs. radical hysterectomy for early cervical cancer over a 5-year time horizon. Quality-adjusted life years (QALYs) were estimated from health utilities derived from EQ-5D-3L surveys. Sensitivity analyses accounted for uncertainty around key parameters. Monte Carlo simulation estimated complication numbers according to surgical procedure., Results: Simple hysterectomy was more effective and less costly than radical hysterectomy. Average overall costs were $11,022 and $12,533, and average gains were 3.56 and 3.54 QALYs for simple and radical hysterectomy, respectively. Baseline health utility scores were 0.81 and 0.83 for simple and radical hysterectomy, respectively. By year 3, these scores improved for simple hysterectomy (0.82) but not for radical hysterectomy (0.82). Assuming 800 early cervical cancer patients annually in Canada, the model estimated 3 vs. 82 patients with urinary retention, and 49 vs. 86 patients with urinary incontinence persisting 4 weeks after simple vs. radical hysterectomy, respectively. Results were most sensitive to variability in health utilities after surgery, but stable through wide ranges of costs and recurrence estimates., Conclusion: Simple hysterectomy is less costly and more effective in terms of quality-adjusted life expectancy compared to radical hysterectomy for early cervical cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT01658930., Competing Interests: JSK discloses research funding from Michael Smith Health Research BC (formerly Michael Smith Foundation for Health Research), ownership of shares from Hexamer Therapeutics, and speaker fee from Astra Zeneca. MP discloses research funding from Astra Zeneca, royalties from UpToDate, and serving as an Advisory Board member for Serono-Merck., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Background: Despite a better understanding of the increasing incidence of young-onset colorectal cancer (yCRC; age at diagnosis <50 years), little is known about its economic burden. Therefore, we estimated direct medical spending on yCRC before and after diagnosis., Methods: We used linked administrative health databases in British Columbia, Canada, to create a study population of yCRC and average-age onset colorectal cancer (aCRC; age at diagnosis ≥50 years) cases, along with cancer-free controls. Over the 1-year period preceding a colorectal cancer diagnosis, we estimated direct medical spending on hospital visits, healthcare practitioners, and prescription medications. After diagnosis, we calculated cost attributable to yCRC and aCRC, which additionally included the cost of cancer treatments (e.g., chemotherapy and radiotherapy) across phases of care., Results: We included 1,058 yCRC (45.4% females; age at diagnosis 42.4 ± 6.2 years) and 12,619 aCRC (44.8% females; age at diagnosis of 68.1 ± 9.2 years) cases. Direct medical spending on the average yCRC and aCRC case during the year before diagnosis was $6,711 and $8,056, respectively. After diagnosis, the overall average annualized cost attributable to yCRC significantly differed in comparison with aCRC for the initial ($50,216 vs. $37,842; P < 0.001), continuing ($8,361 vs. $5,014; P < 0.001), and end-of-life cancer phase ($86,125 vs. $61,512; P < 0.001) but not end-of-life non-cancer phase ($77,273 vs. $23,316; P = 0.372)., Conclusions: Reported cost estimates may be used as inputs for future economic evaluations pertaining to yCRC., Impact: We provided comprehensive cost estimates for healthcare spending on young-onset colorectal cancer., (©2023 The Authors; Published by the American Association for Cancer Research.)

