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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.
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Neoplasias Colorretais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Colúmbia Britânica , Camptotecina/efeitos adversos , Estudos de Coortes , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila , Humanos , Leucovorina , Estudos RetrospectivosRESUMO
BACKGROUND: The reported reexcision rates vary significantly for patients with invasive breast cancer undergoing breast-conserving surgery (BCS). This variability is a function of both the positive pathologic margin rate and the interpretation of an adequate pathologic margin. The influence of the SSO/ASTRO margin guidelines on reexcision rates and the potential cost savings is of interest from both quality and health economics perspectives. METHODS: A retrospective analysis of all patients undergoing BCS during a 3-year period (January 1, 2010-December 31, 2012) was performed. The reexcision rate and the pathologic margin status were assessed to determine the number of patients with pathologic negative margins who underwent reexcision. A decision analysis using previously published case costing information was used to determine the potential savings associated with avoidance of reoperation for patients meeting guidelines criteria. RESULTS: The analysis included 512 patients who underwent attempted BCS for invasive breast cancer. Reoperations occurred for 25% (126/512) of the BCS cohort, but this rate could potentially be decreased to 16% (44/512) if these guidelines were applied. Based on our cost model, application of the guidelines would provide a potential cost savings of $698 (95% confidence interval $523-$893) per patient undergoing attempted BCS in our population. CONCLUSIONS: Adherence to the SSO-ASTRO guidelines could prevent one-third of reoperations among patients undergoing BCS. This would result in significant cost savings to the health care system while avoiding unnecessary operations. Use of guidelines has the potential to improve the quality of care provided to patients.
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Neoplasias da Mama/cirurgia , Fidelidade a Diretrizes/economia , Margens de Excisão , Mastectomia Segmentar/economia , Reoperação/economia , Colúmbia Britânica , Redução de Custos , Feminino , Guias como Assunto , Humanos , Neoplasia Residual , Estudos RetrospectivosRESUMO
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.
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BACKGROUND: Research 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. METHODS: Our 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). RESULTS: The 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. CONCLUSIONS: In 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.
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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.
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DNA methylation (DNAm) plays a determining role in neural cell fate and provides a molecular link between early-life stress and neuropsychiatric disease. Preterm birth is a profound environmental stressor that is closely associated with alterations in connectivity of neural systems and long-term neuropsychiatric impairment. The aims of this study were to examine the relationship between preterm birth and DNAm, and to investigate factors that contribute to variance in DNAm. DNA was collected from preterm infants (birth<33 weeks gestation) and healthy controls (birth>37 weeks), and a genome-wide analysis of DNAm was performed; diffusion magnetic resonance imaging (dMRI) data were acquired from the preterm group. The major fasciculi were segmented, and fractional anisotropy, mean diffusivity and tract shape were calculated. Principal components (PC) analysis was used to investigate the contribution of MRI features and clinical variables to variance in DNAm. Differential methylation was found within 25 gene bodies and 58 promoters of protein-coding genes in preterm infants compared with controls; 10 of these have neural functions. Differences detected in the array were validated with pyrosequencing. Ninety-five percent of the variance in DNAm in preterm infants was explained by 23 PCs; corticospinal tract shape associated with 6th PC, and gender and early nutritional exposure associated with the 7th PC. Preterm birth is associated with alterations in the methylome at sites that influence neural development and function. Differential methylation analysis has identified several promising candidate genes for understanding the genetic/epigenetic basis of preterm brain injury.
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Encéfalo/fisiopatologia , Metilação de DNA/fisiologia , Imagem de Difusão por Ressonância Magnética , Epigenômica/métodos , Recém-Nascido Prematuro/fisiologia , Feminino , Humanos , Recém-Nascido , Masculino , Análise de Componente PrincipalRESUMO
BACKGROUND: The quality of data comparing care at the end of life (eol) in cancer patients across Canada is poor. This project used identical cohorts and definitions to evaluate quality indicators for eol care in British Columbia, Alberta, Ontario, and Nova Scotia. METHODS: This retrospective cohort study of cancer decedents during fiscal years 2004-2009 used administrative health care data to examine health service quality indicators commonly used and previously identified as important to quality eol care: emergency department use, hospitalizations, intensive care unit admissions, chemotherapy, physician house calls, and home care visits near the eol, as well as death in hospital. Crude and standardized rates were calculated. In each province, two separate multivariable logistic regression models examined factors associated with receiving aggressive or supportive care. RESULTS: Overall, among the identified 200,285 cancer patients who died of their disease, 54% died in a hospital, with British Columbia having the lowest standardized rate of such deaths (50.2%). Emergency department use at eol ranged from 30.7% in Nova Scotia to 47.9% in Ontario. Of all patients, 8.7% received aggressive care (similar across all provinces), and 46.3% received supportive care (range: 41.2% in Nova Scotia to 61.8% in British Columbia). Lower neighbourhood income was consistently associated with a decreased likelihood of supportive care receipt. INTERPRETATION: We successfully used administrative health care data from four Canadian provinces to create identical cohorts with commonly defined indicators. This work is an important step toward maturing the field of eol care in Canada. Future work in this arena would be facilitated by national-level data-sharing arrangements.