43 research outputs found
Real world costs and cost-effectiveness of Rituximab for diffuse large B-cell lymphoma patients: a population-based analysis.
BackgroundCurrent treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice.MethodsWe performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG).ResultsRituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of 61,984 (95% CI 135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was 31,800/LYG) but increased to 110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age.ConclusionsOur results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was potentially cost-effective by standard thresholds for patients <60 years old. However, cost-effectiveness decreased significantly with age, suggesting that rituximab may be not as economically attractive in the very elderly on average. This has important clinical implications regarding age-related use and funding decisions on this drug
p19( Arf) Suppresses Growth, Progression, and Metastasis of Hras-Driven Carcinomas through p53-Dependent and -Independent Pathways
Ectopic expression of oncogenes such as Ras induces expression of p19(Arf), which, in turn, activates p53 and growth arrest. Here, we used a multistage model of squamous cell carcinoma development to investigate the functional interactions between Ras, p19(Arf), and p53 during tumor progression in the mouse. Skin tumors were induced in wild-type, p19(Arf)-deficient, and p53-deficient mice using the DMBA/TPA two-step protocol. Activating mutations in Hras were detected in all papillomas and carcinomas examined, regardless of genotype. Relative to wild-type mice, the growth rate of papillomas was greater in p19(Arf)-deficient mice, and reduced in p53-deficient mice. Malignant conversion of papillomas to squamous cell carcinomas, as well as metastasis to lymph nodes and lungs, was markedly accelerated in both p19 (Arf)- and p53-deficient mice. Thus, p19(Arf) inhibits the growth rate of tumors in a p53-independent manner. Through its regulation of p53, p19(Arf) also suppresses malignant conversion and metastasis. p53 expression was upregulated in papillomas from wild-type but not p19( Arf)-null mice, and p53 mutations were more frequently seen in wild-type than in p19( Arf)-null carcinomas. This indicates that selection for p53 mutations is a direct result of signaling from the initiating oncogenic lesion, Hras, acting through p19(Arf)
Phase-specific and lifetime costs of cancer care in Ontario, Canada
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 60,000 for multiple myeloma and leukemia. Lifetime costs ranged from less than 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
Soil Inorganic N Leaching in Edges of Different Forest Types Subject to High N Deposition Loads
Cortisol, cognition and the ageing prefrontal cortex
The structural and functional decline of the ageing human brain varies by brain
region, cognitive function and individual. The underlying biological mechanisms are
poorly understood. One potentially important mechanism is exposure to
glucocorticoids (GCs; cortisol in humans); GC production is increasingly varied with
age in humans, and chronic exposure to high levels is hypothesised to result in
cognitive decline via cerebral remodelling. However, studies of GC exposure in
humans are scarce and methodological differences confound cross-study comparison.
Furthermore, there has been little focus on the effects of GCs on the frontal lobes and
key white matter tracts in the ageing brain. This thesis therefore examines
relationships among cortisol levels, structural brain measures and cognitive
performance in 90 healthy, elderly community-dwelling males from the Lothian
Birth Cohort 1936. Salivary cortisol samples characterised diurnal (morning and
evening) and reactive profiles (before and after a cognitive test battery). Structural
variables comprised Diffusion Tensor Imaging measures of major brain tracts and a
novel manual parcellation method for the frontal lobes. The latter was based on a
systematic review of current manual methods in the context of putative function and
cytoarchitecture. Manual frontal lobe brain parcellation conferred greater spatial and
volumetric accuracy when compared to both single- and multi-atlas parcellation at
the lobar level. Cognitive ability was assessed via tests of general cognitive ability,
and neuropsychological tests thought to show differential sensitivity to the integrity
of frontal lobe sub-regions. The majority of, but not all frontal lobe test scores shared
considerable overlap with general cognitive ability, and cognitive scores correlated
most consistently with the volumes of the anterior cingulate. This is discussed in
light of the diverse connective profile of the cingulate and a need to integrate
information over more diffuse cognitive networks according to proposed de-differentiation
or compensation in ageing. Individuals with higher morning, evening
or pre-test cortisol levels showed consistently negative relationships with specific
regional volumes and tract integrity. Participants whose cortisol levels increased
between the start and end of cognitive testing showed selectively larger regional
volumes and lower tract diffusivity (correlation magnitudes <.44). The significant
relationships between cortisol levels and cognition indicated that flatter diurnal
slopes or higher pre-test levels related to poorer test performance. In contrast, higher
levels in the morning generally correlated with better scores (correlation magnitudes
<.25). Interpretation of all findings was moderated by sensitivity to type I error,
given the large number of comparisons conducted. Though there were limited
candidates for mediation analysis, cortisol-function relationships were partially
mediated by tract integrity (but not sub-regional frontal volumes) for memory and
post-error slowing. This thesis offers a novel perspective on the complex interplay
among glucocorticoids, cognition and the structure of the ageing brain. The findings
suggest some role for cortisol exposure in determining age-related decline in
complex cognition, mediated via brain structure
Benefits and harms of prostate cancer screening – predictions of the ONCOTYROL prostate cancer outcome and policy model
Patterns of Care and Costs for Older Patients With Colorectal Cancer at the End of Life: Descriptive Study of the United States and Canada.
Management of Solitary 1 cm to 2 cm Liver Nodules in Patients with Compensated Cirrhosis: A Decision Analysis
OBJECTIVES: Current guidelines, based on expert opinion, recommend that suspected 1 cm to 2 cm hepatocellular carcinoma (HCC) detected on screening be biopsied and, if positive, treated (eg, resection or transplantation). Alternative strategies are immediate treatment or observation until disease progression occurs
Understanding the costs of cancer care before and after diagnosis for the 21 most common cancers in Ontario: a population-based descriptive study
Background: The first year after cancer diagnosis is a period of intensive treatment and high cost. We sought to estimate costs for the 21 most common cancers in Ontario in the 3-month period before and the first year after diagnosis.
Methods: We used the Ontario Cancer Registry to select patients who received diagnoses between 1997 and 2007 at 19 years of age or older, with valid International Classification of Diseases for Oncology (ICD-O) and histology codes, who survived 30 days or longer after diagnosis and had no second cancer within 90 days of the initial cancer (n = 402 399). We used linked administrative data to calculate mean costs for each cancer during the pre- and postdiagnosis periods for patients who died within 1 year after diagnosis and patients who survived beyond 1 year after diagnosis.
Results: Mean prediagnosis costs were 2023–890 (95% CI 985) for melanoma to 3591–2188 (95% CI 2336) for esophageal cancer to 4664–25 914 (95% CI 26 046). Mean costs were lowest for melanoma (8221–50 620 [95% CI 53 562] among patients who survived beyond 1 year after diagnosis, and ranged from 25 747–81 655 (95% CI 104 949) for testicular cancer among patients who died within 1 year.
Interpretation Our research provides cancer-related cost estimates for the pre- and postdiagnosis phases and offers insight into the economic burden incurred by the Ontario health care system. These estimates can help inform policy-makers’ decisions regarding resource allocation for cancer prevention and control, and can serve as important input for economic evaluations