Aims: To examine the real-world safety of adding bevacizumab to first-line irinotecan-based chemotherapy for patients with metastatic colorectal cancer (mCRC)., Materials and Methods: Patients diagnosed with CRC in three Canadian provinces (Ontario, Saskatchewan and British Columbia) who received publicly funded bevacizumab and/or irinotecan from 2000 to 2016 were identified from cancer registries. Propensity score 1:1 matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to contemporaneous and historical controls, adjusting for baseline demographic and clinical characteristics. Safety end points evaluated during first-line treatment plus 30 days included mortality within 30 days and all-cause-, chemotherapy- and bevacizumab-related hospitalisations. Chemotherapy- and bevacizumab-related visits were defined as hospitalisations for specific conditions commonly associated with chemotherapy (e.g. infections) or bevacizumab (e.g. arteriovenous thromboembolism) using most responsible diagnosis codes. In PSM and IPTW-weighted cohorts, we assessed event frequencies using odds ratios from logistic regressions and event rate ratios using negative binomial regression models. The results from each province and comparison were pooled using random-effects meta-analysis., Results: We identified 16 250 mCRC patients who received first-line irinotecan-based treatment. In PSM cohorts, bevacizumab was associated with fewer deaths within 30 days of treatment compared with contemporaneous (pooled odds ratio = 0.62; 95% confidence interval 0.50-0.75) and historical controls (pooled odds ratio = 0.73; 95% confidence interval 0.58-0.93). Hospitalisations were more frequent among patients treated with bevacizumab compared with historical controls but similar to contemporaneous controls. As patients receiving bevacizumab were exposed to a longer average treatment duration, across their full treatment duration, patients receiving bevacizumab had significantly lower rates of hospitalisations (contemporaneous pooled rate ratio = 0.56; 95% confidence interval 0.47-0.67; historical pooled rate ratio = 0.73; 95% confidence interval 0.56-0.95). Similar trends were observed for chemotherapy- and bevacizumab-related hospitalisations and in IPTW-weighted cohorts., Discussion: We did not observe any increase in rates of hospitalisation or death within 30 days of treatment among mCRC patients treated with bevacizumab plus chemotherapy versus chemotherapy alone; these findings should be interpreted with caution due to the risk of residual confounding., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Purpose: Precision oncology has the potential to improve patient health and reduce treatment costs. Yet the up-front cost of genomic testing with next-generation sequencing (NGS) technologies can be prohibitive. Our study is a structured review of economic evaluations of precision oncology informed by NGS. The aim is to characterize the availability and scope of economic evidence., Materials and Methods: We searched Medline (PubMed), Embase (Ovid), and Web of Science databases for English-language full-text peer-reviewed articles published between 2000 and 2016. We focused our search on articles that estimated the benefit of precision oncology in relation to its costs. We excluded studies that did not undertake full economic evaluations or did not focus on NGS technologies. We reviewed all included studies and summarized key methodological and empirical study characteristics., Results: Fifty-five economic evaluations met our inclusion criteria. The number of published studies increased steadily, from three studies between 2005 and 2007 to 26 between 2014 and 2016. Most studies evaluated multiplex panels (86%). We found testing was frequently used to predict prognosis (67%), to diagnose patients (24%), or to identify targeted therapeutic options (7%). Methods and cost effectiveness differed according to NGS technology, test strategy, and cancer type. Deterministic and probabilistic analyses were typically used to characterize parameter and decision uncertainty (91% and 75%)., Conclusion: Although the availability of economic evidence examining precision oncology increased over time, methods used often did not align with current guidelines. Future evaluations should undertake extensive sensitivity analysis to address all sources of uncertainty associated with rapidly changing NGS technologies. Furthermore, additional research is needed evaluating the cost effectiveness of more comprehensive next-generation technologies before implementing these on a wider scale.

Background: Preterm birth is the leading risk factor for perinatal white matter injury, which can lead to motor and neuropsychiatric impairment across the life course. There is an unmet clinical need for therapeutics. White matter injury is associated with an altered inflammatory response in the brain, primarily led by microglia, and subsequent hypomyelination. However, microglia can release both damaging and trophic factors in response to injury, and a comprehensive assessment of these factors in the preterm central nervous system (CNS) has not been carried out. Method: A custom antibody array was used to assess relative levels of 50 inflammation- and myelination-associated proteins in the cerebrospinal fluid (CSF) of preterm infants in comparison to term controls. Results: Fifteen proteins differed between the groups: BDNF, BTC, C5a, FasL, Follistatin, IL-1β, IL-2, IL-4, IL-9, IL-17A, MIP-1α, MMP8, SPP1, TGFβ, and TNFβ ( p < 0.05). To investigate the temporal regulation of these proteins after injury, we mined a gene expression dataset of microglia isolated from a mouse model of developmental white matter injury. Microglia in the experimental model showed dynamic temporal expression of genes encoding these proteins, with an initial and sustained pro-inflammatory response followed by a delayed anti-inflammatory response, and a continuous expression of genes predicted to inhibit healthy myelination. Conclusion: Preterm CSF shows a distinct neuroinflammatory profile compared to term controls, suggestive of a complex neural environment with concurrent damaging and reparative signals. We propose that limitation of pro-inflammatory responses, which occur early after perinatal insult, may prevent expression of myelination-suppressive genes and support healthy white matter development.

