Outcome with lenalidomide plus dexamethasone followed by early autologous stem cell transplantation in patients with newly diagnosed multiple myeloma on the ECOG-ACRIN E4A03 randomized clinical trial: long-term follow-up

In Eastern Cooperative Oncology Group-ACRIN E4A03, on completion of four cycles of therapy, newly diagnosed multiple myeloma patients had the option of proceeding to autologous peripheral blood stem cell transplant (ASCT) or continuing on their assigned therapy lenalidomide plus low-dose dexamethasone (Ld) or lenalidomide plus high-dose dexamethasone (LD). This landmark analysis compared the outcome of 431 patients surviving their first four cycles of therapy pursuing early ASCT to those continuing on their assigned therapy. Survival distributions were estimated using the Kaplan–Meier method and compared with log-rank test. Ninety patients (21%) opted for early ASCT. The 1-, 2-, 3-, 4- an

The Dynamics of a Meandering River

We present a statistical model of a meandering river on an alluvial plane which is motivated by the physical non-linear dynamics of the river channel migration and by describing heterogeneity of the terrain by noise. We study the dynamics analytically and numerically. The motion of the river channel is unstable and we show that by inclusion of the formation of ox-bow lakes, the system may be stabilised. We then calculate the steady state and show that it is in agreement with simulations and measurements of field data.Comment: Revtex, 12 pages, 2 postscript figure

Expression of tissue factor in non-small-cell lung cancers and its relationship to metastasis

Tissue factor (TF) is an initiator of the extrinsic cascade of blood coagulation. Although recent studies have revealed a relationship between metastatic properties and TF expression in some neoplastic cells, the significance of TF in lung cancer, especially in non-small-cell lung cancer (NSCLC), is still unclear. In this study, TF was detected in NSCLC cell lines by functional study, Western blot analysis and immunocytochemical staining. TF levels in eight NSCLC cell lines were also quantitated by enzyme-linked immunosorbent assay (ELISA), and TF expression was evaluated in 55 specimens of surgically resected NSCLCs. NSCLC cell lines derived from metastatic lesions produced high levels of TF (48.3 ± 23.5 ng 10−6 cells, mean ± s.e.m.), whereas those derived from primary lesions produced low levels of TF (0.2 ± 0.1 ng 10−6 cells). Immunohistochemical studies disclosed significantly stronger staining for TF in cells from NSCLC patients with metastasis than in those without metastasis. Among the 28 patients with metastasis, ten were strongly positive, 16 were moderately positive and two were negative for TF. In contrast, among the 27 patients without metastasis, only two were strongly positive, 18 were moderately positive and seven were negative for TF. Therefore, malignant cells from patients with lung cancer produce various levels of TF, and TF may play an important role in the metastatic process. © 1999 Cancer Research Campaig

Phase 2 study of dovitinib in patients with relapsed or refractory multiple myeloma with or without t(4;14) translocation

Objectives: Approximately 15% of patients with multiple myeloma (MM) exhibit a t(4;14) translocation, which often results in constitutive activation of the receptor tyrosine kinase (RTK) fibroblast growth factor receptor 3 (FGFR3). This study evaluated the efficacy and safety of dovitinib, an RTK inhibitor with in vitro inhibitory activity against FGFR, in patients with r

Tissue factor expression as a possible determinant of thromboembolism in ovarian cancer

Ovarian cancer, and clear cell carcinoma in particular, reportedly increases the risk of venous thromboembolism (VTE). However, the mechanisms remain unclear. Tissue factor (TF) supposedly represents a major factor in the procoagulant activities of cancer cells. The present study examined the involvement of TF expression in VTE for patients with ovarian cancer. Subjects comprised 32 consecutive patients (mean age 49.8 years) with histologically confirmed ovarian cancer. Presence of VTE was examined using a combination of clinical features, D-dimer levels and venous ultrasonography. Immunohistochemical analysis was used to evaluate TF expression into 4 degrees. Venous thromboembolism was identified in 10 of the 32 patients (31%), including five of the 11 patients with clear cell carcinoma. Tissue factor expression was detected in cancer tissues from 24 patients and displayed significant correlations with VTE development (P=0.0003), D-dimer concentration (P=0.003) and clear cell carcinoma (P<0.05). Multivariate analysis identified TF expression as an independent predictive factor of VTE development (P<0.05). Tissue factor (TF) expression is a possible determinant of VTE development in ovarian cancer. In particular, clear cell carcinoma may produce excessive levels of TF and is more likely to develop VTE