Purpose: Measures of white matter (WM) microstructure inferred from diffusion magnetic resonance imaging (dMRI) are useful for studying brain development. There is uncertainty about agreement between FA and MD values obtained from region-of-interest (ROI) versus whole tract approaches. We investigated agreement between dMRI measures using ROI and Probabilistic Neighbourhood Tractography (PNT) in genu of corpus callosum (gCC) and corticospinal tracts (CST)., Materials and Methods: 81 neonates underwent 64 direction DTI at term equivalent age. FA and MD values were extracted from a 8 mm 3 ROI placed within the gCC, right and left posterior limbs of internal capsule. PNT was used to segment gCC and CSTs to calculate whole tract-averaged FA and MD. Agreement between values obtained by each method was compared using Bland-Altman statistics and Pearson's correlation., Results: Across the 3 tracts the mean difference in FA measured by PNT and ROI ranged between 0.13 and 0.17, and the 95% limits of agreement did not include the possibility of no difference. For MD, the mean difference in values obtained from PNT and ROI ranged between 0.101 and 0.184 mm 2 /s × 10 -3  mm 2 /s: the mean difference in gCC was 0.101 × 10 -3  mm 2 /s with 95% limits of agreement that included the possibility of no difference, but there was significant disagreement in MD values measured in the CSTs., Conclusion: Agreement between dMRI measures of neonatal WM microstructure calculated from ROI and whole tract averaged methods is weak. ROI approaches may not provide sufficient representation of tract microstructure at the level of neural systems in newborns., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Expenditure on systemic therapy for cancer has been increasing quickly owing to population growth, increased use, both in the number of users and in prescription volume, and rising drug prices. Our objective was to describe trends in expenditure in British Columbia and Saskatchewan's cancer care systems and to elucidate these drivers of growth., Methods: In this trend analysis, we obtained pharmacy dispensing records from the BC Cancer and Saskatchewan Cancer Agency pharmacies for all anticancer therapies dispensed in 2006-2013. We calculated total annual expenditure directly from the data and conducted a trend analysis of crude and standardized annual expenditure using generalized linear models. We estimated trends in the following components of total expenditure: cancer incidence, number of systemic therapy users per incident case, number of dispensed prescriptions per user and cost per prescription. Analysis was stratified by patient age group, cancer site and route of administration (oral or intravenous/other)., Results: Expenditure on systemic therapies, adjusted for population growth and aging, increased an average of 9.2% (95% confidence interval [CI] 7.2 to 11.2) per year in Saskatchewan and 6.4% (95% CI 5.3 to 7.6) per year in BC. Growth in expenditure on orally administered agents was more than 2 times higher than growth in expenditure on intravenous/other agents. Growth rates varied significantly by cancer site. In both provinces, rising cost per prescription was the largest contributor to overall growth., Interpretation: Price is the primary driver of growth in systemic therapy expenditure in both BC and Saskatchewan. Understanding the mechanisms of expenditure growth may inform system planning and support policy-makers' efforts to manage rising costs., Competing Interests: Competing interests: None declared., (Copyright 2018, Joule Inc. or its licensors.)

A latent measure of white matter microstructure (g WM ) provides a neural basis for information processing speed and intelligence in adults, but the temporal emergence of g WM during human development is unknown. We provide evidence that substantial variance in white matter microstructure is shared across a range of major tracts in the newborn brain. Based on diffusion MRI scans from 145 neonates [gestational age (GA) at birth range 23 +2 -41 +5 weeks], the microstructural properties of eight major white matter tracts were calculated using probabilistic neighborhood tractography. Principal component analyses (PCAs) were carried out on the correlations between the eight tracts, separately for four tract-averaged water diffusion parameters: fractional anisotropy, and mean, radial and axial diffusivities. For all four parameters, PCAs revealed a single latent variable that explained around half of the variance across all eight tracts, and all tracts showed positive loadings. We considered the impact of early environment on general microstructural properties, by comparing term-born infants with preterm infants at term equivalent age. We found significant associations between GA at birth and the latent measure for each water diffusion measure; this effect was most apparent in projection and commissural fibers. These data show that a latent measure of white matter microstructure is present in very early life, well before myelination is widespread. Early exposure to extra-uterine life is associated with altered general properties of white matter microstructure, which could explain the high prevalence of cognitive impairment experienced by children born preterm.

Neuroinflammation contributes to developmental brain injury associated with preterm birth, but the mediators that drive it are incompletely understood. Previous studies have shown that complement C5a is present and injurious in the brains of foetal mice exposed to preterm labour. Here, we demonstrate that C5a is present in the cerebrospinal fluid of newborn human infants and that levels are elevated in those born preterm. The difference is not explained by systemic infection. Complement activation in the neonatal brain and its role as a potential therapeutic target in preterm brain injury warrant further study. Activation in the neonatal brain and its role as a potential therapeutic target for preterm brain injury warrants further study.

Introduction: Lung cancer risk prediction models have the potential to make programs more affordable; however, the economic evidence is limited., Methods: Participants in the National Lung Cancer Screening Trial (NLST) were retrospectively identified with the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. The high-risk subgroup was assessed for lung cancer incidence and demographic characteristics compared with those in the low-risk subgroup and the Pan-Canadian Early Detection of Lung Cancer Study (PanCan), which is an observational study that was high-risk-selected in Canada. A comparison of high-risk screening versus standard care was made with a decision-analytic model using data from the NLST with Canadian cost data from screening and treatment in the PanCan study. Probabilistic and deterministic sensitivity analyses were undertaken to assess uncertainty and identify drivers of program efficiency., Results: Use of the risk prediction tool developed from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial with a threshold set at 2% over 6 years would have reduced the number of individuals who needed to be screened in the NLST by 81%. High-risk screening participants in the NLST had more adverse demographic characteristics than their counterparts in the PanCan study. High-risk screening would cost $20,724 (in 2015 Canadian dollars) per quality-adjusted life-year gained and would be considered cost-effective at a willingness-to-pay threshold of $100,000 in Canadian dollars per quality-adjusted life-year gained with a probability of 0.62. Cost-effectiveness was driven primarily by non-lung cancer outcomes. Higher noncurative drug costs or current costs for immunotherapy and targeted therapies in the United States would render lung cancer screening a cost-saving intervention., Conclusions: Non-lung cancer outcomes drive screening efficiency in diverse, tobacco-exposed populations. Use of risk selection can reduce the budget impact, and screening may even offer cost savings if noncurative treatment costs continue to rise., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Background: Costing studies are useful to measure the economic burden of cancer. Comparing costs between healthcare systems can inform evaluation, development or modification of cancer care policies., Objectives: To estimate and compare cancer costs in British Columbia and Ontario from the payers' perspectives., Methods: Using linked cancer registry and administrative data, and standardized costing methodology and analyses, we estimated costs for 21 cancer sites by phase of care to determine potential differences between provinces., Results: Overall, costs were higher in Ontario. Costs were highest in the initial post-diagnosis and pre-death phases and lowest in the pre-diagnosis and continuing phases, and generally higher for brain cancer and multiple myeloma, and lower for melanoma. Hospitalization was the major cost category. Costs for physician services and diagnostic tests differed the most between provinces., Conclusions: The standardization of data and costing methodology is challenging, but it enables interprovincial and international comparative costing analyses., (Copyright © 2017 Longwoods Publishing.)

Quantitative volumes from brain magnetic resonance imaging (MRI) acquired across the life course may be useful for investigating long term effects of risk and resilience factors for brain development and healthy aging, and for understanding early life determinants of adult brain structure. Therefore, there is an increasing need for automated segmentation tools that can be applied to images acquired at different life stages. We developed an automatic segmentation method for human brain MRI, where a sliding window approach and a multi-class random forest classifier were applied to high-dimensional feature vectors for accurate segmentation. The method performed well on brain MRI data acquired from 179 individuals, analyzed in three age groups: newborns (38-42 weeks gestational age), children and adolescents (4-17 years) and adults (35-71 years). As the method can learn from partially labeled datasets, it can be used to segment large-scale datasets efficiently. It could also be applied to different populations and imaging modalities across the life course.

Preterm infants are susceptible to inflammation-induced white matter injury but the exposures that lead to this are uncertain. Histologic chorioamnionitis (HCA) reflects intrauterine inflammation, can trigger a fetal inflammatory response, and is closely associated with premature birth. In a cohort of 90 preterm infants with detailed placental histology and neonatal brain magnetic resonance imaging (MRI) data at term equivalent age, we used Tract-based Spatial Statistics (TBSS) to perform voxel-wise statistical comparison of fractional anisotropy (FA) data and computational morphometry analysis to compute the volumes of whole brain, tissue compartments and cerebrospinal fluid, to test the hypothesis that HCA is an independent antenatal risk factor for preterm brain injury. Twenty-six (29%) infants had HCA and this was associated with decreased FA in the genu, cingulum cingulate gyri, centrum semiovale, inferior longitudinal fasciculi, limbs of the internal capsule, external capsule and cerebellum (p < 0.05, corrected), independent of degree of prematurity, bronchopulmonary dysplasia and postnatal sepsis. This suggests that diffuse white matter injury begins in utero for a significant proportion of preterm infants, which focuses attention on the development of methods for detecting fetuses and placentas at risk as a means of reducing preterm brain injury., Competing Interests: All co-authors have reviewed and approved the contents of the manuscript. The authors report no real or potential conflicts of interest concerning this work.