The impact of diabetes prevention on labour force participation and income of older Australians: an economic study

Background: Globally, diabetes is estimated to affect 246 million people and is increasing. In Australia diabetes has been made a national health priority. While the direct costs of treating diabetes are substantial, and rising, the indirect costs are considered greater. There is evidence that interventions to prevent diabetes are effective, and cost-effective, but the impact on labour force participation and income has not been assessed. In this study we quantify the potential impact of implementing a diabetes prevention program, using screening and either metformin or a lifestyle intervention on individual economic outcomes of pre-diabetic Australians aged 45-64. Methods. The output of an epidemiological microsimulation model of the reduction in prevalence of diabetes from a lifestyle or metformin intervention, and another microsimulation model, Health&WealthMOD, of health and the associated impacts on labour force participation, personal income, savings, government revenue and expenditure were used to quantify the estimated outcomes of the two interventions. Results: An additional 753 person years in the labour force would have been achieved from 1993 to 2003 for the male cohort aged 60-64 years in 2003, if a lifestyle intervention had been introduced in 1983; with 890 person years for the equivalent female group. The impact on labour force participation was lower for the metformin intervention, and increased with age for both interventions. The male cohort aged 60-64 years in 2003 would have earned an additional $30 million in income with the metformin intervention, and the equivalent female cohort would have earned an additional$25 million. If the lifestyle intervention was introduced, the same male and female cohorts would have earned an additional $34 million and$28 million respectively from 1993 to 2003. For the individuals involved, on average, males would have earned an additional $44,600 per year and females an additional$31,800 per year, if they had continued to work as a result of preventing diabetes. Conclusions: In addition to improved health and wellbeing, considerable benefits to individuals, in terms of both additional working years and increased personal income, could be made by introducing either a lifestyle or metformin intervention to prevent diabetes

Access to general practitioner services amongst underserved Australians: a microsimulation study

<p>Abstract</p> <p>Background</p> <p>One group often identified as having low socioeconomic status, those living in remote or rural areas, are often recognised as bearing an unequal burden of illness in society. This paper aims to examine equity of utilisation of general practitioner services in Australia.</p> <p>Methods</p> <p>Using the 2005 National Health Survey undertaken by the Australian Bureau of Statistics, a microsimulation model was developed to determine the distribution of GP services that would occur if all Australians had equal utilisation of health services relative to need.</p> <p>Results</p> <p>It was estimated that those who are unemployed would experience a 19% increase in GP services. Persons residing in regional areas would receive about 5.7 million additional GP visits per year if they had the same access to care as Australians residing in major cities. This would be a 18% increase. There would be a 20% increase for inner regional residents and a 14% increase for residents of more remote regional areas. Overall there would be a 5% increase in GP visits nationally if those in regional areas had the same access to care as those in major cities.</p> <p>Conclusion</p> <p>Parity is an insufficient goal and disadvantaged persons and underserved areas require greater access to health services than the well served metropolitan areas due to their greater poverty and poorer health status. Currently underserved Australians suffer a double disadvantage: poorer health and poorer access to health services.</p

The personal and national costs of mental health conditions: impacts on income, taxes, government support payments due to lost labour force participation

<p>Abstract</p> <p>Background</p> <p>Mental health conditions have the ability to interrupt an individual's ability to participate in the labour force, and this can have considerable follow on impacts to both the individual and the state.</p> <p>Method</p> <p>Cross-sectional analysis of the base population of Health&WealthMOD, a microsimulation model built on data from the Australian Bureau of Statistics' <it>Survey of Disability, Ageing and Carers </it>and STINMOD, an income and savings microsimulation model was used to quantify the personal cost of lost income and the cost to the state from lost income taxation, increased benefits payments and lost GDP as a result of early retirement due to mental health conditions in Australians aged 45-64 in 2009.</p> <p>Results</p> <p>Individuals aged 45 to 64 years who have retired early due to depression personally have 73% lower income then their full time employed counterparts and those retired early due to other mental health conditions have 78% lower incomes. The national aggregate cost to government due to early retirement from these conditions equated to $278 million (£152.9 million) in lost income taxation revenue,$407 million (£223.9 million) in additional transfer payments and around $1.7 billion in GDP in 2009 alone.</p> <p>Conclusions</p> <p>The costs of mental health conditions to the individuals and the state are considerable. While individuals has to bear the economic costs of lost income in addition to the burden of the conditions itself, the impact on the state is loss of productivity from reduced workforce participation, lost income taxation revenue, and increased government support payments - in addition to direct health care costs.</p