Background: Cancer is a major public health issue and represents a significant economic burden to health care systems worldwide. The objective of this analysis was to estimate phase-specific, 5-year and lifetime net costs for the 21 most prevalent cancer sites, and remaining tumour sites combined, in Ontario, Canada., Methods: We selected all adult patients diagnosed with a primary cancer between 1997 and 2007, with valid ICD-O site and histology codes, and who survived 30 days or more after diagnosis, from the Ontario Cancer Registry (N = 394,092). Patients were linked to treatment data from Cancer Care Ontario and administrative health care databases at the Institute for Clinical and Evaluative Sciences. Net costs (i.e., cost difference between patients and matched non-cancer control subjects) were estimated by phase of care and sex, and used to estimate 5-year and lifetime costs., Results: Mean net costs of care (2009 CAD) were highest in the initial (6 months post-diagnosis) and terminal (12 months pre-death) phases, and lowest in the (3 months) pre-diagnosis and continuing phases of care. Phase-specific net costs were generally lowest for melanoma and highest for brain cancer. Mean 5-year net costs varied from less than $25,000 for melanoma, thyroid and testicular cancers to more than $60,000 for multiple myeloma and leukemia. Lifetime costs ranged from less than $55,000 for lung and liver cancers to over $110,000 for leukemia, multiple myeloma, lymphoma and breast cancer., Conclusions: Costs of cancer care are substantial and vary by cancer site, phase of care and time horizon analyzed. These cost estimates are valuable to decision makers to understand the economic burden of cancer care and may be useful inputs to researchers undertaking cancer-related economic evaluations.

Background: Preterm birth is closely associated with neurocognitive impairment in childhood including increased risk for social difficulties. Eye tracking objectively assesses eye-gaze behaviour in response to visual stimuli, which permits inference about underlying cognitive processes. We tested the hypothesis that social orienting in infancy is altered by preterm birth., Methods: Fifty preterm infants with mean (range) gestational age (GA) at birth of 29(+1) (23(+2) -33(+0) ) weeks and 50 term infants with mean (range) GA at birth 40(+2) (37(+0) -42(+3) ) weeks underwent eye tracking at median age of 7 months. Infants were presented with three categories of social stimuli of increasing complexity. Time to first fixate (TFF) and looking time (LT) on areas of interest (AoIs) were recorded using remote eye tracking., Results: Preterm infants consistently fixated for a shorter time on social content than term infants across all three tasks: face-scanning (fixation to eyes minus mouth 0.61s vs. 1.47s, p = .013); face pop-out task (fixation to face 0.8s vs. 1.34s, p = .023); and social preferential looking (1.16s vs. 1.5s p = .02). Time given to AoIs containing social content as a proportion of LT at the whole stimulus was lower in preterm infants across all three tasks. These results were not explained by differences in overall looking time between the groups., Conclusions: Eye tracking provides early evidence of atypical cognition after preterm birth, and may be a useful tool for stratifying infants at risk of impairment for early interventions designed to improve outcome., (© 2016 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Neuroimage analysis pipelines rely on parcellated atlases generated from healthy individuals to provide anatomic context to structural and diffusion MRI data. Atlases constructed using adult data introduce bias into studies of early brain development. We aimed to create a neonatal brain atlas of healthy subjects that can be applied to multi-modal MRI data. Structural and diffusion 3T MRI scans were acquired soon after birth from 33 typically developing neonates born at term (mean postmenstrual age at birth 39(+5) weeks, range 37(+2)-41(+6)). An adult brain atlas (SRI24/TZO) was propagated to the neonatal data using temporal registration via childhood templates with dense temporal samples (NIH Pediatric Database), with the final atlas (Edinburgh Neonatal Atlas, ENA33) constructed using the Symmetric Group Normalization (SyGN) method. After this step, the computed final transformations were applied to T2-weighted data, and fractional anisotropy, mean diffusivity, and tissue segmentations to provide a multi-modal atlas with 107 anatomical regions; a symmetric version was also created to facilitate studies of laterality. Volumes of each region of interest were measured to provide reference data from normal subjects. Because this atlas is generated from step-wise propagation of adult labels through intermediate time points in childhood, it may serve as a useful starting point for modeling brain growth during development.

Accurate whole-brain segmentation, or brain extraction, of magnetic resonance imaging (MRI) is a critical first step in most neuroimage analysis pipelines. The majority of brain extraction algorithms have been developed and evaluated for adult data and their validity for neonatal brain extraction, which presents age-specific challenges for this task, has not been established. We developed a novel method for brain extraction of multi-modal neonatal brain MR images, named ALFA (Accurate Learning with Few Atlases). The method uses a new sparsity-based atlas selection strategy that requires a very limited number of atlases 'uniformly' distributed in the low-dimensional data space, combined with a machine learning based label fusion technique. The performance of the method for brain extraction from multi-modal data of 50 newborns is evaluated and compared with results obtained using eleven publicly available brain extraction methods. ALFA outperformed the eleven compared methods providing robust and accurate brain extraction results across different modalities. As ALFA can learn from partially labelled datasets, it can be used to segment large-scale datasets efficiently. ALFA could also be applied to other imaging modalities and other stages across the life course.

Objectives: Most cancer patients want to die at home, but scaleable models to achieve this are not well researched. Our objective was to investigate the temporal association of homecare nursing, especially by generalist nurses, with reduced end-of-life hospitalizations., Methods: We conducted a retrospective Canadian cohort study of end-of-life cancer decedents during 2004-2009 in Ontario (ON), Nova Scotia (NS), and British Columbia (BC), which have homecare systems that use generalist nurses to provide end-of-life care. Each province linked administrative databases to examine the association during the last six months of life between the homecare nursing rate and the hospitalization rate in the subsequent week, using standardized definitions and controlling for other covariates. We dichotomized nursing into standard and end-of-life care intent., Results: Our cohort included 83,827 cancer decedents. Approximately 55% of decedents were older than 70 and the most common cancer was lung. Nearly 85% of the cohort had at least one hospital admission. Receiving end-of-life compared to standard homecare nursing significantly reduced a patient's hospitalization rate by 34%, 33%, and 17% in ON, BC, and NS. In the last month of life patients having a standard nursing rate of greater than five hours compared to one hour per week had a significantly lower hospitalization rate (relative reduction of 15%-23%) across the three provinces., Conclusions: Our study showed a protective effect of nursing with an end-of-life intent on hospitalization across the last six months of life and of standard nursing in the last month. This finding's generalizability is strengthened, since the trends were similar across three different homecare systems.

Context: Despite being commonplace in health care systems, little research has described home care nursing's effectiveness to reduce acute care use at the end of life., Objectives: To examine the temporal association between home care nursing rate on emergency department (ED) visit rate in the subsequent week during the last six months of life., Methods: We conducted a retrospective cohort study of end-of-life cancer decedents in Ontario, Canada, from 2004 to 2009 by linking administrative databases. We examined the association between home care nursing rate of one week with the ED rate in the subsequent week closer to death, controlling for covariates and repeated measures among decedents. Nursing was dichotomized into standard and end-of-life care intent., Results: Our cohort included 54,576 decedents who used home care nursing services in the last six months before death, where 85% had an ED visit and 68% received end-of-life home care nursing. Patients receiving end-of-life nursing at any week had a significantly reduced ED rate in the subsequent week of 31% (relative rate [RR] 0.69; 95% confidence interval [CI] 0.68, 0.71) compared with standard nursing. In the last month of life, receiving end-of-life nursing and standard nursing rate of more than five hours/week was associated with a decreased ED rate of 41% (RR 0.59, 95% CI 0.58, 0.61) and 32% (RR 0.68, 95% CI 0.66, 0.70), respectively, compared with standard nursing of one hour/week., Conclusion: Our study showed a temporal association between receiving end-of-life nursing in a given week during the last six months of life, and of more standard nursing in the last month of life, with a reduced ED rate in the subsequent week., (Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: To develop data-driven and achievable benchmark rates for end-of-life quality indicators using administrative data from four provinces in Canada., Methods: Indicators of end-of-life care were defined and measured using linked administrative data for 33 health regions across British Columbia, Alberta, Ontario, and Nova Scotia. These were emergency department use, intensive care unit admission, physician house calls and home care visits before death, and death in hospital. An empiric benchmark was defined using indicator rates from the top-ranked regions to include the top decile of patients overall. Funnel plots were used to graph each region's age- and sex-adjusted indicator rates along with the overall rate and 95% confidence limits., Results: Rates varied approximately two- to four-fold across the regions, with physician house calls showing the greatest variation. Benchmark rates based on the top decile performers were emergency department use, 34%; intensive care unit admission, 2%; physician house calls, 34%; home care visits, 63%; and death in hospital, 38%. With the exception of intensive care unit admission, funnel plots demonstrated that overall indicator rates and their confidence limits were uniformly worse than benchmarks even after adjusting for age and sex. Few regions met the benchmark rates., Conclusion: There is significant variation in end-of-life quality indicators across regions in four provinces in Canada. Using this study's methods-deriving empiric benchmarks and funnel plots-regions can determine their relative performance with greater context that facilitates priority setting and resource deployment. Applying this study's methods can support quality improvement by decreasing variation and striving for a target., (Copyright © 2015 by American Society of Clinical Oncology.)

Background: An important challenge with the application of next-generation sequencing technology is the possibility of uncovering incidental genomic findings. A paucity of evidence on personal utility for incidental findings has hindered clinical guidelines. Our objective was to estimate personal utility for complex information derived from incidental genomic findings., Methods: We used a discrete-choice experiment to evaluate participants' personal utility for the following attributes: disease penetrance, disease treatability, disease severity, carrier status and cost. Study participants were drawn from the Canadian public. We analyzed the data with a mixed logit model., Results: In total, 1200 participants completed our questionnaire (available in English and French). Participants valued receiving information about high-penetrance disorders but expressed disutility for receiving information on low-penetrance disorders. The average willingness to pay was $445 (95% confidence interval [CI] $322-$567) to receive incidental findings in a scenario where clinicians returned information about high-penetrance, medically treatable disorders, but only 66% of participants (95% CI 63%-71%) indicated that they would choose to receive information in that scenario. On average, participants placed an important value ($725, 95% CI $600-$850) on having a choice about what type of findings they would receive, including receipt of information about high-penetrance, treatable disorders or receipt of information about high-penetrance disorders with or without available treatment. The predicted uptake of that scenario was 76% (95% CI 72%-79%)., Interpretation: Most participants valued receiving incidental findings, but personal utility depended on the type of finding, and not all participants wanted to receive incidental results, regardless of the potential health implications. These results indicate that to maximize benefit, participant-level preferences should inform the decision about whether to return incidental findings., (© 2015 Canadian Medical Association or its licensors.)

Preterm birth is associated with altered connectivity of neural circuits. We developed a tract segmentation method that provides measures of tract shape and integrity (probabilistic neighborhood tractography, PNT) from diffusion MRI (dMRI) data to test the hypotheses: 1) preterm birth is associated with alterations in tract topology (R), and tract-averaged mean diffusivity (〈D〉) and fractional anisotropy (FA); 2) neural systems are separable based on tract-averaged dMRI parameters; and 3) PNT can detect neuroprotective treatment effects. dMRI data were collected from 87 preterm infants (mean gestational age 29(+1) weeks, range 23(+2) -34(+6)) at term equivalent age and 24 controls (mean gestational age 39(+6) weeks). PNT was used to segment eight major fasciculi, characterize topology, and extract tract-averaged〈D〉and FA. Tract topology was altered by preterm birth in all tracts except the splenium (p < 0.05, false discovery rate [FDR] corrected). After adjustment for age at scan, tract-averaged〈D〉was increased in the genu and splenium, right corticospinal tract (CST) and the left and right inferior longitudinal fasciculi (ILF) in preterm infants compared with controls (p < 0.05, FDR), while tract-averaged FA was decreased in the splenium and left ILF (p < 0.05, FDR). Specific fasciculi were separable based on tract-averaged〈D〉and FA values. There was a modest decrease in tract-averaged〈D〉in the splenium of preterm infants who had been exposed to antenatal MgSO4 for neuroprotection (p = 0.002). Tract topology is a biomarker of preterm brain injury. The data provide proof of concept that tract-averaged dMRI parameters have utility for evaluating tissue effects of perinatal neuroprotective strategies.

Objectives: The sensitivity of screening mammography is much lower among women who have dense breast tissue, compared with women who have largely fatty breasts, and they are also at much higher risk of developing the disease. Increasing mammography screening frequency from biennially to annually has been suggested as a policy option to address the elevated risk in this population. The purpose of this study was to assess the cost-effectiveness of annual versus biennial screening mammography among women aged 50-79 with dense breast tissue., Methods: A Markov model was constructed based on screening, diagnostic, and treatment pathways for the population-based screening and cancer care programme in British Columbia, Canada. Model probabilities and screening costs were calculated from screening programme data. Costs for breast cancer treatment were calculated from treatment data, and utility values were obtained from the literature. Incremental cost-effectiveness was expressed as cost per quality adjusted life year (QALY), and probabilistic sensitivity analysis was conducted., Results: Compared with biennial screening, annual screening generated an additional 0.0014 QALYs (95% CI: -0.0480-0.0359) at a cost of $819 ($ = Canadian dollars) per patient (95% CI: 506-1185), resulting in an incremental cost effectiveness ratio of $565,912/QALY. Annual screening had a 37.5% probability of being cost-effective at a willingness-to-pay threshold of $100,000/QALY., Conclusion: There is considerable uncertainty about the incremental cost-effectiveness of annual mammography. Further research on the comparative effectiveness of screening strategies for women with high mammographic breast density is warranted, particularly as digital mammography and density measurement become more widespread, before cost-effectiveness can be reevaluated., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Prostate-specific antigen (PSA) screening for prostate cancer may reduce mortality, but it incurs considerable risk of over diagnosis and potential harm to quality of life. Our objective was to evaluate the cost-effectiveness of PSA screening, with and without adjustment for quality of life, for the British Columbia (BC) population. We adapted an existing natural history model using BC incidence, treatment, cost and mortality patterns. The modeled mortality benefit of screening derives from a stage-shift mechanism, assuming mortality reduction consistent with the European Study of Randomized Screening for Prostate Cancer. The model projected outcomes for 40-year-old men under 14 combinations of screening ages and frequencies. Cost and utility estimates were explored with deterministic sensitivity analysis. The incremental cost-effectiveness of regular screening ranged from $36,300/LYG, for screening every four years from ages 55 to 69 years, to $588,300/LYG, for screening every two years from ages 40 to 74 years. The marginal benefits of increasing screening frequency to 2 years or starting screening at age 40 years were small and came at significant cost. After utility adjustment, all screening strategies resulted in a loss of quality-adjusted life years (QALYs); however, this result was very sensitive to utility estimates. Plausible outcomes under a range of screening strategies inform discussion of prostate cancer screening policy in BC and similar jurisdictions. Screening may be cost-effective, but the sensitivity of results to utility values suggests individual preferences for quality versus quantity of life should be a key consideration., (© 2014 UICC.)

Background: Women with mutations in BRCA1 or BRCA2 are at high risk of developing breast cancer and, in British Columbia, Canada, are offered screening with both magnetic resonance imaging (MRI) and mammography to facilitate early detection. MRI is more sensitive than mammography but is more costly and produces more false positive results. The purpose of this study was to calculate the cost-effectiveness of MRI screening for breast cancer in BRCA1/2 mutation carriers in a Canadian setting., Methods: We constructed a Markov model of annual MRI and mammography screening for BRCA1/2 carriers, using local data and published values. We calculated cost-effectiveness as cost per quality-adjusted life-year gained (QALY), and conducted one-way and probabilistic sensitivity analysis., Results: The incremental cost-effectiveness ratio (ICER) of annual mammography plus MRI screening, compared to annual mammography alone, was $50,900/QALY. After incorporating parameter uncertainty, MRI screening is expected to be a cost-effective option 86% of the time at a willingness-to-pay of $100,000/QALY, and 53% of the time at a willingness-to-pay of $50,000/QALY. The model is highly sensitive to the cost of MRI; as the cost is increased from $200 to $700 per scan, the ICER ranges from $37,100/QALY to $133,000/QALY., Conclusions: The cost-effectiveness of using MRI and mammography in combination to screen for breast cancer in BRCA1/2 mutation carriers is finely balanced. The sensitivity of the results to the cost of the MRI screen itself warrants consideration: in jurisdictions with higher MRI costs, screening may not be a cost-effective use of resources, but improving the efficiency of MRI screening will also improve cost-effectiveness.